The Journal of Family Practice

The FP suspected that this was a skin cancer with ulceration rather than a dermatitis because of the ulceration and polymorphous vessels on dermoscopy. The differential diagnosis included squamous cell carcinoma, amelanotic melanoma, and basal cell carcinoma.

The FP explained to the patient that a biopsy would be needed and suggested a broad shave biopsy because it would provide adequate tissue to the pathologist. The physician performed a broad shave biopsy with a DermaBlade. (See the Watch & Learn video on “Shave biopsy.”) The biopsy report came back as amelanotic melanoma with a depth of 1.5 mm.

While most melanomas have visible pigment, some melanomas will present without pigmentation. Based on a Breslow depth of 1.5 mm, the patient was sent to Surgical Oncology for a wide excision with 1 cm margins and sentinel lymph node biopsy. Fortunately, the sentinel lymph node biopsy did not show any metastasis. The FP advised the patient that he would require regular skin surveillance and would need to take skin care precautions when exposed to the sun.

‌

Photo courtesy of Jonathan Karnes, MD and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Squamous cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1103-1111.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The FP suspected that this was a skin cancer with ulceration rather than a dermatitis because of the ulceration and polymorphous vessels on dermoscopy. The differential diagnosis included squamous cell carcinoma, amelanotic melanoma, and basal cell carcinoma.

The FP explained to the patient that a biopsy would be needed and suggested a broad shave biopsy because it would provide adequate tissue to the pathologist. The physician performed a broad shave biopsy with a DermaBlade. (See the Watch & Learn video on “Shave biopsy.”) The biopsy report came back as amelanotic melanoma with a depth of 1.5 mm.

While most melanomas have visible pigment, some melanomas will present without pigmentation. Based on a Breslow depth of 1.5 mm, the patient was sent to Surgical Oncology for a wide excision with 1 cm margins and sentinel lymph node biopsy. Fortunately, the sentinel lymph node biopsy did not show any metastasis. The FP advised the patient that he would require regular skin surveillance and would need to take skin care precautions when exposed to the sun.

‌

Photo courtesy of Jonathan Karnes, MD and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Squamous cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1103-1111.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The FP suspected that this was a skin cancer with ulceration rather than a dermatitis because of the ulceration and polymorphous vessels on dermoscopy. The differential diagnosis included squamous cell carcinoma, amelanotic melanoma, and basal cell carcinoma.

The FP explained to the patient that a biopsy would be needed and suggested a broad shave biopsy because it would provide adequate tissue to the pathologist. The physician performed a broad shave biopsy with a DermaBlade. (See the Watch & Learn video on “Shave biopsy.”) The biopsy report came back as amelanotic melanoma with a depth of 1.5 mm.

While most melanomas have visible pigment, some melanomas will present without pigmentation. Based on a Breslow depth of 1.5 mm, the patient was sent to Surgical Oncology for a wide excision with 1 cm margins and sentinel lymph node biopsy. Fortunately, the sentinel lymph node biopsy did not show any metastasis. The FP advised the patient that he would require regular skin surveillance and would need to take skin care precautions when exposed to the sun.

‌

Photo courtesy of Jonathan Karnes, MD and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Squamous cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1103-1111.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The FP suspected that this was an acral lentiginous melanoma (ALM).

The FP considered the various ways to biopsy this lesion. Doing a biopsy of the whole lesion was neither practical, nor desirable, given that the lesion was >2 cm and located on the bottom of the patient’s foot. And while incomplete sampling could result in a false negative result, this lesion was so suspicious for melanoma that any well-performed biopsy would likely produce a diagnosis of melanoma. (Of course if melanoma was not diagnosable with partial sampling, a full excisional biopsy would be needed.)

The FP also debated doing a 6-mm punch biopsy vs a shave biopsy; his intent was to get below some of the deeper pigment. Incisional biopsy done as a small ellipse with suturing was also an option. It would also be the most time consuming.

The FP presented the biopsy options to the patient and explained that the shave biopsy would require a dressing and the punch biopsy would require sutures, which would need to be removed at the next visit. Both biopsy methods would likely cause the foot to be uncomfortable to walk on for several days.

The FP and patient decided to do a deep shave biopsy (saucerization). After administering local anesthesia with lidocaine and epinephrine, the FP performed a deep shave biopsy that included about 1 cm of the darkest and thickest portion of the suspected melanoma.

The biopsy results indicated that the patient had an acral lentiginous melanoma, which measured 0.7 mm at its deepest point in the biopsied portion. The patient was referred to Orthopedics for a wide excision and repair. A sentinel node biopsy was not needed because the lesion was less than 1 mm in depth and there was no ulceration. The surgery and healing time were challenging for the patient, but she did not lose her foot and has remained cancer free.

‌

Photo courtesy of Jonathan Karnes, MD and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Squamous cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1103-1111.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The FP suspected that this was an acral lentiginous melanoma (ALM).

The FP considered the various ways to biopsy this lesion. Doing a biopsy of the whole lesion was neither practical, nor desirable, given that the lesion was >2 cm and located on the bottom of the patient’s foot. And while incomplete sampling could result in a false negative result, this lesion was so suspicious for melanoma that any well-performed biopsy would likely produce a diagnosis of melanoma. (Of course if melanoma was not diagnosable with partial sampling, a full excisional biopsy would be needed.)

The FP also debated doing a 6-mm punch biopsy vs a shave biopsy; his intent was to get below some of the deeper pigment. Incisional biopsy done as a small ellipse with suturing was also an option. It would also be the most time consuming.

The FP presented the biopsy options to the patient and explained that the shave biopsy would require a dressing and the punch biopsy would require sutures, which would need to be removed at the next visit. Both biopsy methods would likely cause the foot to be uncomfortable to walk on for several days.

The FP and patient decided to do a deep shave biopsy (saucerization). After administering local anesthesia with lidocaine and epinephrine, the FP performed a deep shave biopsy that included about 1 cm of the darkest and thickest portion of the suspected melanoma.

The biopsy results indicated that the patient had an acral lentiginous melanoma, which measured 0.7 mm at its deepest point in the biopsied portion. The patient was referred to Orthopedics for a wide excision and repair. A sentinel node biopsy was not needed because the lesion was less than 1 mm in depth and there was no ulceration. The surgery and healing time were challenging for the patient, but she did not lose her foot and has remained cancer free.

‌

Photo courtesy of Jonathan Karnes, MD and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Squamous cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1103-1111.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The FP suspected that this was an acral lentiginous melanoma (ALM).

The FP considered the various ways to biopsy this lesion. Doing a biopsy of the whole lesion was neither practical, nor desirable, given that the lesion was >2 cm and located on the bottom of the patient’s foot. And while incomplete sampling could result in a false negative result, this lesion was so suspicious for melanoma that any well-performed biopsy would likely produce a diagnosis of melanoma. (Of course if melanoma was not diagnosable with partial sampling, a full excisional biopsy would be needed.)

The FP also debated doing a 6-mm punch biopsy vs a shave biopsy; his intent was to get below some of the deeper pigment. Incisional biopsy done as a small ellipse with suturing was also an option. It would also be the most time consuming.

The FP presented the biopsy options to the patient and explained that the shave biopsy would require a dressing and the punch biopsy would require sutures, which would need to be removed at the next visit. Both biopsy methods would likely cause the foot to be uncomfortable to walk on for several days.

The FP and patient decided to do a deep shave biopsy (saucerization). After administering local anesthesia with lidocaine and epinephrine, the FP performed a deep shave biopsy that included about 1 cm of the darkest and thickest portion of the suspected melanoma.

The biopsy results indicated that the patient had an acral lentiginous melanoma, which measured 0.7 mm at its deepest point in the biopsied portion. The patient was referred to Orthopedics for a wide excision and repair. A sentinel node biopsy was not needed because the lesion was less than 1 mm in depth and there was no ulceration. The surgery and healing time were challenging for the patient, but she did not lose her foot and has remained cancer free.

‌

Photo courtesy of Jonathan Karnes, MD and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Squamous cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1103-1111.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

We read with interest the review article by Keber and Fiebert, “Diabetes in the elderly: Matching meds to needs” (J Fam Pract. 2018;67:408-410,412-415). The authors have provided a timely overview of antidiabetes medications for elderly people with type 2 diabetes mellitus (T2DM) and their relative risks for hypoglycemia.

We’d like to add to this important conversation.

Aging, per se, modifies the glycemic thresholds for autonomic symptoms and cognitive impairment; in older nondiabetic men (mean + SD: age 65 ± 3 years), autonomic symptoms and cognitive dysfunction commence at identical glycemic thresholds (3 ± 0.2 mmol/L [54 ± 4 mg/dL]). By contrast, in younger men (age 23 ± 2 years), a significant gap is observed between the glycemic threshold for symptom generation (3.6 mmol/L [65 mg/dL]) and the onset of cognitive dysfunction (2.6 mmol/L [47 mg/dL]).^1,2 The simultaneous occurrence of symptoms and cognitive impairment in older people may adversely affect their ability to recognize and treat hypoglycemia promptly.

In addition, hypoglycemia in older T2DM patients often presents with atypical neurologic symptoms, including incoordination and ataxia, slurring of speech, and visual disturbances, which either are not identified as hypoglycemia or are misdiagnosed as other medical disorders (eg, transient ischemic attack).³ Knowledge about hypoglycemia symptoms is poor, in both elderly people with diabetes and their relatives and caregivers, which compromises the ability to identify hypoglycemia and provide effective treatment.⁴ Education about the possible presentations of hypoglycemia and its effective treatment is essential for older patients and their relatives.

Jan Brož, MD
Prague, Czech Republic

We read with interest the review article by Keber and Fiebert, “Diabetes in the elderly: Matching meds to needs” (J Fam Pract. 2018;67:408-410,412-415). The authors have provided a timely overview of antidiabetes medications for elderly people with type 2 diabetes mellitus (T2DM) and their relative risks for hypoglycemia.

