The Journal of Family Practice

This month’s editorial was jointly written by the editors of 10 prominent family medicine publications, including JFP, and is being published simultaneously in all 10 publications. In addition to this statement, each editor has developed action steps for their respective journals. At JFP, we plan to take the steps detailed here to help eliminate systemic racism. We will:

• continue to seek Black, Latino, and Native American physicians to serve on the JFP editorial advisory board.
• solicit manuscripts from these underrepresented groups of physicians.
• recruit peer reviewers from underrepresented communities.
• re-evaluate the thoroughness of manuscripts; where there are racial or ethnic differences in presentation of diseases or treatment outcomes, we will ensure that these differences are highlighted.

If you are interested in helping us to achieve these goals, I encourage you to contact me at jfp.eic@gmail.com.

We must all band together to eliminate disparities and biases in medical education and medical care so that all people receive the same high standard of respect and care that every human being deserves.

This month’s editorial was jointly written by the editors of 10 prominent family medicine publications, including JFP, and is being published simultaneously in all 10 publications. In addition to this statement, each editor has developed action steps for their respective journals. At JFP, we plan to take the steps detailed here to help eliminate systemic racism. We will:

• continue to seek Black, Latino, and Native American physicians to serve on the JFP editorial advisory board.
• solicit manuscripts from these underrepresented groups of physicians.
• recruit peer reviewers from underrepresented communities.
• re-evaluate the thoroughness of manuscripts; where there are racial or ethnic differences in presentation of diseases or treatment outcomes, we will ensure that these differences are highlighted.

If you are interested in helping us to achieve these goals, I encourage you to contact me at jfp.eic@gmail.com.

We must all band together to eliminate disparities and biases in medical education and medical care so that all people receive the same high standard of respect and care that every human being deserves.

This month’s editorial was jointly written by the editors of 10 prominent family medicine publications, including JFP, and is being published simultaneously in all 10 publications. In addition to this statement, each editor has developed action steps for their respective journals. At JFP, we plan to take the steps detailed here to help eliminate systemic racism. We will:

• continue to seek Black, Latino, and Native American physicians to serve on the JFP editorial advisory board.
• solicit manuscripts from these underrepresented groups of physicians.
• recruit peer reviewers from underrepresented communities.
• re-evaluate the thoroughness of manuscripts; where there are racial or ethnic differences in presentation of diseases or treatment outcomes, we will ensure that these differences are highlighted.

If you are interested in helping us to achieve these goals, I encourage you to contact me at jfp.eic@gmail.com.

We must all band together to eliminate disparities and biases in medical education and medical care so that all people receive the same high standard of respect and care that every human being deserves.

The history and exam were all suspicious for basal cell carcinoma (BCC), the most common of all cancers in the United States. (In African Americans, the most common skin cancer is squamous cell carcinoma). The suspicious lesion in this case was in a crevice, making it difficult to obtain a shave or punch biopsy.

As a result, a 4-mm disposable sterile curette was used (Figure). After informed consent was obtained, the lesion was cleansed with alcohol and marked with a surgical marker. Then, buffered lidocaine 1% with epinephrine was injected with a small syringe. Using a firm scraping motion with gentle rotation, a 4-mm sample of the lesion was quickly obtained and placed in standard formalin. Hemostasis was immediately obtained with firm application of 70% aluminum chloride in water using a cotton-tipped applicator. Heavy petrolatum was applied as a dressing.

The patient was confirmed to have a BCC and underwent Mohs surgery with clear margins after 1 stage. This case demonstrates the utility of a curette as a biopsy instrument for patients presenting with suspicious lesions in hard-to-reach places.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

The history and exam were all suspicious for basal cell carcinoma (BCC), the most common of all cancers in the United States. (In African Americans, the most common skin cancer is squamous cell carcinoma). The suspicious lesion in this case was in a crevice, making it difficult to obtain a shave or punch biopsy.

As a result, a 4-mm disposable sterile curette was used (Figure). After informed consent was obtained, the lesion was cleansed with alcohol and marked with a surgical marker. Then, buffered lidocaine 1% with epinephrine was injected with a small syringe. Using a firm scraping motion with gentle rotation, a 4-mm sample of the lesion was quickly obtained and placed in standard formalin. Hemostasis was immediately obtained with firm application of 70% aluminum chloride in water using a cotton-tipped applicator. Heavy petrolatum was applied as a dressing.

The patient was confirmed to have a BCC and underwent Mohs surgery with clear margins after 1 stage. This case demonstrates the utility of a curette as a biopsy instrument for patients presenting with suspicious lesions in hard-to-reach places.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

The history and exam were all suspicious for basal cell carcinoma (BCC), the most common of all cancers in the United States. (In African Americans, the most common skin cancer is squamous cell carcinoma). The suspicious lesion in this case was in a crevice, making it difficult to obtain a shave or punch biopsy.

As a result, a 4-mm disposable sterile curette was used (Figure). After informed consent was obtained, the lesion was cleansed with alcohol and marked with a surgical marker. Then, buffered lidocaine 1% with epinephrine was injected with a small syringe. Using a firm scraping motion with gentle rotation, a 4-mm sample of the lesion was quickly obtained and placed in standard formalin. Hemostasis was immediately obtained with firm application of 70% aluminum chloride in water using a cotton-tipped applicator. Heavy petrolatum was applied as a dressing.

The patient was confirmed to have a BCC and underwent Mohs surgery with clear margins after 1 stage. This case demonstrates the utility of a curette as a biopsy instrument for patients presenting with suspicious lesions in hard-to-reach places.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

A 62-year-old man presented to our skin clinic with multiple pruritic, tense, bullous lesions that manifested on his arms, abdomen, back, and upper thighs over a 1-month period. There were no lesions in his oral cavity or around his eyes, nose, or penile region. He denied dysphagia.

The patient had multiple comorbidities, including diabetes, hypertension, recent stroke, and end-stage renal disease. He was being prepared for dialysis. His medications included torsemide, warfarin, amiodarone, metoprolol, pantoprozole, atorvastatin, and nifedipine. About 3 months prior to this presentation, he was started on oral linaglipton 5 mg/d, an oral antihyperglycemic medication. He had no history of skin disease or cancer, and his family history was not significant.

Physical examination showed multiple 5-mm to 2-cm blisters and bullae on the flexural surface of both of his arms (FIGURE), back, lower abdomen, and upper thighs. His palms and soles were not involved. The lesions were nontender, tense, and filled with clear fluid. Some were intact and others were rupturing. There was no mucocutaneous involvement. Nikolsky sign was negative. There were no signs of bleeding.

The family physician (FP) obtained a 4-mm punch biopsy at the edge of a 6-mm blister for light microscopy and a 3-mm perilesional punch biopsy for direct immunofluorescence (DIF) microscopy.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

DIF of the biopsy sample demonstrated linear deposition of complement 3 (C3) and immunoglobulin (Ig) G along the basement membrane zone. Indirect immunofluorescence on salt-split skin demonstrated linear deposition of IgG and C3 on both the roof and floor of the induced blisters. These findings and the patient’s clinical presentation met the criteria for bullous pemphigoid (BP), which is the most common autoimmune skin-blistering disease.¹

FPs are increasingly using DPP-4 inhibitors as oral antihyperglycemic agents for type 2 diabetes mellitus. Therefore, it’s important to recognize this medication class’s association with BP

BP is associated with subepidermal blistering, which can occur in reaction to a variety of triggers. Pathogenesis of this condition involves IgG anti-basement membrane autoantibody complex formation with the hemidesmosomal antigens BP230 and BP180—a process that activates C3 and the release of proteases that can be destructive to tissue along the dermo-epidermal junction.¹

Growing incidence. BP usually occurs in patients > 60 years, with no racial or gender preference.¹ The incidence rate of BP ranges from 2.4 to 21.7 new cases per 1 million individuals among various worldwide populations.² The incidence appears to have increased 1.9- to 4.3-fold over the past 2 decades.²

What you’ll see, who’s at risk

Symptoms of BP include localized areas of erythema or pruritic urticarial plaques that gradually become more extensive. A patient may have pruritis alone for an extended period prior to developing blisters and bullae. The bullae are tense and normally 1 to 7 cm in size.¹ Eruption is generalized, mostly affecting the lower abdomen, as well as the flexural parts of the extremities. The palms and soles also can be affected.

FPs should be aware of the atypical clinical variants of BP. In a review by Kridin and Ludwig, variants can be prurigo-like, eczema-like, urticaria-like, dyshidrosiform type, erosive type, and erythema annulare centrifugum–like type.² At-risk populations, such as elderly patients (> 70 years), whose pruritis manifests with or without bullous formation, should be screened for BP.^3,4

Continue to: Risk factors for BP

Risk factors for BP. Certain conditions linked to developing BP include neurologic disorders (dementia and Parkinson disease) and psychiatric disorders (unipolar and bipolar disorder).⁴ Further, it is important to note any medications that could be the cause of a patient’s BP, including dipeptidyl peptidase-4 (DPP-4) inhibitors, psychotropic medications, spironolactone, furosemide, beta-blockers, and antibiotics.³ This patient was taking a beta-blocker (metoprolol) and a DPP-4 inhibitor (linagliptin). Because he was most recently started on linagliptin, we suspected it may have had a causal role in the development of BP.

The association of DPP-4 inhibitors and BP

FPs are increasingly using DPP-4 inhibitors—including sitagliptin, vildagliptin, and linagliptin—as oral antihyperglycemic agents for type 2 diabetes mellitus. Therefore, it’s important to recognize this medication class’s association with BP.⁵ In a case-control study of 165 patients with BP, Benzaquen et al reported that 28 patients who were taking DPP-4 inhibitors had an associated increased risk for BP (adjusted odds ratio = 2.64; 95% confidence interval [CI], 1.19-5.85).³

The pathophysiology of BP associated with DPP-4 inhibitors remains unclear, but mechanisms have been proposed. The DPP-4 enzyme is expressed on many cells, including keratinocytes, T cells, and endothelial cells.³ It is possible that DPP-4 inhibition at these cells could stimulate activity of inflammatory cytokines, which can lead to enhanced local eosinophil activation and trigger bullous formation. DPP-4 enzymes are also involved in forming plasmin, which is a protease that cleaves BP180.³ Inhibition of this process can affect proper cleavage of BP180, impacting its function and antigenicity.^3,6

Other conditions that also exhibit blisters

There are some skin conditions with similar presentations that need to be ruled out in the work-up.

Bullous diabeticorum is a rare, spontaneous, noninflammatory condition found in patients with diabetes.¹ Blisters usually manifest as large, tense, asymmetrical, mildly tender lesions that commonly affect the feet and lower legs but can involve the trunk. These usually develop overnight without preceding trauma. Biopsy would show both intra-­epidermal and subepidermal bulla with normal DIF findings.¹ This condition usually has an excellent prognosis.

Continue to: Pemphigus vulgaris

Pemphigus vulgaris is characterized by nonpruritic, flaccid, painful blisters. This condition usually begins with manifestation of painful oral lesions that evolve into skin blisters. Some patients can develop mucocutaneous lesions.¹ Nikolsky sign is positive in these cases. Light microscopy would show intra-­epidermal bullae.

