Cutis

The Diagnosis: Leukemia Cutis

Hematoxylin and eosin staining revealed an infiltration of monomorphic atypical myeloid cells with cleaved nuclei within the dermis, with a relatively uninvolved epidermis (Figure, A). The cells formed aggregates in single-file lines along dermal collagen bundles. Occasional Auer rods, which are crystal aggregates of the enzyme myeloperoxidase, a marker unique to cells of the myeloid lineage (Figure, B) were appreciated.

Immunohistochemical staining for myeloperoxidase was weakly positive; however, flow cytometric evaluation of the bone marrow aspirate revealed that approximately 20% of all CD45+ cells were myeloid blasts. These findings confirmed the diagnosis of recurrent acute myeloid leukemia (AML). The diagnosis of AML can be confirmed with a bone marrow biopsy demonstrating more than 20% of the total cells in blast form as well as evidence that the cells are of myeloid origin, which can be inferred by the presence of Auer rods, positive myeloperoxidase staining, or immunophenotyping. In our patient, the Auer rods, myeloperoxidase staining, and atypical myeloid cells on skin biopsy, in conjunction with the bone marrow biopsy results, confirmed leukemia cutis.

Leukemia cutis is the infiltration of neoplastic proliferating leukocytes in the epidermis, dermis, or subcutis from a primary or more commonly metastatic malignancy. Leukemic cutaneous involvement is seen in up to 13% of leukemia patients and most commonly is seen in monocytic or myelomonocytic forms of AML.¹ It may present anywhere on the body but mostly is found on the back, trunk, and head. It also may have a predilection for areas with a history of trauma or inflammation. The lesions most often are firm, erythematous to violaceous papules and nodules, though leukemia cutis can present with hemorrhagic ulcers, purpura, or other cutaneous manifestations of concomitant thrombocytopenia such as petechiae and ecchymoses.² Involvement of the lower extremities mimicking venous stasis dermatitis has been described.^3,4

Treatment of leukemia cutis requires targeting the underlying leukemia² under the guidance of hematology and oncology as well as the use of chemotherapeutic agents.⁵ The presence of leukemia cutis is a poor prognostic sign, and a discussion regarding goals of care often is appropriate. Our patient initially responded to FLAG (fludarabine, cytarabine, filgrastim) chemotherapy induction and consolidation, which was followed by midostaurin maintenance. However, she ultimately regressed, requiring decitabine and gilteritinib treatment, and died 9 months later from the course of the disease.

Although typically asymptomatic and presenting on the lower limbs, capillaritis (also known as the pigmented purpuric dermatoses) consists of a set of cutaneous conditions that often are chronic and relapsing in nature, as opposed to our patient’s subacute presentation. These benign conditions have several distinct morphologies; some are characterized by pigmented macules or pinpoint red-brown petechiae that most often are found on the legs but also are seen on the trunk and upper extremities.⁶ Of the various clinical presentations of capillaritis, our patient’s skin findings may be most consistent with pigmented purpuric lichenoid dermatitis of Gougerot and Blum, in which purpuric red-brown papules coalesce into plaques, though her lesions were not raised. The other pigmented purpuric dermatoses can present with cayenne pepper–colored petechiae, golden-brown macules, pruritic purpuric patches, or red-brown annular patches,6 which were not seen in our patient.

Venous stasis dermatitis also favors the lower extremities⁷; however, it classically includes the medial malleolus and often presents with scaling and hyperpigmentation from hemosiderin deposition.⁸ It often is associated with pruritus, as opposed to the nonpruritic nonpainful lesions in leukemia cutis. Other signs of venous insufficiency also may be appreciated, including edema or varicose veins,⁷ which were not evident in our patient.

Leukocytoclastic vasculitis, a small vessel vasculitis, also appears as palpable or macular purpura, which classically is asymptomatic and erupts on the shins approximately 1 week after an inciting exposure,⁹ such as medications, pathogens, or autoimmune diseases. One of the least distinctive vasculitides is polyarteritis nodosa, a form of medium vessel vasculitis, which presents most often with palpable purpura or painful nodules on the lower extremities and may be accompanied by livedo reticularis or digital necrosis.⁹ Acute leukemia may be accompanied by inflammatory paraneoplastic conditions including vasculitis, which is thought to be due to leukemic cells infiltrating and damaging blood vessels.¹⁰

Pretibial myxedema is closely associated with Graves disease and shares some features seen in the presentation of our patient’s leukemia cutis. It is asymptomatic, classically affects the pretibial regions, and most commonly affects older adults and women.^11,12 Pretibial myxedema presents with thick indurated plaques rather than patches. Our patient did not demonstrate ophthalmopathy, which nearly always precedes pretibial myxedema.¹² The most common form of pretibial myxedema is nonpitting, though nodular, plaquelike, polypoid, and elephantiasic forms also exist.¹¹ Pretibial myxedema classically favors the shins; however, it also can affect the ankles, dorsal aspects of the feet, and toes. The characteristic induration of the skin is believed to be the result of excess fibroblast production of glycosaminoglycans in the dermis and subcutis likely triggered by stimulation of fibroblast thyroid stimulating hormone receptors.¹¹

The Diagnosis: Leukemia Cutis

Hematoxylin and eosin staining revealed an infiltration of monomorphic atypical myeloid cells with cleaved nuclei within the dermis, with a relatively uninvolved epidermis (Figure, A). The cells formed aggregates in single-file lines along dermal collagen bundles. Occasional Auer rods, which are crystal aggregates of the enzyme myeloperoxidase, a marker unique to cells of the myeloid lineage (Figure, B) were appreciated.

Immunohistochemical staining for myeloperoxidase was weakly positive; however, flow cytometric evaluation of the bone marrow aspirate revealed that approximately 20% of all CD45+ cells were myeloid blasts. These findings confirmed the diagnosis of recurrent acute myeloid leukemia (AML). The diagnosis of AML can be confirmed with a bone marrow biopsy demonstrating more than 20% of the total cells in blast form as well as evidence that the cells are of myeloid origin, which can be inferred by the presence of Auer rods, positive myeloperoxidase staining, or immunophenotyping. In our patient, the Auer rods, myeloperoxidase staining, and atypical myeloid cells on skin biopsy, in conjunction with the bone marrow biopsy results, confirmed leukemia cutis.

Leukemia cutis is the infiltration of neoplastic proliferating leukocytes in the epidermis, dermis, or subcutis from a primary or more commonly metastatic malignancy. Leukemic cutaneous involvement is seen in up to 13% of leukemia patients and most commonly is seen in monocytic or myelomonocytic forms of AML.¹ It may present anywhere on the body but mostly is found on the back, trunk, and head. It also may have a predilection for areas with a history of trauma or inflammation. The lesions most often are firm, erythematous to violaceous papules and nodules, though leukemia cutis can present with hemorrhagic ulcers, purpura, or other cutaneous manifestations of concomitant thrombocytopenia such as petechiae and ecchymoses.² Involvement of the lower extremities mimicking venous stasis dermatitis has been described.^3,4

Treatment of leukemia cutis requires targeting the underlying leukemia² under the guidance of hematology and oncology as well as the use of chemotherapeutic agents.⁵ The presence of leukemia cutis is a poor prognostic sign, and a discussion regarding goals of care often is appropriate. Our patient initially responded to FLAG (fludarabine, cytarabine, filgrastim) chemotherapy induction and consolidation, which was followed by midostaurin maintenance. However, she ultimately regressed, requiring decitabine and gilteritinib treatment, and died 9 months later from the course of the disease.

Although typically asymptomatic and presenting on the lower limbs, capillaritis (also known as the pigmented purpuric dermatoses) consists of a set of cutaneous conditions that often are chronic and relapsing in nature, as opposed to our patient’s subacute presentation. These benign conditions have several distinct morphologies; some are characterized by pigmented macules or pinpoint red-brown petechiae that most often are found on the legs but also are seen on the trunk and upper extremities.⁶ Of the various clinical presentations of capillaritis, our patient’s skin findings may be most consistent with pigmented purpuric lichenoid dermatitis of Gougerot and Blum, in which purpuric red-brown papules coalesce into plaques, though her lesions were not raised. The other pigmented purpuric dermatoses can present with cayenne pepper–colored petechiae, golden-brown macules, pruritic purpuric patches, or red-brown annular patches,6 which were not seen in our patient.

Venous stasis dermatitis also favors the lower extremities⁷; however, it classically includes the medial malleolus and often presents with scaling and hyperpigmentation from hemosiderin deposition.⁸ It often is associated with pruritus, as opposed to the nonpruritic nonpainful lesions in leukemia cutis. Other signs of venous insufficiency also may be appreciated, including edema or varicose veins,⁷ which were not evident in our patient.

Leukocytoclastic vasculitis, a small vessel vasculitis, also appears as palpable or macular purpura, which classically is asymptomatic and erupts on the shins approximately 1 week after an inciting exposure,⁹ such as medications, pathogens, or autoimmune diseases. One of the least distinctive vasculitides is polyarteritis nodosa, a form of medium vessel vasculitis, which presents most often with palpable purpura or painful nodules on the lower extremities and may be accompanied by livedo reticularis or digital necrosis.⁹ Acute leukemia may be accompanied by inflammatory paraneoplastic conditions including vasculitis, which is thought to be due to leukemic cells infiltrating and damaging blood vessels.¹⁰

Pretibial myxedema is closely associated with Graves disease and shares some features seen in the presentation of our patient’s leukemia cutis. It is asymptomatic, classically affects the pretibial regions, and most commonly affects older adults and women.^11,12 Pretibial myxedema presents with thick indurated plaques rather than patches. Our patient did not demonstrate ophthalmopathy, which nearly always precedes pretibial myxedema.¹² The most common form of pretibial myxedema is nonpitting, though nodular, plaquelike, polypoid, and elephantiasic forms also exist.¹¹ Pretibial myxedema classically favors the shins; however, it also can affect the ankles, dorsal aspects of the feet, and toes. The characteristic induration of the skin is believed to be the result of excess fibroblast production of glycosaminoglycans in the dermis and subcutis likely triggered by stimulation of fibroblast thyroid stimulating hormone receptors.¹¹

The Diagnosis: Leukemia Cutis

Hematoxylin and eosin staining revealed an infiltration of monomorphic atypical myeloid cells with cleaved nuclei within the dermis, with a relatively uninvolved epidermis (Figure, A). The cells formed aggregates in single-file lines along dermal collagen bundles. Occasional Auer rods, which are crystal aggregates of the enzyme myeloperoxidase, a marker unique to cells of the myeloid lineage (Figure, B) were appreciated.

Immunohistochemical staining for myeloperoxidase was weakly positive; however, flow cytometric evaluation of the bone marrow aspirate revealed that approximately 20% of all CD45+ cells were myeloid blasts. These findings confirmed the diagnosis of recurrent acute myeloid leukemia (AML). The diagnosis of AML can be confirmed with a bone marrow biopsy demonstrating more than 20% of the total cells in blast form as well as evidence that the cells are of myeloid origin, which can be inferred by the presence of Auer rods, positive myeloperoxidase staining, or immunophenotyping. In our patient, the Auer rods, myeloperoxidase staining, and atypical myeloid cells on skin biopsy, in conjunction with the bone marrow biopsy results, confirmed leukemia cutis.

Leukemia cutis is the infiltration of neoplastic proliferating leukocytes in the epidermis, dermis, or subcutis from a primary or more commonly metastatic malignancy. Leukemic cutaneous involvement is seen in up to 13% of leukemia patients and most commonly is seen in monocytic or myelomonocytic forms of AML.¹ It may present anywhere on the body but mostly is found on the back, trunk, and head. It also may have a predilection for areas with a history of trauma or inflammation. The lesions most often are firm, erythematous to violaceous papules and nodules, though leukemia cutis can present with hemorrhagic ulcers, purpura, or other cutaneous manifestations of concomitant thrombocytopenia such as petechiae and ecchymoses.² Involvement of the lower extremities mimicking venous stasis dermatitis has been described.^3,4

Treatment of leukemia cutis requires targeting the underlying leukemia² under the guidance of hematology and oncology as well as the use of chemotherapeutic agents.⁵ The presence of leukemia cutis is a poor prognostic sign, and a discussion regarding goals of care often is appropriate. Our patient initially responded to FLAG (fludarabine, cytarabine, filgrastim) chemotherapy induction and consolidation, which was followed by midostaurin maintenance. However, she ultimately regressed, requiring decitabine and gilteritinib treatment, and died 9 months later from the course of the disease.

Although typically asymptomatic and presenting on the lower limbs, capillaritis (also known as the pigmented purpuric dermatoses) consists of a set of cutaneous conditions that often are chronic and relapsing in nature, as opposed to our patient’s subacute presentation. These benign conditions have several distinct morphologies; some are characterized by pigmented macules or pinpoint red-brown petechiae that most often are found on the legs but also are seen on the trunk and upper extremities.⁶ Of the various clinical presentations of capillaritis, our patient’s skin findings may be most consistent with pigmented purpuric lichenoid dermatitis of Gougerot and Blum, in which purpuric red-brown papules coalesce into plaques, though her lesions were not raised. The other pigmented purpuric dermatoses can present with cayenne pepper–colored petechiae, golden-brown macules, pruritic purpuric patches, or red-brown annular patches,6 which were not seen in our patient.

Venous stasis dermatitis also favors the lower extremities⁷; however, it classically includes the medial malleolus and often presents with scaling and hyperpigmentation from hemosiderin deposition.⁸ It often is associated with pruritus, as opposed to the nonpruritic nonpainful lesions in leukemia cutis. Other signs of venous insufficiency also may be appreciated, including edema or varicose veins,⁷ which were not evident in our patient.

Leukocytoclastic vasculitis, a small vessel vasculitis, also appears as palpable or macular purpura, which classically is asymptomatic and erupts on the shins approximately 1 week after an inciting exposure,⁹ such as medications, pathogens, or autoimmune diseases. One of the least distinctive vasculitides is polyarteritis nodosa, a form of medium vessel vasculitis, which presents most often with palpable purpura or painful nodules on the lower extremities and may be accompanied by livedo reticularis or digital necrosis.⁹ Acute leukemia may be accompanied by inflammatory paraneoplastic conditions including vasculitis, which is thought to be due to leukemic cells infiltrating and damaging blood vessels.¹⁰

Pretibial myxedema is closely associated with Graves disease and shares some features seen in the presentation of our patient’s leukemia cutis. It is asymptomatic, classically affects the pretibial regions, and most commonly affects older adults and women.^11,12 Pretibial myxedema presents with thick indurated plaques rather than patches. Our patient did not demonstrate ophthalmopathy, which nearly always precedes pretibial myxedema.¹² The most common form of pretibial myxedema is nonpitting, though nodular, plaquelike, polypoid, and elephantiasic forms also exist.¹¹ Pretibial myxedema classically favors the shins; however, it also can affect the ankles, dorsal aspects of the feet, and toes. The characteristic induration of the skin is believed to be the result of excess fibroblast production of glycosaminoglycans in the dermis and subcutis likely triggered by stimulation of fibroblast thyroid stimulating hormone receptors.¹¹

THE COMPARISON

A Areas of alopecia with erythema and scale in a young Black boy with tinea capitis. He also had an enlarged posterior cervical lymph node (arrow) from this fungal infection.

B White patches of scale from tinea capitis in a young Black boy with no obvious hair loss; however, a potassium hydroxide preparation from the scale was positive for fungus.

C A subtle area of tinea capitis on the scalp of a Latina girl showed comma hairs.

Photographs courtesy of Richard P. Usatine, MD.

Tinea capitis is a common dermatophyte infection of the scalp in school-aged children. The infection is spread by close contact with infected people or with their personal items, including combs, brushes, pillowcases, and hats, as well as animals. It is uncommon in adults.

Epidemiology

Tinea capitis is the most common fungal infection among school-aged children worldwide.¹ In a US-based study of more than 10,000 school-aged children, the prevalence of tinea capitis ranged from 0% to 19.4%, with Black children having the highest rates of infection at 12.9%.² However, people of all races and ages may develop tinea capitis.³

Tinea capitis most commonly is caused by Trichophyton tonsurans and Microsporum canis. Dermatophyte scalp infections caused by T tonsurans produce fungal spores that may occur within the hair shaft (endothrix) or with fungal elements external to the hair shaft (exothrix) such as M canis. Microsporum canis usually fluoresces an apple green color on Wood lamp examination because of the location of the spores.

Key clinical features

Tinea capitis has a variety of clinical presentations: • broken hairs that appear as black dots on the scalp • diffuse scale mimicking seborrheic dermatitis • well-demarcated annular plaques • exudate and tenderness caused by inflammation • scalp pruritus • occipital scalp lymphadenopathy. Worth noting Tinea capitis impacts all patient groups, not just Black patients. In the United States, Black and Hispanic children are most commonly affected.4 Due to a tendency to have dry hair and hair breakage, those with more tightly coiled, textured hair may routinely apply oil and/or grease to the scalp; however, the application of heavy emollients, oils, and grease to camouflage scale contributes to falsenegative fungal cultures of the scalp if applied within 1 week of the fungal culture, which may delay diagnosis. If tinea capitis is suspected, occipital lymphadenopathy on physical examination should prompt treatment for tinea capitis, even without a fungal culture.5 Health disparity highlight A risk factor for tinea capitis is crowded living environments. Some families may live in crowded environments due to economic and housing disparities. This close contact increases the risk for conditions such as tinea capitis.6 Treatment delays may occur due to some cultural practices of applying oils and grease to the hair and scalp, camouflaging the clinical signs of tinea capitis.

THE COMPARISON

A Areas of alopecia with erythema and scale in a young Black boy with tinea capitis. He also had an enlarged posterior cervical lymph node (arrow) from this fungal infection.

B White patches of scale from tinea capitis in a young Black boy with no obvious hair loss; however, a potassium hydroxide preparation from the scale was positive for fungus.

C A subtle area of tinea capitis on the scalp of a Latina girl showed comma hairs.

Photographs courtesy of Richard P. Usatine, MD.

Tinea capitis is a common dermatophyte infection of the scalp in school-aged children. The infection is spread by close contact with infected people or with their personal items, including combs, brushes, pillowcases, and hats, as well as animals. It is uncommon in adults.

Epidemiology

Tinea capitis is the most common fungal infection among school-aged children worldwide.¹ In a US-based study of more than 10,000 school-aged children, the prevalence of tinea capitis ranged from 0% to 19.4%, with Black children having the highest rates of infection at 12.9%.² However, people of all races and ages may develop tinea capitis.³

Tinea capitis most commonly is caused by Trichophyton tonsurans and Microsporum canis. Dermatophyte scalp infections caused by T tonsurans produce fungal spores that may occur within the hair shaft (endothrix) or with fungal elements external to the hair shaft (exothrix) such as M canis. Microsporum canis usually fluoresces an apple green color on Wood lamp examination because of the location of the spores.

Key clinical features

Tinea capitis has a variety of clinical presentations: • broken hairs that appear as black dots on the scalp • diffuse scale mimicking seborrheic dermatitis • well-demarcated annular plaques • exudate and tenderness caused by inflammation • scalp pruritus • occipital scalp lymphadenopathy. Worth noting Tinea capitis impacts all patient groups, not just Black patients. In the United States, Black and Hispanic children are most commonly affected.4 Due to a tendency to have dry hair and hair breakage, those with more tightly coiled, textured hair may routinely apply oil and/or grease to the scalp; however, the application of heavy emollients, oils, and grease to camouflage scale contributes to falsenegative fungal cultures of the scalp if applied within 1 week of the fungal culture, which may delay diagnosis. If tinea capitis is suspected, occipital lymphadenopathy on physical examination should prompt treatment for tinea capitis, even without a fungal culture.5 Health disparity highlight A risk factor for tinea capitis is crowded living environments. Some families may live in crowded environments due to economic and housing disparities. This close contact increases the risk for conditions such as tinea capitis.6 Treatment delays may occur due to some cultural practices of applying oils and grease to the hair and scalp, camouflaging the clinical signs of tinea capitis.

THE COMPARISON

A Areas of alopecia with erythema and scale in a young Black boy with tinea capitis. He also had an enlarged posterior cervical lymph node (arrow) from this fungal infection.

B White patches of scale from tinea capitis in a young Black boy with no obvious hair loss; however, a potassium hydroxide preparation from the scale was positive for fungus.

C A subtle area of tinea capitis on the scalp of a Latina girl showed comma hairs.

Photographs courtesy of Richard P. Usatine, MD.

Tinea capitis is a common dermatophyte infection of the scalp in school-aged children. The infection is spread by close contact with infected people or with their personal items, including combs, brushes, pillowcases, and hats, as well as animals. It is uncommon in adults.

Epidemiology

Tinea capitis is the most common fungal infection among school-aged children worldwide.¹ In a US-based study of more than 10,000 school-aged children, the prevalence of tinea capitis ranged from 0% to 19.4%, with Black children having the highest rates of infection at 12.9%.² However, people of all races and ages may develop tinea capitis.³

Tinea capitis most commonly is caused by Trichophyton tonsurans and Microsporum canis. Dermatophyte scalp infections caused by T tonsurans produce fungal spores that may occur within the hair shaft (endothrix) or with fungal elements external to the hair shaft (exothrix) such as M canis. Microsporum canis usually fluoresces an apple green color on Wood lamp examination because of the location of the spores.

Key clinical features

Tinea capitis has a variety of clinical presentations: • broken hairs that appear as black dots on the scalp • diffuse scale mimicking seborrheic dermatitis • well-demarcated annular plaques • exudate and tenderness caused by inflammation • scalp pruritus • occipital scalp lymphadenopathy. Worth noting Tinea capitis impacts all patient groups, not just Black patients. In the United States, Black and Hispanic children are most commonly affected.4 Due to a tendency to have dry hair and hair breakage, those with more tightly coiled, textured hair may routinely apply oil and/or grease to the scalp; however, the application of heavy emollients, oils, and grease to camouflage scale contributes to falsenegative fungal cultures of the scalp if applied within 1 week of the fungal culture, which may delay diagnosis. If tinea capitis is suspected, occipital lymphadenopathy on physical examination should prompt treatment for tinea capitis, even without a fungal culture.5 Health disparity highlight A risk factor for tinea capitis is crowded living environments. Some families may live in crowded environments due to economic and housing disparities. This close contact increases the risk for conditions such as tinea capitis.6 Treatment delays may occur due to some cultural practices of applying oils and grease to the hair and scalp, camouflaging the clinical signs of tinea capitis.