We’d like to add to this important conversation.

Aging, per se, modifies the glycemic thresholds for autonomic symptoms and cognitive impairment; in older nondiabetic men (mean + SD: age 65 ± 3 years), autonomic symptoms and cognitive dysfunction commence at identical glycemic thresholds (3 ± 0.2 mmol/L [54 ± 4 mg/dL]). By contrast, in younger men (age 23 ± 2 years), a significant gap is observed between the glycemic threshold for symptom generation (3.6 mmol/L [65 mg/dL]) and the onset of cognitive dysfunction (2.6 mmol/L [47 mg/dL]).^1,2 The simultaneous occurrence of symptoms and cognitive impairment in older people may adversely affect their ability to recognize and treat hypoglycemia promptly.

In addition, hypoglycemia in older T2DM patients often presents with atypical neurologic symptoms, including incoordination and ataxia, slurring of speech, and visual disturbances, which either are not identified as hypoglycemia or are misdiagnosed as other medical disorders (eg, transient ischemic attack).³ Knowledge about hypoglycemia symptoms is poor, in both elderly people with diabetes and their relatives and caregivers, which compromises the ability to identify hypoglycemia and provide effective treatment.⁴ Education about the possible presentations of hypoglycemia and its effective treatment is essential for older patients and their relatives.

Jan Brož, MD
Prague, Czech Republic

We read with interest the review article by Keber and Fiebert, “Diabetes in the elderly: Matching meds to needs” (J Fam Pract. 2018;67:408-410,412-415). The authors have provided a timely overview of antidiabetes medications for elderly people with type 2 diabetes mellitus (T2DM) and their relative risks for hypoglycemia.

We’d like to add to this important conversation.

Aging, per se, modifies the glycemic thresholds for autonomic symptoms and cognitive impairment; in older nondiabetic men (mean + SD: age 65 ± 3 years), autonomic symptoms and cognitive dysfunction commence at identical glycemic thresholds (3 ± 0.2 mmol/L [54 ± 4 mg/dL]). By contrast, in younger men (age 23 ± 2 years), a significant gap is observed between the glycemic threshold for symptom generation (3.6 mmol/L [65 mg/dL]) and the onset of cognitive dysfunction (2.6 mmol/L [47 mg/dL]).^1,2 The simultaneous occurrence of symptoms and cognitive impairment in older people may adversely affect their ability to recognize and treat hypoglycemia promptly.

In addition, hypoglycemia in older T2DM patients often presents with atypical neurologic symptoms, including incoordination and ataxia, slurring of speech, and visual disturbances, which either are not identified as hypoglycemia or are misdiagnosed as other medical disorders (eg, transient ischemic attack).³ Knowledge about hypoglycemia symptoms is poor, in both elderly people with diabetes and their relatives and caregivers, which compromises the ability to identify hypoglycemia and provide effective treatment.⁴ Education about the possible presentations of hypoglycemia and its effective treatment is essential for older patients and their relatives.

Jan Brož, MD
Prague, Czech Republic

It is with much enthusiasm that we read the article “Dialing back opioids for chronic pain one conversation at a time” (J Fam Pract. 2018;67:753-757) about the author’s approach to opioid tapering. We have implemented a similar process in our own medical home practice, based on the continuity relationship and the Ecological Systems Theory.

The use of the human resources within the medical home—care coordinator, pharmacist, community health worker, etc— distributes the responsibility and lessens the burden of care for the family physician. The Ecological Systems Theory provides a structure for understanding the interaction between proximal influencers (eg, the team) and more distal influences (eg, national guidelines and institutional mandates).

Recently, we presented our findings at the 2018 North American Primary Care Research Group (NAPCRG) Annual Meeting. Our results showed a 50% decline in per capita medication use over an almost 14-month period.

We feel that opioid tapering provides both a counterpoint and a complementary method to medication-assisted therapies (MAT). A counterpoint, because MAT involves the diagnosis and treatment of opioid misuse disorder. At the core of that diagnosis is the question of whether all chronic opioid use should be labelled as “misuse.” Tapering involves no such diagnosis and focuses on the safety of minimal opioid use, which, when MAT is used appropriately, is also a primary concern.

We appreciate the approach that the authors took in their project and look forward to seeing further iterations.

Bharat Gopal, MD
Cristina Capannolo, DO
Corvallis, Ore

It is with much enthusiasm that we read the article “Dialing back opioids for chronic pain one conversation at a time” (J Fam Pract. 2018;67:753-757) about the author’s approach to opioid tapering. We have implemented a similar process in our own medical home practice, based on the continuity relationship and the Ecological Systems Theory.

The use of the human resources within the medical home—care coordinator, pharmacist, community health worker, etc— distributes the responsibility and lessens the burden of care for the family physician. The Ecological Systems Theory provides a structure for understanding the interaction between proximal influencers (eg, the team) and more distal influences (eg, national guidelines and institutional mandates).

Recently, we presented our findings at the 2018 North American Primary Care Research Group (NAPCRG) Annual Meeting. Our results showed a 50% decline in per capita medication use over an almost 14-month period.

We feel that opioid tapering provides both a counterpoint and a complementary method to medication-assisted therapies (MAT). A counterpoint, because MAT involves the diagnosis and treatment of opioid misuse disorder. At the core of that diagnosis is the question of whether all chronic opioid use should be labelled as “misuse.” Tapering involves no such diagnosis and focuses on the safety of minimal opioid use, which, when MAT is used appropriately, is also a primary concern.

We appreciate the approach that the authors took in their project and look forward to seeing further iterations.

Bharat Gopal, MD
Cristina Capannolo, DO
Corvallis, Ore

It is with much enthusiasm that we read the article “Dialing back opioids for chronic pain one conversation at a time” (J Fam Pract. 2018;67:753-757) about the author’s approach to opioid tapering. We have implemented a similar process in our own medical home practice, based on the continuity relationship and the Ecological Systems Theory.

The use of the human resources within the medical home—care coordinator, pharmacist, community health worker, etc— distributes the responsibility and lessens the burden of care for the family physician. The Ecological Systems Theory provides a structure for understanding the interaction between proximal influencers (eg, the team) and more distal influences (eg, national guidelines and institutional mandates).

Recently, we presented our findings at the 2018 North American Primary Care Research Group (NAPCRG) Annual Meeting. Our results showed a 50% decline in per capita medication use over an almost 14-month period.

We feel that opioid tapering provides both a counterpoint and a complementary method to medication-assisted therapies (MAT). A counterpoint, because MAT involves the diagnosis and treatment of opioid misuse disorder. At the core of that diagnosis is the question of whether all chronic opioid use should be labelled as “misuse.” Tapering involves no such diagnosis and focuses on the safety of minimal opioid use, which, when MAT is used appropriately, is also a primary concern.

We appreciate the approach that the authors took in their project and look forward to seeing further iterations.

Bharat Gopal, MD
Cristina Capannolo, DO
Corvallis, Ore

In his guest editorial, “Upending this country’s approach to health care” (J Fam Pract. 2018;67:744-745), T. R. Reid makes a number of good points. However, I disagree with his opinion that “This disgraceful state of affairs is not the fault of the nation’s physicians. Rather, the problems with health care in the United States stem from the system that American providers have to work in.”

Through our choices, we have helped create this current system. I started as a family practice attending physician in 1994 and worked in 2 community hospitals. One of these hospitals closed its doors in 2012 and the other merged with a large health care system in 2015. During my 25 years of practice, I watched all of my outstanding primary care colleagues (family medicine, internal medicine, and pediatrics; 25 to 30 in total) stop their practice of combined outpatient and inpatient work. I currently do not see any primary care physicians (who do outpatient work) during my hospital patient care. Yes, it’s lonely.

I believe this significant change in practice across the United States has led to unintended consequences. First, the administrative burdens (and likely costs) for hospitals and health care systems have risen. Newborn, pediatric, and adult hospitalist services had to be built or bolstered, and then maintained, and the growing number of employed physicians had to be managed. Second, primary care’s attractiveness to some medical students has declined. Should students want a practice where they will likely never take care of their patients in the office and the hospital?

I agree we have a “disgraceful state of affairs,” and we need to work together for the tough solutions. However, as health care leaders, we must take responsibility for our roles in creating the current system. We must acknowledge these roles and learn from them.  

Chris Noah, MD
Middleville, Mich

As a longtime family medicine practitioner, I can’t agree more with Mr. Reid’s assessments of the state of our health care system. I have experienced health care from my practice as part of an HMO in Wisconsin, and in a hospital system in Raleigh, NC. Our “system” has done such a poor job of allocating its resources and has sacrificed so much to generate profit for the insurance and pharmaceutical corporations. The question is: How do we develop the political will to overcome these deep pockets to change the system? Victor Fuch’s article in the November issue of JAMA makes a very compelling case for a national health plan.¹

Jeff Keil, MD
Cary, NC

In his guest editorial, “Upending this country’s approach to health care” (J Fam Pract. 2018;67:744-745), T. R. Reid makes a number of good points. However, I disagree with his opinion that “This disgraceful state of affairs is not the fault of the nation’s physicians. Rather, the problems with health care in the United States stem from the system that American providers have to work in.”

Through our choices, we have helped create this current system. I started as a family practice attending physician in 1994 and worked in 2 community hospitals. One of these hospitals closed its doors in 2012 and the other merged with a large health care system in 2015. During my 25 years of practice, I watched all of my outstanding primary care colleagues (family medicine, internal medicine, and pediatrics; 25 to 30 in total) stop their practice of combined outpatient and inpatient work. I currently do not see any primary care physicians (who do outpatient work) during my hospital patient care. Yes, it’s lonely.