Dermatitis herpetiformis. This condition—usually affecting middle-age patients—is associated with severe pruritis and burning. It may start with a few pruritic papules or vesicles that later evolve into urticarial papules, vesicles, or bullae. Dermatitis herpetiformis can resemble herpes simplex virus. It can also be associated with gluten-sensitive enteropathy and small bowel lymphoma.¹ DIF of a biopsy sample would show granular deposition of IgA within the tips of the dermal papillae and along the basement membrane of perilesional skin.¹

Epidermolysis bullosa acquisita is a rare, severe, chronic condition with subepidermal mucocutaneous blistering.¹ It is associated with skin fragility and spontaneous trauma-induced blisters that heal with scar formation and milia. IgG autoantibodies reacting to proteins in the basement membrane zone can cause the disease. It is also associated with Crohn disease.¹ DIF findings are similar in BP, but they are differentiated by location of IgG deposits; they can be found on the dermal side of separation in epidermolysis bullosa acquisita, as compared with the epidermal side in BP.¹

How to make the Dx in 3 steps

To effectively diagnose and classify BP, use the following 3-step method:

1. Establish the presence of 3 of 4 ­clinical characteristics: patient’s age > 60 years, absence of atrophic scars, absence of mucosal involvement, and absence of bullous lesions on the head and neck.
2. Order light microscopy. Findings should be consistent with eosinophils and neutrophils containing subepidermal bullae.
3. Order a punch biopsy to obtain a perilesional specimen. DIF of the biopsy findings should feature linear deposits of IgG with or without C3 along the dermo-epidermal junction. This step is essential for an accurate diagnosis.

Depending on the severity of disease, treatment can include the use of potent topical corticosteroids alone or in combination with systemic corticosteroids and antiinflammatory antibiotics.

There also is benefit in ordering supplemental studies, such as an enzyme-linked immunosorbent assay for the detection of anti-BP180 or anti-BP230 IgG autoantibodies.⁷ However, for this patient, we did not order this study.

Continue to: Management focuses on steroids

Management focuses on steroids

The offending agent should be discontinued immediately. Depending on the severity of disease, treatment can include the use of potent topical corticosteroids alone or in combination with systemic corticosteroids and anti-inflammatory antibiotics (eg, doxycycline, minocycline, erythromycin).^1,7 For patients with resistant or refractory disease, consider azathioprine, methotrexate, dapsone, and chlorambucil.^1,7 Exceptional cases may benefit from the use of mycophenolate mofetil, intravenous immunoglobulin, or plasmapheresis.^1,7

For this patient, initial treatment included discontinuation of linagliption and introduction of topical clobetasol 0.05% and oral prednisone 40 mg/d for 7 days, followed by prednisone 20 mg for 7 days. He was also started on oral doxycycline 100 mg bid and oral nicotinamide 500 mg bid.

A 62-year-old man presented to our skin clinic with multiple pruritic, tense, bullous lesions that manifested on his arms, abdomen, back, and upper thighs over a 1-month period. There were no lesions in his oral cavity or around his eyes, nose, or penile region. He denied dysphagia.

The patient had multiple comorbidities, including diabetes, hypertension, recent stroke, and end-stage renal disease. He was being prepared for dialysis. His medications included torsemide, warfarin, amiodarone, metoprolol, pantoprozole, atorvastatin, and nifedipine. About 3 months prior to this presentation, he was started on oral linaglipton 5 mg/d, an oral antihyperglycemic medication. He had no history of skin disease or cancer, and his family history was not significant.

Physical examination showed multiple 5-mm to 2-cm blisters and bullae on the flexural surface of both of his arms (FIGURE), back, lower abdomen, and upper thighs. His palms and soles were not involved. The lesions were nontender, tense, and filled with clear fluid. Some were intact and others were rupturing. There was no mucocutaneous involvement. Nikolsky sign was negative. There were no signs of bleeding.

The family physician (FP) obtained a 4-mm punch biopsy at the edge of a 6-mm blister for light microscopy and a 3-mm perilesional punch biopsy for direct immunofluorescence (DIF) microscopy.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

DIF of the biopsy sample demonstrated linear deposition of complement 3 (C3) and immunoglobulin (Ig) G along the basement membrane zone. Indirect immunofluorescence on salt-split skin demonstrated linear deposition of IgG and C3 on both the roof and floor of the induced blisters. These findings and the patient’s clinical presentation met the criteria for bullous pemphigoid (BP), which is the most common autoimmune skin-blistering disease.¹

FPs are increasingly using DPP-4 inhibitors as oral antihyperglycemic agents for type 2 diabetes mellitus. Therefore, it’s important to recognize this medication class’s association with BP

BP is associated with subepidermal blistering, which can occur in reaction to a variety of triggers. Pathogenesis of this condition involves IgG anti-basement membrane autoantibody complex formation with the hemidesmosomal antigens BP230 and BP180—a process that activates C3 and the release of proteases that can be destructive to tissue along the dermo-epidermal junction.¹

Growing incidence. BP usually occurs in patients > 60 years, with no racial or gender preference.¹ The incidence rate of BP ranges from 2.4 to 21.7 new cases per 1 million individuals among various worldwide populations.² The incidence appears to have increased 1.9- to 4.3-fold over the past 2 decades.²

What you’ll see, who’s at risk

Symptoms of BP include localized areas of erythema or pruritic urticarial plaques that gradually become more extensive. A patient may have pruritis alone for an extended period prior to developing blisters and bullae. The bullae are tense and normally 1 to 7 cm in size.¹ Eruption is generalized, mostly affecting the lower abdomen, as well as the flexural parts of the extremities. The palms and soles also can be affected.

FPs should be aware of the atypical clinical variants of BP. In a review by Kridin and Ludwig, variants can be prurigo-like, eczema-like, urticaria-like, dyshidrosiform type, erosive type, and erythema annulare centrifugum–like type.² At-risk populations, such as elderly patients (> 70 years), whose pruritis manifests with or without bullous formation, should be screened for BP.^3,4

Continue to: Risk factors for BP

Risk factors for BP. Certain conditions linked to developing BP include neurologic disorders (dementia and Parkinson disease) and psychiatric disorders (unipolar and bipolar disorder).⁴ Further, it is important to note any medications that could be the cause of a patient’s BP, including dipeptidyl peptidase-4 (DPP-4) inhibitors, psychotropic medications, spironolactone, furosemide, beta-blockers, and antibiotics.³ This patient was taking a beta-blocker (metoprolol) and a DPP-4 inhibitor (linagliptin). Because he was most recently started on linagliptin, we suspected it may have had a causal role in the development of BP.

The association of DPP-4 inhibitors and BP

FPs are increasingly using DPP-4 inhibitors—including sitagliptin, vildagliptin, and linagliptin—as oral antihyperglycemic agents for type 2 diabetes mellitus. Therefore, it’s important to recognize this medication class’s association with BP.⁵ In a case-control study of 165 patients with BP, Benzaquen et al reported that 28 patients who were taking DPP-4 inhibitors had an associated increased risk for BP (adjusted odds ratio = 2.64; 95% confidence interval [CI], 1.19-5.85).³

The pathophysiology of BP associated with DPP-4 inhibitors remains unclear, but mechanisms have been proposed. The DPP-4 enzyme is expressed on many cells, including keratinocytes, T cells, and endothelial cells.³ It is possible that DPP-4 inhibition at these cells could stimulate activity of inflammatory cytokines, which can lead to enhanced local eosinophil activation and trigger bullous formation. DPP-4 enzymes are also involved in forming plasmin, which is a protease that cleaves BP180.³ Inhibition of this process can affect proper cleavage of BP180, impacting its function and antigenicity.^3,6

Other conditions that also exhibit blisters

There are some skin conditions with similar presentations that need to be ruled out in the work-up.

Bullous diabeticorum is a rare, spontaneous, noninflammatory condition found in patients with diabetes.¹ Blisters usually manifest as large, tense, asymmetrical, mildly tender lesions that commonly affect the feet and lower legs but can involve the trunk. These usually develop overnight without preceding trauma. Biopsy would show both intra-­epidermal and subepidermal bulla with normal DIF findings.¹ This condition usually has an excellent prognosis.

Continue to: Pemphigus vulgaris

Pemphigus vulgaris is characterized by nonpruritic, flaccid, painful blisters. This condition usually begins with manifestation of painful oral lesions that evolve into skin blisters. Some patients can develop mucocutaneous lesions.¹ Nikolsky sign is positive in these cases. Light microscopy would show intra-­epidermal bullae.

Dermatitis herpetiformis. This condition—usually affecting middle-age patients—is associated with severe pruritis and burning. It may start with a few pruritic papules or vesicles that later evolve into urticarial papules, vesicles, or bullae. Dermatitis herpetiformis can resemble herpes simplex virus. It can also be associated with gluten-sensitive enteropathy and small bowel lymphoma.¹ DIF of a biopsy sample would show granular deposition of IgA within the tips of the dermal papillae and along the basement membrane of perilesional skin.¹

Epidermolysis bullosa acquisita is a rare, severe, chronic condition with subepidermal mucocutaneous blistering.¹ It is associated with skin fragility and spontaneous trauma-induced blisters that heal with scar formation and milia. IgG autoantibodies reacting to proteins in the basement membrane zone can cause the disease. It is also associated with Crohn disease.¹ DIF findings are similar in BP, but they are differentiated by location of IgG deposits; they can be found on the dermal side of separation in epidermolysis bullosa acquisita, as compared with the epidermal side in BP.¹

How to make the Dx in 3 steps

To effectively diagnose and classify BP, use the following 3-step method:

1. Establish the presence of 3 of 4 ­clinical characteristics: patient’s age > 60 years, absence of atrophic scars, absence of mucosal involvement, and absence of bullous lesions on the head and neck.
2. Order light microscopy. Findings should be consistent with eosinophils and neutrophils containing subepidermal bullae.
3. Order a punch biopsy to obtain a perilesional specimen. DIF of the biopsy findings should feature linear deposits of IgG with or without C3 along the dermo-epidermal junction. This step is essential for an accurate diagnosis.

Depending on the severity of disease, treatment can include the use of potent topical corticosteroids alone or in combination with systemic corticosteroids and antiinflammatory antibiotics.

There also is benefit in ordering supplemental studies, such as an enzyme-linked immunosorbent assay for the detection of anti-BP180 or anti-BP230 IgG autoantibodies.⁷ However, for this patient, we did not order this study.

Continue to: Management focuses on steroids

Management focuses on steroids

The offending agent should be discontinued immediately. Depending on the severity of disease, treatment can include the use of potent topical corticosteroids alone or in combination with systemic corticosteroids and anti-inflammatory antibiotics (eg, doxycycline, minocycline, erythromycin).^1,7 For patients with resistant or refractory disease, consider azathioprine, methotrexate, dapsone, and chlorambucil.^1,7 Exceptional cases may benefit from the use of mycophenolate mofetil, intravenous immunoglobulin, or plasmapheresis.^1,7

For this patient, initial treatment included discontinuation of linagliption and introduction of topical clobetasol 0.05% and oral prednisone 40 mg/d for 7 days, followed by prednisone 20 mg for 7 days. He was also started on oral doxycycline 100 mg bid and oral nicotinamide 500 mg bid.

A 62-year-old man presented to our skin clinic with multiple pruritic, tense, bullous lesions that manifested on his arms, abdomen, back, and upper thighs over a 1-month period. There were no lesions in his oral cavity or around his eyes, nose, or penile region. He denied dysphagia.