The Diagnosis: Metastatic Carcinoid Tumor

Carcinoid tumors are derived from neuroendocrine cell compartments and generally arise in the gastrointestinal tract, with a quarter of carcinoids arising in the small bowel.¹ Carcinoid tumors have an incidence of approximately 2 to 5 per 100,000 patients.² Metastasis of carcinoids is approximately 31.2% to 46.7%.¹ Metastasis to the skin is uncommon; we present a rare case of a carcinoid tumor of the terminal ileum with metastasis to the scalp.

Unlike our patient, most patients with carcinoid tumors have an indolent clinical course. The most common cutaneous symptom is flushing, which occurs in 75% of patients.³ Secreted vasoactive peptides such as serotonin may cause other symptoms such as tachycardia, diarrhea, and bronchospasm; together, these symptoms comprise carcinoid syndrome. Carcinoid syndrome requires metastasis of the tumor to the liver or a site outside of the gastrointestinal tract because the liver will metabolize the secreted serotonin. However, even in patients with liver metastasis, carcinoid syndrome only occurs in approximately 10% of patients.⁴ Common skin findings of carcinoid syndrome include pellagralike dermatitis, flushing, and sclerodermalike changes.⁵ Our patient experienced several episodes of presyncope with symptoms of dyspnea, lightheadedness, and flushing but did not have bronchospasm or recurrent diarrhea. Intramuscular octreotide improved some symptoms.

The scalp accounts for approximately 15% of cutaneous metastases, the most common being from the lung, renal, and breast cancers.⁶ Cutaneous metastases of carcinoid tumors are rare. A PubMed search of articles indexed for MEDLINE using the terms metastatic AND [carcinoid OR neuroendocrine] tumors AND [skin OR cutaneous] revealed 47 cases.^7-11 Similar to other skin metastases, cutaneous metastases of carcinoid tumors commonly present as firm erythematous nodules of varying sizes that may be asymptomatic, tender, or pruritic (Figure 1). Cases of carcinoid tumors with cutaneous metastasis as the initial and only presenting sign are exceedingly rare.¹²

Histology of carcinoid tumors reveals a dermal neoplasm composed of loosely cohesive, mildly atypical, polygonal cells with salt-and-pepper chromatin and eosinophilic cytoplasm, which are similar findings to the primary tumor. The cells may grow in the typical trabecular or organoid neuroendocrine pattern or exhibit a pseudoglandular growth pattern with prominent vessels (quiz image, top).¹² Positive chromogranin and synaptophysin immunostaining are the most common and reliable markers used for the diagnosis of carcinoid tumors.

An important histopathologic differential diagnosis is the aggressive Merkel cell carcinoma, which also demonstrates homogenous salt-and-pepper chromatin but exhibits a higher mitotic rate and positive cytokeratin 20 staining (Figure 2).¹³ Basal cell carcinoma (BCC) also may display similar features, including a blue tumor at scanning magnification and nodular or infiltrative growth patterns. The cell morphology of BCC is characterized by islands of basaloid cells with minimal cytoplasm and frequent apoptosis, connecting to the epidermis with peripheral palisading, retraction artifact, and a myxoid stroma; BCC lacks the salt-and-pepper chromatin commonly seen in carcinoid tumors (Figure 3). Basal cell carcinoma is characterized by positive BerEP4 (epithelial cell adhesion molecule immunostain), cytokeratin 5/6, and cytokeratin 14 uptake. Cytokeratin 20, often used to diagnose Merkel cell carcinoma, is negative in BCC. Chromogranin and synaptophysin occasionally may be positive in BCC.¹⁴

The superficial Ewing sarcoma family of tumors also may be included in the differential diagnosis of small round cell tumors of the skin, but they are very rare. These tumors possess strong positive membranous staining of cytokeratin 99 and also can stain positively for synaptophysin and chromogranin.¹⁵ Epithelial membrane antigen, which is negative in Ewing sarcomas, is positive in carcinoid tumors.¹⁶ Neuroendocrine tumors of all sites share similar basic morphologic patterns, and multiple primary tumors should be considered, including small cell lung carcinoma (Figure 4).^17,18 Red granulations and true glandular lumina typically are not seen in the lungs but are common in gastrointestinal carcinoids.¹⁸ Regarding immunohistochemistry, TTF-1 is negative and CDX2 is positive in gastroenteropancreatic carcinoids, suggesting that these 2 markers can help distinguish carcinoids of unknown primary origin.¹⁹

Metastases in carcinoid tumors are common, with one study noting that the highest frequency of small intestinal metastases was from the ileal subset.²⁰ At the time of diagnosis, 58% to 64% of patients with small intestine carcinoid tumors already had nonlocalized disease, with frequent sites being the lymph nodes (89.8%), liver (44.1%), lungs (13.6%), and peritoneum (13.6%). Regional and distant metastases are associated with substantially worse prognoses, with survival rates of 71.7% and 38.5%, respectively.¹ Treatment of symptomatic unresectable disease focuses on symptomatic management with somatostatin analogs that also control tumor growth.²¹

We present a rare case of scalp metastasis of a carcinoid tumor of the terminal ileum. Distant metastasis is associated with poorer prognosis and should be considered in patients with a known history of a carcinoid tumor.

Acknowledgment—We would like to acknowledge the Research Histology and Tissue Imaging Core at University of Illinois Chicago Research Resources Center for the immunohistochemistry studies.

The Diagnosis: Metastatic Carcinoid Tumor

Carcinoid tumors are derived from neuroendocrine cell compartments and generally arise in the gastrointestinal tract, with a quarter of carcinoids arising in the small bowel.¹ Carcinoid tumors have an incidence of approximately 2 to 5 per 100,000 patients.² Metastasis of carcinoids is approximately 31.2% to 46.7%.¹ Metastasis to the skin is uncommon; we present a rare case of a carcinoid tumor of the terminal ileum with metastasis to the scalp.

Unlike our patient, most patients with carcinoid tumors have an indolent clinical course. The most common cutaneous symptom is flushing, which occurs in 75% of patients.³ Secreted vasoactive peptides such as serotonin may cause other symptoms such as tachycardia, diarrhea, and bronchospasm; together, these symptoms comprise carcinoid syndrome. Carcinoid syndrome requires metastasis of the tumor to the liver or a site outside of the gastrointestinal tract because the liver will metabolize the secreted serotonin. However, even in patients with liver metastasis, carcinoid syndrome only occurs in approximately 10% of patients.⁴ Common skin findings of carcinoid syndrome include pellagralike dermatitis, flushing, and sclerodermalike changes.⁵ Our patient experienced several episodes of presyncope with symptoms of dyspnea, lightheadedness, and flushing but did not have bronchospasm or recurrent diarrhea. Intramuscular octreotide improved some symptoms.

The scalp accounts for approximately 15% of cutaneous metastases, the most common being from the lung, renal, and breast cancers.⁶ Cutaneous metastases of carcinoid tumors are rare. A PubMed search of articles indexed for MEDLINE using the terms metastatic AND [carcinoid OR neuroendocrine] tumors AND [skin OR cutaneous] revealed 47 cases.^7-11 Similar to other skin metastases, cutaneous metastases of carcinoid tumors commonly present as firm erythematous nodules of varying sizes that may be asymptomatic, tender, or pruritic (Figure 1). Cases of carcinoid tumors with cutaneous metastasis as the initial and only presenting sign are exceedingly rare.¹²

Histology of carcinoid tumors reveals a dermal neoplasm composed of loosely cohesive, mildly atypical, polygonal cells with salt-and-pepper chromatin and eosinophilic cytoplasm, which are similar findings to the primary tumor. The cells may grow in the typical trabecular or organoid neuroendocrine pattern or exhibit a pseudoglandular growth pattern with prominent vessels (quiz image, top).¹² Positive chromogranin and synaptophysin immunostaining are the most common and reliable markers used for the diagnosis of carcinoid tumors.

An important histopathologic differential diagnosis is the aggressive Merkel cell carcinoma, which also demonstrates homogenous salt-and-pepper chromatin but exhibits a higher mitotic rate and positive cytokeratin 20 staining (Figure 2).¹³ Basal cell carcinoma (BCC) also may display similar features, including a blue tumor at scanning magnification and nodular or infiltrative growth patterns. The cell morphology of BCC is characterized by islands of basaloid cells with minimal cytoplasm and frequent apoptosis, connecting to the epidermis with peripheral palisading, retraction artifact, and a myxoid stroma; BCC lacks the salt-and-pepper chromatin commonly seen in carcinoid tumors (Figure 3). Basal cell carcinoma is characterized by positive BerEP4 (epithelial cell adhesion molecule immunostain), cytokeratin 5/6, and cytokeratin 14 uptake. Cytokeratin 20, often used to diagnose Merkel cell carcinoma, is negative in BCC. Chromogranin and synaptophysin occasionally may be positive in BCC.¹⁴

The superficial Ewing sarcoma family of tumors also may be included in the differential diagnosis of small round cell tumors of the skin, but they are very rare. These tumors possess strong positive membranous staining of cytokeratin 99 and also can stain positively for synaptophysin and chromogranin.¹⁵ Epithelial membrane antigen, which is negative in Ewing sarcomas, is positive in carcinoid tumors.¹⁶ Neuroendocrine tumors of all sites share similar basic morphologic patterns, and multiple primary tumors should be considered, including small cell lung carcinoma (Figure 4).^17,18 Red granulations and true glandular lumina typically are not seen in the lungs but are common in gastrointestinal carcinoids.¹⁸ Regarding immunohistochemistry, TTF-1 is negative and CDX2 is positive in gastroenteropancreatic carcinoids, suggesting that these 2 markers can help distinguish carcinoids of unknown primary origin.¹⁹

Metastases in carcinoid tumors are common, with one study noting that the highest frequency of small intestinal metastases was from the ileal subset.²⁰ At the time of diagnosis, 58% to 64% of patients with small intestine carcinoid tumors already had nonlocalized disease, with frequent sites being the lymph nodes (89.8%), liver (44.1%), lungs (13.6%), and peritoneum (13.6%). Regional and distant metastases are associated with substantially worse prognoses, with survival rates of 71.7% and 38.5%, respectively.¹ Treatment of symptomatic unresectable disease focuses on symptomatic management with somatostatin analogs that also control tumor growth.²¹

We present a rare case of scalp metastasis of a carcinoid tumor of the terminal ileum. Distant metastasis is associated with poorer prognosis and should be considered in patients with a known history of a carcinoid tumor.

Acknowledgment—We would like to acknowledge the Research Histology and Tissue Imaging Core at University of Illinois Chicago Research Resources Center for the immunohistochemistry studies.

The Diagnosis: Metastatic Carcinoid Tumor

Carcinoid tumors are derived from neuroendocrine cell compartments and generally arise in the gastrointestinal tract, with a quarter of carcinoids arising in the small bowel.¹ Carcinoid tumors have an incidence of approximately 2 to 5 per 100,000 patients.² Metastasis of carcinoids is approximately 31.2% to 46.7%.¹ Metastasis to the skin is uncommon; we present a rare case of a carcinoid tumor of the terminal ileum with metastasis to the scalp.

Unlike our patient, most patients with carcinoid tumors have an indolent clinical course. The most common cutaneous symptom is flushing, which occurs in 75% of patients.³ Secreted vasoactive peptides such as serotonin may cause other symptoms such as tachycardia, diarrhea, and bronchospasm; together, these symptoms comprise carcinoid syndrome. Carcinoid syndrome requires metastasis of the tumor to the liver or a site outside of the gastrointestinal tract because the liver will metabolize the secreted serotonin. However, even in patients with liver metastasis, carcinoid syndrome only occurs in approximately 10% of patients.⁴ Common skin findings of carcinoid syndrome include pellagralike dermatitis, flushing, and sclerodermalike changes.⁵ Our patient experienced several episodes of presyncope with symptoms of dyspnea, lightheadedness, and flushing but did not have bronchospasm or recurrent diarrhea. Intramuscular octreotide improved some symptoms.

The scalp accounts for approximately 15% of cutaneous metastases, the most common being from the lung, renal, and breast cancers.⁶ Cutaneous metastases of carcinoid tumors are rare. A PubMed search of articles indexed for MEDLINE using the terms metastatic AND [carcinoid OR neuroendocrine] tumors AND [skin OR cutaneous] revealed 47 cases.^7-11 Similar to other skin metastases, cutaneous metastases of carcinoid tumors commonly present as firm erythematous nodules of varying sizes that may be asymptomatic, tender, or pruritic (Figure 1). Cases of carcinoid tumors with cutaneous metastasis as the initial and only presenting sign are exceedingly rare.¹²

Histology of carcinoid tumors reveals a dermal neoplasm composed of loosely cohesive, mildly atypical, polygonal cells with salt-and-pepper chromatin and eosinophilic cytoplasm, which are similar findings to the primary tumor. The cells may grow in the typical trabecular or organoid neuroendocrine pattern or exhibit a pseudoglandular growth pattern with prominent vessels (quiz image, top).¹² Positive chromogranin and synaptophysin immunostaining are the most common and reliable markers used for the diagnosis of carcinoid tumors.

An important histopathologic differential diagnosis is the aggressive Merkel cell carcinoma, which also demonstrates homogenous salt-and-pepper chromatin but exhibits a higher mitotic rate and positive cytokeratin 20 staining (Figure 2).¹³ Basal cell carcinoma (BCC) also may display similar features, including a blue tumor at scanning magnification and nodular or infiltrative growth patterns. The cell morphology of BCC is characterized by islands of basaloid cells with minimal cytoplasm and frequent apoptosis, connecting to the epidermis with peripheral palisading, retraction artifact, and a myxoid stroma; BCC lacks the salt-and-pepper chromatin commonly seen in carcinoid tumors (Figure 3). Basal cell carcinoma is characterized by positive BerEP4 (epithelial cell adhesion molecule immunostain), cytokeratin 5/6, and cytokeratin 14 uptake. Cytokeratin 20, often used to diagnose Merkel cell carcinoma, is negative in BCC. Chromogranin and synaptophysin occasionally may be positive in BCC.¹⁴

The superficial Ewing sarcoma family of tumors also may be included in the differential diagnosis of small round cell tumors of the skin, but they are very rare. These tumors possess strong positive membranous staining of cytokeratin 99 and also can stain positively for synaptophysin and chromogranin.¹⁵ Epithelial membrane antigen, which is negative in Ewing sarcomas, is positive in carcinoid tumors.¹⁶ Neuroendocrine tumors of all sites share similar basic morphologic patterns, and multiple primary tumors should be considered, including small cell lung carcinoma (Figure 4).^17,18 Red granulations and true glandular lumina typically are not seen in the lungs but are common in gastrointestinal carcinoids.¹⁸ Regarding immunohistochemistry, TTF-1 is negative and CDX2 is positive in gastroenteropancreatic carcinoids, suggesting that these 2 markers can help distinguish carcinoids of unknown primary origin.¹⁹

Metastases in carcinoid tumors are common, with one study noting that the highest frequency of small intestinal metastases was from the ileal subset.²⁰ At the time of diagnosis, 58% to 64% of patients with small intestine carcinoid tumors already had nonlocalized disease, with frequent sites being the lymph nodes (89.8%), liver (44.1%), lungs (13.6%), and peritoneum (13.6%). Regional and distant metastases are associated with substantially worse prognoses, with survival rates of 71.7% and 38.5%, respectively.¹ Treatment of symptomatic unresectable disease focuses on symptomatic management with somatostatin analogs that also control tumor growth.²¹

We present a rare case of scalp metastasis of a carcinoid tumor of the terminal ileum. Distant metastasis is associated with poorer prognosis and should be considered in patients with a known history of a carcinoid tumor.

Acknowledgment—We would like to acknowledge the Research Histology and Tissue Imaging Core at University of Illinois Chicago Research Resources Center for the immunohistochemistry studies.

Mohs micrographic surgery (MMS) is most commonly used for the surgical management of squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs) in high-risk locations. The ability for 100% margin evaluation with MMS also has shown lower recurrence rates compared with wide local excision for less common and/or more aggressive tumors. However, there is a lack of standardization on initial and subsequent margin size when treating these less common skin tumors, such as dermatofibrosarcoma protuberans (DFSP), atypical fibroxanthoma (AFX), and sebaceous carcinoma.

Because Mohs surgeons must balance normal tissue preservation with the importance of tumor clearance in the context of comprehensive margin control, we aimed to assess the practice patterns of Mohs surgeons regarding margin size for these unique tumors. The average margin size for each Mohs layer has been reported to be 1 to 3 mm for BCC compared with 3 to 6 mm or larger for other skin cancers, such as melanoma in situ (MIS).^1-3 We hypothesized that the initial margin size would vary among surgeons and likely be greater for more aggressive and rarer malignancies as well as for lesions on the trunk and extremities.

Methods

A descriptive survey was created using SurveyMonkey and distributed to members of the American College of Mohs Surgery (ACMS). Survey participants and their responses were anonymous. Demographic information on survey participants was collected in addition to initial and subsequent MMS margin size for DFSP, AFX, MIS, invasive melanoma, sebaceous carcinoma, microcystic adnexal carcinoma (MAC), poorly differentiated SCC, Merkel cell carcinoma, extramammary Paget disease, leiomyosarcoma, and endocrine mucin-producing sweat gland carcinoma. Survey participants were asked to choose from a range of margin sizes: 1 to 3 mm, 4 to 6 mm, 7 to 9 mm, and greater than 9 mm. This study was approved by the University of Texas Southwest Medical Center (Dallas, Texas) institutional review board.

Results

Eighty-seven respondents from the ACMS listserve completed the survey (response rate <10%). Of these, 58 respondents (66.7%) reported practicing for more than 5 years, and 58 (66.7%) were male. Practice setting was primarily private/community (71.3% [62/87]), and survey respondents were located across the United States. More than 50% of survey respondents treated the following tumors on the head and neck in their respective practices: DFSP (80.9% [55/68]), AFX (95.6% [65/68]), MIS (67.7% [46/68]), sebaceous carcinoma (92.7% [63/68]), MAC (83.8% [57/68]), poorly differentiated SCC (97.1% [66/68]), and endocrine mucin-producing sweat gland carcinoma (51.5% [35/68]). More than 50% of survey respondents treated the following tumors on the trunk and extremities: DFSP (90.3% [47/52]), AFX (86.4% [45/52]), MIS (55.8% [29/52]), sebaceous carcinoma (80.8% [42/52]), MAC (73.1% [38/52]), poorly differentiated SCC (94.2% [49/52]), and extramammary Paget disease (53.9% [28/52]). Invasive melanoma, Merkel cell carcinoma, and leiomyosarcoma were overall less commonly treated.

In general, respondent Mohs surgeons were more likely to take larger initial and subsequent margins for tumors treated on the trunk and extremities compared with the head and neck (Table). In addition, initial margin size often was larger than the 1- to 3-mm margin commonly used in Mohs surgery for BCCs and less aggressive SCCs (Table). A larger initial margin size (>9 mm) and subsequent margin size (4–6 mm) was more commonly reported for certain tumors known to be more aggressive and/or have extensive subclinical extension, such as DFSP and invasive melanoma. Of note, most respondents performed 4- to 6-mm margins (37/67 [55.2%]) for poorly differentiated SCC. Overall, there was a high range of margin size variability among Mohs surgeons for these unique and/or more aggressive skin tumors.

Comment

Given that no guidelines exist on margins with MMS for less commonly treated skin tumors, this study helps give Mohs surgeons perspective on current practice patterns for both initial and subsequent Mohs margin sizes. High margin-size variability among Mohs surgeons is expected, as surgeons also need to account for high-risk features of the tumor or specific locations where tissue sparing is critical. Overall, Mohs surgeons are more likely to take larger initial margins for these less common skin tumors compared with BCCs or SCCs. Initial margin size was consistently larger on the trunk and extremities where tissue sparing often is less critical.

Our survey was limited by a small sample size and incomplete response of the ACMS membership. In addition, most respondents practiced in a private/community setting, which may have led to bias, as academic centers may manage rare malignancies more commonly and/or have increased access to immunostains and multispecialty care. Future registries for rare skin malignancies will hopefully be developed that will allow for further consensus on standardized margins. Additional studies on the average number of stages required to clear these less common tumors also are warranted.

Mohs micrographic surgery (MMS) is most commonly used for the surgical management of squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs) in high-risk locations. The ability for 100% margin evaluation with MMS also has shown lower recurrence rates compared with wide local excision for less common and/or more aggressive tumors. However, there is a lack of standardization on initial and subsequent margin size when treating these less common skin tumors, such as dermatofibrosarcoma protuberans (DFSP), atypical fibroxanthoma (AFX), and sebaceous carcinoma.

Because Mohs surgeons must balance normal tissue preservation with the importance of tumor clearance in the context of comprehensive margin control, we aimed to assess the practice patterns of Mohs surgeons regarding margin size for these unique tumors. The average margin size for each Mohs layer has been reported to be 1 to 3 mm for BCC compared with 3 to 6 mm or larger for other skin cancers, such as melanoma in situ (MIS).^1-3 We hypothesized that the initial margin size would vary among surgeons and likely be greater for more aggressive and rarer malignancies as well as for lesions on the trunk and extremities.