I believe this significant change in practice across the United States has led to unintended consequences. First, the administrative burdens (and likely costs) for hospitals and health care systems have risen. Newborn, pediatric, and adult hospitalist services had to be built or bolstered, and then maintained, and the growing number of employed physicians had to be managed. Second, primary care’s attractiveness to some medical students has declined. Should students want a practice where they will likely never take care of their patients in the office and the hospital?

I agree we have a “disgraceful state of affairs,” and we need to work together for the tough solutions. However, as health care leaders, we must take responsibility for our roles in creating the current system. We must acknowledge these roles and learn from them.  

Chris Noah, MD
Middleville, Mich

As a longtime family medicine practitioner, I can’t agree more with Mr. Reid’s assessments of the state of our health care system. I have experienced health care from my practice as part of an HMO in Wisconsin, and in a hospital system in Raleigh, NC. Our “system” has done such a poor job of allocating its resources and has sacrificed so much to generate profit for the insurance and pharmaceutical corporations. The question is: How do we develop the political will to overcome these deep pockets to change the system? Victor Fuch’s article in the November issue of JAMA makes a very compelling case for a national health plan.¹

Jeff Keil, MD
Cary, NC

In his guest editorial, “Upending this country’s approach to health care” (J Fam Pract. 2018;67:744-745), T. R. Reid makes a number of good points. However, I disagree with his opinion that “This disgraceful state of affairs is not the fault of the nation’s physicians. Rather, the problems with health care in the United States stem from the system that American providers have to work in.”

Through our choices, we have helped create this current system. I started as a family practice attending physician in 1994 and worked in 2 community hospitals. One of these hospitals closed its doors in 2012 and the other merged with a large health care system in 2015. During my 25 years of practice, I watched all of my outstanding primary care colleagues (family medicine, internal medicine, and pediatrics; 25 to 30 in total) stop their practice of combined outpatient and inpatient work. I currently do not see any primary care physicians (who do outpatient work) during my hospital patient care. Yes, it’s lonely.

I believe this significant change in practice across the United States has led to unintended consequences. First, the administrative burdens (and likely costs) for hospitals and health care systems have risen. Newborn, pediatric, and adult hospitalist services had to be built or bolstered, and then maintained, and the growing number of employed physicians had to be managed. Second, primary care’s attractiveness to some medical students has declined. Should students want a practice where they will likely never take care of their patients in the office and the hospital?

I agree we have a “disgraceful state of affairs,” and we need to work together for the tough solutions. However, as health care leaders, we must take responsibility for our roles in creating the current system. We must acknowledge these roles and learn from them.  

Chris Noah, MD
Middleville, Mich

As a longtime family medicine practitioner, I can’t agree more with Mr. Reid’s assessments of the state of our health care system. I have experienced health care from my practice as part of an HMO in Wisconsin, and in a hospital system in Raleigh, NC. Our “system” has done such a poor job of allocating its resources and has sacrificed so much to generate profit for the insurance and pharmaceutical corporations. The question is: How do we develop the political will to overcome these deep pockets to change the system? Victor Fuch’s article in the November issue of JAMA makes a very compelling case for a national health plan.¹

Jeff Keil, MD
Cary, NC

Even the best physicians make mistakes.

Each of us can recall a patient for whom our initial diagnosis was incorrect, or conversely, where we uncovered the correct diagnosis. My memorable mistake was missing an obvious case of hypothyroidism, and my happier encounter was correcting an incorrect diagnosis of asthma when the patient actually had primary pulmonary fibrosis. These patients came to mind as I read this month’s cover story, “COPD and asthma: Diagnostic accuracy requires spirometry.”

In a previous editorial, “When our biases derail the diagnosis,”¹ I discussed types of cognitive bias that can lead us to the wrong conclusion. Today, I want to address diagnostic errors in medicine as a patient safety issue.

Listening closely to the patient's and family's concerns can lead in a direction other than my initial impression.

The patient safety movement gained traction in 1999 with the publication of the Institute of Medicine (IOM, now National Academy of Medicine) report, To Err is Human: Building a Safer Health System. That report focused on health care system issues and had little to offer regarding improving diagnoses. It was not until 2015, with the publication of the IOM report Improving Diagnosis in Health Care, that serious national attention was directed to accurate diagnosis. It is worth reading the summary of this report, which includes 8 goals and is available at nas.edu/improvingdiagnosis.

The recommendations most pertinent to family physicians are to: 1) facilitate more effective teamwork among health care professionals, patients, and families, 2) teach health care professionals about the diagnostic process, 3) ensure that technology supports proper diagnosis, 4) establish a work culture that supports diagnostic processes, and 5) identify diagnostic errors and learn from them.

Teamwork. The first recommendation is intriguing because the focus on teamwork includes patients and their families. I have found that listening closely to the patient’s and family’s concerns can lead me in a direction other than my initial impression—especially when they are insistent about a particular diagnosis.

Technology. Despite all of their “warts,” electronic health records are gradually incorporating clinical decision support tools that really do help steer us in the right direction. I have found that electronic point-of-care references can be very helpful in establishing an accurate diagnosis in the exam room—and can help convince patients that my diagnosis is correct when they read it for themselves!

Continue to: Finally, discussing our mistakes...

Finally, discussing our mistakes openly with our colleagues helps us—and them—to avoid that mistake in the future. Let’s be sure to keep that dialogue open. And let’s continue to refine our diagnostic skills so that we can continue to keep our patients safe.

Even the best physicians make mistakes.

Each of us can recall a patient for whom our initial diagnosis was incorrect, or conversely, where we uncovered the correct diagnosis. My memorable mistake was missing an obvious case of hypothyroidism, and my happier encounter was correcting an incorrect diagnosis of asthma when the patient actually had primary pulmonary fibrosis. These patients came to mind as I read this month’s cover story, “COPD and asthma: Diagnostic accuracy requires spirometry.”

In a previous editorial, “When our biases derail the diagnosis,”¹ I discussed types of cognitive bias that can lead us to the wrong conclusion. Today, I want to address diagnostic errors in medicine as a patient safety issue.

Listening closely to the patient's and family's concerns can lead in a direction other than my initial impression.

The patient safety movement gained traction in 1999 with the publication of the Institute of Medicine (IOM, now National Academy of Medicine) report, To Err is Human: Building a Safer Health System. That report focused on health care system issues and had little to offer regarding improving diagnoses. It was not until 2015, with the publication of the IOM report Improving Diagnosis in Health Care, that serious national attention was directed to accurate diagnosis. It is worth reading the summary of this report, which includes 8 goals and is available at nas.edu/improvingdiagnosis.

The recommendations most pertinent to family physicians are to: 1) facilitate more effective teamwork among health care professionals, patients, and families, 2) teach health care professionals about the diagnostic process, 3) ensure that technology supports proper diagnosis, 4) establish a work culture that supports diagnostic processes, and 5) identify diagnostic errors and learn from them.

Teamwork. The first recommendation is intriguing because the focus on teamwork includes patients and their families. I have found that listening closely to the patient’s and family’s concerns can lead me in a direction other than my initial impression—especially when they are insistent about a particular diagnosis.

Technology. Despite all of their “warts,” electronic health records are gradually incorporating clinical decision support tools that really do help steer us in the right direction. I have found that electronic point-of-care references can be very helpful in establishing an accurate diagnosis in the exam room—and can help convince patients that my diagnosis is correct when they read it for themselves!

Continue to: Finally, discussing our mistakes...

Finally, discussing our mistakes openly with our colleagues helps us—and them—to avoid that mistake in the future. Let’s be sure to keep that dialogue open. And let’s continue to refine our diagnostic skills so that we can continue to keep our patients safe.

Even the best physicians make mistakes.

Each of us can recall a patient for whom our initial diagnosis was incorrect, or conversely, where we uncovered the correct diagnosis. My memorable mistake was missing an obvious case of hypothyroidism, and my happier encounter was correcting an incorrect diagnosis of asthma when the patient actually had primary pulmonary fibrosis. These patients came to mind as I read this month’s cover story, “COPD and asthma: Diagnostic accuracy requires spirometry.”

In a previous editorial, “When our biases derail the diagnosis,”¹ I discussed types of cognitive bias that can lead us to the wrong conclusion. Today, I want to address diagnostic errors in medicine as a patient safety issue.

Listening closely to the patient's and family's concerns can lead in a direction other than my initial impression.

The patient safety movement gained traction in 1999 with the publication of the Institute of Medicine (IOM, now National Academy of Medicine) report, To Err is Human: Building a Safer Health System. That report focused on health care system issues and had little to offer regarding improving diagnoses. It was not until 2015, with the publication of the IOM report Improving Diagnosis in Health Care, that serious national attention was directed to accurate diagnosis. It is worth reading the summary of this report, which includes 8 goals and is available at nas.edu/improvingdiagnosis.

The recommendations most pertinent to family physicians are to: 1) facilitate more effective teamwork among health care professionals, patients, and families, 2) teach health care professionals about the diagnostic process, 3) ensure that technology supports proper diagnosis, 4) establish a work culture that supports diagnostic processes, and 5) identify diagnostic errors and learn from them.

Teamwork. The first recommendation is intriguing because the focus on teamwork includes patients and their families. I have found that listening closely to the patient’s and family’s concerns can lead me in a direction other than my initial impression—especially when they are insistent about a particular diagnosis.

Technology. Despite all of their “warts,” electronic health records are gradually incorporating clinical decision support tools that really do help steer us in the right direction. I have found that electronic point-of-care references can be very helpful in establishing an accurate diagnosis in the exam room—and can help convince patients that my diagnosis is correct when they read it for themselves!

Continue to: Finally, discussing our mistakes...

Finally, discussing our mistakes openly with our colleagues helps us—and them—to avoid that mistake in the future. Let’s be sure to keep that dialogue open. And let’s continue to refine our diagnostic skills so that we can continue to keep our patients safe.