The patient had multiple comorbidities, including diabetes, hypertension, recent stroke, and end-stage renal disease. He was being prepared for dialysis. His medications included torsemide, warfarin, amiodarone, metoprolol, pantoprozole, atorvastatin, and nifedipine. About 3 months prior to this presentation, he was started on oral linaglipton 5 mg/d, an oral antihyperglycemic medication. He had no history of skin disease or cancer, and his family history was not significant.

Physical examination showed multiple 5-mm to 2-cm blisters and bullae on the flexural surface of both of his arms (FIGURE), back, lower abdomen, and upper thighs. His palms and soles were not involved. The lesions were nontender, tense, and filled with clear fluid. Some were intact and others were rupturing. There was no mucocutaneous involvement. Nikolsky sign was negative. There were no signs of bleeding.

The family physician (FP) obtained a 4-mm punch biopsy at the edge of a 6-mm blister for light microscopy and a 3-mm perilesional punch biopsy for direct immunofluorescence (DIF) microscopy.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

DIF of the biopsy sample demonstrated linear deposition of complement 3 (C3) and immunoglobulin (Ig) G along the basement membrane zone. Indirect immunofluorescence on salt-split skin demonstrated linear deposition of IgG and C3 on both the roof and floor of the induced blisters. These findings and the patient’s clinical presentation met the criteria for bullous pemphigoid (BP), which is the most common autoimmune skin-blistering disease.¹

FPs are increasingly using DPP-4 inhibitors as oral antihyperglycemic agents for type 2 diabetes mellitus. Therefore, it’s important to recognize this medication class’s association with BP

BP is associated with subepidermal blistering, which can occur in reaction to a variety of triggers. Pathogenesis of this condition involves IgG anti-basement membrane autoantibody complex formation with the hemidesmosomal antigens BP230 and BP180—a process that activates C3 and the release of proteases that can be destructive to tissue along the dermo-epidermal junction.¹

Growing incidence. BP usually occurs in patients > 60 years, with no racial or gender preference.¹ The incidence rate of BP ranges from 2.4 to 21.7 new cases per 1 million individuals among various worldwide populations.² The incidence appears to have increased 1.9- to 4.3-fold over the past 2 decades.²

What you’ll see, who’s at risk

Symptoms of BP include localized areas of erythema or pruritic urticarial plaques that gradually become more extensive. A patient may have pruritis alone for an extended period prior to developing blisters and bullae. The bullae are tense and normally 1 to 7 cm in size.¹ Eruption is generalized, mostly affecting the lower abdomen, as well as the flexural parts of the extremities. The palms and soles also can be affected.

FPs should be aware of the atypical clinical variants of BP. In a review by Kridin and Ludwig, variants can be prurigo-like, eczema-like, urticaria-like, dyshidrosiform type, erosive type, and erythema annulare centrifugum–like type.² At-risk populations, such as elderly patients (> 70 years), whose pruritis manifests with or without bullous formation, should be screened for BP.^3,4

Continue to: Risk factors for BP

Risk factors for BP. Certain conditions linked to developing BP include neurologic disorders (dementia and Parkinson disease) and psychiatric disorders (unipolar and bipolar disorder).⁴ Further, it is important to note any medications that could be the cause of a patient’s BP, including dipeptidyl peptidase-4 (DPP-4) inhibitors, psychotropic medications, spironolactone, furosemide, beta-blockers, and antibiotics.³ This patient was taking a beta-blocker (metoprolol) and a DPP-4 inhibitor (linagliptin). Because he was most recently started on linagliptin, we suspected it may have had a causal role in the development of BP.

The association of DPP-4 inhibitors and BP

FPs are increasingly using DPP-4 inhibitors—including sitagliptin, vildagliptin, and linagliptin—as oral antihyperglycemic agents for type 2 diabetes mellitus. Therefore, it’s important to recognize this medication class’s association with BP.⁵ In a case-control study of 165 patients with BP, Benzaquen et al reported that 28 patients who were taking DPP-4 inhibitors had an associated increased risk for BP (adjusted odds ratio = 2.64; 95% confidence interval [CI], 1.19-5.85).³

The pathophysiology of BP associated with DPP-4 inhibitors remains unclear, but mechanisms have been proposed. The DPP-4 enzyme is expressed on many cells, including keratinocytes, T cells, and endothelial cells.³ It is possible that DPP-4 inhibition at these cells could stimulate activity of inflammatory cytokines, which can lead to enhanced local eosinophil activation and trigger bullous formation. DPP-4 enzymes are also involved in forming plasmin, which is a protease that cleaves BP180.³ Inhibition of this process can affect proper cleavage of BP180, impacting its function and antigenicity.^3,6

Other conditions that also exhibit blisters

There are some skin conditions with similar presentations that need to be ruled out in the work-up.

Bullous diabeticorum is a rare, spontaneous, noninflammatory condition found in patients with diabetes.¹ Blisters usually manifest as large, tense, asymmetrical, mildly tender lesions that commonly affect the feet and lower legs but can involve the trunk. These usually develop overnight without preceding trauma. Biopsy would show both intra-­epidermal and subepidermal bulla with normal DIF findings.¹ This condition usually has an excellent prognosis.

Continue to: Pemphigus vulgaris

Pemphigus vulgaris is characterized by nonpruritic, flaccid, painful blisters. This condition usually begins with manifestation of painful oral lesions that evolve into skin blisters. Some patients can develop mucocutaneous lesions.¹ Nikolsky sign is positive in these cases. Light microscopy would show intra-­epidermal bullae.

Dermatitis herpetiformis. This condition—usually affecting middle-age patients—is associated with severe pruritis and burning. It may start with a few pruritic papules or vesicles that later evolve into urticarial papules, vesicles, or bullae. Dermatitis herpetiformis can resemble herpes simplex virus. It can also be associated with gluten-sensitive enteropathy and small bowel lymphoma.¹ DIF of a biopsy sample would show granular deposition of IgA within the tips of the dermal papillae and along the basement membrane of perilesional skin.¹

Epidermolysis bullosa acquisita is a rare, severe, chronic condition with subepidermal mucocutaneous blistering.¹ It is associated with skin fragility and spontaneous trauma-induced blisters that heal with scar formation and milia. IgG autoantibodies reacting to proteins in the basement membrane zone can cause the disease. It is also associated with Crohn disease.¹ DIF findings are similar in BP, but they are differentiated by location of IgG deposits; they can be found on the dermal side of separation in epidermolysis bullosa acquisita, as compared with the epidermal side in BP.¹

How to make the Dx in 3 steps

To effectively diagnose and classify BP, use the following 3-step method:

1. Establish the presence of 3 of 4 ­clinical characteristics: patient’s age > 60 years, absence of atrophic scars, absence of mucosal involvement, and absence of bullous lesions on the head and neck.
2. Order light microscopy. Findings should be consistent with eosinophils and neutrophils containing subepidermal bullae.
3. Order a punch biopsy to obtain a perilesional specimen. DIF of the biopsy findings should feature linear deposits of IgG with or without C3 along the dermo-epidermal junction. This step is essential for an accurate diagnosis.

Depending on the severity of disease, treatment can include the use of potent topical corticosteroids alone or in combination with systemic corticosteroids and antiinflammatory antibiotics.

There also is benefit in ordering supplemental studies, such as an enzyme-linked immunosorbent assay for the detection of anti-BP180 or anti-BP230 IgG autoantibodies.⁷ However, for this patient, we did not order this study.

Continue to: Management focuses on steroids

Management focuses on steroids

The offending agent should be discontinued immediately. Depending on the severity of disease, treatment can include the use of potent topical corticosteroids alone or in combination with systemic corticosteroids and anti-inflammatory antibiotics (eg, doxycycline, minocycline, erythromycin).^1,7 For patients with resistant or refractory disease, consider azathioprine, methotrexate, dapsone, and chlorambucil.^1,7 Exceptional cases may benefit from the use of mycophenolate mofetil, intravenous immunoglobulin, or plasmapheresis.^1,7

For this patient, initial treatment included discontinuation of linagliption and introduction of topical clobetasol 0.05% and oral prednisone 40 mg/d for 7 days, followed by prednisone 20 mg for 7 days. He was also started on oral doxycycline 100 mg bid and oral nicotinamide 500 mg bid.

THE CASE

A 20-year-old man presented to our clinic with a 3-day history of nonradiating chest pain located at the center of his chest. Past medical history included idiopathic neonatal giant-cell hepatitis and subsequent liver transplant at 1 month of age; he had been followed by the transplant team without rejection or infection and was in otherwise good health prior to the chest pain.

On the day of symptom onset, he was walking inside his house and fell to his knees with a chest pain described as “a punch” to the center of the chest that lasted for a few seconds. He was able to continue his daily activities without limitation despite a constant, squeezing, centrally located chest pain. The pain worsened with cough and exertion.

A few hours later, he went to an urgent care center for evaluation. There, he reported, his chest radiograph and electrocardiogram (EKG) results were normal and he was given a diagnosis of musculoskeletal chest pain. Over the next 3 days, his chest pain persisted but did not worsen. He was taking 500 mg of naproxen every 8 hours with no improvement. No other acute or chronic medications were being taken. He had no significant family history. A review of systems was otherwise negative.

On physical exam, his vital statistics included a height of 6’4”; weight, 261 lb; body mass index, 31.8; temperature, 98.7 °F; blood pressure, 134/77 mm Hg; heart rate, 92 beats/min; respiratory rate, 18 breaths/min; and oxygen saturation, 96%. Throughout the exam, he demonstrated no acute distress, appeared well, and was talkative; however, he reported having a “constant, squeezing” chest pain that did not worsen with palpation of the chest. The rest of his physical exam was unremarkable.

Although he reported that his EKG and chest radiograph were normal 3 days prior, repeat chest radiograph and EKG were ordered due to his unexplained, active chest pain and the lack of immediate access to the prior results.

THE DIAGNOSIS

The chest radiograph (FIGURE 1A) showed a “mildly ectatic ascending thoracic aorta” that had increased since a chest radiograph from 6 years prior (FIGURE 1B) and “was concerning for an aneurysm.” Computed tomography (CT) angiography (FIGURE 2) then confirmed a 7-cm aneurysm of the ascending aorta, with findings suggestive of a retrograde ascending aortic dissection.

DISCUSSION

The average age of a patient with acute aortic dissection (AAD) is 63 years; only 7% occur in people younger than 40.¹ AAD is often accompanied by a predisposing risk factor such as a connective tissue disease, bicuspid aortic valve, longstanding hypertension, trauma, or larger aortic dimensions.^2,3 Younger patients are more likely to have predisposing risk factors of Marfan syndrome, prior aortic surgery, or a bicuspid aortic valve.³

Continue to: A literature review did not reveal...

A literature review did not reveal any known correlation between the patient’s history of giant-cell hepatitis or antirejection therapy with thoracic aortic dissection. Furthermore, liver transplant is not known to be a specific risk factor for AAD in pediatric patients or outside the immediate postoperative period. Therefore, there were no known predisposing risk factors for AAD in our patient.