Methods

A descriptive survey was created using SurveyMonkey and distributed to members of the American College of Mohs Surgery (ACMS). Survey participants and their responses were anonymous. Demographic information on survey participants was collected in addition to initial and subsequent MMS margin size for DFSP, AFX, MIS, invasive melanoma, sebaceous carcinoma, microcystic adnexal carcinoma (MAC), poorly differentiated SCC, Merkel cell carcinoma, extramammary Paget disease, leiomyosarcoma, and endocrine mucin-producing sweat gland carcinoma. Survey participants were asked to choose from a range of margin sizes: 1 to 3 mm, 4 to 6 mm, 7 to 9 mm, and greater than 9 mm. This study was approved by the University of Texas Southwest Medical Center (Dallas, Texas) institutional review board.

Results

Eighty-seven respondents from the ACMS listserve completed the survey (response rate <10%). Of these, 58 respondents (66.7%) reported practicing for more than 5 years, and 58 (66.7%) were male. Practice setting was primarily private/community (71.3% [62/87]), and survey respondents were located across the United States. More than 50% of survey respondents treated the following tumors on the head and neck in their respective practices: DFSP (80.9% [55/68]), AFX (95.6% [65/68]), MIS (67.7% [46/68]), sebaceous carcinoma (92.7% [63/68]), MAC (83.8% [57/68]), poorly differentiated SCC (97.1% [66/68]), and endocrine mucin-producing sweat gland carcinoma (51.5% [35/68]). More than 50% of survey respondents treated the following tumors on the trunk and extremities: DFSP (90.3% [47/52]), AFX (86.4% [45/52]), MIS (55.8% [29/52]), sebaceous carcinoma (80.8% [42/52]), MAC (73.1% [38/52]), poorly differentiated SCC (94.2% [49/52]), and extramammary Paget disease (53.9% [28/52]). Invasive melanoma, Merkel cell carcinoma, and leiomyosarcoma were overall less commonly treated.

In general, respondent Mohs surgeons were more likely to take larger initial and subsequent margins for tumors treated on the trunk and extremities compared with the head and neck (Table). In addition, initial margin size often was larger than the 1- to 3-mm margin commonly used in Mohs surgery for BCCs and less aggressive SCCs (Table). A larger initial margin size (>9 mm) and subsequent margin size (4–6 mm) was more commonly reported for certain tumors known to be more aggressive and/or have extensive subclinical extension, such as DFSP and invasive melanoma. Of note, most respondents performed 4- to 6-mm margins (37/67 [55.2%]) for poorly differentiated SCC. Overall, there was a high range of margin size variability among Mohs surgeons for these unique and/or more aggressive skin tumors.

Comment

Given that no guidelines exist on margins with MMS for less commonly treated skin tumors, this study helps give Mohs surgeons perspective on current practice patterns for both initial and subsequent Mohs margin sizes. High margin-size variability among Mohs surgeons is expected, as surgeons also need to account for high-risk features of the tumor or specific locations where tissue sparing is critical. Overall, Mohs surgeons are more likely to take larger initial margins for these less common skin tumors compared with BCCs or SCCs. Initial margin size was consistently larger on the trunk and extremities where tissue sparing often is less critical.

Our survey was limited by a small sample size and incomplete response of the ACMS membership. In addition, most respondents practiced in a private/community setting, which may have led to bias, as academic centers may manage rare malignancies more commonly and/or have increased access to immunostains and multispecialty care. Future registries for rare skin malignancies will hopefully be developed that will allow for further consensus on standardized margins. Additional studies on the average number of stages required to clear these less common tumors also are warranted.

Mohs micrographic surgery (MMS) is most commonly used for the surgical management of squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs) in high-risk locations. The ability for 100% margin evaluation with MMS also has shown lower recurrence rates compared with wide local excision for less common and/or more aggressive tumors. However, there is a lack of standardization on initial and subsequent margin size when treating these less common skin tumors, such as dermatofibrosarcoma protuberans (DFSP), atypical fibroxanthoma (AFX), and sebaceous carcinoma.

Because Mohs surgeons must balance normal tissue preservation with the importance of tumor clearance in the context of comprehensive margin control, we aimed to assess the practice patterns of Mohs surgeons regarding margin size for these unique tumors. The average margin size for each Mohs layer has been reported to be 1 to 3 mm for BCC compared with 3 to 6 mm or larger for other skin cancers, such as melanoma in situ (MIS).^1-3 We hypothesized that the initial margin size would vary among surgeons and likely be greater for more aggressive and rarer malignancies as well as for lesions on the trunk and extremities.

Methods

A descriptive survey was created using SurveyMonkey and distributed to members of the American College of Mohs Surgery (ACMS). Survey participants and their responses were anonymous. Demographic information on survey participants was collected in addition to initial and subsequent MMS margin size for DFSP, AFX, MIS, invasive melanoma, sebaceous carcinoma, microcystic adnexal carcinoma (MAC), poorly differentiated SCC, Merkel cell carcinoma, extramammary Paget disease, leiomyosarcoma, and endocrine mucin-producing sweat gland carcinoma. Survey participants were asked to choose from a range of margin sizes: 1 to 3 mm, 4 to 6 mm, 7 to 9 mm, and greater than 9 mm. This study was approved by the University of Texas Southwest Medical Center (Dallas, Texas) institutional review board.

Results

Eighty-seven respondents from the ACMS listserve completed the survey (response rate <10%). Of these, 58 respondents (66.7%) reported practicing for more than 5 years, and 58 (66.7%) were male. Practice setting was primarily private/community (71.3% [62/87]), and survey respondents were located across the United States. More than 50% of survey respondents treated the following tumors on the head and neck in their respective practices: DFSP (80.9% [55/68]), AFX (95.6% [65/68]), MIS (67.7% [46/68]), sebaceous carcinoma (92.7% [63/68]), MAC (83.8% [57/68]), poorly differentiated SCC (97.1% [66/68]), and endocrine mucin-producing sweat gland carcinoma (51.5% [35/68]). More than 50% of survey respondents treated the following tumors on the trunk and extremities: DFSP (90.3% [47/52]), AFX (86.4% [45/52]), MIS (55.8% [29/52]), sebaceous carcinoma (80.8% [42/52]), MAC (73.1% [38/52]), poorly differentiated SCC (94.2% [49/52]), and extramammary Paget disease (53.9% [28/52]). Invasive melanoma, Merkel cell carcinoma, and leiomyosarcoma were overall less commonly treated.

In general, respondent Mohs surgeons were more likely to take larger initial and subsequent margins for tumors treated on the trunk and extremities compared with the head and neck (Table). In addition, initial margin size often was larger than the 1- to 3-mm margin commonly used in Mohs surgery for BCCs and less aggressive SCCs (Table). A larger initial margin size (>9 mm) and subsequent margin size (4–6 mm) was more commonly reported for certain tumors known to be more aggressive and/or have extensive subclinical extension, such as DFSP and invasive melanoma. Of note, most respondents performed 4- to 6-mm margins (37/67 [55.2%]) for poorly differentiated SCC. Overall, there was a high range of margin size variability among Mohs surgeons for these unique and/or more aggressive skin tumors.

Comment

Given that no guidelines exist on margins with MMS for less commonly treated skin tumors, this study helps give Mohs surgeons perspective on current practice patterns for both initial and subsequent Mohs margin sizes. High margin-size variability among Mohs surgeons is expected, as surgeons also need to account for high-risk features of the tumor or specific locations where tissue sparing is critical. Overall, Mohs surgeons are more likely to take larger initial margins for these less common skin tumors compared with BCCs or SCCs. Initial margin size was consistently larger on the trunk and extremities where tissue sparing often is less critical.

Our survey was limited by a small sample size and incomplete response of the ACMS membership. In addition, most respondents practiced in a private/community setting, which may have led to bias, as academic centers may manage rare malignancies more commonly and/or have increased access to immunostains and multispecialty care. Future registries for rare skin malignancies will hopefully be developed that will allow for further consensus on standardized margins. Additional studies on the average number of stages required to clear these less common tumors also are warranted.

To the Editor:

Segmental neurofibromatosis, or neurofibromatosis type 5 (NF5), is a rare subtype of neurofibromatosis type 1 (NF1)(also known as von Recklinghausen disease). Phenotypic manifestations of NF5 include café-au-lait macules, neurofibromas, or both in 1 or more adjacent dermatomes. In contrast to the systemic features of NF1, the dermatomal distribution of NF5 demonstrates mosaicism due to a spontaneous postzygotic mutation in the neurofibromin 1 gene, NF1. We describe an atypical presentation of NF5 with bilateral features on the upper extremities.

A 74-year-old woman presented with soft pink- to flesh-colored growths on the left dorsal forearm and hand that were observed incidentally during a Mohs procedure for treatment of a basal cell carcinoma on the upper cutaneous lip. The patient reported that the lesions initially appeared on the left dorsal hand at approximately 16 years of age and had since spread proximally up to the mid dorsal forearm over the course of her lifetime. She denied any pain but claimed the affected area could be itchy. The lesions did not interfere with her daily activities, but they negatively impacted her social life due to their cosmetic appearance as well as her fear that they could be contagious. She denied any family history of NF1.

Physical examination revealed innumerable soft, pink- to flesh-colored cutaneous nodules ranging from 3 to 9 mm in diameter clustered uniformly on the left dorsal hand and lower forearm within the C6, C7, and C8 dermatomal regions (Figure, A). A singular brown patch measuring 20 mm in diameter also was observed on the right dorsal hand within the C6 dermatome, which the patient reported had been present since birth (Figure, B). The nodules and pigmented patch were clinically diagnosed as cutaneous neurofibromas on the left arm and a café-au-lait macule on the right arm, each manifesting within the C6 dermatome on separate upper extremities. Lisch nodules, axillary freckling, and acoustic schwannomas were not observed. Because of the dermatomal distribution of the lesions and lack of family history of NF1, a diagnosis of bilateral NF5 was made. The patient stated she had declined treatment of the neurofibromas from her referring general dermatologist due to possible risk for recurrence.

Segmental neurofibromatosis was first described in 1931 by Gammel,¹ and in 1982, segmental neurofibromatosis was classified as NF5 by Riccardi.² After Tinschert et al³ later demonstrated NF5 to be a somatic mutation of NF1,³ Ruggieri and Huson⁴ proposed the term mosaic neurofibromatosis 1 in 2001.

While the prevalence of NF1 is 1 in 3000 individuals,⁵ NF5 is rare with an occurrence of 1 in 40,000.⁶ In NF5, a spontaneous NF1 gene mutation occurs on chromosome 17 in a dividing cell after conception.⁷ Individuals with NF5 are born mosaic with 2 genotypes—one normal and one abnormal—for the NF1 gene.⁸ This contrasts with the autosomal-dominant and systemic characteristics of NF1, which has the NF1 gene mutation in all cells. Patients with NF5 generally are not expected to have affected offspring because the spontaneous mutation usually arises in somatic cells; however, a postzygotic mutation in the gonadal region could potentially affect germline cells, resulting in vertical transmission, with documented cases of offspring with systemic NF1.⁴ Because of the risk for malignancy with systemic neurofibromatosis, early diagnosis with genetic counseling is imperative in patients with both NF1 and NF5.

Neurofibromatosis type 5 is a clinical diagnosis based on the presence of neurofibromas and/or café-au-lait macules in a dermatomal distribution. The clinical presentation depends on when and where the NF1 gene mutation occurs in utero as cells multiply, differentiate, and migrate.⁸ Earlier mutations result in a broader manifestation of NF5 in comparison to late mutations, which have more localized features. An NF1 gene mutation causes a loss of function of neurofibromin, a tumor suppressor protein, in Schwann cells and fibroblasts.⁸ This produces neurofibromas and café-au-lait macules, respectively.⁸

A large literature review on segmental neurofibromatosis by Garcia-Romero et al⁶ identified 320 individuals who did not meet full inclusion criteria for NF1 between 1977 and 2012. Overall, 76% of cases were unilaterally distributed. The investigators identified 157 individual case reports in which the most to least common presentation was pigmentary changes only, neurofibromas only, mixed pigmentary changes with neurofibromas, and plexiform neurofibromas only; however, many of these cases were children who may have later developed both neurofibromas and pigmentary changes during puberty.⁶ Additional features of NF5 may include freckling, Lisch nodules, optic gliomas, malignant peripheral nerve sheath tumors, skeletal abnormalities, precocious puberty, vascular malformations, hypertension, seizures, and/or learning difficulties based on the affected anatomy.

Segmental neurofibromatosis, or NF5, is a rare subtype of NF1. Our case demonstrates an unusual bilateral distribution of NF5 with cutaneous neurofibromas and a café-au-lait macule on the upper extremities. Awareness of variations of neurofibromatosis and their genetic implications is essential in establishing earlier clinical diagnoses in cases with subtle manifestations.

To the Editor:

Segmental neurofibromatosis, or neurofibromatosis type 5 (NF5), is a rare subtype of neurofibromatosis type 1 (NF1)(also known as von Recklinghausen disease). Phenotypic manifestations of NF5 include café-au-lait macules, neurofibromas, or both in 1 or more adjacent dermatomes. In contrast to the systemic features of NF1, the dermatomal distribution of NF5 demonstrates mosaicism due to a spontaneous postzygotic mutation in the neurofibromin 1 gene, NF1. We describe an atypical presentation of NF5 with bilateral features on the upper extremities.

A 74-year-old woman presented with soft pink- to flesh-colored growths on the left dorsal forearm and hand that were observed incidentally during a Mohs procedure for treatment of a basal cell carcinoma on the upper cutaneous lip. The patient reported that the lesions initially appeared on the left dorsal hand at approximately 16 years of age and had since spread proximally up to the mid dorsal forearm over the course of her lifetime. She denied any pain but claimed the affected area could be itchy. The lesions did not interfere with her daily activities, but they negatively impacted her social life due to their cosmetic appearance as well as her fear that they could be contagious. She denied any family history of NF1.

Physical examination revealed innumerable soft, pink- to flesh-colored cutaneous nodules ranging from 3 to 9 mm in diameter clustered uniformly on the left dorsal hand and lower forearm within the C6, C7, and C8 dermatomal regions (Figure, A). A singular brown patch measuring 20 mm in diameter also was observed on the right dorsal hand within the C6 dermatome, which the patient reported had been present since birth (Figure, B). The nodules and pigmented patch were clinically diagnosed as cutaneous neurofibromas on the left arm and a café-au-lait macule on the right arm, each manifesting within the C6 dermatome on separate upper extremities. Lisch nodules, axillary freckling, and acoustic schwannomas were not observed. Because of the dermatomal distribution of the lesions and lack of family history of NF1, a diagnosis of bilateral NF5 was made. The patient stated she had declined treatment of the neurofibromas from her referring general dermatologist due to possible risk for recurrence.

Segmental neurofibromatosis was first described in 1931 by Gammel,¹ and in 1982, segmental neurofibromatosis was classified as NF5 by Riccardi.² After Tinschert et al³ later demonstrated NF5 to be a somatic mutation of NF1,³ Ruggieri and Huson⁴ proposed the term mosaic neurofibromatosis 1 in 2001.

While the prevalence of NF1 is 1 in 3000 individuals,⁵ NF5 is rare with an occurrence of 1 in 40,000.⁶ In NF5, a spontaneous NF1 gene mutation occurs on chromosome 17 in a dividing cell after conception.⁷ Individuals with NF5 are born mosaic with 2 genotypes—one normal and one abnormal—for the NF1 gene.⁸ This contrasts with the autosomal-dominant and systemic characteristics of NF1, which has the NF1 gene mutation in all cells. Patients with NF5 generally are not expected to have affected offspring because the spontaneous mutation usually arises in somatic cells; however, a postzygotic mutation in the gonadal region could potentially affect germline cells, resulting in vertical transmission, with documented cases of offspring with systemic NF1.⁴ Because of the risk for malignancy with systemic neurofibromatosis, early diagnosis with genetic counseling is imperative in patients with both NF1 and NF5.

Neurofibromatosis type 5 is a clinical diagnosis based on the presence of neurofibromas and/or café-au-lait macules in a dermatomal distribution. The clinical presentation depends on when and where the NF1 gene mutation occurs in utero as cells multiply, differentiate, and migrate.⁸ Earlier mutations result in a broader manifestation of NF5 in comparison to late mutations, which have more localized features. An NF1 gene mutation causes a loss of function of neurofibromin, a tumor suppressor protein, in Schwann cells and fibroblasts.⁸ This produces neurofibromas and café-au-lait macules, respectively.⁸

A large literature review on segmental neurofibromatosis by Garcia-Romero et al⁶ identified 320 individuals who did not meet full inclusion criteria for NF1 between 1977 and 2012. Overall, 76% of cases were unilaterally distributed. The investigators identified 157 individual case reports in which the most to least common presentation was pigmentary changes only, neurofibromas only, mixed pigmentary changes with neurofibromas, and plexiform neurofibromas only; however, many of these cases were children who may have later developed both neurofibromas and pigmentary changes during puberty.⁶ Additional features of NF5 may include freckling, Lisch nodules, optic gliomas, malignant peripheral nerve sheath tumors, skeletal abnormalities, precocious puberty, vascular malformations, hypertension, seizures, and/or learning difficulties based on the affected anatomy.

Segmental neurofibromatosis, or NF5, is a rare subtype of NF1. Our case demonstrates an unusual bilateral distribution of NF5 with cutaneous neurofibromas and a café-au-lait macule on the upper extremities. Awareness of variations of neurofibromatosis and their genetic implications is essential in establishing earlier clinical diagnoses in cases with subtle manifestations.

To the Editor:

Segmental neurofibromatosis, or neurofibromatosis type 5 (NF5), is a rare subtype of neurofibromatosis type 1 (NF1)(also known as von Recklinghausen disease). Phenotypic manifestations of NF5 include café-au-lait macules, neurofibromas, or both in 1 or more adjacent dermatomes. In contrast to the systemic features of NF1, the dermatomal distribution of NF5 demonstrates mosaicism due to a spontaneous postzygotic mutation in the neurofibromin 1 gene, NF1. We describe an atypical presentation of NF5 with bilateral features on the upper extremities.

A 74-year-old woman presented with soft pink- to flesh-colored growths on the left dorsal forearm and hand that were observed incidentally during a Mohs procedure for treatment of a basal cell carcinoma on the upper cutaneous lip. The patient reported that the lesions initially appeared on the left dorsal hand at approximately 16 years of age and had since spread proximally up to the mid dorsal forearm over the course of her lifetime. She denied any pain but claimed the affected area could be itchy. The lesions did not interfere with her daily activities, but they negatively impacted her social life due to their cosmetic appearance as well as her fear that they could be contagious. She denied any family history of NF1.

Physical examination revealed innumerable soft, pink- to flesh-colored cutaneous nodules ranging from 3 to 9 mm in diameter clustered uniformly on the left dorsal hand and lower forearm within the C6, C7, and C8 dermatomal regions (Figure, A). A singular brown patch measuring 20 mm in diameter also was observed on the right dorsal hand within the C6 dermatome, which the patient reported had been present since birth (Figure, B). The nodules and pigmented patch were clinically diagnosed as cutaneous neurofibromas on the left arm and a café-au-lait macule on the right arm, each manifesting within the C6 dermatome on separate upper extremities. Lisch nodules, axillary freckling, and acoustic schwannomas were not observed. Because of the dermatomal distribution of the lesions and lack of family history of NF1, a diagnosis of bilateral NF5 was made. The patient stated she had declined treatment of the neurofibromas from her referring general dermatologist due to possible risk for recurrence.

Segmental neurofibromatosis was first described in 1931 by Gammel,¹ and in 1982, segmental neurofibromatosis was classified as NF5 by Riccardi.² After Tinschert et al³ later demonstrated NF5 to be a somatic mutation of NF1,³ Ruggieri and Huson⁴ proposed the term mosaic neurofibromatosis 1 in 2001.

While the prevalence of NF1 is 1 in 3000 individuals,⁵ NF5 is rare with an occurrence of 1 in 40,000.⁶ In NF5, a spontaneous NF1 gene mutation occurs on chromosome 17 in a dividing cell after conception.⁷ Individuals with NF5 are born mosaic with 2 genotypes—one normal and one abnormal—for the NF1 gene.⁸ This contrasts with the autosomal-dominant and systemic characteristics of NF1, which has the NF1 gene mutation in all cells. Patients with NF5 generally are not expected to have affected offspring because the spontaneous mutation usually arises in somatic cells; however, a postzygotic mutation in the gonadal region could potentially affect germline cells, resulting in vertical transmission, with documented cases of offspring with systemic NF1.⁴ Because of the risk for malignancy with systemic neurofibromatosis, early diagnosis with genetic counseling is imperative in patients with both NF1 and NF5.

Neurofibromatosis type 5 is a clinical diagnosis based on the presence of neurofibromas and/or café-au-lait macules in a dermatomal distribution. The clinical presentation depends on when and where the NF1 gene mutation occurs in utero as cells multiply, differentiate, and migrate.⁸ Earlier mutations result in a broader manifestation of NF5 in comparison to late mutations, which have more localized features. An NF1 gene mutation causes a loss of function of neurofibromin, a tumor suppressor protein, in Schwann cells and fibroblasts.⁸ This produces neurofibromas and café-au-lait macules, respectively.⁸

A large literature review on segmental neurofibromatosis by Garcia-Romero et al⁶ identified 320 individuals who did not meet full inclusion criteria for NF1 between 1977 and 2012. Overall, 76% of cases were unilaterally distributed. The investigators identified 157 individual case reports in which the most to least common presentation was pigmentary changes only, neurofibromas only, mixed pigmentary changes with neurofibromas, and plexiform neurofibromas only; however, many of these cases were children who may have later developed both neurofibromas and pigmentary changes during puberty.⁶ Additional features of NF5 may include freckling, Lisch nodules, optic gliomas, malignant peripheral nerve sheath tumors, skeletal abnormalities, precocious puberty, vascular malformations, hypertension, seizures, and/or learning difficulties based on the affected anatomy.

Segmental neurofibromatosis, or NF5, is a rare subtype of NF1. Our case demonstrates an unusual bilateral distribution of NF5 with cutaneous neurofibromas and a café-au-lait macule on the upper extremities. Awareness of variations of neurofibromatosis and their genetic implications is essential in establishing earlier clinical diagnoses in cases with subtle manifestations.