A 36-year-old African-American man presented to our clinic for evaluation of a chronic “rash” on his trunk, arms, and legs that had been present for 3 years. Empiric therapy for tinea corporis, nummular eczema, and confluent and reticulated papillomatosis had failed to improve his lesions.

Physical examination revealed a widespread skin eruption consisting of well-demarcated, hyperpigmented, scaly patches and plaques distributed throughout the patient’s trunk and extremities. Initial biopsies of the skin lesions (performed at an outside institution prior to current presentation) were nondiagnostic.

Over the next several months, the patient developed numerous cutaneous nodules and tumors within the background of his persistent patches and plaques (FIGURE). These nodules and tumors intermittently disappeared and recurred, seemingly independent of therapies including psoralen and ultraviolet A phototherapy (PUVA), interferon, and methotrexate.

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

Repeat biopsies ultimately confirmed a diagnosis of mycosis fungoides (MF), a primary cutaneous non-Hodgkin lymphoma of T-cell origin.

Lymphomas occurring in the skin without evidence of disease in other areas of the body at the time of diagnosis are referred to as primary cutaneous lymphomas. They are broadly divided by their cell of origin into cutaneous T-cell and cutaneous B-cell lymphomas. Differentiating primary cutaneous lymphoma from systemic lymphomas with secondary skin involvement is an important distinction, as primary cutaneous lymphomas have different clinical courses and prognoses and require different treatments.¹

One literature review found that 25 unique dermatoses can be mimicked clinically by mycosis fungoides.

MF is the most common type of cutaneous T-cell lymphoma (CTCL), yet it remains an uncommon diagnosis as cutaneous lymphomas comprise only 3.9% of all non-Hodgkin lymphomas.² The CD30+ transformed variant identified in this patient is a rare subtype of MF that is associated with increased morbidity and mortality.³ Other types of CTCL include primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, and adult T-cell leukemia/lymphoma, all of which can resemble MF clinically and are diagnosed by histopathology.

A nonspecific presentation

Patients with MF typically present with a complaint of chronic, slowly progressive skin lesions of various sizes and morphologies including scaly patches, plaques, and tumors, often in skin distributions that are not directly exposed to the sun (often referred to as a “bathing suit” distribution).⁴ Pruritus typically accompanies these skin lesions, and alopecia and poikiloderma are common findings. Patients with more advanced cases may present with generalized erythroderma. This finding should raise concern for progression to Sézary syndrome, a more aggressive type of CTCL that manifests with leukemic involvement of malignant T-cells matching the T-cell clones found in the skin.²

Alopecia is a common manifestation of MF that can be clinically indistinguishable from alopecia areata.⁵ While isolated alopecia is unlikely to be a consequence of MF, alopecia in the setting of widespread patches and plaques should raise suspicion for a diagnosis of MF.

Continue to: Diagnostic dilemma

This case illustrates the diagnostic dilemma posed by MF due to its propensity to mimic more benign skin disorders, both clinically and histologically.² One literature review of MF cases in which the diagnosis was not suspected clinically but was eventually confirmed histopathologically found that 25 unique dermatoses can be mimicked clinically by MF.⁶ The more common conditions that MF can be mistaken for are discussed below. In light of the diagnostic challenge posed by this multitude of morphologic presentations, referral to Dermatology for histopathologic evaluation is a reasonable next step when empiric treatment fails to improve symptoms of these common skin disorders.

Chronic atopic dermatitis (eczema) is characterized by dry skin and severe pruritis, usually associated with lichenified plaques and a history of atopic disease. The pruritic, scaly plaques typical of MF may be misdiagnosed as eczema; however, a distribution involving the “bathing suit” area is more suggestive of MF. Patients with atopic dermatitis are more likely to display a flexural distribution.²

Tinea corporis typically presents as annular, erythematous, pruritic, scaly patches or plaques that are similar to the scaling lesions of MF. Tinea corporis can be distinguished from MF via potassium hydroxide preparation of skin scrapings from an active lesion, which should demonstrate the segmented hyphae characteristic of this infection. If lesions of this type fail to respond to topical antifungal therapy, a skin biopsy may be warranted for further evaluation.

Nummular eczema, like tinea corporis, presents with round, coin-shaped patches that are highly pruritic and can be difficult to distinguish from the pruritic patches of MF. Unlike MF, however, nummular eczema typically is observed in patients with diffusely dry skin⁷; the lack of this finding should prompt consideration of alternative diagnoses, including MF.

Psoriasis classically presents with symmetrically distributed, well-demarcated plaques with prominent scaling that are usually asymptomatic, but may be associated with pruritis. Psoriatic plaques may be difficult to distinguish clinically from the plaques of MF, but their distribution may offer clues; psoriasis typically follows an extensor surface distribution, whereas MF is more commonly identified in a “bathing suit” or generalized distribution.⁴

Continue to: Tx based on disease extent, impact on quality of life

Staging of MF is the primary determinant of treatment and involves evaluation of skin, lymph node, viscera, and blood involvement. Early-stage MF has a favorable prognosis and can be effectively managed with skin-directed treatments. These include topical corticosteroids, topical nitrogen mustard agents, topical retinoids, and phototherapy (PUVA).⁸ Total skin electron beam therapy has been proven effective in the treatment of refractory and extensive MF, and local radiation therapy also is an effective treatment for isolated cutaneous tumors. Prolonged complete remissions of early-stage MF have been achieved using skin-directed treatments.⁸

In contrast, advanced MF often is treatment refractory and carries a poor prognosis. Systemic treatments such as interferon therapy, oral retinoids, extracorporeal photopheresis, and chemotherapy are added in patients with advanced disease after skin-directed therapy fails to adequately control tumor burden.

Our patient initially was treated with PUVA as well as 6 million U of interferon alfa-2B 3 times weekly, which he eventually elected to discontinue after 8 months because he wanted to father a child. His disease became more widespread after discontinuing these treatments despite interim therapy with clobetasol ointment .05%. His larger nodules and tumors were intermittently treated with local radiation with good response. Methotrexate 15 mg weekly was initiated following his decline after discontinuing PUVA and interferon treatment. Treatment with methotrexate resulted in an overall decrease in his tumor burden and several months of clinical stability.

Early stage mycosis fungoides has a favorable prognosis and can be effectively managed with skin-directed treatments. Advanced MF often is treatment refractory and has a poor prognosis.

Approximately 6 months after initiating methotrexate, his condition notably worsened. He developed generalized erythroderma, systemic symptoms including fever, chills, and unintentional 9.07-kg weight loss, in addition to new findings of palmoplantar keratoderma and nail dystrophy. In light of this systemic progression and concern for developing Sézary syndrome, extracorporeal photopheresis, bexarotene (an oral retinoid) 75 mg twice daily, and interferon alfa-2B 5 million U 3 times weekly were initiated. His condition continued to decline despite these therapies, culminating in a hospital admission for sepsis.

The patient recovered, and his regimen was changed to PUVA 3 times weekly in addition to treatment with intravenous brentuximab 1.8 mg/kg, a monoclonal antibody that targets CD30 receptors. Unfortunately, his condition continued to decline on this treatment regimen, which was subsequently abandoned in favor of chemotherapy with gemcitabine 1980 mg/250 mL normal saline. The patient was improving clinically with each cycle of gemcitabine and the plan was to transition him to extracorporeal photopheresis and bexarotene for maintenance therapy; however, the patient succumbed to his disease and passed away at the age of 37.

CORRESPONDENCE
Jonathan Banta, MD, PSC 103, Box 3613, APO, AE 09603 jonathan.c.banta.mil@mail.mil

A 36-year-old African-American man presented to our clinic for evaluation of a chronic “rash” on his trunk, arms, and legs that had been present for 3 years. Empiric therapy for tinea corporis, nummular eczema, and confluent and reticulated papillomatosis had failed to improve his lesions.

Physical examination revealed a widespread skin eruption consisting of well-demarcated, hyperpigmented, scaly patches and plaques distributed throughout the patient’s trunk and extremities. Initial biopsies of the skin lesions (performed at an outside institution prior to current presentation) were nondiagnostic.

Over the next several months, the patient developed numerous cutaneous nodules and tumors within the background of his persistent patches and plaques (FIGURE). These nodules and tumors intermittently disappeared and recurred, seemingly independent of therapies including psoralen and ultraviolet A phototherapy (PUVA), interferon, and methotrexate.

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

Repeat biopsies ultimately confirmed a diagnosis of mycosis fungoides (MF), a primary cutaneous non-Hodgkin lymphoma of T-cell origin.

Lymphomas occurring in the skin without evidence of disease in other areas of the body at the time of diagnosis are referred to as primary cutaneous lymphomas. They are broadly divided by their cell of origin into cutaneous T-cell and cutaneous B-cell lymphomas. Differentiating primary cutaneous lymphoma from systemic lymphomas with secondary skin involvement is an important distinction, as primary cutaneous lymphomas have different clinical courses and prognoses and require different treatments.¹

One literature review found that 25 unique dermatoses can be mimicked clinically by mycosis fungoides.

MF is the most common type of cutaneous T-cell lymphoma (CTCL), yet it remains an uncommon diagnosis as cutaneous lymphomas comprise only 3.9% of all non-Hodgkin lymphomas.² The CD30+ transformed variant identified in this patient is a rare subtype of MF that is associated with increased morbidity and mortality.³ Other types of CTCL include primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, and adult T-cell leukemia/lymphoma, all of which can resemble MF clinically and are diagnosed by histopathology.