The most common clinical feature of AAD is chest pain, which occurs in 75% of patients.¹ Other clinical symptoms include hypertension and diaphoresis.^2,4 However, classic clinical findings are not always displayed, making the diagnosis difficult.^2,4 The classical description of “tearing pain” is seen in only 51% of patients, and 5% to 15% of patients present without any pain.¹

Commonly missed or misdiagnosed. The diagnosis of AAD has been missed during the initial exam in 38% of patients.⁴ As seen in our case, symptoms may be initially diagnosed as musculoskeletal chest pain. Based on symptoms, AAD can be incorrectly diagnosed as an acute myocardial infarction or vascular embolization.^2,4

Every hour after symptom onset, the mortality rate of untreated AAD increases 1% to 2%,with no difference based on age.^3,4 Different reports have shown mortality rates between 7% and 30%.⁴

Effective imaging is crucial to the diagnosis and treatment of AAD, given the occurrence of atypical presentation, missed diagnosis, and high mortality rate.⁴ A chest radiograph will show a widened mediastinum, but the preferred diagnostic tests are a CT or transthoracic echocardiogram.^2,4 Once the diagnosis of AAD is confirmed, an aortic angiogram is the preferred test to determine the extent of the dissection prior to surgical treatment.²

Continue to: Classification dictates treatment

Classification dictates treatment. AAD is classified based on where the dissection of the aorta occurs. If the dissection involves the ascending aorta, it is classified as a type A AAD and should immediately be treated with emergent surgery in order to prevent complications including myocardial infarction, cardiac tamponade, and aortic rupture.^2,4,5 If the dissection is limited to the descending aorta, it is classified as a type B AAD and can be medically managed by controlling pain and lowering blood pressure; if symptoms persist, surgical management may be required.² After hospital discharge, AAD patients are followed closely with medical therapy, serial imaging, and reoperation if necessary.⁴

Our patient underwent emergent surgery for aortic root/ascending aortic replacement with a mechanical valve. He tolerated the procedure well. Surgical tissue pathology of the aortic segment showed a wall of elastic vessel with medial degeneration and dissection, and the tissue pathology of the aorta leaflets showed valvular tissue with myxoid degeneration.

THE TAKEAWAY

It is critical to keep AAD in the differential diagnosis of a patient presenting with acute onset of chest pain, as AAD often has an atypical presentation and can easily be misdiagnosed. Effective imaging is crucial to diagnosis, and immediate treatment is essential to patient survival.

CORRESPONDENCE
Rachel A. Reedy, PA, University of Florida, Department of General Pediatrics, 7046 SW Archer Road, Gainesville, FL 32608; rreedy@ufl.edu

THE CASE

A 20-year-old man presented to our clinic with a 3-day history of nonradiating chest pain located at the center of his chest. Past medical history included idiopathic neonatal giant-cell hepatitis and subsequent liver transplant at 1 month of age; he had been followed by the transplant team without rejection or infection and was in otherwise good health prior to the chest pain.

On the day of symptom onset, he was walking inside his house and fell to his knees with a chest pain described as “a punch” to the center of the chest that lasted for a few seconds. He was able to continue his daily activities without limitation despite a constant, squeezing, centrally located chest pain. The pain worsened with cough and exertion.

A few hours later, he went to an urgent care center for evaluation. There, he reported, his chest radiograph and electrocardiogram (EKG) results were normal and he was given a diagnosis of musculoskeletal chest pain. Over the next 3 days, his chest pain persisted but did not worsen. He was taking 500 mg of naproxen every 8 hours with no improvement. No other acute or chronic medications were being taken. He had no significant family history. A review of systems was otherwise negative.

On physical exam, his vital statistics included a height of 6’4”; weight, 261 lb; body mass index, 31.8; temperature, 98.7 °F; blood pressure, 134/77 mm Hg; heart rate, 92 beats/min; respiratory rate, 18 breaths/min; and oxygen saturation, 96%. Throughout the exam, he demonstrated no acute distress, appeared well, and was talkative; however, he reported having a “constant, squeezing” chest pain that did not worsen with palpation of the chest. The rest of his physical exam was unremarkable.

Although he reported that his EKG and chest radiograph were normal 3 days prior, repeat chest radiograph and EKG were ordered due to his unexplained, active chest pain and the lack of immediate access to the prior results.

THE DIAGNOSIS

The chest radiograph (FIGURE 1A) showed a “mildly ectatic ascending thoracic aorta” that had increased since a chest radiograph from 6 years prior (FIGURE 1B) and “was concerning for an aneurysm.” Computed tomography (CT) angiography (FIGURE 2) then confirmed a 7-cm aneurysm of the ascending aorta, with findings suggestive of a retrograde ascending aortic dissection.

DISCUSSION

The average age of a patient with acute aortic dissection (AAD) is 63 years; only 7% occur in people younger than 40.¹ AAD is often accompanied by a predisposing risk factor such as a connective tissue disease, bicuspid aortic valve, longstanding hypertension, trauma, or larger aortic dimensions.^2,3 Younger patients are more likely to have predisposing risk factors of Marfan syndrome, prior aortic surgery, or a bicuspid aortic valve.³

Continue to: A literature review did not reveal...

A literature review did not reveal any known correlation between the patient’s history of giant-cell hepatitis or antirejection therapy with thoracic aortic dissection. Furthermore, liver transplant is not known to be a specific risk factor for AAD in pediatric patients or outside the immediate postoperative period. Therefore, there were no known predisposing risk factors for AAD in our patient.

The most common clinical feature of AAD is chest pain, which occurs in 75% of patients.¹ Other clinical symptoms include hypertension and diaphoresis.^2,4 However, classic clinical findings are not always displayed, making the diagnosis difficult.^2,4 The classical description of “tearing pain” is seen in only 51% of patients, and 5% to 15% of patients present without any pain.¹

Commonly missed or misdiagnosed. The diagnosis of AAD has been missed during the initial exam in 38% of patients.⁴ As seen in our case, symptoms may be initially diagnosed as musculoskeletal chest pain. Based on symptoms, AAD can be incorrectly diagnosed as an acute myocardial infarction or vascular embolization.^2,4

Every hour after symptom onset, the mortality rate of untreated AAD increases 1% to 2%,with no difference based on age.^3,4 Different reports have shown mortality rates between 7% and 30%.⁴

Effective imaging is crucial to the diagnosis and treatment of AAD, given the occurrence of atypical presentation, missed diagnosis, and high mortality rate.⁴ A chest radiograph will show a widened mediastinum, but the preferred diagnostic tests are a CT or transthoracic echocardiogram.^2,4 Once the diagnosis of AAD is confirmed, an aortic angiogram is the preferred test to determine the extent of the dissection prior to surgical treatment.²

Continue to: Classification dictates treatment

Classification dictates treatment. AAD is classified based on where the dissection of the aorta occurs. If the dissection involves the ascending aorta, it is classified as a type A AAD and should immediately be treated with emergent surgery in order to prevent complications including myocardial infarction, cardiac tamponade, and aortic rupture.^2,4,5 If the dissection is limited to the descending aorta, it is classified as a type B AAD and can be medically managed by controlling pain and lowering blood pressure; if symptoms persist, surgical management may be required.² After hospital discharge, AAD patients are followed closely with medical therapy, serial imaging, and reoperation if necessary.⁴

Our patient underwent emergent surgery for aortic root/ascending aortic replacement with a mechanical valve. He tolerated the procedure well. Surgical tissue pathology of the aortic segment showed a wall of elastic vessel with medial degeneration and dissection, and the tissue pathology of the aorta leaflets showed valvular tissue with myxoid degeneration.

THE TAKEAWAY

It is critical to keep AAD in the differential diagnosis of a patient presenting with acute onset of chest pain, as AAD often has an atypical presentation and can easily be misdiagnosed. Effective imaging is crucial to diagnosis, and immediate treatment is essential to patient survival.

CORRESPONDENCE
Rachel A. Reedy, PA, University of Florida, Department of General Pediatrics, 7046 SW Archer Road, Gainesville, FL 32608; rreedy@ufl.edu

THE CASE

A 20-year-old man presented to our clinic with a 3-day history of nonradiating chest pain located at the center of his chest. Past medical history included idiopathic neonatal giant-cell hepatitis and subsequent liver transplant at 1 month of age; he had been followed by the transplant team without rejection or infection and was in otherwise good health prior to the chest pain.

On the day of symptom onset, he was walking inside his house and fell to his knees with a chest pain described as “a punch” to the center of the chest that lasted for a few seconds. He was able to continue his daily activities without limitation despite a constant, squeezing, centrally located chest pain. The pain worsened with cough and exertion.

A few hours later, he went to an urgent care center for evaluation. There, he reported, his chest radiograph and electrocardiogram (EKG) results were normal and he was given a diagnosis of musculoskeletal chest pain. Over the next 3 days, his chest pain persisted but did not worsen. He was taking 500 mg of naproxen every 8 hours with no improvement. No other acute or chronic medications were being taken. He had no significant family history. A review of systems was otherwise negative.

On physical exam, his vital statistics included a height of 6’4”; weight, 261 lb; body mass index, 31.8; temperature, 98.7 °F; blood pressure, 134/77 mm Hg; heart rate, 92 beats/min; respiratory rate, 18 breaths/min; and oxygen saturation, 96%. Throughout the exam, he demonstrated no acute distress, appeared well, and was talkative; however, he reported having a “constant, squeezing” chest pain that did not worsen with palpation of the chest. The rest of his physical exam was unremarkable.

Although he reported that his EKG and chest radiograph were normal 3 days prior, repeat chest radiograph and EKG were ordered due to his unexplained, active chest pain and the lack of immediate access to the prior results.

THE DIAGNOSIS

The chest radiograph (FIGURE 1A) showed a “mildly ectatic ascending thoracic aorta” that had increased since a chest radiograph from 6 years prior (FIGURE 1B) and “was concerning for an aneurysm.” Computed tomography (CT) angiography (FIGURE 2) then confirmed a 7-cm aneurysm of the ascending aorta, with findings suggestive of a retrograde ascending aortic dissection.

DISCUSSION

The average age of a patient with acute aortic dissection (AAD) is 63 years; only 7% occur in people younger than 40.¹ AAD is often accompanied by a predisposing risk factor such as a connective tissue disease, bicuspid aortic valve, longstanding hypertension, trauma, or larger aortic dimensions.^2,3 Younger patients are more likely to have predisposing risk factors of Marfan syndrome, prior aortic surgery, or a bicuspid aortic valve.³

Continue to: A literature review did not reveal...

A literature review did not reveal any known correlation between the patient’s history of giant-cell hepatitis or antirejection therapy with thoracic aortic dissection. Furthermore, liver transplant is not known to be a specific risk factor for AAD in pediatric patients or outside the immediate postoperative period. Therefore, there were no known predisposing risk factors for AAD in our patient.