To the Editor:

Vedolizumab is an innovative monoclonal antibody targeted against the α4β7 integrin that is approved for treatment of moderate to severe ulcerative colitis and Crohn disease refractory to standard treatment.¹ Vedolizumab is thought to be gut specific, blocking integrins specific to T lymphocytes destined for the gastrointestinal tract and their interaction with endothelial cells, thereby modulating the adaptive immune system in the gut without systemic immunosuppression.² It generally is well tolerated, and acne rarely has been reported as an adverse event.^3,4 We present a case of acne fulminans without systemic symptoms (AF-WOSS) as a severe side effect of vedolizumab that responded very well to systemic steroids and oral isotretinoin in addition to the discontinuation of treatment.

A 46-year-old obese man presented to our dermatology clinic with a chief complaint of rapidly progressive tender skin lesions. The patient had a long-standing history of severe fistulating and stricturing Crohn disease status post–bowel resection with ileostomy and had recently started treatment with vedolizumab after failing treatment with infliximab, adalimumab, certolizumab pegol, ustekinumab, and methotrexate. Several weeks after beginning infusions of vedolizumab, the patient began to develop many erythematous papules and pustules on the face, chest (Figure 1), and buttocks that rapidly progressed into painful and coalescing nodules and cysts over the next several months. He was prescribed benzoyl peroxide wash 10% as well as several weeks of oral doxycycline 100 mg twice daily with no improvement. The patient denied any other new medications or triggers, fever, chills, bone pain, headache, fatigue, or myalgia. The skin involvement continued to worsen with successive vedolizumab infusions over a period of 8 weeks, which ultimately resulted in cessation of vedolizumab.

Physical examination revealed large, tender, pink, erythematous, and indurated plaques that were heavily studded with pink papules, pustules, and nodules on the cheeks (Figure 2), central chest, and buttocks. A punch biopsy of a pustule on the cheek showed ruptured suppurative folliculitis. The patient subsequently was diagnosed with AF-WOSS.

The patient then completed a 7-day course of sulfamethoxazole-trimethoprim followed by a 10-day course of amoxicillin-clavulanic acid, neither of which led to improvement of the lesions. He then was started on an oral prednisone taper (1 mg/kg starting dose) that ultimately totaled 14 weeks in length due to his frequent flares any time prednisone was decreased below 40 mg daily. After 3 weeks on the oral prednisone, the patient was started on 0.3 mg/kg of concomitant oral isotretinoin every other day, which slowly was increased as tolerated until he reached a goal dose of roughly 150 mg/kg, which resolved the acneform papules and pustules and allowed for successful tapering off the prednisone.

Many studies have been published regarding the safety and side-effect profile of vedolizumab, but most do not report acne as an adverse event.^3-5 A German cohort study by Baumgart et al³ reported acne as a side effect in 15 of 212 (7.1%) patients but did not classify the severity. Another case report noted nodulocystic acne in a patient receiving vedolizumab for treatment of inflammatory bowel disease; however, this patient responded well to the use of a tetracycline antibiotic and was able to continue therapy with vedolizumab.⁵ Our patient demonstrated a severe and uncommon case of acne classified as AF-WOSS following initiation of therapy with vedolizumab, which required treatment with systemic steroids plus oral isotretinoin and resulted in cessation of vedolizumab.

As new therapies emerge, it is important to document new or severe adverse effects so providers can choose an appropriate therapy and adequately counsel patients regarding the side effects. Although vedolizumab was thought to have gut-specific action, there is new evidence to suggest that the principal ligand of the α4β7 integrin, mucosal addressin cell adhesion molecule-1, is not only expressed on gut endothelial cells but also on fibroblasts and melanomas, which may provide insight into the observed extraintestinal side effects of vedolizumab.⁶

To the Editor:

Vedolizumab is an innovative monoclonal antibody targeted against the α4β7 integrin that is approved for treatment of moderate to severe ulcerative colitis and Crohn disease refractory to standard treatment.¹ Vedolizumab is thought to be gut specific, blocking integrins specific to T lymphocytes destined for the gastrointestinal tract and their interaction with endothelial cells, thereby modulating the adaptive immune system in the gut without systemic immunosuppression.² It generally is well tolerated, and acne rarely has been reported as an adverse event.^3,4 We present a case of acne fulminans without systemic symptoms (AF-WOSS) as a severe side effect of vedolizumab that responded very well to systemic steroids and oral isotretinoin in addition to the discontinuation of treatment.

A 46-year-old obese man presented to our dermatology clinic with a chief complaint of rapidly progressive tender skin lesions. The patient had a long-standing history of severe fistulating and stricturing Crohn disease status post–bowel resection with ileostomy and had recently started treatment with vedolizumab after failing treatment with infliximab, adalimumab, certolizumab pegol, ustekinumab, and methotrexate. Several weeks after beginning infusions of vedolizumab, the patient began to develop many erythematous papules and pustules on the face, chest (Figure 1), and buttocks that rapidly progressed into painful and coalescing nodules and cysts over the next several months. He was prescribed benzoyl peroxide wash 10% as well as several weeks of oral doxycycline 100 mg twice daily with no improvement. The patient denied any other new medications or triggers, fever, chills, bone pain, headache, fatigue, or myalgia. The skin involvement continued to worsen with successive vedolizumab infusions over a period of 8 weeks, which ultimately resulted in cessation of vedolizumab.

Physical examination revealed large, tender, pink, erythematous, and indurated plaques that were heavily studded with pink papules, pustules, and nodules on the cheeks (Figure 2), central chest, and buttocks. A punch biopsy of a pustule on the cheek showed ruptured suppurative folliculitis. The patient subsequently was diagnosed with AF-WOSS.

The patient then completed a 7-day course of sulfamethoxazole-trimethoprim followed by a 10-day course of amoxicillin-clavulanic acid, neither of which led to improvement of the lesions. He then was started on an oral prednisone taper (1 mg/kg starting dose) that ultimately totaled 14 weeks in length due to his frequent flares any time prednisone was decreased below 40 mg daily. After 3 weeks on the oral prednisone, the patient was started on 0.3 mg/kg of concomitant oral isotretinoin every other day, which slowly was increased as tolerated until he reached a goal dose of roughly 150 mg/kg, which resolved the acneform papules and pustules and allowed for successful tapering off the prednisone.

Many studies have been published regarding the safety and side-effect profile of vedolizumab, but most do not report acne as an adverse event.^3-5 A German cohort study by Baumgart et al³ reported acne as a side effect in 15 of 212 (7.1%) patients but did not classify the severity. Another case report noted nodulocystic acne in a patient receiving vedolizumab for treatment of inflammatory bowel disease; however, this patient responded well to the use of a tetracycline antibiotic and was able to continue therapy with vedolizumab.⁵ Our patient demonstrated a severe and uncommon case of acne classified as AF-WOSS following initiation of therapy with vedolizumab, which required treatment with systemic steroids plus oral isotretinoin and resulted in cessation of vedolizumab.

As new therapies emerge, it is important to document new or severe adverse effects so providers can choose an appropriate therapy and adequately counsel patients regarding the side effects. Although vedolizumab was thought to have gut-specific action, there is new evidence to suggest that the principal ligand of the α4β7 integrin, mucosal addressin cell adhesion molecule-1, is not only expressed on gut endothelial cells but also on fibroblasts and melanomas, which may provide insight into the observed extraintestinal side effects of vedolizumab.⁶

To the Editor:

Vedolizumab is an innovative monoclonal antibody targeted against the α4β7 integrin that is approved for treatment of moderate to severe ulcerative colitis and Crohn disease refractory to standard treatment.¹ Vedolizumab is thought to be gut specific, blocking integrins specific to T lymphocytes destined for the gastrointestinal tract and their interaction with endothelial cells, thereby modulating the adaptive immune system in the gut without systemic immunosuppression.² It generally is well tolerated, and acne rarely has been reported as an adverse event.^3,4 We present a case of acne fulminans without systemic symptoms (AF-WOSS) as a severe side effect of vedolizumab that responded very well to systemic steroids and oral isotretinoin in addition to the discontinuation of treatment.

A 46-year-old obese man presented to our dermatology clinic with a chief complaint of rapidly progressive tender skin lesions. The patient had a long-standing history of severe fistulating and stricturing Crohn disease status post–bowel resection with ileostomy and had recently started treatment with vedolizumab after failing treatment with infliximab, adalimumab, certolizumab pegol, ustekinumab, and methotrexate. Several weeks after beginning infusions of vedolizumab, the patient began to develop many erythematous papules and pustules on the face, chest (Figure 1), and buttocks that rapidly progressed into painful and coalescing nodules and cysts over the next several months. He was prescribed benzoyl peroxide wash 10% as well as several weeks of oral doxycycline 100 mg twice daily with no improvement. The patient denied any other new medications or triggers, fever, chills, bone pain, headache, fatigue, or myalgia. The skin involvement continued to worsen with successive vedolizumab infusions over a period of 8 weeks, which ultimately resulted in cessation of vedolizumab.

Physical examination revealed large, tender, pink, erythematous, and indurated plaques that were heavily studded with pink papules, pustules, and nodules on the cheeks (Figure 2), central chest, and buttocks. A punch biopsy of a pustule on the cheek showed ruptured suppurative folliculitis. The patient subsequently was diagnosed with AF-WOSS.

The patient then completed a 7-day course of sulfamethoxazole-trimethoprim followed by a 10-day course of amoxicillin-clavulanic acid, neither of which led to improvement of the lesions. He then was started on an oral prednisone taper (1 mg/kg starting dose) that ultimately totaled 14 weeks in length due to his frequent flares any time prednisone was decreased below 40 mg daily. After 3 weeks on the oral prednisone, the patient was started on 0.3 mg/kg of concomitant oral isotretinoin every other day, which slowly was increased as tolerated until he reached a goal dose of roughly 150 mg/kg, which resolved the acneform papules and pustules and allowed for successful tapering off the prednisone.

Many studies have been published regarding the safety and side-effect profile of vedolizumab, but most do not report acne as an adverse event.^3-5 A German cohort study by Baumgart et al³ reported acne as a side effect in 15 of 212 (7.1%) patients but did not classify the severity. Another case report noted nodulocystic acne in a patient receiving vedolizumab for treatment of inflammatory bowel disease; however, this patient responded well to the use of a tetracycline antibiotic and was able to continue therapy with vedolizumab.⁵ Our patient demonstrated a severe and uncommon case of acne classified as AF-WOSS following initiation of therapy with vedolizumab, which required treatment with systemic steroids plus oral isotretinoin and resulted in cessation of vedolizumab.

As new therapies emerge, it is important to document new or severe adverse effects so providers can choose an appropriate therapy and adequately counsel patients regarding the side effects. Although vedolizumab was thought to have gut-specific action, there is new evidence to suggest that the principal ligand of the α4β7 integrin, mucosal addressin cell adhesion molecule-1, is not only expressed on gut endothelial cells but also on fibroblasts and melanomas, which may provide insight into the observed extraintestinal side effects of vedolizumab.⁶

Practice Gap

One of the most important elements of successful reconstruction is effective undermining prior to placement of buried sutures. The main benefit of an evenly undermined plane is that tension is reduced, thus permitting seamless tissue mobilization and wound edge approximation.¹

However, achieving a consistent and appropriate plane can present challenges in certain blind spots within one’s field of work. A right hand–dominant surgeon might find it difficult to undermine tissue between the 3-o’clock and 6-o’clock positions (Figure 1) and often must resort to unnatural positioning to obtain adequate reach.

We propose a technique of reversing the grip on undermining scissors that improves efficiency without sacrificing technique.

Technique

The surgeon simply grasps the ring handles with the ring finger and thumb with the tip pointing to the wrist (Figure 2). Most of the control comes from rotating the wrist while spreading with the thumb (Figure 3).

The main advantage of the reverse-grip technique is that it prevents abduction of the arm at the shoulder joint, which reduces shoulder fatigue and keeps the elbow close to the trunk and away from the sterile surgical field. Achieving optimal ergonomics during surgery has been shown to reduce pain and likely prolong the surgeon’s career.²

A limitation of the reverse-grip technique is that direct visualization of the undermining plane is not achieved; however, direct visualization also is not obtained when undermining in the standard fashion unless the instruments are passed to the surgical assistant or the surgeon moves to the other side of the table.

Undermining can be performed safely without direct visualization as long as several rules are followed:

• The undermining plane is first established under direct visualization on the far side of the wound—at the 6-o’clock to 12-o’clock positions—and then followed to the area where direct visualization is not obtained.

• A blunt-tipped scissor is used to prevent penetrating trauma to neurovascular bundles. Blunt-tipped instruments allow more “feel” through tactile feedback to the surgeon and prevent accidental injury to these critical structures.

• A curved scissor is used with “tips up,” such that the surgeon does not unintentionally make the undermining plane deeper than anticipated.

Practice Implications

With practice, one can perform circumferential undermining independently with few alterations in stance and while maintaining a natural position throughout. Use of skin hooks to elevate the skin can further aid in visualizing the correct depth of undermining. If executed correctly, the reverse-grip technique can expand the surgeon’s work field, thus providing ease of dissection in difficult-to-reach areas.

Practice Gap

One of the most important elements of successful reconstruction is effective undermining prior to placement of buried sutures. The main benefit of an evenly undermined plane is that tension is reduced, thus permitting seamless tissue mobilization and wound edge approximation.¹

However, achieving a consistent and appropriate plane can present challenges in certain blind spots within one’s field of work. A right hand–dominant surgeon might find it difficult to undermine tissue between the 3-o’clock and 6-o’clock positions (Figure 1) and often must resort to unnatural positioning to obtain adequate reach.

We propose a technique of reversing the grip on undermining scissors that improves efficiency without sacrificing technique.

Technique

The surgeon simply grasps the ring handles with the ring finger and thumb with the tip pointing to the wrist (Figure 2). Most of the control comes from rotating the wrist while spreading with the thumb (Figure 3).

The main advantage of the reverse-grip technique is that it prevents abduction of the arm at the shoulder joint, which reduces shoulder fatigue and keeps the elbow close to the trunk and away from the sterile surgical field. Achieving optimal ergonomics during surgery has been shown to reduce pain and likely prolong the surgeon’s career.²

A limitation of the reverse-grip technique is that direct visualization of the undermining plane is not achieved; however, direct visualization also is not obtained when undermining in the standard fashion unless the instruments are passed to the surgical assistant or the surgeon moves to the other side of the table.

Undermining can be performed safely without direct visualization as long as several rules are followed:

• The undermining plane is first established under direct visualization on the far side of the wound—at the 6-o’clock to 12-o’clock positions—and then followed to the area where direct visualization is not obtained.

• A blunt-tipped scissor is used to prevent penetrating trauma to neurovascular bundles. Blunt-tipped instruments allow more “feel” through tactile feedback to the surgeon and prevent accidental injury to these critical structures.

• A curved scissor is used with “tips up,” such that the surgeon does not unintentionally make the undermining plane deeper than anticipated.

Practice Implications

With practice, one can perform circumferential undermining independently with few alterations in stance and while maintaining a natural position throughout. Use of skin hooks to elevate the skin can further aid in visualizing the correct depth of undermining. If executed correctly, the reverse-grip technique can expand the surgeon’s work field, thus providing ease of dissection in difficult-to-reach areas.

Practice Gap

One of the most important elements of successful reconstruction is effective undermining prior to placement of buried sutures. The main benefit of an evenly undermined plane is that tension is reduced, thus permitting seamless tissue mobilization and wound edge approximation.¹

However, achieving a consistent and appropriate plane can present challenges in certain blind spots within one’s field of work. A right hand–dominant surgeon might find it difficult to undermine tissue between the 3-o’clock and 6-o’clock positions (Figure 1) and often must resort to unnatural positioning to obtain adequate reach.

We propose a technique of reversing the grip on undermining scissors that improves efficiency without sacrificing technique.

Technique

The surgeon simply grasps the ring handles with the ring finger and thumb with the tip pointing to the wrist (Figure 2). Most of the control comes from rotating the wrist while spreading with the thumb (Figure 3).

The main advantage of the reverse-grip technique is that it prevents abduction of the arm at the shoulder joint, which reduces shoulder fatigue and keeps the elbow close to the trunk and away from the sterile surgical field. Achieving optimal ergonomics during surgery has been shown to reduce pain and likely prolong the surgeon’s career.²

A limitation of the reverse-grip technique is that direct visualization of the undermining plane is not achieved; however, direct visualization also is not obtained when undermining in the standard fashion unless the instruments are passed to the surgical assistant or the surgeon moves to the other side of the table.

Undermining can be performed safely without direct visualization as long as several rules are followed:

• The undermining plane is first established under direct visualization on the far side of the wound—at the 6-o’clock to 12-o’clock positions—and then followed to the area where direct visualization is not obtained.

• A blunt-tipped scissor is used to prevent penetrating trauma to neurovascular bundles. Blunt-tipped instruments allow more “feel” through tactile feedback to the surgeon and prevent accidental injury to these critical structures.

• A curved scissor is used with “tips up,” such that the surgeon does not unintentionally make the undermining plane deeper than anticipated.

Practice Implications

With practice, one can perform circumferential undermining independently with few alterations in stance and while maintaining a natural position throughout. Use of skin hooks to elevate the skin can further aid in visualizing the correct depth of undermining. If executed correctly, the reverse-grip technique can expand the surgeon’s work field, thus providing ease of dissection in difficult-to-reach areas.

To the Editor:

Brodalumab, a monoclonal antibody targeting IL-17RA, was approved by the US Food and Drug Administration (FDA) in 2017 for the treatment of moderate to severe chronic plaque psoriasis. The drug is the only biologic agent available for the treatment of psoriasis for which a psoriasis area severity index score of 100 is a primary end point.^1,2 Brodalumab is associated with an FDA boxed warning due to an increased risk for suicidal ideation and behavior (SIB), including completed suicides, during clinical trials.

We sought to characterize national utilization of this effective yet underutilized drug among Medicare beneficiaries by surveying the Medicare Part D Prescriber dataset.³ We tabulated brodalumab utilization statistics and characteristics of high-volume prescribers who had 11 or more annual claims for brodalumab.

Despite its associated boxed warning, the number of Medicare D claims for brodalumab increased by 1756 from 2017 to 2019, surpassing $7 million in costs by 2019. The number of beneficiaries also increased from 11 to 292—a 415.2% annual increase in beneficiaries for whom brodalumab was prescribed (Table 1).

In addition, states in the West and South had the highest utilization rates of brodalumab in 2019. There also was an increasing trend toward high-volume prescribers of brodalumab, with private practice clinicians constituting the majority (Table 2).

There was a substantial increase in advanced practice providers including nurse practitioners and physician assistants who were brodalumab prescribers. Although this trend might promote greater access to brodalumab, it is vital to ensure that advanced practice providers receive targeted training to properly understand the complexities of treatment with brodalumab.

Although the utilization of brodalumab has increased since 2017 (P<.001), it is still underutilized compared to the other IL-17 inhibitors secukinumab and ixekizumab. Secukinumab was FDA approved for the treatment of moderate to severe plaque psoriasis in 2015, followed by ixekizumab in 2016.⁴

According to the Medicare Part D database, both secukinumab and ixekizumab had a higher number of total claims and prescribers compared to brodalumab in the years of their debut.³ In 2015, there were 3593 claims for and 862 prescribers of secukinumab; in 2016, there were 1731 claims for and 681 prescribers of ixekizumab. In contrast, there were only 29 claims for and 11 prescribers of brodalumab in 2017, the year that the drug was approved by the FDA. During the same 3-year period, secukinumab and ixekizumab had a substantially greater number of claims—totals of 176,823 and 55,289, respectively—than brodalumab. The higher number of claims for secukinumab and ixekizumab compared to brodalumab may reflect clinicians’ increasing confidence in prescribing those drugs, given their long-term safety and efficacy. In addition, secukinumab and ixekizumab do not require completion of a Risk Evaluation and Mitigation Strategy (REMS) program, which makes them more readily prescribable.³

Overall, most experts agree that there is no increase in the risk for suicide associated with brodalumab compared to the general population. A 2-year pharmacovigilance report on brodalumab supports the safety of this drug.⁵ All participants who completed suicide during the clinical trials harbored an underlying psychiatric disorder or stressor(s).⁶

Although causation between brodalumab and SIB has not been demonstrated, it remains imperative that prescribers diligently assess patients’ risk of SIB and subsequently their access to appropriate psychiatric services as a precaution, if necessary. This is particularly important for private practice prescribers, who constitute the majority of Medicare D brodalumab claims, because they must ensure collaboration with a multidisciplinary team involving mental health providers. Lastly, considering that the highest number of brodalumab Medicare D claims were in western and southern states, it is critical to note that those 2 regions also harbor comparatively fewer mental health facilities that accept Medicare than other regions of the country.⁷ Prescribers in western and southern states must be mindful of mental health coverage limitations when treating psoriasis patients with brodalumab.

The increase in the number of claims, beneficiaries, and prescribers of brodalumab during its first 3 years of availability might be attributed to its efficacy and safety. On the other hand, the boxed warning and REMS associated with brodalumab might have led to underutilization of this drug compared to other IL-17 inhibitors.

Our analysis is limited by its representative restriction to Medicare patients. There also are limited data on brodalumab given its novelty. Individual attributes of prescribers with fewer than 11 annual claims for brodalumab could not be obtained because of dataset regulations; however, aggregated utilization statistics provide an indication of brodalumab prescribing patterns among all providers. Furthermore, during this analysis, data on the Medicare D database were limited to 2013 through 2020. Studies are needed to determine prescribing patterns of brodalumab since this study period.

To the Editor:

Brodalumab, a monoclonal antibody targeting IL-17RA, was approved by the US Food and Drug Administration (FDA) in 2017 for the treatment of moderate to severe chronic plaque psoriasis. The drug is the only biologic agent available for the treatment of psoriasis for which a psoriasis area severity index score of 100 is a primary end point.^1,2 Brodalumab is associated with an FDA boxed warning due to an increased risk for suicidal ideation and behavior (SIB), including completed suicides, during clinical trials.