A nonspecific presentation

Patients with MF typically present with a complaint of chronic, slowly progressive skin lesions of various sizes and morphologies including scaly patches, plaques, and tumors, often in skin distributions that are not directly exposed to the sun (often referred to as a “bathing suit” distribution).⁴ Pruritus typically accompanies these skin lesions, and alopecia and poikiloderma are common findings. Patients with more advanced cases may present with generalized erythroderma. This finding should raise concern for progression to Sézary syndrome, a more aggressive type of CTCL that manifests with leukemic involvement of malignant T-cells matching the T-cell clones found in the skin.²

Alopecia is a common manifestation of MF that can be clinically indistinguishable from alopecia areata.⁵ While isolated alopecia is unlikely to be a consequence of MF, alopecia in the setting of widespread patches and plaques should raise suspicion for a diagnosis of MF.

Continue to: Diagnostic dilemma

This case illustrates the diagnostic dilemma posed by MF due to its propensity to mimic more benign skin disorders, both clinically and histologically.² One literature review of MF cases in which the diagnosis was not suspected clinically but was eventually confirmed histopathologically found that 25 unique dermatoses can be mimicked clinically by MF.⁶ The more common conditions that MF can be mistaken for are discussed below. In light of the diagnostic challenge posed by this multitude of morphologic presentations, referral to Dermatology for histopathologic evaluation is a reasonable next step when empiric treatment fails to improve symptoms of these common skin disorders.

Chronic atopic dermatitis (eczema) is characterized by dry skin and severe pruritis, usually associated with lichenified plaques and a history of atopic disease. The pruritic, scaly plaques typical of MF may be misdiagnosed as eczema; however, a distribution involving the “bathing suit” area is more suggestive of MF. Patients with atopic dermatitis are more likely to display a flexural distribution.²

Tinea corporis typically presents as annular, erythematous, pruritic, scaly patches or plaques that are similar to the scaling lesions of MF. Tinea corporis can be distinguished from MF via potassium hydroxide preparation of skin scrapings from an active lesion, which should demonstrate the segmented hyphae characteristic of this infection. If lesions of this type fail to respond to topical antifungal therapy, a skin biopsy may be warranted for further evaluation.

Nummular eczema, like tinea corporis, presents with round, coin-shaped patches that are highly pruritic and can be difficult to distinguish from the pruritic patches of MF. Unlike MF, however, nummular eczema typically is observed in patients with diffusely dry skin⁷; the lack of this finding should prompt consideration of alternative diagnoses, including MF.

Psoriasis classically presents with symmetrically distributed, well-demarcated plaques with prominent scaling that are usually asymptomatic, but may be associated with pruritis. Psoriatic plaques may be difficult to distinguish clinically from the plaques of MF, but their distribution may offer clues; psoriasis typically follows an extensor surface distribution, whereas MF is more commonly identified in a “bathing suit” or generalized distribution.⁴

Continue to: Tx based on disease extent, impact on quality of life

Staging of MF is the primary determinant of treatment and involves evaluation of skin, lymph node, viscera, and blood involvement. Early-stage MF has a favorable prognosis and can be effectively managed with skin-directed treatments. These include topical corticosteroids, topical nitrogen mustard agents, topical retinoids, and phototherapy (PUVA).⁸ Total skin electron beam therapy has been proven effective in the treatment of refractory and extensive MF, and local radiation therapy also is an effective treatment for isolated cutaneous tumors. Prolonged complete remissions of early-stage MF have been achieved using skin-directed treatments.⁸

In contrast, advanced MF often is treatment refractory and carries a poor prognosis. Systemic treatments such as interferon therapy, oral retinoids, extracorporeal photopheresis, and chemotherapy are added in patients with advanced disease after skin-directed therapy fails to adequately control tumor burden.

Our patient initially was treated with PUVA as well as 6 million U of interferon alfa-2B 3 times weekly, which he eventually elected to discontinue after 8 months because he wanted to father a child. His disease became more widespread after discontinuing these treatments despite interim therapy with clobetasol ointment .05%. His larger nodules and tumors were intermittently treated with local radiation with good response. Methotrexate 15 mg weekly was initiated following his decline after discontinuing PUVA and interferon treatment. Treatment with methotrexate resulted in an overall decrease in his tumor burden and several months of clinical stability.

Early stage mycosis fungoides has a favorable prognosis and can be effectively managed with skin-directed treatments. Advanced MF often is treatment refractory and has a poor prognosis.

Approximately 6 months after initiating methotrexate, his condition notably worsened. He developed generalized erythroderma, systemic symptoms including fever, chills, and unintentional 9.07-kg weight loss, in addition to new findings of palmoplantar keratoderma and nail dystrophy. In light of this systemic progression and concern for developing Sézary syndrome, extracorporeal photopheresis, bexarotene (an oral retinoid) 75 mg twice daily, and interferon alfa-2B 5 million U 3 times weekly were initiated. His condition continued to decline despite these therapies, culminating in a hospital admission for sepsis.

The patient recovered, and his regimen was changed to PUVA 3 times weekly in addition to treatment with intravenous brentuximab 1.8 mg/kg, a monoclonal antibody that targets CD30 receptors. Unfortunately, his condition continued to decline on this treatment regimen, which was subsequently abandoned in favor of chemotherapy with gemcitabine 1980 mg/250 mL normal saline. The patient was improving clinically with each cycle of gemcitabine and the plan was to transition him to extracorporeal photopheresis and bexarotene for maintenance therapy; however, the patient succumbed to his disease and passed away at the age of 37.

CORRESPONDENCE
Jonathan Banta, MD, PSC 103, Box 3613, APO, AE 09603 jonathan.c.banta.mil@mail.mil

A 36-year-old African-American man presented to our clinic for evaluation of a chronic “rash” on his trunk, arms, and legs that had been present for 3 years. Empiric therapy for tinea corporis, nummular eczema, and confluent and reticulated papillomatosis had failed to improve his lesions.

Physical examination revealed a widespread skin eruption consisting of well-demarcated, hyperpigmented, scaly patches and plaques distributed throughout the patient’s trunk and extremities. Initial biopsies of the skin lesions (performed at an outside institution prior to current presentation) were nondiagnostic.

Over the next several months, the patient developed numerous cutaneous nodules and tumors within the background of his persistent patches and plaques (FIGURE). These nodules and tumors intermittently disappeared and recurred, seemingly independent of therapies including psoralen and ultraviolet A phototherapy (PUVA), interferon, and methotrexate.

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

Repeat biopsies ultimately confirmed a diagnosis of mycosis fungoides (MF), a primary cutaneous non-Hodgkin lymphoma of T-cell origin.

Lymphomas occurring in the skin without evidence of disease in other areas of the body at the time of diagnosis are referred to as primary cutaneous lymphomas. They are broadly divided by their cell of origin into cutaneous T-cell and cutaneous B-cell lymphomas. Differentiating primary cutaneous lymphoma from systemic lymphomas with secondary skin involvement is an important distinction, as primary cutaneous lymphomas have different clinical courses and prognoses and require different treatments.¹

One literature review found that 25 unique dermatoses can be mimicked clinically by mycosis fungoides.

MF is the most common type of cutaneous T-cell lymphoma (CTCL), yet it remains an uncommon diagnosis as cutaneous lymphomas comprise only 3.9% of all non-Hodgkin lymphomas.² The CD30+ transformed variant identified in this patient is a rare subtype of MF that is associated with increased morbidity and mortality.³ Other types of CTCL include primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, and adult T-cell leukemia/lymphoma, all of which can resemble MF clinically and are diagnosed by histopathology.

A nonspecific presentation

Patients with MF typically present with a complaint of chronic, slowly progressive skin lesions of various sizes and morphologies including scaly patches, plaques, and tumors, often in skin distributions that are not directly exposed to the sun (often referred to as a “bathing suit” distribution).⁴ Pruritus typically accompanies these skin lesions, and alopecia and poikiloderma are common findings. Patients with more advanced cases may present with generalized erythroderma. This finding should raise concern for progression to Sézary syndrome, a more aggressive type of CTCL that manifests with leukemic involvement of malignant T-cells matching the T-cell clones found in the skin.²

Alopecia is a common manifestation of MF that can be clinically indistinguishable from alopecia areata.⁵ While isolated alopecia is unlikely to be a consequence of MF, alopecia in the setting of widespread patches and plaques should raise suspicion for a diagnosis of MF.

Continue to: Diagnostic dilemma

This case illustrates the diagnostic dilemma posed by MF due to its propensity to mimic more benign skin disorders, both clinically and histologically.² One literature review of MF cases in which the diagnosis was not suspected clinically but was eventually confirmed histopathologically found that 25 unique dermatoses can be mimicked clinically by MF.⁶ The more common conditions that MF can be mistaken for are discussed below. In light of the diagnostic challenge posed by this multitude of morphologic presentations, referral to Dermatology for histopathologic evaluation is a reasonable next step when empiric treatment fails to improve symptoms of these common skin disorders.

Chronic atopic dermatitis (eczema) is characterized by dry skin and severe pruritis, usually associated with lichenified plaques and a history of atopic disease. The pruritic, scaly plaques typical of MF may be misdiagnosed as eczema; however, a distribution involving the “bathing suit” area is more suggestive of MF. Patients with atopic dermatitis are more likely to display a flexural distribution.²

Tinea corporis typically presents as annular, erythematous, pruritic, scaly patches or plaques that are similar to the scaling lesions of MF. Tinea corporis can be distinguished from MF via potassium hydroxide preparation of skin scrapings from an active lesion, which should demonstrate the segmented hyphae characteristic of this infection. If lesions of this type fail to respond to topical antifungal therapy, a skin biopsy may be warranted for further evaluation.

Nummular eczema, like tinea corporis, presents with round, coin-shaped patches that are highly pruritic and can be difficult to distinguish from the pruritic patches of MF. Unlike MF, however, nummular eczema typically is observed in patients with diffusely dry skin⁷; the lack of this finding should prompt consideration of alternative diagnoses, including MF.