The most common clinical feature of AAD is chest pain, which occurs in 75% of patients.¹ Other clinical symptoms include hypertension and diaphoresis.^2,4 However, classic clinical findings are not always displayed, making the diagnosis difficult.^2,4 The classical description of “tearing pain” is seen in only 51% of patients, and 5% to 15% of patients present without any pain.¹

Commonly missed or misdiagnosed. The diagnosis of AAD has been missed during the initial exam in 38% of patients.⁴ As seen in our case, symptoms may be initially diagnosed as musculoskeletal chest pain. Based on symptoms, AAD can be incorrectly diagnosed as an acute myocardial infarction or vascular embolization.^2,4

Every hour after symptom onset, the mortality rate of untreated AAD increases 1% to 2%,with no difference based on age.^3,4 Different reports have shown mortality rates between 7% and 30%.⁴

Effective imaging is crucial to the diagnosis and treatment of AAD, given the occurrence of atypical presentation, missed diagnosis, and high mortality rate.⁴ A chest radiograph will show a widened mediastinum, but the preferred diagnostic tests are a CT or transthoracic echocardiogram.^2,4 Once the diagnosis of AAD is confirmed, an aortic angiogram is the preferred test to determine the extent of the dissection prior to surgical treatment.²

Continue to: Classification dictates treatment

Classification dictates treatment. AAD is classified based on where the dissection of the aorta occurs. If the dissection involves the ascending aorta, it is classified as a type A AAD and should immediately be treated with emergent surgery in order to prevent complications including myocardial infarction, cardiac tamponade, and aortic rupture.^2,4,5 If the dissection is limited to the descending aorta, it is classified as a type B AAD and can be medically managed by controlling pain and lowering blood pressure; if symptoms persist, surgical management may be required.² After hospital discharge, AAD patients are followed closely with medical therapy, serial imaging, and reoperation if necessary.⁴

Our patient underwent emergent surgery for aortic root/ascending aortic replacement with a mechanical valve. He tolerated the procedure well. Surgical tissue pathology of the aortic segment showed a wall of elastic vessel with medial degeneration and dissection, and the tissue pathology of the aorta leaflets showed valvular tissue with myxoid degeneration.

THE TAKEAWAY

It is critical to keep AAD in the differential diagnosis of a patient presenting with acute onset of chest pain, as AAD often has an atypical presentation and can easily be misdiagnosed. Effective imaging is crucial to diagnosis, and immediate treatment is essential to patient survival.

CORRESPONDENCE
Rachel A. Reedy, PA, University of Florida, Department of General Pediatrics, 7046 SW Archer Road, Gainesville, FL 32608; rreedy@ufl.edu

ILLUSTRATIVE CASE

A 57-year-old man who was given a diagnosis of T2D a year ago presents for an office visit. His hemoglobin A1C level at diagnosis was 8.3%. He is otherwise healthy and has been adhering well to a plan of metformin 1000 mg twice daily, regular exercise, and a low-­carbohydrate diet you recommended. His most recent hemoglobin A1C is 7.3%. He is pleased with his progress, so he is discouraged when you tell him that he is not yet at goal. He asks if there are other things that he can do to further lower his hemoglobin A1C. What can you recommend for him?

According to the National Diabetes Statistics Report, 2020 from the Centers for Disease Control and Prevention, approximately 34.1 million US adults ≥ 18 years of age (13% of the adult population) have diabetes, 50% of whom have a hemoglobin A1C > 7%. The report also states that approximately 88 million US adults—more than one-third of the population—have prediabetes.²

The American Diabetes Association (ADA) estimated that diabetes-related health care costs in the United States for 2017 totaled $237 billion, an increase of 26% from 2012. More than $30 billion of this expense comes directly from diabetes medications; the remainder of these costs are related to lost wages, clinic visits, hospitalizations, and treatment for diabetic complications and comorbidities. After controlling for age and gender, medical expenditures for people with diabetes are 2.3 times higher than for those without diabetes.³

The 2019 ADA Nutrition Therapy for Adults With Diabetes or Prediabetes: A Consensus Report makes general recommendations concerning fiber intake for patients with diabetes or prediabetes, stating that these patients should consume approximately 14 g of fiber for every 1000 kcal consumed, giving preference to whole-food sources rather than supplements.⁴ The report indicates that some studies have shown hemoglobin A1C reductions of 0.2% to 0.3% with daily fiber intake exceeding 50 g. However, this level of intake can cause unpleasant gastrointestinal adverse effects, including bloating, diarrhea, and flatulence.^4,5

STUDY SUMMARY

Effect on A1C exceeded the FDA threshold for new drugs

This systematic review and meta-analysis searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials that studied the effects of viscous fiber supplementation on glycemic control in patients with T2D. Eligible studies included those that: (1) had a duration ≥ 3 weeks; (2) allowed isolation of the viscous fiber effects; and (3) reported at least 1 of the following glycemic measures: hemoglobin A1C (n = 1148 patients), fasting glucose (n = 1394), fasting insulin (n = 228), homeostatic model assessment of insulin resistance (HOMA-IR; n = 652), and fructosamine (n = 23).

As an adjunct to standard of care, viscous fiber supplements significantly improved hemoglobin A1C and other glycemic markers in patients with T2D.

Data were pooled using the generic inverse variance method and expressed as mean difference (MD) with 95% confidence intervals (CIs). Heterogeneity was assessed and quantified (Cochran Q and I² statistics, respectively). I² ≥ 50% indicates substantial heterogeneity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the overall strength of evidence.

Twenty-eight eligible studies were compared. The median age of included patients was 60 years. The median dose of viscous fiber was 13.1 g/d (range, 2.55-21). Viscous fiber type varied between the studies and included psyllium, guar gum, β-glucan, and konjac, and was consumed in powder, tablet, capsule, and limited food-based forms (in 1 of the included studies). The median trial duration was 8 weeks, with 11 trials lasting ≥ 12 weeks.

Continue to: The study found...

The study found moderate-grade evidence that, when added to standard of care, viscous fiber supplementation reduced hemoglobin A1C (MD = –0.58%; 95% CI, –0.88 to –0.28; P = .0002; I² = 91%), fasting glucose (MD = –14.8 mg/dL; 95% CI, –23.8 to –5.58; P = .001; I² = 92%), and HOMA-IR (MD = –1.89; 95% CI, –3.45 to –0.33; P = .02; I² = 94%) compared with control. The effect on hemoglobin A1C exceeds the ≥ 0.3% threshold established by the US Food and Drug Administration for new antihyperglycemic drug development. There was no significant effect on fasting insulin or fructosamine, although the sample size for fructosamine was small. No significant evidence of a dose-dependent response effect was found. The studies had substantial heterogeneity. No evaluation of potential or real harm was noted in the analysis.

WHAT’S NEW

Potential glycemic benefit without large dietary increase

The glucose-lowering effects of increased fiber intake have often been hypothesized, but this meta-analysis is the first to focus specifically on the effect of viscous fiber supplements in patients with T2D. Prior meta-analyses, including those cited in the 2019 ADA recommendations mentioned above, included primarily whole-food dietary sources of fiber in the treatment arms and generally had more modest effects on outcomes.^4,6,7

By focusing on viscous fiber supplements, this study isolated the effect of these supplements vs fiber-rich dietary changes. It illustrates a greater potential benefit with supplements than whole-food dietary ­sources of fiber, and at a lower dose of fiber than was seen in prior studies without requiring substantial increases in caloric intake. Viscous fiber supplementation is a potential adjunct to the usual evidence-based standards of care for glycemic control in patients with T2D.

CAVEATS

Limited study durations may raise uncertainty about long-term benefits

This meta-analysis does have its limitations. The heterogeneity among the studies analyzed makes it difficult to establish a single recommendation regarding dose, type, and brand of fiber to be used. Only 11 of the 28 studies lasted longer than 12 weeks, with a median duration of 8 weeks, making any long-term effects on hemoglobin A1C unknown. No adverse effects or reactions were described to evaluate safety and tolerability of the viscous fiber supplementation. No patient-oriented outcomes were reported.

CHALLENGES TO IMPLEMENTATION

Patients may not be eager to supplement with viscous fiber

The biggest challenge to implementation is patient compliance. Some forms of supplemental fiber are less palatable than others and may cause unpleasant gastrointestinal adverse effects, which may be an impediment for some patients. Cost may also be an issue for some patients. Diabetes medications can be expensive; however, they are often covered, at least partially, by medical insurance. Over-the-counter supplements are unlikely to be covered for most patients.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 57-year-old man who was given a diagnosis of T2D a year ago presents for an office visit. His hemoglobin A1C level at diagnosis was 8.3%. He is otherwise healthy and has been adhering well to a plan of metformin 1000 mg twice daily, regular exercise, and a low-­carbohydrate diet you recommended. His most recent hemoglobin A1C is 7.3%. He is pleased with his progress, so he is discouraged when you tell him that he is not yet at goal. He asks if there are other things that he can do to further lower his hemoglobin A1C. What can you recommend for him?

According to the National Diabetes Statistics Report, 2020 from the Centers for Disease Control and Prevention, approximately 34.1 million US adults ≥ 18 years of age (13% of the adult population) have diabetes, 50% of whom have a hemoglobin A1C > 7%. The report also states that approximately 88 million US adults—more than one-third of the population—have prediabetes.²

The American Diabetes Association (ADA) estimated that diabetes-related health care costs in the United States for 2017 totaled $237 billion, an increase of 26% from 2012. More than $30 billion of this expense comes directly from diabetes medications; the remainder of these costs are related to lost wages, clinic visits, hospitalizations, and treatment for diabetic complications and comorbidities. After controlling for age and gender, medical expenditures for people with diabetes are 2.3 times higher than for those without diabetes.³

The 2019 ADA Nutrition Therapy for Adults With Diabetes or Prediabetes: A Consensus Report makes general recommendations concerning fiber intake for patients with diabetes or prediabetes, stating that these patients should consume approximately 14 g of fiber for every 1000 kcal consumed, giving preference to whole-food sources rather than supplements.⁴ The report indicates that some studies have shown hemoglobin A1C reductions of 0.2% to 0.3% with daily fiber intake exceeding 50 g. However, this level of intake can cause unpleasant gastrointestinal adverse effects, including bloating, diarrhea, and flatulence.^4,5

STUDY SUMMARY

Effect on A1C exceeded the FDA threshold for new drugs

This systematic review and meta-analysis searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials that studied the effects of viscous fiber supplementation on glycemic control in patients with T2D. Eligible studies included those that: (1) had a duration ≥ 3 weeks; (2) allowed isolation of the viscous fiber effects; and (3) reported at least 1 of the following glycemic measures: hemoglobin A1C (n = 1148 patients), fasting glucose (n = 1394), fasting insulin (n = 228), homeostatic model assessment of insulin resistance (HOMA-IR; n = 652), and fructosamine (n = 23).

As an adjunct to standard of care, viscous fiber supplements significantly improved hemoglobin A1C and other glycemic markers in patients with T2D.

Data were pooled using the generic inverse variance method and expressed as mean difference (MD) with 95% confidence intervals (CIs). Heterogeneity was assessed and quantified (Cochran Q and I² statistics, respectively). I² ≥ 50% indicates substantial heterogeneity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the overall strength of evidence.

Twenty-eight eligible studies were compared. The median age of included patients was 60 years. The median dose of viscous fiber was 13.1 g/d (range, 2.55-21). Viscous fiber type varied between the studies and included psyllium, guar gum, β-glucan, and konjac, and was consumed in powder, tablet, capsule, and limited food-based forms (in 1 of the included studies). The median trial duration was 8 weeks, with 11 trials lasting ≥ 12 weeks.

Continue to: The study found...