We sought to characterize national utilization of this effective yet underutilized drug among Medicare beneficiaries by surveying the Medicare Part D Prescriber dataset.³ We tabulated brodalumab utilization statistics and characteristics of high-volume prescribers who had 11 or more annual claims for brodalumab.

Despite its associated boxed warning, the number of Medicare D claims for brodalumab increased by 1756 from 2017 to 2019, surpassing $7 million in costs by 2019. The number of beneficiaries also increased from 11 to 292—a 415.2% annual increase in beneficiaries for whom brodalumab was prescribed (Table 1).

In addition, states in the West and South had the highest utilization rates of brodalumab in 2019. There also was an increasing trend toward high-volume prescribers of brodalumab, with private practice clinicians constituting the majority (Table 2).

There was a substantial increase in advanced practice providers including nurse practitioners and physician assistants who were brodalumab prescribers. Although this trend might promote greater access to brodalumab, it is vital to ensure that advanced practice providers receive targeted training to properly understand the complexities of treatment with brodalumab.

Although the utilization of brodalumab has increased since 2017 (P<.001), it is still underutilized compared to the other IL-17 inhibitors secukinumab and ixekizumab. Secukinumab was FDA approved for the treatment of moderate to severe plaque psoriasis in 2015, followed by ixekizumab in 2016.⁴

According to the Medicare Part D database, both secukinumab and ixekizumab had a higher number of total claims and prescribers compared to brodalumab in the years of their debut.³ In 2015, there were 3593 claims for and 862 prescribers of secukinumab; in 2016, there were 1731 claims for and 681 prescribers of ixekizumab. In contrast, there were only 29 claims for and 11 prescribers of brodalumab in 2017, the year that the drug was approved by the FDA. During the same 3-year period, secukinumab and ixekizumab had a substantially greater number of claims—totals of 176,823 and 55,289, respectively—than brodalumab. The higher number of claims for secukinumab and ixekizumab compared to brodalumab may reflect clinicians’ increasing confidence in prescribing those drugs, given their long-term safety and efficacy. In addition, secukinumab and ixekizumab do not require completion of a Risk Evaluation and Mitigation Strategy (REMS) program, which makes them more readily prescribable.³

Overall, most experts agree that there is no increase in the risk for suicide associated with brodalumab compared to the general population. A 2-year pharmacovigilance report on brodalumab supports the safety of this drug.⁵ All participants who completed suicide during the clinical trials harbored an underlying psychiatric disorder or stressor(s).⁶

Although causation between brodalumab and SIB has not been demonstrated, it remains imperative that prescribers diligently assess patients’ risk of SIB and subsequently their access to appropriate psychiatric services as a precaution, if necessary. This is particularly important for private practice prescribers, who constitute the majority of Medicare D brodalumab claims, because they must ensure collaboration with a multidisciplinary team involving mental health providers. Lastly, considering that the highest number of brodalumab Medicare D claims were in western and southern states, it is critical to note that those 2 regions also harbor comparatively fewer mental health facilities that accept Medicare than other regions of the country.⁷ Prescribers in western and southern states must be mindful of mental health coverage limitations when treating psoriasis patients with brodalumab.

The increase in the number of claims, beneficiaries, and prescribers of brodalumab during its first 3 years of availability might be attributed to its efficacy and safety. On the other hand, the boxed warning and REMS associated with brodalumab might have led to underutilization of this drug compared to other IL-17 inhibitors.

Our analysis is limited by its representative restriction to Medicare patients. There also are limited data on brodalumab given its novelty. Individual attributes of prescribers with fewer than 11 annual claims for brodalumab could not be obtained because of dataset regulations; however, aggregated utilization statistics provide an indication of brodalumab prescribing patterns among all providers. Furthermore, during this analysis, data on the Medicare D database were limited to 2013 through 2020. Studies are needed to determine prescribing patterns of brodalumab since this study period.

To the Editor:

Brodalumab, a monoclonal antibody targeting IL-17RA, was approved by the US Food and Drug Administration (FDA) in 2017 for the treatment of moderate to severe chronic plaque psoriasis. The drug is the only biologic agent available for the treatment of psoriasis for which a psoriasis area severity index score of 100 is a primary end point.^1,2 Brodalumab is associated with an FDA boxed warning due to an increased risk for suicidal ideation and behavior (SIB), including completed suicides, during clinical trials.

We sought to characterize national utilization of this effective yet underutilized drug among Medicare beneficiaries by surveying the Medicare Part D Prescriber dataset.³ We tabulated brodalumab utilization statistics and characteristics of high-volume prescribers who had 11 or more annual claims for brodalumab.

Despite its associated boxed warning, the number of Medicare D claims for brodalumab increased by 1756 from 2017 to 2019, surpassing $7 million in costs by 2019. The number of beneficiaries also increased from 11 to 292—a 415.2% annual increase in beneficiaries for whom brodalumab was prescribed (Table 1).

In addition, states in the West and South had the highest utilization rates of brodalumab in 2019. There also was an increasing trend toward high-volume prescribers of brodalumab, with private practice clinicians constituting the majority (Table 2).

There was a substantial increase in advanced practice providers including nurse practitioners and physician assistants who were brodalumab prescribers. Although this trend might promote greater access to brodalumab, it is vital to ensure that advanced practice providers receive targeted training to properly understand the complexities of treatment with brodalumab.

Although the utilization of brodalumab has increased since 2017 (P<.001), it is still underutilized compared to the other IL-17 inhibitors secukinumab and ixekizumab. Secukinumab was FDA approved for the treatment of moderate to severe plaque psoriasis in 2015, followed by ixekizumab in 2016.⁴

According to the Medicare Part D database, both secukinumab and ixekizumab had a higher number of total claims and prescribers compared to brodalumab in the years of their debut.³ In 2015, there were 3593 claims for and 862 prescribers of secukinumab; in 2016, there were 1731 claims for and 681 prescribers of ixekizumab. In contrast, there were only 29 claims for and 11 prescribers of brodalumab in 2017, the year that the drug was approved by the FDA. During the same 3-year period, secukinumab and ixekizumab had a substantially greater number of claims—totals of 176,823 and 55,289, respectively—than brodalumab. The higher number of claims for secukinumab and ixekizumab compared to brodalumab may reflect clinicians’ increasing confidence in prescribing those drugs, given their long-term safety and efficacy. In addition, secukinumab and ixekizumab do not require completion of a Risk Evaluation and Mitigation Strategy (REMS) program, which makes them more readily prescribable.³

Overall, most experts agree that there is no increase in the risk for suicide associated with brodalumab compared to the general population. A 2-year pharmacovigilance report on brodalumab supports the safety of this drug.⁵ All participants who completed suicide during the clinical trials harbored an underlying psychiatric disorder or stressor(s).⁶

Although causation between brodalumab and SIB has not been demonstrated, it remains imperative that prescribers diligently assess patients’ risk of SIB and subsequently their access to appropriate psychiatric services as a precaution, if necessary. This is particularly important for private practice prescribers, who constitute the majority of Medicare D brodalumab claims, because they must ensure collaboration with a multidisciplinary team involving mental health providers. Lastly, considering that the highest number of brodalumab Medicare D claims were in western and southern states, it is critical to note that those 2 regions also harbor comparatively fewer mental health facilities that accept Medicare than other regions of the country.⁷ Prescribers in western and southern states must be mindful of mental health coverage limitations when treating psoriasis patients with brodalumab.

The increase in the number of claims, beneficiaries, and prescribers of brodalumab during its first 3 years of availability might be attributed to its efficacy and safety. On the other hand, the boxed warning and REMS associated with brodalumab might have led to underutilization of this drug compared to other IL-17 inhibitors.

Our analysis is limited by its representative restriction to Medicare patients. There also are limited data on brodalumab given its novelty. Individual attributes of prescribers with fewer than 11 annual claims for brodalumab could not be obtained because of dataset regulations; however, aggregated utilization statistics provide an indication of brodalumab prescribing patterns among all providers. Furthermore, during this analysis, data on the Medicare D database were limited to 2013 through 2020. Studies are needed to determine prescribing patterns of brodalumab since this study period.

Glucocorticoids (GCs) are among the most widely prescribed medications in dermatologic practice. Although GCs are highly effective anti-inflammatory agents, long-term systemic therapy can result in dangerous adverse effects, including GC-induced osteoporosis (GIO), a bone disease associated with a heightened risk for fragility fractures.^1,2 In the United States, an estimated 10.2 million adults have osteoporosis—defined as a T-score lower than −2.5 measured via a bone densitometry scan—and 43.4 million adults have low bone mineral density (BMD).^3,4 The prevalence of osteoporosis is increasing, and the diagnosis is more common in females and adults 55 years and older.² More than 2 million individuals have osteoporosis-related fractures annually, and the mortality risk is increased at 5 and 10 years following low-energy osteoporosis-related fractures.^3-5

Glucocorticoid therapy is the leading iatrogenic cause of secondary osteoporosis. As many as 30% of all patients treated with systemic GCs for more than 6 months develop GIO.^1,6,7 Glucocorticoid-induced BMD loss occurs at a rate of 6% to 12% of total BMD during the first year, slowing to approximately 3% per year during subsequent therapy.¹ The risk for insufficiency fractures increases by as much as 75% from baseline in adults with rheumatic, pulmonary, and skin disorders within the first 3 months of therapy and peaks at approximately 12 months.^1,2

Despite the risks, many long-term GC users never receive therapy to prevent bone loss; others are only started on therapy once they have sustained an insufficiency fracture. A 5-year international observational study including more than 40,000 postmenopausal women found that only 51% of patients who were on continuous GC therapy were undergoing BMD testing and appropriate medical management.⁸ This review highlights the existing evidence on the risks of osteoporosis and osteoporotic (OP) fractures in the setting of topical, intralesional, intramuscular, and systemic GC treatment, as well as recommendations for nutritional supplementation to reduce these risks.

Pathophysiology

The pathophysiology of GIO is multifactorial and occurs in both early and late phases.^9,10 The early phase is characterized by rapid BMD reduction due to excessive bone resorption. The late phase is characterized by slower and more progressive BMD reduction due to impaired bone formation.⁹ At the osteocyte level, GCs decrease cell viability and induce apoptosis.¹¹ At the osteoblast level, GCs impair cell replication and differentiation and have proapoptotic effects, resulting in decreased cell numbers and subsequent bone formation.¹⁰ At the osteoclast level, GCs increase expression of pro-osteoclastic cytokines and decrease mature osteoclast apoptosis, resulting in an expanded osteoclastic life span and prolonged bone resorption.^12,13 Indirectly, GCs alter calcium metabolism by decreasing gastrointestinal calcium absorption and impairing renal absorption.^14,15

GCs and Osteoporosis

Oral GCs—Glucocorticoid-induced osteoporosis and fracture risk are dose and duration dependent.⁶ A study of 244,235 patients taking GCs and 244,235 controls found the relative risk of vertebral fracture was 1.55 (range, 1.20–2.01) for daily prednisone use at less than 2.5 mg, 2.59 (range, 2.16–3.10) for daily prednisone use from 2.5 to 7.4 mg, and 5.18 (range, 4.25–6.31) for daily doses of 7.5 mg or higher; the relative risk for hip fractures was 0.99 (range, 0.82–1.20), 1.77 (range, 1.55–2.02), and 2.27 (range, 1.94–2.66), respectively.¹⁶ Another large retrospective cohort study found that continuous treatment with prednisone 10 mg/d for more than 90 days compared to no GC exposure increased the risk for hip fractures 7-fold and 17-fold for vertebral fractures.¹⁷ Although the minimum cumulative dose of GCs known to cause osteoporosis is not clearly established, the American College of Rheumatology has proposed an algorithm as a basic approach to anticipate, prevent, and treat GIO (Figure).^18,19 Fracture risk should be assessed in all patients who are prescribed prednisone 2.5 mg/d for 3 months or longer or an anticipated cumulative dose of more than 1 g per year. Patients 40 years and older with anticipated GC use of 3 months or longer should have both a bone densitometry scan and a Fracture Risk Assessment (FRAX) score. The FRAX tool estimates the 10-year probability of fracture in patients aged 40 to 80 years, and those patients can be further risk stratified as low (FRAX <10%), moderate (FRAX 10%–19%), or high (FRAX ≥20%) risk. In patients with moderate to high risk of fracture (FRAX >10%), initiation of pharmacologic treatment or referral to a metabolic bone specialist should be considered.^18,19 First-line therapy is an oral bisphosphonate, and second-line therapies include intravenous bisphosphonates, teriparatide, denosumab, or raloxifene for patients at high risk for GIO.¹⁹ Adults younger than 40 years with a history of OP fracture or considerable risk factors for OP fractures should have a bone densitometry scan, and, if results are abnormal, the patient should be referred to a metabolic bone specialist. Those with low fracture risk based on bone densitometry and FRAX and those with no risk factors should be assessed annually for bone health (additional risk factors, GC dose and duration, bone densitometry/FRAX if indicated).¹⁸ In addition to GC dose and duration, additional risk factors for GIO, which are factored into the FRAX tool, include advanced age, low body mass index, history of bone fracture, smoking, excessive alcohol use (≥3 drinks/d), history of falls, low BMD, family history of bone fracture, and hypovitaminosis D.⁶

Topical GCs—Although there is strong evidence and clear guidelines regarding oral GIO, there is a dearth of data surrounding OP risk due to treatment with topical GCs. A recent retrospective nationwide Danish study evaluating the risk of osteoporosis and major OP fracture in 723,251 adults treated with potent or very potent topical steroids sought to evaluate these risks.²⁰ Patients were included if they had filled prescriptions of at least 500 g of topical mometasone or an equivalent alternative. The investigators reported a 3% increase in relative risk of osteoporosis and major OP fracture with doubling of the cumulative topical GC dose (hazard ratio [HR], 1.03 [95% CI, 1.02-1.04] for both). The overall population-attributable risk was 4.3% (95% CI, 2.7%-5.8%) for osteoporosis and 2.7% (95% CI, 1.7%-3.8%) for major OP fracture. Notably, at least 10,000 g of mometasone was required for 1 additional patient to have a major OP fracture.²⁰ In a commentary based on this study, Jackson²¹ noted that the number of patient-years of topical GC use needed for 1 fracture was 4-fold higher than that for high-dose oral GCs (40 mg/d prednisolone for ≥30 days). Another study assessed the effects of topical GCs on BMD in adults with moderate to severe atopic dermatitis over a 2-year period.²² No significant difference in BMD assessed via bone densitometry of either the lumbar spine or total hip at baseline or at 2-year follow-up was reported for either group treated with corticosteroids (<75 g per month or ≥75 g per month). Of note, the authors did not account for steroid potency, which ranged from class 1 through class 4.²² Although limited data exist, these studies suggest topical GCs used at conventional doses with appropriate breaks in therapy will not substantially increase risk for GIO or OP fracture; however, in the small subset of patients requiring chronic use of superpotent topical corticosteroids with other OP risk factors, transitioning to non–GC-based therapy or initiating bone health therapy may be advised to improve patient outcomes. Risk assessment, as in cases of chronic topical GC use, may be beneficial.

Intralesional GCs—Intralesional GCs are indicated for numerous inflammatory conditions including alopecia areata, discoid lupus erythematosus, keloids, and granuloma annulare. It generally is accepted that doses of triamcinolone acetonide should not exceed 20 mg per session spaced at least 3 weeks apart or up to 40 mg per month.¹⁸ One study demonstrated that doses of triamcinolone diacetate of 25 mg or less were unlikely to produce systemic effects and were determined to be a safe dose for intralesional injections.²³ A retrospective cross-sectional case series including 18 patients with alopecia areata reported decreased BMD in 9 patients receiving intralesional triamcinolone acetonide 10 mg/mL at 4- to 8-week intervals for at least 20 months, with cumulative doses greater than 500 mg. This was particularly notable in postmenopausal women and men older than 50 years; participants with a body mass index less than 18.5 kg/m², history of a stress fracture, family history of osteopenia or osteoporosis, and history of smoking; and those who did not regularly engage in weight-bearing exercises.²⁴ Patients receiving long-term (ie, >1 year) intralesional steroids should be evaluated for osteoporosis risk and preventative strategies should be considered (ie, regular weight-bearing exercises, calcium and vitamin D supplementation, bisphosphate therapy). As with topical GCs, there are no clear guidelines for risk assessment or treatment recommendations for GIO.

Intramuscular GCs—The data regarding intramuscular (IM) GCs and dermatologic disease is severely limited, and to the best of our knowledge, no studies specifically assess the risk for GIO or fracture secondary to intramuscular GCs; however, a retrospective study of 27 patients (4 female, 23 male; mean age, 33 years [range, 12–61 years]) with refractory alopecia areata receiving IM triamcinolone acetonide (40 mg every 4 weeks for 3–6 months) reported 1 patient (a 56-year-old woman) with notably decreased bone densitometry from baseline requiring treatment discontinuation.²⁵ No other patients at risk for osteoporosis had decreased BMD from treatment with IM triamcinolone; however, it was noted that 1 month following treatment, 10 of 11 assessed patients demonstrated decreased levels of morning serum cortisol and plasma adrenocorticotropic hormone—despite baseline levels within reference range—that resolved 3 months after treatment completion,²⁵ which suggests a prolonged release of IM triamcinolone and sustained systemic effect. One systematic review of 342 patients with dermatologic diseases treated with IM corticosteroids found the primary side effects included dysmenorrhea, injection-site lipoatrophy, and adrenocortical suppression, with only a single reported case of low BMD.²⁶ Given the paucity of evidence, additional studies are required to assess the effect of IM triamcinolone on BMD and risk for major OP fractures with regard to dosing and frequency. As there are no clear guidelines for osteoporosis evaluation in the setting of intramuscular GCs, it may be prudent to follow the algorithmic model recommended for oral steroids when anticipating at least 3 months of intramuscular GCs.

Diet and Prevention of Bone Loss

Given the profound impact that systemic GCs have on osteoporosis and fracture risk and the sparse data regarding risk from topical, intralesional, or intramuscular GCs, diet and nutrition represent a simple, safe, and potentially preventative method of slowing BMD loss and minimizing fracture risk. In higher-risk patients, nutritional assessment in combination with medical therapy also is likely warranted.

Calcium and Vitamin D₃—Patients treated with any GC dose longer than 3 months should undergo calcium and vitamin D optimization.¹⁹ Exceptions for supplementation include certain patients with sarcoidosis, which can be associated with high vitamin D levels; patients with a history of hypercalcemia or hypercalciuria; and patients with chronic kidney disease.⁶ In a meta-analysis including 30,970 patients in 8 randomized controlled trials, calcium (500–1200 mg/d) and vitamin D (400–800 IU/d) supplementation reduced the risk of total fractures by 15% (summary relative risk estimate, 0.85 [95% CI, 0.73-0.98]) and hip fractures by 30% (summary relative risk estimate, 0.70 [95% CI, 0.56-0.87]).⁴ One double-blind, placebo-controlled clinical trial conducted by the Women’s Health Initiative that included 36,282 postmenopausal women who were taking 1000 mg of calcium and 400 IU of vitamin D₃ daily for more than 5 years reported an HR of 0.62 (95% CI, 0.38-1.00) for hip fracture for supplementation vs placebo.²⁷ Lastly, a 2016 Cochrane Review including 12 randomized trials and 1343 participants reported a 43% lower risk of new vertebral fractures following supplementation with calcium, vitamin D, or both compared with controls.²⁸

Specific recommendations for calcium and vitamin D₃ supplementation vary based on age and sex. The US Preventive Services Task Force concluded that insufficient evidence exists to support calcium and vitamin D₃ supplementation in asymptomatic men and premenopausal women.²⁹ The National Osteoporosis Foundation (NOF) supports the use of calcium supplementation for fracture risk reduction in middle-aged and older adults.⁴ Furthermore, the NOF supports the Institute of Medicine recommendations³¹ that men aged 50 to 70 years consume 1000 mg/d of calcium and that women 51 years and older as well as men 71 years and older consume 1200 mg/d of calcium.³⁰ The NOF recommends 800 to 1000 IU/d of vitamin D in adults 50 years and older, while the Institute of Medicine recommends 600 IU/d in adults 70 years and younger and 800 IU/d in adults 71 years and older.³¹ These recommendations are similar to both the Endocrine Society and the American Geriatric Society.^32,33 Total calcium should not exceed 2000 mg/d due to risk of adverse effects.

Dietary sources of vitamin D include fatty fish, mushrooms, and fortified dairy products, though recommended doses rarely can be achieved through diet alone.³⁴ Dairy products are the primary source of dietary calcium. Other high-calcium foods include green leafy vegetables, nuts and seeds, soft-boned fish, and fortified beverages and cereals.³⁵

Probiotics—A growing body of evidence suggests that probiotics may be beneficial in promoting bone health by improving calcium homeostasis, reducing risk for hyperparathyroidism secondary to GC therapy, and decreasing age-related bone resorption.³⁶ An animal study demonstrated that probiotics can regulate bone resorption and formation as well as reduce bone loss secondary to GC therapy.³⁷ A randomized, double-blind, placebo-controlled, multicenter trial randomly assigned 249 healthy, early postmenopausal women to receive probiotic treatment containing 3 lactobacillus strains (Lactobacillus paracasei DSM 13434, Lactobacillus plantarum DSM 15312, and L plantarum DSM 15313) or placebo once daily for 12 months.³⁸ Bone mineral density was measured at baseline and at 12 months. Of the 234 participants who completed the study, lactobacillus treatment reduced lumbosacral BMD loss compared to the placebo group (mean difference, 0.71% [95% CI, 0.06-1.35]). They also reported significant lumbosacral BMD loss in the placebo group (−0.72% [95% CI, −1.22 to −0.22]) compared to no BMD loss in the group treated with lactobacillus (−0.01% [95% CI, −0.50 to 0.48]).³⁸ Although the data may be encouraging, more studies are needed to determine if probiotics should be regarded as an adjuvant treatment to calcium, vitamin D, and pharmacologic therapy for long-term prevention of bone loss in the setting of GIO.³⁹ Because existing studies on probiotics include varying compositions and doses, larger studies with consistent supplementation are required. Encouraging probiotic intake through fermented dairy products may represent a simple low-risk intervention to support bone health.