Psoriasis classically presents with symmetrically distributed, well-demarcated plaques with prominent scaling that are usually asymptomatic, but may be associated with pruritis. Psoriatic plaques may be difficult to distinguish clinically from the plaques of MF, but their distribution may offer clues; psoriasis typically follows an extensor surface distribution, whereas MF is more commonly identified in a “bathing suit” or generalized distribution.⁴

Continue to: Tx based on disease extent, impact on quality of life

Staging of MF is the primary determinant of treatment and involves evaluation of skin, lymph node, viscera, and blood involvement. Early-stage MF has a favorable prognosis and can be effectively managed with skin-directed treatments. These include topical corticosteroids, topical nitrogen mustard agents, topical retinoids, and phototherapy (PUVA).⁸ Total skin electron beam therapy has been proven effective in the treatment of refractory and extensive MF, and local radiation therapy also is an effective treatment for isolated cutaneous tumors. Prolonged complete remissions of early-stage MF have been achieved using skin-directed treatments.⁸

In contrast, advanced MF often is treatment refractory and carries a poor prognosis. Systemic treatments such as interferon therapy, oral retinoids, extracorporeal photopheresis, and chemotherapy are added in patients with advanced disease after skin-directed therapy fails to adequately control tumor burden.

Our patient initially was treated with PUVA as well as 6 million U of interferon alfa-2B 3 times weekly, which he eventually elected to discontinue after 8 months because he wanted to father a child. His disease became more widespread after discontinuing these treatments despite interim therapy with clobetasol ointment .05%. His larger nodules and tumors were intermittently treated with local radiation with good response. Methotrexate 15 mg weekly was initiated following his decline after discontinuing PUVA and interferon treatment. Treatment with methotrexate resulted in an overall decrease in his tumor burden and several months of clinical stability.

Early stage mycosis fungoides has a favorable prognosis and can be effectively managed with skin-directed treatments. Advanced MF often is treatment refractory and has a poor prognosis.

Approximately 6 months after initiating methotrexate, his condition notably worsened. He developed generalized erythroderma, systemic symptoms including fever, chills, and unintentional 9.07-kg weight loss, in addition to new findings of palmoplantar keratoderma and nail dystrophy. In light of this systemic progression and concern for developing Sézary syndrome, extracorporeal photopheresis, bexarotene (an oral retinoid) 75 mg twice daily, and interferon alfa-2B 5 million U 3 times weekly were initiated. His condition continued to decline despite these therapies, culminating in a hospital admission for sepsis.

The patient recovered, and his regimen was changed to PUVA 3 times weekly in addition to treatment with intravenous brentuximab 1.8 mg/kg, a monoclonal antibody that targets CD30 receptors. Unfortunately, his condition continued to decline on this treatment regimen, which was subsequently abandoned in favor of chemotherapy with gemcitabine 1980 mg/250 mL normal saline. The patient was improving clinically with each cycle of gemcitabine and the plan was to transition him to extracorporeal photopheresis and bexarotene for maintenance therapy; however, the patient succumbed to his disease and passed away at the age of 37.

CORRESPONDENCE
Jonathan Banta, MD, PSC 103, Box 3613, APO, AE 09603 jonathan.c.banta.mil@mail.mil

A 26-year-old woman presented to our clinic with pruritic, hyperpigmented, symmetric edematous plaques on her upper flank, chest, and lower back (FIGURE) 3 weeks after starting a strict ketogenic (high fat/low carbohydrate) diet for postpartum weight loss. The patient was an otherwise healthy stay-at-home mother with an unremarkable medical history.

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

We recognized that this was a case of prurigo pigmentosa based on the characteristic pruritic rash that had developed after the patient started a strict ketogenic diet.

Prurigo pigmentosa is a benign, pruritic rash that most commonly presents with erythematous or hyperpigmented, symmetrically distributed urticarial papules and plaques on the chest and back. Females represent approximately 70% of cases with a predominant age range of 11 to 30.¹

While the pathophysiology remains unknown, the rash most often is reported in association with ketogenic diets.¹ Despite occurring in only a fraction of patients on the ketogenic diet, the characteristic presentation has led to the alternative name of the “keto rash” in online nutritional forums and blogs.

The characteristic presentation of prurigo pigmentosa has led to the alternative name of the “keto rash” in online nutritional forums.

Although prurigo pigmentosa is relatively uncommon (with an unknown incidence), primary care physicians may begin to encounter the characteristic rash more frequently, given the number of articles over the past 5 years in the primary care and nutritional literature highlighting the diet’s health benefits.² The ketogenic diet is a high-fat, low-carbohydrate diet with preliminary evidence of improved weight loss, cardiovascular health, and glycemic control suggested by a meta-analysis of 13 randomized controlled trials.³ Additionally, the popular press and general public’s rising interest are likely to increase the number of patients on this diet.

A clinical diagnosis

The diagnosis is made clinically, so the appearance of a symmetric pruritic, hyperpigmented rash on the chest and back should prompt the physician to ask about any recent changes in diet. Laboratory analysis is unnecessary, as a complete blood count, basic metabolic panel, and liver function panel are almost always normal. Urinary ketones are present in only 30% to 50% of patients; there is, however, an absence of blood ketones.^1,4

Continue to: Other conditions can mimic prurigo pigmentosa

Urticaria presents as individual lesions that often have a pale center. The lesions may occur anywhere on the body and generally last less than 24 hours. History may reveal a trigger including drugs, infection, food, or emotional stress in up to 50% of cases.⁵

Irritant contact dermatitis often is associated with a stinging or burning sensation. Irritant and allergic contact dermatitis may have a geometric, or “outside job,” distribution suggestive of external contact, potentially with plants, alkalis, acids, or solvents.⁵

Confluent and reticulated papillomatosis is a rare asymptomatic dermatosis of unknown etiology that presents as hyperpigmented papules on the upper trunk, neck, and axillae. Most patients lack associated pruritis which is in contrast to prurigo pigmentosa.⁶

Pityriasis rosea is a viral exanthem that may be associated with constitutional symptoms and often presents initially with a herald patch progressing to a classic “Christmas tree” distribution with a fine collarette of scale. It often is asymptomatic, although some cases may be pruritic.⁵

Treatment focuses on dietary modification

Primary treatment includes resumption of a normal diet. This often leads to rapid resolution of pruritis. Residual hyperpigmentation may take months to fade.

Continue to: Pharmaceutical intervention may be necessary

If additional treatment is required, minocycline 100 to 200 mg/d has been reported most effective, likely due to its anti-inflammatory properties.^1,4 Topical corticosteroids and oral antihistamines provide symptomatic relief in some patients.^1,4

Our patient had resolution of the pruritis and urticarial lesions within 2 days of resuming a normal diet; however, residual asymptomatic hyperpigmentation persisted. A retrial of the ketogenic diet initiated a flare of the rash in the same distribution. It rapidly resolved with carbohydrate intake.

CORRESPONDENCE
Daniel Croom, MD, 34520 Bob Wilson Dr, Naval Medical Center San Diego, San Diego, CA 92134; daniel.l.croom.mil@mail.mil

A 26-year-old woman presented to our clinic with pruritic, hyperpigmented, symmetric edematous plaques on her upper flank, chest, and lower back (FIGURE) 3 weeks after starting a strict ketogenic (high fat/low carbohydrate) diet for postpartum weight loss. The patient was an otherwise healthy stay-at-home mother with an unremarkable medical history.

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

We recognized that this was a case of prurigo pigmentosa based on the characteristic pruritic rash that had developed after the patient started a strict ketogenic diet.

Prurigo pigmentosa is a benign, pruritic rash that most commonly presents with erythematous or hyperpigmented, symmetrically distributed urticarial papules and plaques on the chest and back. Females represent approximately 70% of cases with a predominant age range of 11 to 30.¹

While the pathophysiology remains unknown, the rash most often is reported in association with ketogenic diets.¹ Despite occurring in only a fraction of patients on the ketogenic diet, the characteristic presentation has led to the alternative name of the “keto rash” in online nutritional forums and blogs.

The characteristic presentation of prurigo pigmentosa has led to the alternative name of the “keto rash” in online nutritional forums.

Although prurigo pigmentosa is relatively uncommon (with an unknown incidence), primary care physicians may begin to encounter the characteristic rash more frequently, given the number of articles over the past 5 years in the primary care and nutritional literature highlighting the diet’s health benefits.² The ketogenic diet is a high-fat, low-carbohydrate diet with preliminary evidence of improved weight loss, cardiovascular health, and glycemic control suggested by a meta-analysis of 13 randomized controlled trials.³ Additionally, the popular press and general public’s rising interest are likely to increase the number of patients on this diet.

A clinical diagnosis

The diagnosis is made clinically, so the appearance of a symmetric pruritic, hyperpigmented rash on the chest and back should prompt the physician to ask about any recent changes in diet. Laboratory analysis is unnecessary, as a complete blood count, basic metabolic panel, and liver function panel are almost always normal. Urinary ketones are present in only 30% to 50% of patients; there is, however, an absence of blood ketones.^1,4

Continue to: Other conditions can mimic prurigo pigmentosa

Urticaria presents as individual lesions that often have a pale center. The lesions may occur anywhere on the body and generally last less than 24 hours. History may reveal a trigger including drugs, infection, food, or emotional stress in up to 50% of cases.⁵

Irritant contact dermatitis often is associated with a stinging or burning sensation. Irritant and allergic contact dermatitis may have a geometric, or “outside job,” distribution suggestive of external contact, potentially with plants, alkalis, acids, or solvents.⁵

Confluent and reticulated papillomatosis is a rare asymptomatic dermatosis of unknown etiology that presents as hyperpigmented papules on the upper trunk, neck, and axillae. Most patients lack associated pruritis which is in contrast to prurigo pigmentosa.⁶

Pityriasis rosea is a viral exanthem that may be associated with constitutional symptoms and often presents initially with a herald patch progressing to a classic “Christmas tree” distribution with a fine collarette of scale. It often is asymptomatic, although some cases may be pruritic.⁵

Treatment focuses on dietary modification

Primary treatment includes resumption of a normal diet. This often leads to rapid resolution of pruritis. Residual hyperpigmentation may take months to fade.