The study found moderate-grade evidence that, when added to standard of care, viscous fiber supplementation reduced hemoglobin A1C (MD = –0.58%; 95% CI, –0.88 to –0.28; P = .0002; I² = 91%), fasting glucose (MD = –14.8 mg/dL; 95% CI, –23.8 to –5.58; P = .001; I² = 92%), and HOMA-IR (MD = –1.89; 95% CI, –3.45 to –0.33; P = .02; I² = 94%) compared with control. The effect on hemoglobin A1C exceeds the ≥ 0.3% threshold established by the US Food and Drug Administration for new antihyperglycemic drug development. There was no significant effect on fasting insulin or fructosamine, although the sample size for fructosamine was small. No significant evidence of a dose-dependent response effect was found. The studies had substantial heterogeneity. No evaluation of potential or real harm was noted in the analysis.

WHAT’S NEW

Potential glycemic benefit without large dietary increase

The glucose-lowering effects of increased fiber intake have often been hypothesized, but this meta-analysis is the first to focus specifically on the effect of viscous fiber supplements in patients with T2D. Prior meta-analyses, including those cited in the 2019 ADA recommendations mentioned above, included primarily whole-food dietary sources of fiber in the treatment arms and generally had more modest effects on outcomes.^4,6,7

By focusing on viscous fiber supplements, this study isolated the effect of these supplements vs fiber-rich dietary changes. It illustrates a greater potential benefit with supplements than whole-food dietary ­sources of fiber, and at a lower dose of fiber than was seen in prior studies without requiring substantial increases in caloric intake. Viscous fiber supplementation is a potential adjunct to the usual evidence-based standards of care for glycemic control in patients with T2D.

CAVEATS

Limited study durations may raise uncertainty about long-term benefits

This meta-analysis does have its limitations. The heterogeneity among the studies analyzed makes it difficult to establish a single recommendation regarding dose, type, and brand of fiber to be used. Only 11 of the 28 studies lasted longer than 12 weeks, with a median duration of 8 weeks, making any long-term effects on hemoglobin A1C unknown. No adverse effects or reactions were described to evaluate safety and tolerability of the viscous fiber supplementation. No patient-oriented outcomes were reported.

CHALLENGES TO IMPLEMENTATION

Patients may not be eager to supplement with viscous fiber

The biggest challenge to implementation is patient compliance. Some forms of supplemental fiber are less palatable than others and may cause unpleasant gastrointestinal adverse effects, which may be an impediment for some patients. Cost may also be an issue for some patients. Diabetes medications can be expensive; however, they are often covered, at least partially, by medical insurance. Over-the-counter supplements are unlikely to be covered for most patients.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 57-year-old man who was given a diagnosis of T2D a year ago presents for an office visit. His hemoglobin A1C level at diagnosis was 8.3%. He is otherwise healthy and has been adhering well to a plan of metformin 1000 mg twice daily, regular exercise, and a low-­carbohydrate diet you recommended. His most recent hemoglobin A1C is 7.3%. He is pleased with his progress, so he is discouraged when you tell him that he is not yet at goal. He asks if there are other things that he can do to further lower his hemoglobin A1C. What can you recommend for him?

According to the National Diabetes Statistics Report, 2020 from the Centers for Disease Control and Prevention, approximately 34.1 million US adults ≥ 18 years of age (13% of the adult population) have diabetes, 50% of whom have a hemoglobin A1C > 7%. The report also states that approximately 88 million US adults—more than one-third of the population—have prediabetes.²

The American Diabetes Association (ADA) estimated that diabetes-related health care costs in the United States for 2017 totaled $237 billion, an increase of 26% from 2012. More than $30 billion of this expense comes directly from diabetes medications; the remainder of these costs are related to lost wages, clinic visits, hospitalizations, and treatment for diabetic complications and comorbidities. After controlling for age and gender, medical expenditures for people with diabetes are 2.3 times higher than for those without diabetes.³

The 2019 ADA Nutrition Therapy for Adults With Diabetes or Prediabetes: A Consensus Report makes general recommendations concerning fiber intake for patients with diabetes or prediabetes, stating that these patients should consume approximately 14 g of fiber for every 1000 kcal consumed, giving preference to whole-food sources rather than supplements.⁴ The report indicates that some studies have shown hemoglobin A1C reductions of 0.2% to 0.3% with daily fiber intake exceeding 50 g. However, this level of intake can cause unpleasant gastrointestinal adverse effects, including bloating, diarrhea, and flatulence.^4,5

STUDY SUMMARY

Effect on A1C exceeded the FDA threshold for new drugs

This systematic review and meta-analysis searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials that studied the effects of viscous fiber supplementation on glycemic control in patients with T2D. Eligible studies included those that: (1) had a duration ≥ 3 weeks; (2) allowed isolation of the viscous fiber effects; and (3) reported at least 1 of the following glycemic measures: hemoglobin A1C (n = 1148 patients), fasting glucose (n = 1394), fasting insulin (n = 228), homeostatic model assessment of insulin resistance (HOMA-IR; n = 652), and fructosamine (n = 23).

As an adjunct to standard of care, viscous fiber supplements significantly improved hemoglobin A1C and other glycemic markers in patients with T2D.

Data were pooled using the generic inverse variance method and expressed as mean difference (MD) with 95% confidence intervals (CIs). Heterogeneity was assessed and quantified (Cochran Q and I² statistics, respectively). I² ≥ 50% indicates substantial heterogeneity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the overall strength of evidence.

Twenty-eight eligible studies were compared. The median age of included patients was 60 years. The median dose of viscous fiber was 13.1 g/d (range, 2.55-21). Viscous fiber type varied between the studies and included psyllium, guar gum, β-glucan, and konjac, and was consumed in powder, tablet, capsule, and limited food-based forms (in 1 of the included studies). The median trial duration was 8 weeks, with 11 trials lasting ≥ 12 weeks.

Continue to: The study found...

The study found moderate-grade evidence that, when added to standard of care, viscous fiber supplementation reduced hemoglobin A1C (MD = –0.58%; 95% CI, –0.88 to –0.28; P = .0002; I² = 91%), fasting glucose (MD = –14.8 mg/dL; 95% CI, –23.8 to –5.58; P = .001; I² = 92%), and HOMA-IR (MD = –1.89; 95% CI, –3.45 to –0.33; P = .02; I² = 94%) compared with control. The effect on hemoglobin A1C exceeds the ≥ 0.3% threshold established by the US Food and Drug Administration for new antihyperglycemic drug development. There was no significant effect on fasting insulin or fructosamine, although the sample size for fructosamine was small. No significant evidence of a dose-dependent response effect was found. The studies had substantial heterogeneity. No evaluation of potential or real harm was noted in the analysis.

WHAT’S NEW

Potential glycemic benefit without large dietary increase

The glucose-lowering effects of increased fiber intake have often been hypothesized, but this meta-analysis is the first to focus specifically on the effect of viscous fiber supplements in patients with T2D. Prior meta-analyses, including those cited in the 2019 ADA recommendations mentioned above, included primarily whole-food dietary sources of fiber in the treatment arms and generally had more modest effects on outcomes.^4,6,7

By focusing on viscous fiber supplements, this study isolated the effect of these supplements vs fiber-rich dietary changes. It illustrates a greater potential benefit with supplements than whole-food dietary ­sources of fiber, and at a lower dose of fiber than was seen in prior studies without requiring substantial increases in caloric intake. Viscous fiber supplementation is a potential adjunct to the usual evidence-based standards of care for glycemic control in patients with T2D.

CAVEATS

Limited study durations may raise uncertainty about long-term benefits

This meta-analysis does have its limitations. The heterogeneity among the studies analyzed makes it difficult to establish a single recommendation regarding dose, type, and brand of fiber to be used. Only 11 of the 28 studies lasted longer than 12 weeks, with a median duration of 8 weeks, making any long-term effects on hemoglobin A1C unknown. No adverse effects or reactions were described to evaluate safety and tolerability of the viscous fiber supplementation. No patient-oriented outcomes were reported.

CHALLENGES TO IMPLEMENTATION

Patients may not be eager to supplement with viscous fiber

The biggest challenge to implementation is patient compliance. Some forms of supplemental fiber are less palatable than others and may cause unpleasant gastrointestinal adverse effects, which may be an impediment for some patients. Cost may also be an issue for some patients. Diabetes medications can be expensive; however, they are often covered, at least partially, by medical insurance. Over-the-counter supplements are unlikely to be covered for most patients.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

THE CASE

Emily T.* is a 15-year-old, cisgender, homeless runaway. While on the streets, she was lured to a hotel where a “pimp” informed her she was going to work for him. She repeatedly tried to leave, but he would strike her, so she eventually succumbed. She was forced to have sex with several men and rarely allowed to use condoms.

On 1 occasion, when she went to a hospital with her pimp to visit a patient, her aunt (a nurse on duty at that facility) saw Ms. T and called the police. The pimp was arrested. Ms. T was interviewed by the police and gave a statement but refused a forensic exam.

Because of her involvement with the pimp, she was incarcerated. In prison, she was seen by a physician. On evaluation, she reported difficulty sleeping, flashbacks, and feelings of shame and guilt.¹

● How would you proceed with this patient?

* The patient’s name has been changed to protect her identity.

Child and adolescent sex trafficking is defined as the sexual exploitation of minors through force, fraud, or coercion. Specifically, it includes the recruitment, harboring, transportation, or advertising of a minor, and includes the exchange of anything of value in return for sexual activity. Commercial sexual exploitation and sex trafficking against minors include crimes such as prostitution; survival sex (exchanging sex/sexual acts for money or something of value, such as shelter, food, or drugs); pornography; sex tourism, mail-order-bride trade, and early marriage; or sexual performances (peep shows or strip clubs).²

Providing optimal care for children and adolescents exploited by sex trafficking depends on knowing risk factors, having an awareness of recommended screening and assessment tools, and employing a trauma-­informed approach to interviews, examination, and support.²

Continue to: Recognize clues to trafficking

The Centers for Disease Control and Prevention (CDC) offers a framework for trafficking prevention. Health care providers are encouraged to use the CDC Social-Ecological Model which describes targeted prevention strategies at the individual, relationship, community, and societal levels.³

Risk factors for entering trafficking. Younger age increases a child’s vulnerability to exploitation, due to a lack of maturity, limited cognitive development, and ease of deception. The mean age of trafficking survivors is 15 years.⁴ History of child abuse and other traumatic experiences can lead children to run away from home. It is estimated that, once on the streets, most teens will be recruited by a trafficker within 48 hours.⁵ Poor self-esteem, depression, substance abuse, history of truancy, and early sexual maturation also increase the risk of becoming involved in trafficking (TABLE 1).^2,6-8

Clinical findings suggestive of trafficking. Many physicians grasp the critical role they play in confronting trafficking, but they lack specific training, experience, and assessment tools.³ Notably, in 1 retrospective study, 46% of victims had been seen by a provider within the previous 2 months.⁶ One of the major challenges to identifying survivors of trafficking is to recognize critical signs, of which there are many (TABLE 1^2,6-8). Often these include a history of sexual assault, multiple pregnancies, requests for contraception at an early age, or evidence of physical injury.

