Dermatology

Continued use of tumor necrosis factor inhibitors or methotrexate is acceptable in most patients who acquire COVID-19, results of a recent cohort study suggest.

Among patients on tumor necrosis factor inhibitors (TNFi) or methotrexate who developed COVID-19, death and hospitalization rates were similar to matched COVID-19 patients not on those medications, according to authors of the multicenter research network study.

Reassuringly, likelihood of hospitalization and mortality were not significantly different between 214 patients with COVID-19 taking TNFi or methotrexate and 31,862 matched COVID-19 patients not on those medications, according to the investigators, whose findings were published recently in the Journal of the American Academy of Dermatology.

Zachary Zinn, MD, corresponding author on the study, said in an interview that the findings suggest these medicines can be safely continued in the majority of patients taking them during the COVID-19 pandemic.

“If you’re a prescribing physician who’s giving patients TNF inhibitors or methotrexate or both, I think you can comfortably tell your patients there is good data that these do not lead to worse outcomes if you get COVID-19,” said Dr. Zinn, associate professor in the department of dermatology at West Virginia University, Morgantown.

The findings from these researchers corroborate a growing body of evidence suggesting that immunosuppressive treatments can be continued in patients with dermatologic and rheumatic conditions.

In recent guidance from the National Psoriasis Foundation, released Sept. 4, an expert consensus panel cited 15 studies that they said suggested that treatments for psoriasis or psoriatic arthritis “do not meaningfully alter the risk of acquiring SARS-CoV-2 infection or having worse COVID-19 outcomes.”

That said, the data to date are mainly from small case series and registry studies based on spontaneously reported COVID-19 cases, which suggests a continued need for shared decision making. In addition, chronic systemic corticosteroids should be avoided for management of psoriatic arthritis, the guidance states, based on rheumatology and gastroenterology literature suggesting this treatment is linked to worse COVID-19 outcomes.

In the interview, Dr. Zinn noted that some previous studies of immunosuppressive treatments in patients who acquire COVID-19 have aggregated data on numerous classes of biologic medications, lessening the strength of data for each specific medication.

“By focusing specifically on TNF inhibitors and methotrexate, this study gives better guidance to prescribers of these medications,” he said.

To see whether TNFi or methotrexate increased risk of worsened COVID-19 outcomes, Dr. Zinn and coinvestigators evaluated data from TriNetX, a research network that includes approximately 53 million unique patient records, predominantly in the United States.

They identified 32,076 adult patients with COVID-19, of whom 214 had recent exposure to TNFi or methotrexate. The patients in the TNFi/methotrexate group were similar in age to those without exposure to those drugs, at 55.1 versus 53.2 years, respectively. However, patients in the drug exposure group were more frequently White, female, and had substantially more comorbidities, including diabetes and obesity, according to the investigators.

Nevertheless, the likelihood of hospitalization was not statistically different in the TNFi/methotrexate group versus the non-TNFi/methotrexate group, with a risk ratio of 0.91 (95% confidence interval, 0.68-1.22; P = .5260).

Likewise, the likelihood of death was not different between groups, with a RR of 0.87 (95% CI, 0.42-1.78; P = .6958). Looking at subgroups of patients exposed to TNFi or methotrexate only didn’t change the results, the investigators added.

Taken together, the findings argue against interruption of these treatments because of the fear of the possibly worse COVID-19 outcomes, the investigators concluded, although they emphasized the need for more research.

“Because the COVID-19 pandemic is ongoing, there is a desperate need for evidence-based data on biologic and immunomodulator exposure in the setting of COVID-19 infection,” they wrote.

Dr. Zinn and coauthors reported no conflicts of interest and no funding sources related to the study.

SOURCE: Zinn Z et al. J Am Acad Dermatol. 2020 Sep 11. doi: 10.1016/j.jaad.2020.09.009.

Continued use of tumor necrosis factor inhibitors or methotrexate is acceptable in most patients who acquire COVID-19, results of a recent cohort study suggest.

Among patients on tumor necrosis factor inhibitors (TNFi) or methotrexate who developed COVID-19, death and hospitalization rates were similar to matched COVID-19 patients not on those medications, according to authors of the multicenter research network study.

Reassuringly, likelihood of hospitalization and mortality were not significantly different between 214 patients with COVID-19 taking TNFi or methotrexate and 31,862 matched COVID-19 patients not on those medications, according to the investigators, whose findings were published recently in the Journal of the American Academy of Dermatology.

Zachary Zinn, MD, corresponding author on the study, said in an interview that the findings suggest these medicines can be safely continued in the majority of patients taking them during the COVID-19 pandemic.

“If you’re a prescribing physician who’s giving patients TNF inhibitors or methotrexate or both, I think you can comfortably tell your patients there is good data that these do not lead to worse outcomes if you get COVID-19,” said Dr. Zinn, associate professor in the department of dermatology at West Virginia University, Morgantown.