Anti-inflammatory Diet—The traditional Mediterranean diet is rich in fruits, vegetables, fish, nuts, whole grains, legumes, and monounsaturated fats and low in meat and dairy products. The Mediterranean diet has been shown to be modestly protective against osteoporosis and fracture risk. A large US observational study including 93,676 women showed that those with the highest quintile of the alternate Mediterranean diet score had a lower risk for hip fracture (HR, 0.80 [95% CI, 0.66-0.97]), with an absolute risk reduction of 0.29% and number needed to treat at 342.⁴⁰ A multicenter study involving adults from 8 European countries found that increased adherence to the Mediterranean diet was associated with a 7% reduction in hip fracture incidence (HR per 1 unit increase in Mediterranean diet, 0.93 [95% CI, 0.89-0.98]). High vegetable and fruit intake was associated with decreased hip fracture incidence (HR, 0.86 and 0.89 [95% CI, 0.79-0.94 and 0.82-0.97, respectively]), and high meat and excessive ethanol consumption were associated with increased fracture incidence (HR, 1.18 and 1.74 [95% CI, 1.06-1.31 and 1.32-2.31, respectively]).⁴¹ Similarly, a large observational study in Sweden that included 37,903 men and 33,403 women reported similar findings, noting a 6% lower hip fracture rate per one unit increase in alternate Mediterranean diet score (adjusted HR, 0.94 [95% CI, 0.92-0.96]).⁴² This is thought to be due in part to higher levels of dietary vitamin D present in many foods traditionally included in the Mediterranean diet.⁴³ Additionally, olive oil, a staple in the Mediterranean diet, appears to reduce bone loss by promoting osteoblast proliferation and maturation, inhibiting bone resorption, suppressing oxidative stress and inflammation, and increasing calcium deposition in the extracellular matrix.^44,45 Fruits, vegetables, legumes, and nuts also are rich in minerals including potassium and magnesium, which are important in bone health to promote osteoblast proliferation and vitamin D activation.^36,46-48

Final Thoughts

Osteoporosis-related fractures are common and are associated with high morbidity and health care costs. Dermatologists using and prescribing corticosteroids must be aware of the risk for GIO, particularly in patients with a pre-existing diagnosis of osteopenia or osteoporosis. There likely is no oral corticosteroid dose that does not increase a patient’s risk for osteoporosis; therefore, oral GCs should be used at the lowest effective daily dose for the shortest duration possible. Patients with an anticipated duration of at least 3 months—regardless of dose—should be assessed for their risk for GIO. Patients using topical and intralesional corticosteroids are unlikely to develop GIO; however, those with risk factors and a considerable cumulative dose may warrant further evaluation. In all cases, we advocate for supplementing with calcium and vitamin D as well as promoting probiotic intake and the Mediterranean diet. Those at moderate to high risk for fracture may require additional medical therapy. Dermatologists are uniquely positioned to identify this at-risk population, and because osteoporosis is a chronic illness, primary care providers should be notified of prolonged GC therapy to help with risk assessment, initiation of vitamin and mineral supplementation, and follow-up with metabolic bone health specialists. Through a multidisciplinary approach and patient education, GIO and the potential risk for fracture can be successfully mitigated in most patients.

Glucocorticoids (GCs) are among the most widely prescribed medications in dermatologic practice. Although GCs are highly effective anti-inflammatory agents, long-term systemic therapy can result in dangerous adverse effects, including GC-induced osteoporosis (GIO), a bone disease associated with a heightened risk for fragility fractures.^1,2 In the United States, an estimated 10.2 million adults have osteoporosis—defined as a T-score lower than −2.5 measured via a bone densitometry scan—and 43.4 million adults have low bone mineral density (BMD).^3,4 The prevalence of osteoporosis is increasing, and the diagnosis is more common in females and adults 55 years and older.² More than 2 million individuals have osteoporosis-related fractures annually, and the mortality risk is increased at 5 and 10 years following low-energy osteoporosis-related fractures.^3-5

Glucocorticoid therapy is the leading iatrogenic cause of secondary osteoporosis. As many as 30% of all patients treated with systemic GCs for more than 6 months develop GIO.^1,6,7 Glucocorticoid-induced BMD loss occurs at a rate of 6% to 12% of total BMD during the first year, slowing to approximately 3% per year during subsequent therapy.¹ The risk for insufficiency fractures increases by as much as 75% from baseline in adults with rheumatic, pulmonary, and skin disorders within the first 3 months of therapy and peaks at approximately 12 months.^1,2

Despite the risks, many long-term GC users never receive therapy to prevent bone loss; others are only started on therapy once they have sustained an insufficiency fracture. A 5-year international observational study including more than 40,000 postmenopausal women found that only 51% of patients who were on continuous GC therapy were undergoing BMD testing and appropriate medical management.⁸ This review highlights the existing evidence on the risks of osteoporosis and osteoporotic (OP) fractures in the setting of topical, intralesional, intramuscular, and systemic GC treatment, as well as recommendations for nutritional supplementation to reduce these risks.

Pathophysiology

The pathophysiology of GIO is multifactorial and occurs in both early and late phases.^9,10 The early phase is characterized by rapid BMD reduction due to excessive bone resorption. The late phase is characterized by slower and more progressive BMD reduction due to impaired bone formation.⁹ At the osteocyte level, GCs decrease cell viability and induce apoptosis.¹¹ At the osteoblast level, GCs impair cell replication and differentiation and have proapoptotic effects, resulting in decreased cell numbers and subsequent bone formation.¹⁰ At the osteoclast level, GCs increase expression of pro-osteoclastic cytokines and decrease mature osteoclast apoptosis, resulting in an expanded osteoclastic life span and prolonged bone resorption.^12,13 Indirectly, GCs alter calcium metabolism by decreasing gastrointestinal calcium absorption and impairing renal absorption.^14,15

GCs and Osteoporosis

Oral GCs—Glucocorticoid-induced osteoporosis and fracture risk are dose and duration dependent.⁶ A study of 244,235 patients taking GCs and 244,235 controls found the relative risk of vertebral fracture was 1.55 (range, 1.20–2.01) for daily prednisone use at less than 2.5 mg, 2.59 (range, 2.16–3.10) for daily prednisone use from 2.5 to 7.4 mg, and 5.18 (range, 4.25–6.31) for daily doses of 7.5 mg or higher; the relative risk for hip fractures was 0.99 (range, 0.82–1.20), 1.77 (range, 1.55–2.02), and 2.27 (range, 1.94–2.66), respectively.¹⁶ Another large retrospective cohort study found that continuous treatment with prednisone 10 mg/d for more than 90 days compared to no GC exposure increased the risk for hip fractures 7-fold and 17-fold for vertebral fractures.¹⁷ Although the minimum cumulative dose of GCs known to cause osteoporosis is not clearly established, the American College of Rheumatology has proposed an algorithm as a basic approach to anticipate, prevent, and treat GIO (Figure).^18,19 Fracture risk should be assessed in all patients who are prescribed prednisone 2.5 mg/d for 3 months or longer or an anticipated cumulative dose of more than 1 g per year. Patients 40 years and older with anticipated GC use of 3 months or longer should have both a bone densitometry scan and a Fracture Risk Assessment (FRAX) score. The FRAX tool estimates the 10-year probability of fracture in patients aged 40 to 80 years, and those patients can be further risk stratified as low (FRAX <10%), moderate (FRAX 10%–19%), or high (FRAX ≥20%) risk. In patients with moderate to high risk of fracture (FRAX >10%), initiation of pharmacologic treatment or referral to a metabolic bone specialist should be considered.^18,19 First-line therapy is an oral bisphosphonate, and second-line therapies include intravenous bisphosphonates, teriparatide, denosumab, or raloxifene for patients at high risk for GIO.¹⁹ Adults younger than 40 years with a history of OP fracture or considerable risk factors for OP fractures should have a bone densitometry scan, and, if results are abnormal, the patient should be referred to a metabolic bone specialist. Those with low fracture risk based on bone densitometry and FRAX and those with no risk factors should be assessed annually for bone health (additional risk factors, GC dose and duration, bone densitometry/FRAX if indicated).¹⁸ In addition to GC dose and duration, additional risk factors for GIO, which are factored into the FRAX tool, include advanced age, low body mass index, history of bone fracture, smoking, excessive alcohol use (≥3 drinks/d), history of falls, low BMD, family history of bone fracture, and hypovitaminosis D.⁶

Topical GCs—Although there is strong evidence and clear guidelines regarding oral GIO, there is a dearth of data surrounding OP risk due to treatment with topical GCs. A recent retrospective nationwide Danish study evaluating the risk of osteoporosis and major OP fracture in 723,251 adults treated with potent or very potent topical steroids sought to evaluate these risks.²⁰ Patients were included if they had filled prescriptions of at least 500 g of topical mometasone or an equivalent alternative. The investigators reported a 3% increase in relative risk of osteoporosis and major OP fracture with doubling of the cumulative topical GC dose (hazard ratio [HR], 1.03 [95% CI, 1.02-1.04] for both). The overall population-attributable risk was 4.3% (95% CI, 2.7%-5.8%) for osteoporosis and 2.7% (95% CI, 1.7%-3.8%) for major OP fracture. Notably, at least 10,000 g of mometasone was required for 1 additional patient to have a major OP fracture.²⁰ In a commentary based on this study, Jackson²¹ noted that the number of patient-years of topical GC use needed for 1 fracture was 4-fold higher than that for high-dose oral GCs (40 mg/d prednisolone for ≥30 days). Another study assessed the effects of topical GCs on BMD in adults with moderate to severe atopic dermatitis over a 2-year period.²² No significant difference in BMD assessed via bone densitometry of either the lumbar spine or total hip at baseline or at 2-year follow-up was reported for either group treated with corticosteroids (<75 g per month or ≥75 g per month). Of note, the authors did not account for steroid potency, which ranged from class 1 through class 4.²² Although limited data exist, these studies suggest topical GCs used at conventional doses with appropriate breaks in therapy will not substantially increase risk for GIO or OP fracture; however, in the small subset of patients requiring chronic use of superpotent topical corticosteroids with other OP risk factors, transitioning to non–GC-based therapy or initiating bone health therapy may be advised to improve patient outcomes. Risk assessment, as in cases of chronic topical GC use, may be beneficial.

Intralesional GCs—Intralesional GCs are indicated for numerous inflammatory conditions including alopecia areata, discoid lupus erythematosus, keloids, and granuloma annulare. It generally is accepted that doses of triamcinolone acetonide should not exceed 20 mg per session spaced at least 3 weeks apart or up to 40 mg per month.¹⁸ One study demonstrated that doses of triamcinolone diacetate of 25 mg or less were unlikely to produce systemic effects and were determined to be a safe dose for intralesional injections.²³ A retrospective cross-sectional case series including 18 patients with alopecia areata reported decreased BMD in 9 patients receiving intralesional triamcinolone acetonide 10 mg/mL at 4- to 8-week intervals for at least 20 months, with cumulative doses greater than 500 mg. This was particularly notable in postmenopausal women and men older than 50 years; participants with a body mass index less than 18.5 kg/m², history of a stress fracture, family history of osteopenia or osteoporosis, and history of smoking; and those who did not regularly engage in weight-bearing exercises.²⁴ Patients receiving long-term (ie, >1 year) intralesional steroids should be evaluated for osteoporosis risk and preventative strategies should be considered (ie, regular weight-bearing exercises, calcium and vitamin D supplementation, bisphosphate therapy). As with topical GCs, there are no clear guidelines for risk assessment or treatment recommendations for GIO.

Intramuscular GCs—The data regarding intramuscular (IM) GCs and dermatologic disease is severely limited, and to the best of our knowledge, no studies specifically assess the risk for GIO or fracture secondary to intramuscular GCs; however, a retrospective study of 27 patients (4 female, 23 male; mean age, 33 years [range, 12–61 years]) with refractory alopecia areata receiving IM triamcinolone acetonide (40 mg every 4 weeks for 3–6 months) reported 1 patient (a 56-year-old woman) with notably decreased bone densitometry from baseline requiring treatment discontinuation.²⁵ No other patients at risk for osteoporosis had decreased BMD from treatment with IM triamcinolone; however, it was noted that 1 month following treatment, 10 of 11 assessed patients demonstrated decreased levels of morning serum cortisol and plasma adrenocorticotropic hormone—despite baseline levels within reference range—that resolved 3 months after treatment completion,²⁵ which suggests a prolonged release of IM triamcinolone and sustained systemic effect. One systematic review of 342 patients with dermatologic diseases treated with IM corticosteroids found the primary side effects included dysmenorrhea, injection-site lipoatrophy, and adrenocortical suppression, with only a single reported case of low BMD.²⁶ Given the paucity of evidence, additional studies are required to assess the effect of IM triamcinolone on BMD and risk for major OP fractures with regard to dosing and frequency. As there are no clear guidelines for osteoporosis evaluation in the setting of intramuscular GCs, it may be prudent to follow the algorithmic model recommended for oral steroids when anticipating at least 3 months of intramuscular GCs.

Diet and Prevention of Bone Loss

Given the profound impact that systemic GCs have on osteoporosis and fracture risk and the sparse data regarding risk from topical, intralesional, or intramuscular GCs, diet and nutrition represent a simple, safe, and potentially preventative method of slowing BMD loss and minimizing fracture risk. In higher-risk patients, nutritional assessment in combination with medical therapy also is likely warranted.

Calcium and Vitamin D₃—Patients treated with any GC dose longer than 3 months should undergo calcium and vitamin D optimization.¹⁹ Exceptions for supplementation include certain patients with sarcoidosis, which can be associated with high vitamin D levels; patients with a history of hypercalcemia or hypercalciuria; and patients with chronic kidney disease.⁶ In a meta-analysis including 30,970 patients in 8 randomized controlled trials, calcium (500–1200 mg/d) and vitamin D (400–800 IU/d) supplementation reduced the risk of total fractures by 15% (summary relative risk estimate, 0.85 [95% CI, 0.73-0.98]) and hip fractures by 30% (summary relative risk estimate, 0.70 [95% CI, 0.56-0.87]).⁴ One double-blind, placebo-controlled clinical trial conducted by the Women’s Health Initiative that included 36,282 postmenopausal women who were taking 1000 mg of calcium and 400 IU of vitamin D₃ daily for more than 5 years reported an HR of 0.62 (95% CI, 0.38-1.00) for hip fracture for supplementation vs placebo.²⁷ Lastly, a 2016 Cochrane Review including 12 randomized trials and 1343 participants reported a 43% lower risk of new vertebral fractures following supplementation with calcium, vitamin D, or both compared with controls.²⁸

Specific recommendations for calcium and vitamin D₃ supplementation vary based on age and sex. The US Preventive Services Task Force concluded that insufficient evidence exists to support calcium and vitamin D₃ supplementation in asymptomatic men and premenopausal women.²⁹ The National Osteoporosis Foundation (NOF) supports the use of calcium supplementation for fracture risk reduction in middle-aged and older adults.⁴ Furthermore, the NOF supports the Institute of Medicine recommendations³¹ that men aged 50 to 70 years consume 1000 mg/d of calcium and that women 51 years and older as well as men 71 years and older consume 1200 mg/d of calcium.³⁰ The NOF recommends 800 to 1000 IU/d of vitamin D in adults 50 years and older, while the Institute of Medicine recommends 600 IU/d in adults 70 years and younger and 800 IU/d in adults 71 years and older.³¹ These recommendations are similar to both the Endocrine Society and the American Geriatric Society.^32,33 Total calcium should not exceed 2000 mg/d due to risk of adverse effects.

Dietary sources of vitamin D include fatty fish, mushrooms, and fortified dairy products, though recommended doses rarely can be achieved through diet alone.³⁴ Dairy products are the primary source of dietary calcium. Other high-calcium foods include green leafy vegetables, nuts and seeds, soft-boned fish, and fortified beverages and cereals.³⁵

Probiotics—A growing body of evidence suggests that probiotics may be beneficial in promoting bone health by improving calcium homeostasis, reducing risk for hyperparathyroidism secondary to GC therapy, and decreasing age-related bone resorption.³⁶ An animal study demonstrated that probiotics can regulate bone resorption and formation as well as reduce bone loss secondary to GC therapy.³⁷ A randomized, double-blind, placebo-controlled, multicenter trial randomly assigned 249 healthy, early postmenopausal women to receive probiotic treatment containing 3 lactobacillus strains (Lactobacillus paracasei DSM 13434, Lactobacillus plantarum DSM 15312, and L plantarum DSM 15313) or placebo once daily for 12 months.³⁸ Bone mineral density was measured at baseline and at 12 months. Of the 234 participants who completed the study, lactobacillus treatment reduced lumbosacral BMD loss compared to the placebo group (mean difference, 0.71% [95% CI, 0.06-1.35]). They also reported significant lumbosacral BMD loss in the placebo group (−0.72% [95% CI, −1.22 to −0.22]) compared to no BMD loss in the group treated with lactobacillus (−0.01% [95% CI, −0.50 to 0.48]).³⁸ Although the data may be encouraging, more studies are needed to determine if probiotics should be regarded as an adjuvant treatment to calcium, vitamin D, and pharmacologic therapy for long-term prevention of bone loss in the setting of GIO.³⁹ Because existing studies on probiotics include varying compositions and doses, larger studies with consistent supplementation are required. Encouraging probiotic intake through fermented dairy products may represent a simple low-risk intervention to support bone health.

Anti-inflammatory Diet—The traditional Mediterranean diet is rich in fruits, vegetables, fish, nuts, whole grains, legumes, and monounsaturated fats and low in meat and dairy products. The Mediterranean diet has been shown to be modestly protective against osteoporosis and fracture risk. A large US observational study including 93,676 women showed that those with the highest quintile of the alternate Mediterranean diet score had a lower risk for hip fracture (HR, 0.80 [95% CI, 0.66-0.97]), with an absolute risk reduction of 0.29% and number needed to treat at 342.⁴⁰ A multicenter study involving adults from 8 European countries found that increased adherence to the Mediterranean diet was associated with a 7% reduction in hip fracture incidence (HR per 1 unit increase in Mediterranean diet, 0.93 [95% CI, 0.89-0.98]). High vegetable and fruit intake was associated with decreased hip fracture incidence (HR, 0.86 and 0.89 [95% CI, 0.79-0.94 and 0.82-0.97, respectively]), and high meat and excessive ethanol consumption were associated with increased fracture incidence (HR, 1.18 and 1.74 [95% CI, 1.06-1.31 and 1.32-2.31, respectively]).⁴¹ Similarly, a large observational study in Sweden that included 37,903 men and 33,403 women reported similar findings, noting a 6% lower hip fracture rate per one unit increase in alternate Mediterranean diet score (adjusted HR, 0.94 [95% CI, 0.92-0.96]).⁴² This is thought to be due in part to higher levels of dietary vitamin D present in many foods traditionally included in the Mediterranean diet.⁴³ Additionally, olive oil, a staple in the Mediterranean diet, appears to reduce bone loss by promoting osteoblast proliferation and maturation, inhibiting bone resorption, suppressing oxidative stress and inflammation, and increasing calcium deposition in the extracellular matrix.^44,45 Fruits, vegetables, legumes, and nuts also are rich in minerals including potassium and magnesium, which are important in bone health to promote osteoblast proliferation and vitamin D activation.^36,46-48

Final Thoughts

Osteoporosis-related fractures are common and are associated with high morbidity and health care costs. Dermatologists using and prescribing corticosteroids must be aware of the risk for GIO, particularly in patients with a pre-existing diagnosis of osteopenia or osteoporosis. There likely is no oral corticosteroid dose that does not increase a patient’s risk for osteoporosis; therefore, oral GCs should be used at the lowest effective daily dose for the shortest duration possible. Patients with an anticipated duration of at least 3 months—regardless of dose—should be assessed for their risk for GIO. Patients using topical and intralesional corticosteroids are unlikely to develop GIO; however, those with risk factors and a considerable cumulative dose may warrant further evaluation. In all cases, we advocate for supplementing with calcium and vitamin D as well as promoting probiotic intake and the Mediterranean diet. Those at moderate to high risk for fracture may require additional medical therapy. Dermatologists are uniquely positioned to identify this at-risk population, and because osteoporosis is a chronic illness, primary care providers should be notified of prolonged GC therapy to help with risk assessment, initiation of vitamin and mineral supplementation, and follow-up with metabolic bone health specialists. Through a multidisciplinary approach and patient education, GIO and the potential risk for fracture can be successfully mitigated in most patients.

Glucocorticoids (GCs) are among the most widely prescribed medications in dermatologic practice. Although GCs are highly effective anti-inflammatory agents, long-term systemic therapy can result in dangerous adverse effects, including GC-induced osteoporosis (GIO), a bone disease associated with a heightened risk for fragility fractures.^1,2 In the United States, an estimated 10.2 million adults have osteoporosis—defined as a T-score lower than −2.5 measured via a bone densitometry scan—and 43.4 million adults have low bone mineral density (BMD).^3,4 The prevalence of osteoporosis is increasing, and the diagnosis is more common in females and adults 55 years and older.² More than 2 million individuals have osteoporosis-related fractures annually, and the mortality risk is increased at 5 and 10 years following low-energy osteoporosis-related fractures.^3-5

Glucocorticoid therapy is the leading iatrogenic cause of secondary osteoporosis. As many as 30% of all patients treated with systemic GCs for more than 6 months develop GIO.^1,6,7 Glucocorticoid-induced BMD loss occurs at a rate of 6% to 12% of total BMD during the first year, slowing to approximately 3% per year during subsequent therapy.¹ The risk for insufficiency fractures increases by as much as 75% from baseline in adults with rheumatic, pulmonary, and skin disorders within the first 3 months of therapy and peaks at approximately 12 months.^1,2

Despite the risks, many long-term GC users never receive therapy to prevent bone loss; others are only started on therapy once they have sustained an insufficiency fracture. A 5-year international observational study including more than 40,000 postmenopausal women found that only 51% of patients who were on continuous GC therapy were undergoing BMD testing and appropriate medical management.⁸ This review highlights the existing evidence on the risks of osteoporosis and osteoporotic (OP) fractures in the setting of topical, intralesional, intramuscular, and systemic GC treatment, as well as recommendations for nutritional supplementation to reduce these risks.