Screen to identify trafficking

Universal, validated screening tools to accurately identify trafficked youth is an area of growing research. Some tools have been validated, but only for specific populations such as homeless or incarcerated youth or in emergency department (ED) patients. Tools for sex trafficking identification that may be useful in primary care include the Child Sex Trafficking (CST) screen validated in ED settings (TABLE 2),⁹ the Commercial Sexual Exploitation-Identification Tool (CSE-IT) in multiple settings (TABLE 3),^10,11 and the Quick Youth Indicators for Trafficking (QYIT) in homeless youth (TABLE 4).¹¹ The QYIT is the first validated labor and sex trafficking screening tool in homeless young adults. Children who screen positive for sex trafficking should be further assessed using a comprehensive tool.

Barriers to effective recognition of trafficked individuals. Financial factors limit access to health care. Also, survivors have cited multiple barriers for health professionals that prevent identification of survivors’ trafficked status.^12,13 Once in the medical setting, disclosure is impacted by time constraints, fear of judgment by clinicians, and the risk of re-traumatization. Survivors have also cited lack of privacy, control strategies by their traffickers, lack of provider empathy, and fear of police as barriers to disclosure.¹⁴

Continue to: The medical impact of trafficking

The medical impact of trafficking

Sexual exploitation is a traumatic experience that is known to cause harm across multiple domains including serious physical injuries related to violence, as well as reproductive and mental health consequences.^15,16

Acute and chronic illnesses. In an initial evaluation, assess the survivor’s acute medical conditions (TABLE 5).^15,16 Common acute issues include physical injuries due to assault, infections, and reproductive complications.¹⁷ Health concerns can also result from stressors such as deprivation of food and sleep, hazardous living conditions, and limited access to care.¹⁷

Suspect possible sex trafficking when a patient has a history of sexual assault and multiple pregnancies, requests contraception at an early age, and/or has evidence of physical injury.

As part of caring for sex-trafficking survivors, assess for, and treat, chronic health issues such as pain, gastrointestinal complaints, poor dental care, malnutrition, and fatigue.^16,18 Substance use, as well as chronic mental health concerns (eg, anxiety, depression, posttraumatic stress disorder [PTSD]) may also influence the clinical presentation.

Physical injuries. A cross-sectional study of female survivors of sex trafficking in the United States found that 89% sustained physical injury resulting from violence, including fractures, open wounds, head injury, dental problems, burns, and anogenital trauma.^16,17 In many cases, acute injury may not be present in the clinical setting since care is often delayed, but a full examination can reveal signs of prior trauma.¹⁶

Reproductive health concerns. Significant, long-term impact on reproductive health can result due to forced penetration by multiple perpetrators, sodomy, and sex without protection or lubricants. Survivors are therefore at high risk for unplanned and unwanted pregnancies, sexually transmitted infections (STIs), pelvic pain, and infertility.¹⁶

Continue to: Psychological effects and trauma exposure

Psychological effects and trauma exposure. Survivors often have experienced abuse and neglect prior to commercial exploitation, and they may exhibit long-term sequelae. Survivors may present with major depression, anxiety, panic attacks, suicidality, addiction, PTSD, or aggression.¹⁶ Long-term sequelae for patients can include dysfunctional relationships due to an inability to trust, self-destructive behaviors, and significant shame.^2,18

Care and treatment of trafficked youth

Initial presentation may occur in a variety of health care settings. Use a trauma-informed approach emphasizing physical and emotional safety and positive relationships, to reduce risk to the survivor, staff, and providers.¹⁹ Establishing trust and rapport may provide better short-term safety, as well as help build stronger long-term relationships that can lead to better health outcomes.

Clinical examination. Provide traumatized patients with a sense of safety, control, and autonomy in the health care setting. During the physical exam, be aware of the impact of re-traumatization as patients are asked to undress, endure sensitive examinations, and undergo invasive procedures. Explain the examination, ask for permission at each step, and use slow movements. Allow the patient to guide certain sensitive exams.¹⁵ Adopt an approach that recognizes the impact of trauma, avoids revictimization, and acknowledges the resilience of survivors.²⁰

Treatment plan. After the initial exam, treat acute physical injuries and determine if any further testing is needed. Offer emergency contraception, STI prophylaxis, pre-exposure prophylaxis, and vaccines.¹⁵ After assessing patient readiness, offer local resources, identify safe methods for communication, identify individuals who could intervene in a crisis, and consider a safety plan (TABLE 6).

Coordination of care. Consider referrals to behavioral health services, substance recovery centers, food programs, housing resources, and a primary care clinic.¹⁵ ED clinicians may be asked to complete a sexual or physical assault forensic examination. After obtaining informed consent, one needs to¹⁹

• document skin signs such as scars, bites, strangulation marks, and tattoos. Note the size, shape, color, location, and other characteristics of each lesion.
• perform an oral, genital, and rectal examination and use a sexual assault evidence kit as indicated.
• use body diagrams and take photographs of all injuries/physical findings.
• order diagnostic testing as appropriate (eg, imaging to assess fractures).

Continue to: THE CASE

THE CASE

During Ms. T’s incarceration, she was tested for STIs and treated for gonorrhea, trichomonas, and bacterial vaginosis. She was educated about sexual health, was counseled on contraception, and accepted condoms. She was referred to a therapist and given information on additional community resources she could contact upon her release.

During a physical examination, explain the process, ask for permission at each step, use slow movements, and allow the patient to guide certain sensitive exams.

A year after her release, she was incarcerated again. She also had an unplanned pregnancy. With the support she received from community programs, social workers, and her primary care provider, she moved in with her family, where she is currently living. She denies any ongoing trafficking activity.

CORRESPONDENCE
Piali Basu, DO, MPH, UCSF Primary Care, 185 Berry Street, Lobby 1, Suite 1000, San Francisco, CA 94107; piali.basu@ucsf.edu

THE CASE

Emily T.* is a 15-year-old, cisgender, homeless runaway. While on the streets, she was lured to a hotel where a “pimp” informed her she was going to work for him. She repeatedly tried to leave, but he would strike her, so she eventually succumbed. She was forced to have sex with several men and rarely allowed to use condoms.

On 1 occasion, when she went to a hospital with her pimp to visit a patient, her aunt (a nurse on duty at that facility) saw Ms. T and called the police. The pimp was arrested. Ms. T was interviewed by the police and gave a statement but refused a forensic exam.

Because of her involvement with the pimp, she was incarcerated. In prison, she was seen by a physician. On evaluation, she reported difficulty sleeping, flashbacks, and feelings of shame and guilt.¹

● How would you proceed with this patient?

* The patient’s name has been changed to protect her identity.

Child and adolescent sex trafficking is defined as the sexual exploitation of minors through force, fraud, or coercion. Specifically, it includes the recruitment, harboring, transportation, or advertising of a minor, and includes the exchange of anything of value in return for sexual activity. Commercial sexual exploitation and sex trafficking against minors include crimes such as prostitution; survival sex (exchanging sex/sexual acts for money or something of value, such as shelter, food, or drugs); pornography; sex tourism, mail-order-bride trade, and early marriage; or sexual performances (peep shows or strip clubs).²

Providing optimal care for children and adolescents exploited by sex trafficking depends on knowing risk factors, having an awareness of recommended screening and assessment tools, and employing a trauma-­informed approach to interviews, examination, and support.²

Continue to: Recognize clues to trafficking

The Centers for Disease Control and Prevention (CDC) offers a framework for trafficking prevention. Health care providers are encouraged to use the CDC Social-Ecological Model which describes targeted prevention strategies at the individual, relationship, community, and societal levels.³

Risk factors for entering trafficking. Younger age increases a child’s vulnerability to exploitation, due to a lack of maturity, limited cognitive development, and ease of deception. The mean age of trafficking survivors is 15 years.⁴ History of child abuse and other traumatic experiences can lead children to run away from home. It is estimated that, once on the streets, most teens will be recruited by a trafficker within 48 hours.⁵ Poor self-esteem, depression, substance abuse, history of truancy, and early sexual maturation also increase the risk of becoming involved in trafficking (TABLE 1).^2,6-8

Clinical findings suggestive of trafficking. Many physicians grasp the critical role they play in confronting trafficking, but they lack specific training, experience, and assessment tools.³ Notably, in 1 retrospective study, 46% of victims had been seen by a provider within the previous 2 months.⁶ One of the major challenges to identifying survivors of trafficking is to recognize critical signs, of which there are many (TABLE 1^2,6-8). Often these include a history of sexual assault, multiple pregnancies, requests for contraception at an early age, or evidence of physical injury.

Screen to identify trafficking

Universal, validated screening tools to accurately identify trafficked youth is an area of growing research. Some tools have been validated, but only for specific populations such as homeless or incarcerated youth or in emergency department (ED) patients. Tools for sex trafficking identification that may be useful in primary care include the Child Sex Trafficking (CST) screen validated in ED settings (TABLE 2),⁹ the Commercial Sexual Exploitation-Identification Tool (CSE-IT) in multiple settings (TABLE 3),^10,11 and the Quick Youth Indicators for Trafficking (QYIT) in homeless youth (TABLE 4).¹¹ The QYIT is the first validated labor and sex trafficking screening tool in homeless young adults. Children who screen positive for sex trafficking should be further assessed using a comprehensive tool.

Barriers to effective recognition of trafficked individuals. Financial factors limit access to health care. Also, survivors have cited multiple barriers for health professionals that prevent identification of survivors’ trafficked status.^12,13 Once in the medical setting, disclosure is impacted by time constraints, fear of judgment by clinicians, and the risk of re-traumatization. Survivors have also cited lack of privacy, control strategies by their traffickers, lack of provider empathy, and fear of police as barriers to disclosure.¹⁴

Continue to: The medical impact of trafficking

The medical impact of trafficking

Sexual exploitation is a traumatic experience that is known to cause harm across multiple domains including serious physical injuries related to violence, as well as reproductive and mental health consequences.^15,16

Acute and chronic illnesses. In an initial evaluation, assess the survivor’s acute medical conditions (TABLE 5).^15,16 Common acute issues include physical injuries due to assault, infections, and reproductive complications.¹⁷ Health concerns can also result from stressors such as deprivation of food and sleep, hazardous living conditions, and limited access to care.¹⁷

Suspect possible sex trafficking when a patient has a history of sexual assault and multiple pregnancies, requests contraception at an early age, and/or has evidence of physical injury.

As part of caring for sex-trafficking survivors, assess for, and treat, chronic health issues such as pain, gastrointestinal complaints, poor dental care, malnutrition, and fatigue.^16,18 Substance use, as well as chronic mental health concerns (eg, anxiety, depression, posttraumatic stress disorder [PTSD]) may also influence the clinical presentation.

Physical injuries. A cross-sectional study of female survivors of sex trafficking in the United States found that 89% sustained physical injury resulting from violence, including fractures, open wounds, head injury, dental problems, burns, and anogenital trauma.^16,17 In many cases, acute injury may not be present in the clinical setting since care is often delayed, but a full examination can reveal signs of prior trauma.¹⁶

Reproductive health concerns. Significant, long-term impact on reproductive health can result due to forced penetration by multiple perpetrators, sodomy, and sex without protection or lubricants. Survivors are therefore at high risk for unplanned and unwanted pregnancies, sexually transmitted infections (STIs), pelvic pain, and infertility.¹⁶

Continue to: Psychological effects and trauma exposure

Psychological effects and trauma exposure. Survivors often have experienced abuse and neglect prior to commercial exploitation, and they may exhibit long-term sequelae. Survivors may present with major depression, anxiety, panic attacks, suicidality, addiction, PTSD, or aggression.¹⁶ Long-term sequelae for patients can include dysfunctional relationships due to an inability to trust, self-destructive behaviors, and significant shame.^2,18

Care and treatment of trafficked youth

Initial presentation may occur in a variety of health care settings. Use a trauma-informed approach emphasizing physical and emotional safety and positive relationships, to reduce risk to the survivor, staff, and providers.¹⁹ Establishing trust and rapport may provide better short-term safety, as well as help build stronger long-term relationships that can lead to better health outcomes.