The findings from these researchers corroborate a growing body of evidence suggesting that immunosuppressive treatments can be continued in patients with dermatologic and rheumatic conditions.

In recent guidance from the National Psoriasis Foundation, released Sept. 4, an expert consensus panel cited 15 studies that they said suggested that treatments for psoriasis or psoriatic arthritis “do not meaningfully alter the risk of acquiring SARS-CoV-2 infection or having worse COVID-19 outcomes.”

That said, the data to date are mainly from small case series and registry studies based on spontaneously reported COVID-19 cases, which suggests a continued need for shared decision making. In addition, chronic systemic corticosteroids should be avoided for management of psoriatic arthritis, the guidance states, based on rheumatology and gastroenterology literature suggesting this treatment is linked to worse COVID-19 outcomes.

In the interview, Dr. Zinn noted that some previous studies of immunosuppressive treatments in patients who acquire COVID-19 have aggregated data on numerous classes of biologic medications, lessening the strength of data for each specific medication.

“By focusing specifically on TNF inhibitors and methotrexate, this study gives better guidance to prescribers of these medications,” he said.

To see whether TNFi or methotrexate increased risk of worsened COVID-19 outcomes, Dr. Zinn and coinvestigators evaluated data from TriNetX, a research network that includes approximately 53 million unique patient records, predominantly in the United States.

They identified 32,076 adult patients with COVID-19, of whom 214 had recent exposure to TNFi or methotrexate. The patients in the TNFi/methotrexate group were similar in age to those without exposure to those drugs, at 55.1 versus 53.2 years, respectively. However, patients in the drug exposure group were more frequently White, female, and had substantially more comorbidities, including diabetes and obesity, according to the investigators.

Nevertheless, the likelihood of hospitalization was not statistically different in the TNFi/methotrexate group versus the non-TNFi/methotrexate group, with a risk ratio of 0.91 (95% confidence interval, 0.68-1.22; P = .5260).

Likewise, the likelihood of death was not different between groups, with a RR of 0.87 (95% CI, 0.42-1.78; P = .6958). Looking at subgroups of patients exposed to TNFi or methotrexate only didn’t change the results, the investigators added.

Taken together, the findings argue against interruption of these treatments because of the fear of the possibly worse COVID-19 outcomes, the investigators concluded, although they emphasized the need for more research.

“Because the COVID-19 pandemic is ongoing, there is a desperate need for evidence-based data on biologic and immunomodulator exposure in the setting of COVID-19 infection,” they wrote.

Dr. Zinn and coauthors reported no conflicts of interest and no funding sources related to the study.

SOURCE: Zinn Z et al. J Am Acad Dermatol. 2020 Sep 11. doi: 10.1016/j.jaad.2020.09.009.

Continued use of tumor necrosis factor inhibitors or methotrexate is acceptable in most patients who acquire COVID-19, results of a recent cohort study suggest.

Among patients on tumor necrosis factor inhibitors (TNFi) or methotrexate who developed COVID-19, death and hospitalization rates were similar to matched COVID-19 patients not on those medications, according to authors of the multicenter research network study.

Reassuringly, likelihood of hospitalization and mortality were not significantly different between 214 patients with COVID-19 taking TNFi or methotrexate and 31,862 matched COVID-19 patients not on those medications, according to the investigators, whose findings were published recently in the Journal of the American Academy of Dermatology.

Zachary Zinn, MD, corresponding author on the study, said in an interview that the findings suggest these medicines can be safely continued in the majority of patients taking them during the COVID-19 pandemic.

“If you’re a prescribing physician who’s giving patients TNF inhibitors or methotrexate or both, I think you can comfortably tell your patients there is good data that these do not lead to worse outcomes if you get COVID-19,” said Dr. Zinn, associate professor in the department of dermatology at West Virginia University, Morgantown.

The findings from these researchers corroborate a growing body of evidence suggesting that immunosuppressive treatments can be continued in patients with dermatologic and rheumatic conditions.

In recent guidance from the National Psoriasis Foundation, released Sept. 4, an expert consensus panel cited 15 studies that they said suggested that treatments for psoriasis or psoriatic arthritis “do not meaningfully alter the risk of acquiring SARS-CoV-2 infection or having worse COVID-19 outcomes.”

That said, the data to date are mainly from small case series and registry studies based on spontaneously reported COVID-19 cases, which suggests a continued need for shared decision making. In addition, chronic systemic corticosteroids should be avoided for management of psoriatic arthritis, the guidance states, based on rheumatology and gastroenterology literature suggesting this treatment is linked to worse COVID-19 outcomes.

In the interview, Dr. Zinn noted that some previous studies of immunosuppressive treatments in patients who acquire COVID-19 have aggregated data on numerous classes of biologic medications, lessening the strength of data for each specific medication.

“By focusing specifically on TNF inhibitors and methotrexate, this study gives better guidance to prescribers of these medications,” he said.