Continue to: Pharmaceutical intervention may be necessary

If additional treatment is required, minocycline 100 to 200 mg/d has been reported most effective, likely due to its anti-inflammatory properties.^1,4 Topical corticosteroids and oral antihistamines provide symptomatic relief in some patients.^1,4

Our patient had resolution of the pruritis and urticarial lesions within 2 days of resuming a normal diet; however, residual asymptomatic hyperpigmentation persisted. A retrial of the ketogenic diet initiated a flare of the rash in the same distribution. It rapidly resolved with carbohydrate intake.

CORRESPONDENCE
Daniel Croom, MD, 34520 Bob Wilson Dr, Naval Medical Center San Diego, San Diego, CA 92134; daniel.l.croom.mil@mail.mil

A 26-year-old woman presented to our clinic with pruritic, hyperpigmented, symmetric edematous plaques on her upper flank, chest, and lower back (FIGURE) 3 weeks after starting a strict ketogenic (high fat/low carbohydrate) diet for postpartum weight loss. The patient was an otherwise healthy stay-at-home mother with an unremarkable medical history.

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

We recognized that this was a case of prurigo pigmentosa based on the characteristic pruritic rash that had developed after the patient started a strict ketogenic diet.

Prurigo pigmentosa is a benign, pruritic rash that most commonly presents with erythematous or hyperpigmented, symmetrically distributed urticarial papules and plaques on the chest and back. Females represent approximately 70% of cases with a predominant age range of 11 to 30.¹

While the pathophysiology remains unknown, the rash most often is reported in association with ketogenic diets.¹ Despite occurring in only a fraction of patients on the ketogenic diet, the characteristic presentation has led to the alternative name of the “keto rash” in online nutritional forums and blogs.

The characteristic presentation of prurigo pigmentosa has led to the alternative name of the “keto rash” in online nutritional forums.

Although prurigo pigmentosa is relatively uncommon (with an unknown incidence), primary care physicians may begin to encounter the characteristic rash more frequently, given the number of articles over the past 5 years in the primary care and nutritional literature highlighting the diet’s health benefits.² The ketogenic diet is a high-fat, low-carbohydrate diet with preliminary evidence of improved weight loss, cardiovascular health, and glycemic control suggested by a meta-analysis of 13 randomized controlled trials.³ Additionally, the popular press and general public’s rising interest are likely to increase the number of patients on this diet.

A clinical diagnosis

The diagnosis is made clinically, so the appearance of a symmetric pruritic, hyperpigmented rash on the chest and back should prompt the physician to ask about any recent changes in diet. Laboratory analysis is unnecessary, as a complete blood count, basic metabolic panel, and liver function panel are almost always normal. Urinary ketones are present in only 30% to 50% of patients; there is, however, an absence of blood ketones.^1,4

Continue to: Other conditions can mimic prurigo pigmentosa

Urticaria presents as individual lesions that often have a pale center. The lesions may occur anywhere on the body and generally last less than 24 hours. History may reveal a trigger including drugs, infection, food, or emotional stress in up to 50% of cases.⁵

Irritant contact dermatitis often is associated with a stinging or burning sensation. Irritant and allergic contact dermatitis may have a geometric, or “outside job,” distribution suggestive of external contact, potentially with plants, alkalis, acids, or solvents.⁵

Confluent and reticulated papillomatosis is a rare asymptomatic dermatosis of unknown etiology that presents as hyperpigmented papules on the upper trunk, neck, and axillae. Most patients lack associated pruritis which is in contrast to prurigo pigmentosa.⁶

Pityriasis rosea is a viral exanthem that may be associated with constitutional symptoms and often presents initially with a herald patch progressing to a classic “Christmas tree” distribution with a fine collarette of scale. It often is asymptomatic, although some cases may be pruritic.⁵

Treatment focuses on dietary modification

Primary treatment includes resumption of a normal diet. This often leads to rapid resolution of pruritis. Residual hyperpigmentation may take months to fade.

Continue to: Pharmaceutical intervention may be necessary

If additional treatment is required, minocycline 100 to 200 mg/d has been reported most effective, likely due to its anti-inflammatory properties.^1,4 Topical corticosteroids and oral antihistamines provide symptomatic relief in some patients.^1,4

Our patient had resolution of the pruritis and urticarial lesions within 2 days of resuming a normal diet; however, residual asymptomatic hyperpigmentation persisted. A retrial of the ketogenic diet initiated a flare of the rash in the same distribution. It rapidly resolved with carbohydrate intake.

CORRESPONDENCE
Daniel Croom, MD, 34520 Bob Wilson Dr, Naval Medical Center San Diego, San Diego, CA 92134; daniel.l.croom.mil@mail.mil

Juvenile idiopathic arthritis (JIA) is a clinically heterogeneous group of arthritides that are characterized by onset before 16 years of age and defined in part as lasting ≥6 weeks.¹ Significantly, the etiology of JIA is unknown, making it a diagnosis of exclusion.²

The most common autoimmune condition of childhood, JIA has a prevalence of 3.8 to 400 affected children for every 100,000 people.^3,4 As the leading cause of musculoskeletal disability in children,⁵ and comprising 7 categories of disease, JIA must be managed with appropriate initial and ongoing intervention.

The amalgam of care that a JIA patient requires—medical, social, physical, psychological—calls for a primary care physician’s expert ability to collaborate and coordinate with medical specialists and subspecialists, including rheumatology, ophthalmology, social work, physical and occupational therapy, and psychology. The goal? As this article describes, the goal is to provide prompt diagnosis, suitable and effective intervention, and continuity of care. (JIA is a lifelong disease, in many cases.)

How JIA is classifiedfor diagnosis and treatment

JIA comprises 7 categories, or classes.⁶ The scheme devised by the International League of Associations for Rheumatology (ILAR), now widely accepted, classifies JIA on the basis of clinical and biochemical markers that aid detection and treatment of the disorder, as well as research. (See “How efforts to classify JIA have caused confusion.”^7-10) The ILAR classes (TABLE¹¹) are:

• enthesitis-related arthritis (ERA)
• extended oligo-articular JIA (eoJIA), which involves ≤4 joints
• juvenile psoriatic arthritis (jPsA)
• rheumatoid factor (RF)-positive polyarticular JIA (RF+ pJIA)
• RF-negative polyarticular JIA (RF– pJIA)
• systemic-onset JIA (sJIA)
• undifferentiated JIA, which, generally, involves ≥4 joints.

Updated guidelines regarding the 7 ILAR classes of JIA emphasize heterogeneity among disease subtypes, with overlapping and exclusive features noted from class to class.¹¹

Extended oligo-articular JIA (27%-56%), pJIA (13%-35%), sJIA (4%-17%), and ERA,(3%-11%) are the most common JIA subtypes,¹² with age of onset and sex predilection differing according to JIA class.¹¹ The disease occurs more often in girls than in boys,¹¹ and the predisposition is higher among Whites and Asians. The incidence of JIA (all classes taken together, for every 100,000 people) is: in Japan, 10 to 15 cases¹³; in Turkey, 64 cases¹⁴; in Norway, 65 cases¹⁵; and in the United States and Canada, taken together, 10 to 15 cases.¹⁶

What causes JIA?

The etiology of JIA remains unclear. It is known that the disease involves inflammation of the synovium and destruction of hard and soft tissues in joints.¹⁷ It has been postulated, therefore, that a combination of genetic, environmental, and immunogenic mechanisms might be responsible for JIA.

Continue to: For example, there is an increased...

For example, there is an increased frequency of autoimmune diseases among JIA patients.¹⁸ There are also reports documenting an increased rate of infection, including with enteric pathogens, parvovirus B,¹⁹ rubella, mumps, hepatitis B, Epstein-Barr virus, mycoplasma, and chlamydia.¹⁹ Stress and trauma have also been implicated.¹²

The T-lymphocyte percentage is increased in the synovial fluid of JIA patients, although that percentage varies from subtype to subtype.²⁰ This elevation results in an increase in the number of macrophages, which are induced by secreted cytokines to produce interleukin (IL)-1, IL-6, and tumor necrosis factor alpha (TNF-a). This activity of cellular immunity leads to joint destruction.²¹

Clinical features

The most common signs and symptoms of JIA are arthralgias (39%), arthritis (25%), fever (18%), limping (9%), rash (8%), abdominal pain (1.3%), and uveitis (1.3%).¹⁵ Forty percent of JIA patients are reported to have temporomandibular joint involvement at some point in their life; mandibular asymmetry secondary to condylar resorption and remodeling¹⁷ is the most common presenting complaint—not arthralgia or pain, as would be expected.

Most JIA patients (52%) first present to the emergency department; another 42% present to the office of a general medical practitioner.¹⁵ On average, 3 visits to a physician, over the course of approximately 3 months, are made before a definitive diagnosis (usually by a pediatric rheumatologist) is made.¹⁵

Pertinent questions to ask a patient who has a confirmed diagnosis of JIA include the nature, severity, and duration of morning stiffness and pain, as well as any encumbering factors to regular functioning at home or school.²² Different scoring charts can be used to determine the extent of pain and disability, including the Juvenile Arthritis Disease Activity Score (JADAS)²³ and the clinical JADAS (cJADAS),²⁴ which measure minimal disease activity²⁵ and clinically inactive disease²⁶ cutoffs.