Pathophysiology

The pathophysiology of GIO is multifactorial and occurs in both early and late phases.^9,10 The early phase is characterized by rapid BMD reduction due to excessive bone resorption. The late phase is characterized by slower and more progressive BMD reduction due to impaired bone formation.⁹ At the osteocyte level, GCs decrease cell viability and induce apoptosis.¹¹ At the osteoblast level, GCs impair cell replication and differentiation and have proapoptotic effects, resulting in decreased cell numbers and subsequent bone formation.¹⁰ At the osteoclast level, GCs increase expression of pro-osteoclastic cytokines and decrease mature osteoclast apoptosis, resulting in an expanded osteoclastic life span and prolonged bone resorption.^12,13 Indirectly, GCs alter calcium metabolism by decreasing gastrointestinal calcium absorption and impairing renal absorption.^14,15

GCs and Osteoporosis

Oral GCs—Glucocorticoid-induced osteoporosis and fracture risk are dose and duration dependent.⁶ A study of 244,235 patients taking GCs and 244,235 controls found the relative risk of vertebral fracture was 1.55 (range, 1.20–2.01) for daily prednisone use at less than 2.5 mg, 2.59 (range, 2.16–3.10) for daily prednisone use from 2.5 to 7.4 mg, and 5.18 (range, 4.25–6.31) for daily doses of 7.5 mg or higher; the relative risk for hip fractures was 0.99 (range, 0.82–1.20), 1.77 (range, 1.55–2.02), and 2.27 (range, 1.94–2.66), respectively.¹⁶ Another large retrospective cohort study found that continuous treatment with prednisone 10 mg/d for more than 90 days compared to no GC exposure increased the risk for hip fractures 7-fold and 17-fold for vertebral fractures.¹⁷ Although the minimum cumulative dose of GCs known to cause osteoporosis is not clearly established, the American College of Rheumatology has proposed an algorithm as a basic approach to anticipate, prevent, and treat GIO (Figure).^18,19 Fracture risk should be assessed in all patients who are prescribed prednisone 2.5 mg/d for 3 months or longer or an anticipated cumulative dose of more than 1 g per year. Patients 40 years and older with anticipated GC use of 3 months or longer should have both a bone densitometry scan and a Fracture Risk Assessment (FRAX) score. The FRAX tool estimates the 10-year probability of fracture in patients aged 40 to 80 years, and those patients can be further risk stratified as low (FRAX <10%), moderate (FRAX 10%–19%), or high (FRAX ≥20%) risk. In patients with moderate to high risk of fracture (FRAX >10%), initiation of pharmacologic treatment or referral to a metabolic bone specialist should be considered.^18,19 First-line therapy is an oral bisphosphonate, and second-line therapies include intravenous bisphosphonates, teriparatide, denosumab, or raloxifene for patients at high risk for GIO.¹⁹ Adults younger than 40 years with a history of OP fracture or considerable risk factors for OP fractures should have a bone densitometry scan, and, if results are abnormal, the patient should be referred to a metabolic bone specialist. Those with low fracture risk based on bone densitometry and FRAX and those with no risk factors should be assessed annually for bone health (additional risk factors, GC dose and duration, bone densitometry/FRAX if indicated).¹⁸ In addition to GC dose and duration, additional risk factors for GIO, which are factored into the FRAX tool, include advanced age, low body mass index, history of bone fracture, smoking, excessive alcohol use (≥3 drinks/d), history of falls, low BMD, family history of bone fracture, and hypovitaminosis D.⁶

Topical GCs—Although there is strong evidence and clear guidelines regarding oral GIO, there is a dearth of data surrounding OP risk due to treatment with topical GCs. A recent retrospective nationwide Danish study evaluating the risk of osteoporosis and major OP fracture in 723,251 adults treated with potent or very potent topical steroids sought to evaluate these risks.²⁰ Patients were included if they had filled prescriptions of at least 500 g of topical mometasone or an equivalent alternative. The investigators reported a 3% increase in relative risk of osteoporosis and major OP fracture with doubling of the cumulative topical GC dose (hazard ratio [HR], 1.03 [95% CI, 1.02-1.04] for both). The overall population-attributable risk was 4.3% (95% CI, 2.7%-5.8%) for osteoporosis and 2.7% (95% CI, 1.7%-3.8%) for major OP fracture. Notably, at least 10,000 g of mometasone was required for 1 additional patient to have a major OP fracture.²⁰ In a commentary based on this study, Jackson²¹ noted that the number of patient-years of topical GC use needed for 1 fracture was 4-fold higher than that for high-dose oral GCs (40 mg/d prednisolone for ≥30 days). Another study assessed the effects of topical GCs on BMD in adults with moderate to severe atopic dermatitis over a 2-year period.²² No significant difference in BMD assessed via bone densitometry of either the lumbar spine or total hip at baseline or at 2-year follow-up was reported for either group treated with corticosteroids (<75 g per month or ≥75 g per month). Of note, the authors did not account for steroid potency, which ranged from class 1 through class 4.²² Although limited data exist, these studies suggest topical GCs used at conventional doses with appropriate breaks in therapy will not substantially increase risk for GIO or OP fracture; however, in the small subset of patients requiring chronic use of superpotent topical corticosteroids with other OP risk factors, transitioning to non–GC-based therapy or initiating bone health therapy may be advised to improve patient outcomes. Risk assessment, as in cases of chronic topical GC use, may be beneficial.

Intralesional GCs—Intralesional GCs are indicated for numerous inflammatory conditions including alopecia areata, discoid lupus erythematosus, keloids, and granuloma annulare. It generally is accepted that doses of triamcinolone acetonide should not exceed 20 mg per session spaced at least 3 weeks apart or up to 40 mg per month.¹⁸ One study demonstrated that doses of triamcinolone diacetate of 25 mg or less were unlikely to produce systemic effects and were determined to be a safe dose for intralesional injections.²³ A retrospective cross-sectional case series including 18 patients with alopecia areata reported decreased BMD in 9 patients receiving intralesional triamcinolone acetonide 10 mg/mL at 4- to 8-week intervals for at least 20 months, with cumulative doses greater than 500 mg. This was particularly notable in postmenopausal women and men older than 50 years; participants with a body mass index less than 18.5 kg/m², history of a stress fracture, family history of osteopenia or osteoporosis, and history of smoking; and those who did not regularly engage in weight-bearing exercises.²⁴ Patients receiving long-term (ie, >1 year) intralesional steroids should be evaluated for osteoporosis risk and preventative strategies should be considered (ie, regular weight-bearing exercises, calcium and vitamin D supplementation, bisphosphate therapy). As with topical GCs, there are no clear guidelines for risk assessment or treatment recommendations for GIO.

Intramuscular GCs—The data regarding intramuscular (IM) GCs and dermatologic disease is severely limited, and to the best of our knowledge, no studies specifically assess the risk for GIO or fracture secondary to intramuscular GCs; however, a retrospective study of 27 patients (4 female, 23 male; mean age, 33 years [range, 12–61 years]) with refractory alopecia areata receiving IM triamcinolone acetonide (40 mg every 4 weeks for 3–6 months) reported 1 patient (a 56-year-old woman) with notably decreased bone densitometry from baseline requiring treatment discontinuation.²⁵ No other patients at risk for osteoporosis had decreased BMD from treatment with IM triamcinolone; however, it was noted that 1 month following treatment, 10 of 11 assessed patients demonstrated decreased levels of morning serum cortisol and plasma adrenocorticotropic hormone—despite baseline levels within reference range—that resolved 3 months after treatment completion,²⁵ which suggests a prolonged release of IM triamcinolone and sustained systemic effect. One systematic review of 342 patients with dermatologic diseases treated with IM corticosteroids found the primary side effects included dysmenorrhea, injection-site lipoatrophy, and adrenocortical suppression, with only a single reported case of low BMD.²⁶ Given the paucity of evidence, additional studies are required to assess the effect of IM triamcinolone on BMD and risk for major OP fractures with regard to dosing and frequency. As there are no clear guidelines for osteoporosis evaluation in the setting of intramuscular GCs, it may be prudent to follow the algorithmic model recommended for oral steroids when anticipating at least 3 months of intramuscular GCs.

Diet and Prevention of Bone Loss

Given the profound impact that systemic GCs have on osteoporosis and fracture risk and the sparse data regarding risk from topical, intralesional, or intramuscular GCs, diet and nutrition represent a simple, safe, and potentially preventative method of slowing BMD loss and minimizing fracture risk. In higher-risk patients, nutritional assessment in combination with medical therapy also is likely warranted.

Calcium and Vitamin D₃—Patients treated with any GC dose longer than 3 months should undergo calcium and vitamin D optimization.¹⁹ Exceptions for supplementation include certain patients with sarcoidosis, which can be associated with high vitamin D levels; patients with a history of hypercalcemia or hypercalciuria; and patients with chronic kidney disease.⁶ In a meta-analysis including 30,970 patients in 8 randomized controlled trials, calcium (500–1200 mg/d) and vitamin D (400–800 IU/d) supplementation reduced the risk of total fractures by 15% (summary relative risk estimate, 0.85 [95% CI, 0.73-0.98]) and hip fractures by 30% (summary relative risk estimate, 0.70 [95% CI, 0.56-0.87]).⁴ One double-blind, placebo-controlled clinical trial conducted by the Women’s Health Initiative that included 36,282 postmenopausal women who were taking 1000 mg of calcium and 400 IU of vitamin D₃ daily for more than 5 years reported an HR of 0.62 (95% CI, 0.38-1.00) for hip fracture for supplementation vs placebo.²⁷ Lastly, a 2016 Cochrane Review including 12 randomized trials and 1343 participants reported a 43% lower risk of new vertebral fractures following supplementation with calcium, vitamin D, or both compared with controls.²⁸

Specific recommendations for calcium and vitamin D₃ supplementation vary based on age and sex. The US Preventive Services Task Force concluded that insufficient evidence exists to support calcium and vitamin D₃ supplementation in asymptomatic men and premenopausal women.²⁹ The National Osteoporosis Foundation (NOF) supports the use of calcium supplementation for fracture risk reduction in middle-aged and older adults.⁴ Furthermore, the NOF supports the Institute of Medicine recommendations³¹ that men aged 50 to 70 years consume 1000 mg/d of calcium and that women 51 years and older as well as men 71 years and older consume 1200 mg/d of calcium.³⁰ The NOF recommends 800 to 1000 IU/d of vitamin D in adults 50 years and older, while the Institute of Medicine recommends 600 IU/d in adults 70 years and younger and 800 IU/d in adults 71 years and older.³¹ These recommendations are similar to both the Endocrine Society and the American Geriatric Society.^32,33 Total calcium should not exceed 2000 mg/d due to risk of adverse effects.

Dietary sources of vitamin D include fatty fish, mushrooms, and fortified dairy products, though recommended doses rarely can be achieved through diet alone.³⁴ Dairy products are the primary source of dietary calcium. Other high-calcium foods include green leafy vegetables, nuts and seeds, soft-boned fish, and fortified beverages and cereals.³⁵

Probiotics—A growing body of evidence suggests that probiotics may be beneficial in promoting bone health by improving calcium homeostasis, reducing risk for hyperparathyroidism secondary to GC therapy, and decreasing age-related bone resorption.³⁶ An animal study demonstrated that probiotics can regulate bone resorption and formation as well as reduce bone loss secondary to GC therapy.³⁷ A randomized, double-blind, placebo-controlled, multicenter trial randomly assigned 249 healthy, early postmenopausal women to receive probiotic treatment containing 3 lactobacillus strains (Lactobacillus paracasei DSM 13434, Lactobacillus plantarum DSM 15312, and L plantarum DSM 15313) or placebo once daily for 12 months.³⁸ Bone mineral density was measured at baseline and at 12 months. Of the 234 participants who completed the study, lactobacillus treatment reduced lumbosacral BMD loss compared to the placebo group (mean difference, 0.71% [95% CI, 0.06-1.35]). They also reported significant lumbosacral BMD loss in the placebo group (−0.72% [95% CI, −1.22 to −0.22]) compared to no BMD loss in the group treated with lactobacillus (−0.01% [95% CI, −0.50 to 0.48]).³⁸ Although the data may be encouraging, more studies are needed to determine if probiotics should be regarded as an adjuvant treatment to calcium, vitamin D, and pharmacologic therapy for long-term prevention of bone loss in the setting of GIO.³⁹ Because existing studies on probiotics include varying compositions and doses, larger studies with consistent supplementation are required. Encouraging probiotic intake through fermented dairy products may represent a simple low-risk intervention to support bone health.

Anti-inflammatory Diet—The traditional Mediterranean diet is rich in fruits, vegetables, fish, nuts, whole grains, legumes, and monounsaturated fats and low in meat and dairy products. The Mediterranean diet has been shown to be modestly protective against osteoporosis and fracture risk. A large US observational study including 93,676 women showed that those with the highest quintile of the alternate Mediterranean diet score had a lower risk for hip fracture (HR, 0.80 [95% CI, 0.66-0.97]), with an absolute risk reduction of 0.29% and number needed to treat at 342.⁴⁰ A multicenter study involving adults from 8 European countries found that increased adherence to the Mediterranean diet was associated with a 7% reduction in hip fracture incidence (HR per 1 unit increase in Mediterranean diet, 0.93 [95% CI, 0.89-0.98]). High vegetable and fruit intake was associated with decreased hip fracture incidence (HR, 0.86 and 0.89 [95% CI, 0.79-0.94 and 0.82-0.97, respectively]), and high meat and excessive ethanol consumption were associated with increased fracture incidence (HR, 1.18 and 1.74 [95% CI, 1.06-1.31 and 1.32-2.31, respectively]).⁴¹ Similarly, a large observational study in Sweden that included 37,903 men and 33,403 women reported similar findings, noting a 6% lower hip fracture rate per one unit increase in alternate Mediterranean diet score (adjusted HR, 0.94 [95% CI, 0.92-0.96]).⁴² This is thought to be due in part to higher levels of dietary vitamin D present in many foods traditionally included in the Mediterranean diet.⁴³ Additionally, olive oil, a staple in the Mediterranean diet, appears to reduce bone loss by promoting osteoblast proliferation and maturation, inhibiting bone resorption, suppressing oxidative stress and inflammation, and increasing calcium deposition in the extracellular matrix.^44,45 Fruits, vegetables, legumes, and nuts also are rich in minerals including potassium and magnesium, which are important in bone health to promote osteoblast proliferation and vitamin D activation.^36,46-48

Final Thoughts

Osteoporosis-related fractures are common and are associated with high morbidity and health care costs. Dermatologists using and prescribing corticosteroids must be aware of the risk for GIO, particularly in patients with a pre-existing diagnosis of osteopenia or osteoporosis. There likely is no oral corticosteroid dose that does not increase a patient’s risk for osteoporosis; therefore, oral GCs should be used at the lowest effective daily dose for the shortest duration possible. Patients with an anticipated duration of at least 3 months—regardless of dose—should be assessed for their risk for GIO. Patients using topical and intralesional corticosteroids are unlikely to develop GIO; however, those with risk factors and a considerable cumulative dose may warrant further evaluation. In all cases, we advocate for supplementing with calcium and vitamin D as well as promoting probiotic intake and the Mediterranean diet. Those at moderate to high risk for fracture may require additional medical therapy. Dermatologists are uniquely positioned to identify this at-risk population, and because osteoporosis is a chronic illness, primary care providers should be notified of prolonged GC therapy to help with risk assessment, initiation of vitamin and mineral supplementation, and follow-up with metabolic bone health specialists. Through a multidisciplinary approach and patient education, GIO and the potential risk for fracture can be successfully mitigated in most patients.

Hair loss is a primary reason why women with skin of color seek dermatologic care.^1-3 In addition to physical disfigurement, patients with hair loss are more likely to report feelings of depression, anxiety, and low self-esteem compared to the general population.⁴ There is a critical gap in advocacy efforts and educational information intended for women with skin of color. The American Academy of Dermatology (AAD) has 6 main public health programs (https://www.aad.org/public/public-health) and 8 stated advocacy priorities (https://www.aad.org/member/advocacy/priorities) but none of them focus on outreach to minority communities.

Historically, hair in patients with skin of color also has been a systemic tangible target for race-based discrimination. The Create a Respectful and Open World for Natural Hair (CROWN) Act was passed to protect against discrimination based on race-based hairstyles in schools and workplaces.⁵ Health care providers play an important role in advocating for their patients, but studies have shown that barriers to effective advocacy include a lack of knowledge, resources, or time.^6-8 Virtual advocacy events improve participants’ understanding and interest in community engagement and advocacy.^6,7 With the mission to engage, educate, and empower women with skin of color and the dermatologists who treat them, the Virginia Dermatology Society hosted the virtual CROWNing Event on Hair Loss in Women of Color in July 2021. We believe that this event, as well as this column, can serve as a template to improve advocacy and educational efforts for additional topics and diseases that affect marginalized or underserved populations. Survey data were collected and analyzed to establish a baseline of awareness and understanding of hair loss in women with skin of color and to evaluate the impact of a virtual event on participants’ empowerment and familiarity with resources for this population.

Methods

The Virginia Dermatology Society organized a virtual event focused on hair loss and practical political advocacy for women with skin of color. As members of the Virginia Dermatology Society and as part of the planning and execution of this event, the authors engaged relevant stakeholder organizations and collaborated with faculty at a local historically Black university to create a targeted, culturally sensitive communication strategy known as the Framework for Advocacy and Community Engagement (FACE) model (Figure). The agenda included presentations by 2 patients of color living with a hair loss disorder, a dermatologist with experience in advocacy, a Virginia state legislator, and a dermatologic hair loss expert, followed by a final question-and-answer session.

We created pre- and postevent Likert scale surveys assessing participant attitudes, knowledge, and awareness surrounding hair loss that were distributed electronically to all 399 registrants before and after the event, respectively. The responses were analyzed using a Mann-Whitney U test.

Results

All 399 registrants completed the pre-event survey; 115 (28.8%) and 189 (47.4%) identified as patients and health care professionals, respectively (Table 1). Overall, 137 (34.3%) respondents disagreed or strongly disagreed with the statement, “I am familiar with the various and specific resources for hair loss in women of color.” Treatments and resources emerged as prevalent themes when respondents were asked about information or support they wished they had on hair loss. Respondents reported self-esteem/self-worth, treatment efficacy, and lack of knowledge/understanding as the most challenging aspects for women with skin of color experiencing hair loss.

Based on preliminary pre-event survey data, we created a resource toolkit (https://bit.ly/vadermhairlosstoolkit) for distribution to both patients and physicians. The toolkit included articles about evaluating, diagnosing, and treating different types of hair loss that would be beneficial for dermatologists, as well as informational articles, online resources, and videos that would be helpful to patients.

Of the 399 registrants, 165 (41.4%) attended the live virtual event. The postevent survey was completed by 70 (42.4%) participants and showed that familiarity with resources and treatments (z=−3.34, P=.0008) and feelings of empowerment (z=−3.55, P=.0004) significantly increased from before the event (Table 2). Participants indicated that the event exceeded (84.3%) or met (15.7%) their expectations.

Hair Loss Is Prevalent in Skin of Color Patients—Alopecia is the fourth most common reason women with skin of color seek care from a dermatologist, accounting for 8.3% of all visits in a study of 1412 patient visits; however, it was not among the leading 10 diagnoses made during visits for White patients.³ Traction alopecia, discoid lupus erythematosus, and central centrifugal cicatricial alopecia occur more commonly in Black women,⁹ many of whom do not feel their dermatologists understand hair in this population.^10,11 Lack of skin of color education in medical school and dermatology residency programs has been reported and must be improved to eliminate the knowledge gaps, acquire cultural competence, and improve all aspects of care for patients with skin of color.^11-14 Our survey results similarly demonstrated that only 66% of board-certified dermatologists reported being familiar with the various and specific resources and treatments for hair loss in women of color. Improved understanding of hair in patients of color is a first step in diagnosing and treating hair loss.¹⁵ Expertise of dermatologists in skin of color improves the dermatology experience of patients of color.¹¹

Hair loss is more than a cosmetic issue, and it is essential that it is regarded as such. Patients with hair loss have an increased prevalence of depression and anxiety compared to the general population and report lower self-esteem, heightened self-consciousness, and loss of confidence.^4,9 Historically, the lives of patients of color have been drastically affected by society’s perceptions of their skin color and hairstyle.¹⁶

Hair-Based Discrimination in the Workplace—To compound the problem, hair also is a common target of race-based discrimination behind the illusion of “professionalism.” Hair-based discrimination keeps people of color out of professional workplaces; for instance, women of color are more likely to be sent home due to hair appearance than White women.⁵ The CROWN Act, created in 2019, extends statutory protection to hair texture and protective hairstyles such as braids, locs, twists, and knots in the workplace and public schools to protect against discrimination due to race-based hairstyles. The CROWN Act provides an opportunity for dermatologists to support legislation that protects patients of color and the fundamental human right to nondiscrimination. As societal pressure for damaging hair practices such as hot combing or chemical relaxants decreases, patient outcomes will improve.⁵

How to Support the CROWN Act—There are various meaningful ways for dermatologists to support the CROWN act, including but not limited to signing petitions, sending letters of support to elected representatives, joining the CROWN Coalition, raising awareness and educating the public through social media, vocalizing against hair discrimination in our own workplaces and communities, and asking patients about their experiences with hair discrimination.5 In addition to advocacy, other antiracist actions suggested to improve health equity include creating curricula on racial inequity and increasing diversity in dermatology.¹⁶

There are many advocacy and public health campaigns promoted on the AAD website; however, despite the AAD’s formation of the Access to Dermatologic Care Task Force (ATDCTF) with the goal to raise awareness among dermatologists of health disparities affecting marginalized and underserved populations and to develop policies that increase access to care for these groups, there are still critical gaps in advocacy and information.¹³ This gap in both advocacy and understanding of hair loss conditions in women of color is one reason the CROWNing Event in July 2021 was held, and we believe this event along with this column can serve as a template for addressing additional topics and diseases that affect marginalized or underserved populations.