Clinical examination. Provide traumatized patients with a sense of safety, control, and autonomy in the health care setting. During the physical exam, be aware of the impact of re-traumatization as patients are asked to undress, endure sensitive examinations, and undergo invasive procedures. Explain the examination, ask for permission at each step, and use slow movements. Allow the patient to guide certain sensitive exams.¹⁵ Adopt an approach that recognizes the impact of trauma, avoids revictimization, and acknowledges the resilience of survivors.²⁰

Treatment plan. After the initial exam, treat acute physical injuries and determine if any further testing is needed. Offer emergency contraception, STI prophylaxis, pre-exposure prophylaxis, and vaccines.¹⁵ After assessing patient readiness, offer local resources, identify safe methods for communication, identify individuals who could intervene in a crisis, and consider a safety plan (TABLE 6).

Coordination of care. Consider referrals to behavioral health services, substance recovery centers, food programs, housing resources, and a primary care clinic.¹⁵ ED clinicians may be asked to complete a sexual or physical assault forensic examination. After obtaining informed consent, one needs to¹⁹

• document skin signs such as scars, bites, strangulation marks, and tattoos. Note the size, shape, color, location, and other characteristics of each lesion.
• perform an oral, genital, and rectal examination and use a sexual assault evidence kit as indicated.
• use body diagrams and take photographs of all injuries/physical findings.
• order diagnostic testing as appropriate (eg, imaging to assess fractures).

Continue to: THE CASE

THE CASE

During Ms. T’s incarceration, she was tested for STIs and treated for gonorrhea, trichomonas, and bacterial vaginosis. She was educated about sexual health, was counseled on contraception, and accepted condoms. She was referred to a therapist and given information on additional community resources she could contact upon her release.

During a physical examination, explain the process, ask for permission at each step, use slow movements, and allow the patient to guide certain sensitive exams.

A year after her release, she was incarcerated again. She also had an unplanned pregnancy. With the support she received from community programs, social workers, and her primary care provider, she moved in with her family, where she is currently living. She denies any ongoing trafficking activity.

CORRESPONDENCE
Piali Basu, DO, MPH, UCSF Primary Care, 185 Berry Street, Lobby 1, Suite 1000, San Francisco, CA 94107; piali.basu@ucsf.edu

THE CASE

Emily T.* is a 15-year-old, cisgender, homeless runaway. While on the streets, she was lured to a hotel where a “pimp” informed her she was going to work for him. She repeatedly tried to leave, but he would strike her, so she eventually succumbed. She was forced to have sex with several men and rarely allowed to use condoms.

On 1 occasion, when she went to a hospital with her pimp to visit a patient, her aunt (a nurse on duty at that facility) saw Ms. T and called the police. The pimp was arrested. Ms. T was interviewed by the police and gave a statement but refused a forensic exam.

Because of her involvement with the pimp, she was incarcerated. In prison, she was seen by a physician. On evaluation, she reported difficulty sleeping, flashbacks, and feelings of shame and guilt.¹

● How would you proceed with this patient?

* The patient’s name has been changed to protect her identity.

Child and adolescent sex trafficking is defined as the sexual exploitation of minors through force, fraud, or coercion. Specifically, it includes the recruitment, harboring, transportation, or advertising of a minor, and includes the exchange of anything of value in return for sexual activity. Commercial sexual exploitation and sex trafficking against minors include crimes such as prostitution; survival sex (exchanging sex/sexual acts for money or something of value, such as shelter, food, or drugs); pornography; sex tourism, mail-order-bride trade, and early marriage; or sexual performances (peep shows or strip clubs).²

Providing optimal care for children and adolescents exploited by sex trafficking depends on knowing risk factors, having an awareness of recommended screening and assessment tools, and employing a trauma-­informed approach to interviews, examination, and support.²

Continue to: Recognize clues to trafficking

The Centers for Disease Control and Prevention (CDC) offers a framework for trafficking prevention. Health care providers are encouraged to use the CDC Social-Ecological Model which describes targeted prevention strategies at the individual, relationship, community, and societal levels.³

Risk factors for entering trafficking. Younger age increases a child’s vulnerability to exploitation, due to a lack of maturity, limited cognitive development, and ease of deception. The mean age of trafficking survivors is 15 years.⁴ History of child abuse and other traumatic experiences can lead children to run away from home. It is estimated that, once on the streets, most teens will be recruited by a trafficker within 48 hours.⁵ Poor self-esteem, depression, substance abuse, history of truancy, and early sexual maturation also increase the risk of becoming involved in trafficking (TABLE 1).^2,6-8

Clinical findings suggestive of trafficking. Many physicians grasp the critical role they play in confronting trafficking, but they lack specific training, experience, and assessment tools.³ Notably, in 1 retrospective study, 46% of victims had been seen by a provider within the previous 2 months.⁶ One of the major challenges to identifying survivors of trafficking is to recognize critical signs, of which there are many (TABLE 1^2,6-8). Often these include a history of sexual assault, multiple pregnancies, requests for contraception at an early age, or evidence of physical injury.

Screen to identify trafficking

Universal, validated screening tools to accurately identify trafficked youth is an area of growing research. Some tools have been validated, but only for specific populations such as homeless or incarcerated youth or in emergency department (ED) patients. Tools for sex trafficking identification that may be useful in primary care include the Child Sex Trafficking (CST) screen validated in ED settings (TABLE 2),⁹ the Commercial Sexual Exploitation-Identification Tool (CSE-IT) in multiple settings (TABLE 3),^10,11 and the Quick Youth Indicators for Trafficking (QYIT) in homeless youth (TABLE 4).¹¹ The QYIT is the first validated labor and sex trafficking screening tool in homeless young adults. Children who screen positive for sex trafficking should be further assessed using a comprehensive tool.

Barriers to effective recognition of trafficked individuals. Financial factors limit access to health care. Also, survivors have cited multiple barriers for health professionals that prevent identification of survivors’ trafficked status.^12,13 Once in the medical setting, disclosure is impacted by time constraints, fear of judgment by clinicians, and the risk of re-traumatization. Survivors have also cited lack of privacy, control strategies by their traffickers, lack of provider empathy, and fear of police as barriers to disclosure.¹⁴

Continue to: The medical impact of trafficking

The medical impact of trafficking

Sexual exploitation is a traumatic experience that is known to cause harm across multiple domains including serious physical injuries related to violence, as well as reproductive and mental health consequences.^15,16

Acute and chronic illnesses. In an initial evaluation, assess the survivor’s acute medical conditions (TABLE 5).^15,16 Common acute issues include physical injuries due to assault, infections, and reproductive complications.¹⁷ Health concerns can also result from stressors such as deprivation of food and sleep, hazardous living conditions, and limited access to care.¹⁷

Suspect possible sex trafficking when a patient has a history of sexual assault and multiple pregnancies, requests contraception at an early age, and/or has evidence of physical injury.

As part of caring for sex-trafficking survivors, assess for, and treat, chronic health issues such as pain, gastrointestinal complaints, poor dental care, malnutrition, and fatigue.^16,18 Substance use, as well as chronic mental health concerns (eg, anxiety, depression, posttraumatic stress disorder [PTSD]) may also influence the clinical presentation.

Physical injuries. A cross-sectional study of female survivors of sex trafficking in the United States found that 89% sustained physical injury resulting from violence, including fractures, open wounds, head injury, dental problems, burns, and anogenital trauma.^16,17 In many cases, acute injury may not be present in the clinical setting since care is often delayed, but a full examination can reveal signs of prior trauma.¹⁶

Reproductive health concerns. Significant, long-term impact on reproductive health can result due to forced penetration by multiple perpetrators, sodomy, and sex without protection or lubricants. Survivors are therefore at high risk for unplanned and unwanted pregnancies, sexually transmitted infections (STIs), pelvic pain, and infertility.¹⁶

Continue to: Psychological effects and trauma exposure

Psychological effects and trauma exposure. Survivors often have experienced abuse and neglect prior to commercial exploitation, and they may exhibit long-term sequelae. Survivors may present with major depression, anxiety, panic attacks, suicidality, addiction, PTSD, or aggression.¹⁶ Long-term sequelae for patients can include dysfunctional relationships due to an inability to trust, self-destructive behaviors, and significant shame.^2,18

Care and treatment of trafficked youth

Initial presentation may occur in a variety of health care settings. Use a trauma-informed approach emphasizing physical and emotional safety and positive relationships, to reduce risk to the survivor, staff, and providers.¹⁹ Establishing trust and rapport may provide better short-term safety, as well as help build stronger long-term relationships that can lead to better health outcomes.

Clinical examination. Provide traumatized patients with a sense of safety, control, and autonomy in the health care setting. During the physical exam, be aware of the impact of re-traumatization as patients are asked to undress, endure sensitive examinations, and undergo invasive procedures. Explain the examination, ask for permission at each step, and use slow movements. Allow the patient to guide certain sensitive exams.¹⁵ Adopt an approach that recognizes the impact of trauma, avoids revictimization, and acknowledges the resilience of survivors.²⁰

Treatment plan. After the initial exam, treat acute physical injuries and determine if any further testing is needed. Offer emergency contraception, STI prophylaxis, pre-exposure prophylaxis, and vaccines.¹⁵ After assessing patient readiness, offer local resources, identify safe methods for communication, identify individuals who could intervene in a crisis, and consider a safety plan (TABLE 6).

Coordination of care. Consider referrals to behavioral health services, substance recovery centers, food programs, housing resources, and a primary care clinic.¹⁵ ED clinicians may be asked to complete a sexual or physical assault forensic examination. After obtaining informed consent, one needs to¹⁹

• document skin signs such as scars, bites, strangulation marks, and tattoos. Note the size, shape, color, location, and other characteristics of each lesion.
• perform an oral, genital, and rectal examination and use a sexual assault evidence kit as indicated.
• use body diagrams and take photographs of all injuries/physical findings.
• order diagnostic testing as appropriate (eg, imaging to assess fractures).

Continue to: THE CASE

THE CASE

During Ms. T’s incarceration, she was tested for STIs and treated for gonorrhea, trichomonas, and bacterial vaginosis. She was educated about sexual health, was counseled on contraception, and accepted condoms. She was referred to a therapist and given information on additional community resources she could contact upon her release.

During a physical examination, explain the process, ask for permission at each step, use slow movements, and allow the patient to guide certain sensitive exams.

A year after her release, she was incarcerated again. She also had an unplanned pregnancy. With the support she received from community programs, social workers, and her primary care provider, she moved in with her family, where she is currently living. She denies any ongoing trafficking activity.

CORRESPONDENCE
Piali Basu, DO, MPH, UCSF Primary Care, 185 Berry Street, Lobby 1, Suite 1000, San Francisco, CA 94107; piali.basu@ucsf.edu