Continue to: Macrophage-activating syndrome increases risk of morbidity, mortality

An overactivation and expansion of T lymphocytes and macrophagic histiocytes with hemophagocytic activity, macrophage-activating syndrome (MAS) occurs in approximately 10% of JIA patients,²⁷ increasing their risk of morbidity and mortality. The syndrome, which typically presents as fever, seizures, hypotension, purpura, hepatitis, splenomegaly, and occasionally, multisystem organ failure, is seen in 30% to 40% of sJIA patients; approximately 11% of them experience sudden death as a consequence.²⁸

The clinical setting of MAS includes presenting symptoms of fever and a salmon-pink macular rash (FIGURE). For many sJIA patients with MAS, the diagnosis is made when laboratory results show hyperferritinemia, thrombocytopenia, anemia, leukopenia, coagulopathy, and elevated levels of C-reactive protein and D-dimer.²⁷

Different classes, different features

The following clinical profiles have been documented in different classes of JIA:

Systemic JIA presents with intermittent fever of at least 2 weeks’ duration, arthritis, and occasionally, a rash.

Extended oligo-articular JIA involves pain, in a mono-articular lower-extremity joint, that can develop suddenly or insidiously, and is characterized by early-morning stiffness and uveitis (especially in early-onset, antinuclear antibody-positive JIA patients).

Continue to: Poly-articular JIA

Poly-articular JIA patients present with mild fever, weight loss, and anemia.

Enthesis-related arthritis patients have findings of enthesopathy; asymmetric arthritis of the lower extremities, particularly the Achilles tendon²⁹; and recurrent acute, symptomatic iridocyclitis.³⁰

Juvenile psoriatic arthritis can involve any joint but is readily differentiated from pJIA by involvement of distal interphalangeal joints and psoriatic skin and nail changes.²⁹

Investigations

Imaging

Radiography is still the most widely used imaging tool for making the diagnosis of JIA. Plain films demonstrate structural joint damage and disturbances of growth and maturation in bones. Radiography has poor sensitivity for detecting acute synovitis and limited utility in visualizing erosion changes early in the course of disease, however, which has led to increased use of ultrasonography (US) and contrast-enhanced magnetic resonance imaging (MRI) to diagnose JIA.³⁰

Contrast-enhanced MRI is superior to US for detecting early inflammation and monitoring subsequent joint disease. Of course, MRI is more expensive than US, and less widely available. Other imaging options are computed tomography and positron emission tomography, but these scans are not as sensitive as contrast-enhanced MRI and have the disadvantage of radiation exposure (in the former) and cost (in the latter).

Continue to: Laboratory testing

Mandibular asymmetry secondary to condylar resorption and remodeling is the most common presenting complaint of juvenile idiopathic arthritis—not arthralgia or pain, as you might expect.

No diagnostic tests for JIA exist. Assays of acute-phase reactants, including C-reactive protein, the erythrocyte sedimentation rate, and serum amyloid-A proteins, can be utilized to demonstrate inflammation but not to confirm the diagnosis. For some classes of JIA, various tests, including rheumatoid factor, antinuclear antibody, human leukocyte antigen B-27, and cyclic citrullated peptide antibodies, can be used to confirm a specific class but, again, are not recommended for confirming JIA.⁶

The complete blood count, blood cultures, and tests of uric acid and lactate dehydrogenase can be ordered during treatment to monitor for complications, such as malignancy, infection, MAS, and sepsis.

Treatment is based on disease class

Nonsteroidal anti-inflammatory drugs (NSAIDs) and intra-articular steroids are used in all JIA classes, as an adjunct to class-specific treatment, or as induction agents.³¹ These therapies, although they alleviate acute signs and symptoms, such as pain, inflammation, swelling and joint contractures, are not useful for long-term treatment of JIA because they do not halt disease progression.

Systemic steroids can be utilized in exceptional cases, including chronic uveitis with arthritis or in patients with destructive arthritis and poor prognostic features, including cyclic citrullated peptide antibodies, positive RF, erosions, and joint-space narrowing.³²

Other drugs. Options include traditional disease-modifying anti-rheumatic drugs (csDMARDs), such as methotrexate and leflunomide; biologic agents, such as TNF-a inhibitors (eg, etanercept, adalimumab, and infliximab); and anti-IL monoclonal antibody drugs (eg, the IL-6 inhibitor tocilizumab and IL-1 inhibitors anakinra, and canakinumab).³¹ Indications by class include:

• csDMARDs as first-line therapy in persistent eoJIA and pJIA;
• TNF-Symbolα inhibitors for refractory eoJIA and for pJIA episodes³¹;
• tocilizumab, recommended for sJIA patients who have persistent systemic signs; and
• anakinra and canakinumab for refractory SJIA patients.³²

Continue to: Failure

When treatment of JIA fails with a given drug, options include increasing the dosage; switching to another agent in the same drug class; switching to a different class; and combining an NSAID with a csDMARD or a biologic agent.³² In class-specific JIA cases, a change in a drug regimen is warranted on the basis of the evidence-based historical clinical response rate.³²

What is the prognosis?

Treatment of JIA with novel agents, such as biologics, has opened up the possibility that JIA patients can live not just with suppressed symptoms but immunologically inactive disease. This is the result of better understanding of the pathogenesis of JIA and the mechanism of action of targeted drugs, and identification of biomarkers that are helpful in predicting prognosis, adverse effects, and response to treatment.

On average, it takes 3 visits to a physician, over the course of about 3 months, before definitive diagnosis of JIA is made.

JIA is often a lifelong disease; one-third of patients continue to exhibit symptoms into adulthood.⁴ If their disease is properly managed, however, these patients do not develop typical features of rheumatoid arthritis, including hand, limb, and spine deformities. Last, patients with JIA who have only intermittent disease tend to do better over the long term than those whose disease is continual.³²

The mortality rate of JIA has dropped: from 1% to 4% in the mid-1970s to 0.3% to 1% today⁴—an improvement in life expectancy that is echoed in enhanced quality of life for patients. According to the 4-level Steinbrocker functional classification scale³³ (used to rate the extent of physical disability), 15% of JIA patients were Class III (limited to few or no activities of the patient’s usual occupation) or Class IV (bedridden with little or no self-care) in the period from 1976 to 1994—a percentage that had declined to 5% by 2002.³⁴

The family physician plays pivotal role in JIA care

For the family physician, appropriate initial intervention in the management of JIA is imperative. This includes ordering imaging (whether plain films or MRI), laboratory tests as described earlier (although not to make the diagnosis), and the use of NSAIDs, intra-articular steroids, and other induction agents. Once the diagnosis is made, and a drug regimen is put in place, you will need to monitor for adverse effects. This monitoring will need to occur when a patient is escalated to csDMARDs, biological agents, or systemic steroids; is maintained on an NSAID; or is placed on a combination regimen.

Continue to: Before beginning therapy with a biologic agent...

Before beginning therapy with a biologic agent, it’s important to screen for hepatitis B, hepatitis C, human immunodeficiency virus infection, tuberculosis, and fungal infection (eg, Histoplasma capsulatum, Coccidioides immitis³²). Be sure to make a timely referral to the ophthalmology service for a bi-annual eye exam and, in the event that surgery is necessary, conduct a preoperative evaluation, with the knowledge of how long before surgery a biologic agent must be withheld (duration varies by drug).³²

CORRESPONDENCE
Tobe Momah, MD, Department of Family Medicine, Clinical Science Building, 4th Floor, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216; tmomah@umc.edu.

Juvenile idiopathic arthritis (JIA) is a clinically heterogeneous group of arthritides that are characterized by onset before 16 years of age and defined in part as lasting ≥6 weeks.¹ Significantly, the etiology of JIA is unknown, making it a diagnosis of exclusion.²

The most common autoimmune condition of childhood, JIA has a prevalence of 3.8 to 400 affected children for every 100,000 people.^3,4 As the leading cause of musculoskeletal disability in children,⁵ and comprising 7 categories of disease, JIA must be managed with appropriate initial and ongoing intervention.

The amalgam of care that a JIA patient requires—medical, social, physical, psychological—calls for a primary care physician’s expert ability to collaborate and coordinate with medical specialists and subspecialists, including rheumatology, ophthalmology, social work, physical and occupational therapy, and psychology. The goal? As this article describes, the goal is to provide prompt diagnosis, suitable and effective intervention, and continuity of care. (JIA is a lifelong disease, in many cases.)

How JIA is classifiedfor diagnosis and treatment

JIA comprises 7 categories, or classes.⁶ The scheme devised by the International League of Associations for Rheumatology (ILAR), now widely accepted, classifies JIA on the basis of clinical and biochemical markers that aid detection and treatment of the disorder, as well as research. (See “How efforts to classify JIA have caused confusion.”^7-10) The ILAR classes (TABLE¹¹) are:

• enthesitis-related arthritis (ERA)
• extended oligo-articular JIA (eoJIA), which involves ≤4 joints
• juvenile psoriatic arthritis (jPsA)
• rheumatoid factor (RF)-positive polyarticular JIA (RF+ pJIA)
• RF-negative polyarticular JIA (RF– pJIA)
• systemic-onset JIA (sJIA)
• undifferentiated JIA, which, generally, involves ≥4 joints.

Updated guidelines regarding the 7 ILAR classes of JIA emphasize heterogeneity among disease subtypes, with overlapping and exclusive features noted from class to class.¹¹

Extended oligo-articular JIA (27%-56%), pJIA (13%-35%), sJIA (4%-17%), and ERA,(3%-11%) are the most common JIA subtypes,¹² with age of onset and sex predilection differing according to JIA class.¹¹ The disease occurs more often in girls than in boys,¹¹ and the predisposition is higher among Whites and Asians. The incidence of JIA (all classes taken together, for every 100,000 people) is: in Japan, 10 to 15 cases¹³; in Turkey, 64 cases¹⁴; in Norway, 65 cases¹⁵; and in the United States and Canada, taken together, 10 to 15 cases.¹⁶