Dermatologists can play a vital role in advocating for skin and hair needs in all patient populations from the personal or clinical encounter level to population-level policy legislation.^5,8 As experts in skin and hair, dermatologists are best prepared to assume leadership in addressing racial health inequities, educating the public, and improving awareness.^5,16 Dermatologists must be able to diagnose and manage skin conditions in people of color.¹² However, health advocacy should extend beyond changes to health behavior or health interventions and instead address the root causes of systemic issues that drive disparate health outcomes.⁶ Every dermatologist has a contribution to make; it is time for us to acknowledge that patients’ ailments neither begin nor end at the clinic door.^8,16 As dermatologists, we must speak out against the racial inequities and discriminatory policies affecting the lives of patients of color.¹⁶

Although the CROWNing event should be considered successful, reflection in hindsight has allowed us to find ways to improve the impact of future events, including incorporating more lay members of the respective community in the planning process, allocating more time during the event programming for questions, and streamlining the distribution of pre-event and postevent surveys to better gauge knowledge retention among participants and gain crucial feedback for future event planning.

How to Use the FACE Model—We believe that the FACE model (Figure) can help providers engage lay members of the community with additional topics and diseases that affect marginalized and underserved populations. We recommend that future organizers engage stakeholders early during the design, planning, and implementation phases to ensure that the community’s most pressing needs are addressed. Dermatologists possess the knowledge and influence to serve as powerful advocates and champions for health equity. As physicians on the front lines of dermatologic health, we are uniquely positioned to engage and partner with patients through educational and advocacy events such as ours. Similarly, informed and empowered patients can advocate for policies and be proponents for greater research funding.⁵ We call on the AAD and other dermatologic organizations to expand community outreach and advocacy efforts to include underserved and underrepresented populations.

Acknowledgments—The authors would like to thank and acknowledge the faculty at Hampton University (Hampton, Virginia)—specifically Ms. B. DáVida Plummer, MA—for assistance with communication strategies, including organizing the radio and television announcements and proofreading the public service announcements. We also would like to thank other CROWNing Event Planning Committee members, including Natalia Mendoza, MD (Newport News, Virginia); Farhaad Riyaz, MD (Gainesville, Virginia); Deborah Elder, MD (Charlottesville, Virginia); and David Rowe, MD (Charlottesville, Virginia), as well as Sandra Ring, MS, CCLS, CNP (Chicago, Illinois), from the AAD and the various speakers at the event, including the 2 patients; Victoria Barbosa, MD, MPH, MBA (Chicago, Illinois); Avery LaChance, MD, MPH (Boston, Massachusetts); and Senator Lionell Spruill Sr (Chesapeake, Virginia). We acknowledge Marieke K. Jones, PhD, at the Claude Moore Health Sciences Library at the University of Virginia (Charlottesville, Virginia), for her statistical expertise.

Hair loss is a primary reason why women with skin of color seek dermatologic care.^1-3 In addition to physical disfigurement, patients with hair loss are more likely to report feelings of depression, anxiety, and low self-esteem compared to the general population.⁴ There is a critical gap in advocacy efforts and educational information intended for women with skin of color. The American Academy of Dermatology (AAD) has 6 main public health programs (https://www.aad.org/public/public-health) and 8 stated advocacy priorities (https://www.aad.org/member/advocacy/priorities) but none of them focus on outreach to minority communities.

Historically, hair in patients with skin of color also has been a systemic tangible target for race-based discrimination. The Create a Respectful and Open World for Natural Hair (CROWN) Act was passed to protect against discrimination based on race-based hairstyles in schools and workplaces.⁵ Health care providers play an important role in advocating for their patients, but studies have shown that barriers to effective advocacy include a lack of knowledge, resources, or time.^6-8 Virtual advocacy events improve participants’ understanding and interest in community engagement and advocacy.^6,7 With the mission to engage, educate, and empower women with skin of color and the dermatologists who treat them, the Virginia Dermatology Society hosted the virtual CROWNing Event on Hair Loss in Women of Color in July 2021. We believe that this event, as well as this column, can serve as a template to improve advocacy and educational efforts for additional topics and diseases that affect marginalized or underserved populations. Survey data were collected and analyzed to establish a baseline of awareness and understanding of hair loss in women with skin of color and to evaluate the impact of a virtual event on participants’ empowerment and familiarity with resources for this population.

Methods

The Virginia Dermatology Society organized a virtual event focused on hair loss and practical political advocacy for women with skin of color. As members of the Virginia Dermatology Society and as part of the planning and execution of this event, the authors engaged relevant stakeholder organizations and collaborated with faculty at a local historically Black university to create a targeted, culturally sensitive communication strategy known as the Framework for Advocacy and Community Engagement (FACE) model (Figure). The agenda included presentations by 2 patients of color living with a hair loss disorder, a dermatologist with experience in advocacy, a Virginia state legislator, and a dermatologic hair loss expert, followed by a final question-and-answer session.

We created pre- and postevent Likert scale surveys assessing participant attitudes, knowledge, and awareness surrounding hair loss that were distributed electronically to all 399 registrants before and after the event, respectively. The responses were analyzed using a Mann-Whitney U test.

Results

All 399 registrants completed the pre-event survey; 115 (28.8%) and 189 (47.4%) identified as patients and health care professionals, respectively (Table 1). Overall, 137 (34.3%) respondents disagreed or strongly disagreed with the statement, “I am familiar with the various and specific resources for hair loss in women of color.” Treatments and resources emerged as prevalent themes when respondents were asked about information or support they wished they had on hair loss. Respondents reported self-esteem/self-worth, treatment efficacy, and lack of knowledge/understanding as the most challenging aspects for women with skin of color experiencing hair loss.

Based on preliminary pre-event survey data, we created a resource toolkit (https://bit.ly/vadermhairlosstoolkit) for distribution to both patients and physicians. The toolkit included articles about evaluating, diagnosing, and treating different types of hair loss that would be beneficial for dermatologists, as well as informational articles, online resources, and videos that would be helpful to patients.

Of the 399 registrants, 165 (41.4%) attended the live virtual event. The postevent survey was completed by 70 (42.4%) participants and showed that familiarity with resources and treatments (z=−3.34, P=.0008) and feelings of empowerment (z=−3.55, P=.0004) significantly increased from before the event (Table 2). Participants indicated that the event exceeded (84.3%) or met (15.7%) their expectations.

Hair Loss Is Prevalent in Skin of Color Patients—Alopecia is the fourth most common reason women with skin of color seek care from a dermatologist, accounting for 8.3% of all visits in a study of 1412 patient visits; however, it was not among the leading 10 diagnoses made during visits for White patients.³ Traction alopecia, discoid lupus erythematosus, and central centrifugal cicatricial alopecia occur more commonly in Black women,⁹ many of whom do not feel their dermatologists understand hair in this population.^10,11 Lack of skin of color education in medical school and dermatology residency programs has been reported and must be improved to eliminate the knowledge gaps, acquire cultural competence, and improve all aspects of care for patients with skin of color.^11-14 Our survey results similarly demonstrated that only 66% of board-certified dermatologists reported being familiar with the various and specific resources and treatments for hair loss in women of color. Improved understanding of hair in patients of color is a first step in diagnosing and treating hair loss.¹⁵ Expertise of dermatologists in skin of color improves the dermatology experience of patients of color.¹¹

Hair loss is more than a cosmetic issue, and it is essential that it is regarded as such. Patients with hair loss have an increased prevalence of depression and anxiety compared to the general population and report lower self-esteem, heightened self-consciousness, and loss of confidence.^4,9 Historically, the lives of patients of color have been drastically affected by society’s perceptions of their skin color and hairstyle.¹⁶

Hair-Based Discrimination in the Workplace—To compound the problem, hair also is a common target of race-based discrimination behind the illusion of “professionalism.” Hair-based discrimination keeps people of color out of professional workplaces; for instance, women of color are more likely to be sent home due to hair appearance than White women.⁵ The CROWN Act, created in 2019, extends statutory protection to hair texture and protective hairstyles such as braids, locs, twists, and knots in the workplace and public schools to protect against discrimination due to race-based hairstyles. The CROWN Act provides an opportunity for dermatologists to support legislation that protects patients of color and the fundamental human right to nondiscrimination. As societal pressure for damaging hair practices such as hot combing or chemical relaxants decreases, patient outcomes will improve.⁵

How to Support the CROWN Act—There are various meaningful ways for dermatologists to support the CROWN act, including but not limited to signing petitions, sending letters of support to elected representatives, joining the CROWN Coalition, raising awareness and educating the public through social media, vocalizing against hair discrimination in our own workplaces and communities, and asking patients about their experiences with hair discrimination.5 In addition to advocacy, other antiracist actions suggested to improve health equity include creating curricula on racial inequity and increasing diversity in dermatology.¹⁶

There are many advocacy and public health campaigns promoted on the AAD website; however, despite the AAD’s formation of the Access to Dermatologic Care Task Force (ATDCTF) with the goal to raise awareness among dermatologists of health disparities affecting marginalized and underserved populations and to develop policies that increase access to care for these groups, there are still critical gaps in advocacy and information.¹³ This gap in both advocacy and understanding of hair loss conditions in women of color is one reason the CROWNing Event in July 2021 was held, and we believe this event along with this column can serve as a template for addressing additional topics and diseases that affect marginalized or underserved populations.

Dermatologists can play a vital role in advocating for skin and hair needs in all patient populations from the personal or clinical encounter level to population-level policy legislation.^5,8 As experts in skin and hair, dermatologists are best prepared to assume leadership in addressing racial health inequities, educating the public, and improving awareness.^5,16 Dermatologists must be able to diagnose and manage skin conditions in people of color.¹² However, health advocacy should extend beyond changes to health behavior or health interventions and instead address the root causes of systemic issues that drive disparate health outcomes.⁶ Every dermatologist has a contribution to make; it is time for us to acknowledge that patients’ ailments neither begin nor end at the clinic door.^8,16 As dermatologists, we must speak out against the racial inequities and discriminatory policies affecting the lives of patients of color.¹⁶

Although the CROWNing event should be considered successful, reflection in hindsight has allowed us to find ways to improve the impact of future events, including incorporating more lay members of the respective community in the planning process, allocating more time during the event programming for questions, and streamlining the distribution of pre-event and postevent surveys to better gauge knowledge retention among participants and gain crucial feedback for future event planning.

How to Use the FACE Model—We believe that the FACE model (Figure) can help providers engage lay members of the community with additional topics and diseases that affect marginalized and underserved populations. We recommend that future organizers engage stakeholders early during the design, planning, and implementation phases to ensure that the community’s most pressing needs are addressed. Dermatologists possess the knowledge and influence to serve as powerful advocates and champions for health equity. As physicians on the front lines of dermatologic health, we are uniquely positioned to engage and partner with patients through educational and advocacy events such as ours. Similarly, informed and empowered patients can advocate for policies and be proponents for greater research funding.⁵ We call on the AAD and other dermatologic organizations to expand community outreach and advocacy efforts to include underserved and underrepresented populations.

Acknowledgments—The authors would like to thank and acknowledge the faculty at Hampton University (Hampton, Virginia)—specifically Ms. B. DáVida Plummer, MA—for assistance with communication strategies, including organizing the radio and television announcements and proofreading the public service announcements. We also would like to thank other CROWNing Event Planning Committee members, including Natalia Mendoza, MD (Newport News, Virginia); Farhaad Riyaz, MD (Gainesville, Virginia); Deborah Elder, MD (Charlottesville, Virginia); and David Rowe, MD (Charlottesville, Virginia), as well as Sandra Ring, MS, CCLS, CNP (Chicago, Illinois), from the AAD and the various speakers at the event, including the 2 patients; Victoria Barbosa, MD, MPH, MBA (Chicago, Illinois); Avery LaChance, MD, MPH (Boston, Massachusetts); and Senator Lionell Spruill Sr (Chesapeake, Virginia). We acknowledge Marieke K. Jones, PhD, at the Claude Moore Health Sciences Library at the University of Virginia (Charlottesville, Virginia), for her statistical expertise.

Hair loss is a primary reason why women with skin of color seek dermatologic care.^1-3 In addition to physical disfigurement, patients with hair loss are more likely to report feelings of depression, anxiety, and low self-esteem compared to the general population.⁴ There is a critical gap in advocacy efforts and educational information intended for women with skin of color. The American Academy of Dermatology (AAD) has 6 main public health programs (https://www.aad.org/public/public-health) and 8 stated advocacy priorities (https://www.aad.org/member/advocacy/priorities) but none of them focus on outreach to minority communities.

Historically, hair in patients with skin of color also has been a systemic tangible target for race-based discrimination. The Create a Respectful and Open World for Natural Hair (CROWN) Act was passed to protect against discrimination based on race-based hairstyles in schools and workplaces.⁵ Health care providers play an important role in advocating for their patients, but studies have shown that barriers to effective advocacy include a lack of knowledge, resources, or time.^6-8 Virtual advocacy events improve participants’ understanding and interest in community engagement and advocacy.^6,7 With the mission to engage, educate, and empower women with skin of color and the dermatologists who treat them, the Virginia Dermatology Society hosted the virtual CROWNing Event on Hair Loss in Women of Color in July 2021. We believe that this event, as well as this column, can serve as a template to improve advocacy and educational efforts for additional topics and diseases that affect marginalized or underserved populations. Survey data were collected and analyzed to establish a baseline of awareness and understanding of hair loss in women with skin of color and to evaluate the impact of a virtual event on participants’ empowerment and familiarity with resources for this population.

Methods

The Virginia Dermatology Society organized a virtual event focused on hair loss and practical political advocacy for women with skin of color. As members of the Virginia Dermatology Society and as part of the planning and execution of this event, the authors engaged relevant stakeholder organizations and collaborated with faculty at a local historically Black university to create a targeted, culturally sensitive communication strategy known as the Framework for Advocacy and Community Engagement (FACE) model (Figure). The agenda included presentations by 2 patients of color living with a hair loss disorder, a dermatologist with experience in advocacy, a Virginia state legislator, and a dermatologic hair loss expert, followed by a final question-and-answer session.

We created pre- and postevent Likert scale surveys assessing participant attitudes, knowledge, and awareness surrounding hair loss that were distributed electronically to all 399 registrants before and after the event, respectively. The responses were analyzed using a Mann-Whitney U test.

Results

All 399 registrants completed the pre-event survey; 115 (28.8%) and 189 (47.4%) identified as patients and health care professionals, respectively (Table 1). Overall, 137 (34.3%) respondents disagreed or strongly disagreed with the statement, “I am familiar with the various and specific resources for hair loss in women of color.” Treatments and resources emerged as prevalent themes when respondents were asked about information or support they wished they had on hair loss. Respondents reported self-esteem/self-worth, treatment efficacy, and lack of knowledge/understanding as the most challenging aspects for women with skin of color experiencing hair loss.

Based on preliminary pre-event survey data, we created a resource toolkit (https://bit.ly/vadermhairlosstoolkit) for distribution to both patients and physicians. The toolkit included articles about evaluating, diagnosing, and treating different types of hair loss that would be beneficial for dermatologists, as well as informational articles, online resources, and videos that would be helpful to patients.

Of the 399 registrants, 165 (41.4%) attended the live virtual event. The postevent survey was completed by 70 (42.4%) participants and showed that familiarity with resources and treatments (z=−3.34, P=.0008) and feelings of empowerment (z=−3.55, P=.0004) significantly increased from before the event (Table 2). Participants indicated that the event exceeded (84.3%) or met (15.7%) their expectations.

Hair Loss Is Prevalent in Skin of Color Patients—Alopecia is the fourth most common reason women with skin of color seek care from a dermatologist, accounting for 8.3% of all visits in a study of 1412 patient visits; however, it was not among the leading 10 diagnoses made during visits for White patients.³ Traction alopecia, discoid lupus erythematosus, and central centrifugal cicatricial alopecia occur more commonly in Black women,⁹ many of whom do not feel their dermatologists understand hair in this population.^10,11 Lack of skin of color education in medical school and dermatology residency programs has been reported and must be improved to eliminate the knowledge gaps, acquire cultural competence, and improve all aspects of care for patients with skin of color.^11-14 Our survey results similarly demonstrated that only 66% of board-certified dermatologists reported being familiar with the various and specific resources and treatments for hair loss in women of color. Improved understanding of hair in patients of color is a first step in diagnosing and treating hair loss.¹⁵ Expertise of dermatologists in skin of color improves the dermatology experience of patients of color.¹¹

Hair loss is more than a cosmetic issue, and it is essential that it is regarded as such. Patients with hair loss have an increased prevalence of depression and anxiety compared to the general population and report lower self-esteem, heightened self-consciousness, and loss of confidence.^4,9 Historically, the lives of patients of color have been drastically affected by society’s perceptions of their skin color and hairstyle.¹⁶

Hair-Based Discrimination in the Workplace—To compound the problem, hair also is a common target of race-based discrimination behind the illusion of “professionalism.” Hair-based discrimination keeps people of color out of professional workplaces; for instance, women of color are more likely to be sent home due to hair appearance than White women.⁵ The CROWN Act, created in 2019, extends statutory protection to hair texture and protective hairstyles such as braids, locs, twists, and knots in the workplace and public schools to protect against discrimination due to race-based hairstyles. The CROWN Act provides an opportunity for dermatologists to support legislation that protects patients of color and the fundamental human right to nondiscrimination. As societal pressure for damaging hair practices such as hot combing or chemical relaxants decreases, patient outcomes will improve.⁵

How to Support the CROWN Act—There are various meaningful ways for dermatologists to support the CROWN act, including but not limited to signing petitions, sending letters of support to elected representatives, joining the CROWN Coalition, raising awareness and educating the public through social media, vocalizing against hair discrimination in our own workplaces and communities, and asking patients about their experiences with hair discrimination.5 In addition to advocacy, other antiracist actions suggested to improve health equity include creating curricula on racial inequity and increasing diversity in dermatology.¹⁶

There are many advocacy and public health campaigns promoted on the AAD website; however, despite the AAD’s formation of the Access to Dermatologic Care Task Force (ATDCTF) with the goal to raise awareness among dermatologists of health disparities affecting marginalized and underserved populations and to develop policies that increase access to care for these groups, there are still critical gaps in advocacy and information.¹³ This gap in both advocacy and understanding of hair loss conditions in women of color is one reason the CROWNing Event in July 2021 was held, and we believe this event along with this column can serve as a template for addressing additional topics and diseases that affect marginalized or underserved populations.

Dermatologists can play a vital role in advocating for skin and hair needs in all patient populations from the personal or clinical encounter level to population-level policy legislation.^5,8 As experts in skin and hair, dermatologists are best prepared to assume leadership in addressing racial health inequities, educating the public, and improving awareness.^5,16 Dermatologists must be able to diagnose and manage skin conditions in people of color.¹² However, health advocacy should extend beyond changes to health behavior or health interventions and instead address the root causes of systemic issues that drive disparate health outcomes.⁶ Every dermatologist has a contribution to make; it is time for us to acknowledge that patients’ ailments neither begin nor end at the clinic door.^8,16 As dermatologists, we must speak out against the racial inequities and discriminatory policies affecting the lives of patients of color.¹⁶

Although the CROWNing event should be considered successful, reflection in hindsight has allowed us to find ways to improve the impact of future events, including incorporating more lay members of the respective community in the planning process, allocating more time during the event programming for questions, and streamlining the distribution of pre-event and postevent surveys to better gauge knowledge retention among participants and gain crucial feedback for future event planning.

How to Use the FACE Model—We believe that the FACE model (Figure) can help providers engage lay members of the community with additional topics and diseases that affect marginalized and underserved populations. We recommend that future organizers engage stakeholders early during the design, planning, and implementation phases to ensure that the community’s most pressing needs are addressed. Dermatologists possess the knowledge and influence to serve as powerful advocates and champions for health equity. As physicians on the front lines of dermatologic health, we are uniquely positioned to engage and partner with patients through educational and advocacy events such as ours. Similarly, informed and empowered patients can advocate for policies and be proponents for greater research funding.⁵ We call on the AAD and other dermatologic organizations to expand community outreach and advocacy efforts to include underserved and underrepresented populations.

Acknowledgments—The authors would like to thank and acknowledge the faculty at Hampton University (Hampton, Virginia)—specifically Ms. B. DáVida Plummer, MA—for assistance with communication strategies, including organizing the radio and television announcements and proofreading the public service announcements. We also would like to thank other CROWNing Event Planning Committee members, including Natalia Mendoza, MD (Newport News, Virginia); Farhaad Riyaz, MD (Gainesville, Virginia); Deborah Elder, MD (Charlottesville, Virginia); and David Rowe, MD (Charlottesville, Virginia), as well as Sandra Ring, MS, CCLS, CNP (Chicago, Illinois), from the AAD and the various speakers at the event, including the 2 patients; Victoria Barbosa, MD, MPH, MBA (Chicago, Illinois); Avery LaChance, MD, MPH (Boston, Massachusetts); and Senator Lionell Spruill Sr (Chesapeake, Virginia). We acknowledge Marieke K. Jones, PhD, at the Claude Moore Health Sciences Library at the University of Virginia (Charlottesville, Virginia), for her statistical expertise.