To see whether TNFi or methotrexate increased risk of worsened COVID-19 outcomes, Dr. Zinn and coinvestigators evaluated data from TriNetX, a research network that includes approximately 53 million unique patient records, predominantly in the United States.

They identified 32,076 adult patients with COVID-19, of whom 214 had recent exposure to TNFi or methotrexate. The patients in the TNFi/methotrexate group were similar in age to those without exposure to those drugs, at 55.1 versus 53.2 years, respectively. However, patients in the drug exposure group were more frequently White, female, and had substantially more comorbidities, including diabetes and obesity, according to the investigators.

Nevertheless, the likelihood of hospitalization was not statistically different in the TNFi/methotrexate group versus the non-TNFi/methotrexate group, with a risk ratio of 0.91 (95% confidence interval, 0.68-1.22; P = .5260).

Likewise, the likelihood of death was not different between groups, with a RR of 0.87 (95% CI, 0.42-1.78; P = .6958). Looking at subgroups of patients exposed to TNFi or methotrexate only didn’t change the results, the investigators added.

Taken together, the findings argue against interruption of these treatments because of the fear of the possibly worse COVID-19 outcomes, the investigators concluded, although they emphasized the need for more research.

“Because the COVID-19 pandemic is ongoing, there is a desperate need for evidence-based data on biologic and immunomodulator exposure in the setting of COVID-19 infection,” they wrote.

Dr. Zinn and coauthors reported no conflicts of interest and no funding sources related to the study.

SOURCE: Zinn Z et al. J Am Acad Dermatol. 2020 Sep 11. doi: 10.1016/j.jaad.2020.09.009.

Aquagenic wrinkling of the palms (AWP) is a condition characterized by excessive wrinkling and sudden appearance or aggravation of white papules and plaques localized to the palms upon exposure to water. This eruption can be accompanied by a mild burning or tingling sensation, which will subside with the rest of the symptoms in minutes to hours after drying.¹

AWP is most frequently associated with cystic fibrosis (CF).² It can be observed in up to 80% of CF patients and is considered a clinical sign of the disease. AWP can be present in CF carriers to a lesser extent,^2,4 and has also been associated with focal hyperhidrosis, atopic dermatitis, Raynaud phenomenon, and COX-2 inhibitor use.⁵

While a definitive cause is unknown, it is thought that AWP is caused by dysregulation of sweat glands in the palms through increased expression of aquaporin, a protein crucial in the transport of water between cells.³

AWP is quite rare and benign in nature. However, because of its strong association with CF, genetic screening should be considered in asymptomatic patients. Our patient had been screened in the past and is not a CF carrier. Often, the itching or burning associated with CF is mild and easily controlled. The patient was placed on low dose isotretinoin for treatment of her acne. Interestingly, the patient claimed her eruption no longer appeared after starting isotretinoin therapy. To our knowledge, this is the first reported case of AWP resolving with isotretinoin use.

This case and photo were submitted by Mr. Birk, University of Texas, Austin, Texas; and Dr. Mamelak, Sanova Dermatology, in Austin. Donna Bilu Martin, MD, edited the column.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at MDedge.com/Dermatology. To submit a case for possible publication, send an email to [email protected].

References

1. Katz M, Ramot Y. CMAJ. 2015 Dec 8;187(18):E515.

2. Tolland JP et al. Dermatology. 2010;221(4):326-30.

3. Kabashima K et al. J Am Acad Dermatol. 2008 Aug;59(2 Suppl 1):S28-32.

4. Gild R et al. Br J Dermatol. 2010 Nov;163(5):1082-4.

5. Glatz M and Muellegger RR. BMJ Case Rep. 2014. doi: 10.1136/bcr-2014-203929.

Aquagenic wrinkling of the palms (AWP) is a condition characterized by excessive wrinkling and sudden appearance or aggravation of white papules and plaques localized to the palms upon exposure to water. This eruption can be accompanied by a mild burning or tingling sensation, which will subside with the rest of the symptoms in minutes to hours after drying.¹

AWP is most frequently associated with cystic fibrosis (CF).² It can be observed in up to 80% of CF patients and is considered a clinical sign of the disease. AWP can be present in CF carriers to a lesser extent,^2,4 and has also been associated with focal hyperhidrosis, atopic dermatitis, Raynaud phenomenon, and COX-2 inhibitor use.⁵

While a definitive cause is unknown, it is thought that AWP is caused by dysregulation of sweat glands in the palms through increased expression of aquaporin, a protein crucial in the transport of water between cells.³

AWP is quite rare and benign in nature. However, because of its strong association with CF, genetic screening should be considered in asymptomatic patients. Our patient had been screened in the past and is not a CF carrier. Often, the itching or burning associated with CF is mild and easily controlled. The patient was placed on low dose isotretinoin for treatment of her acne. Interestingly, the patient claimed her eruption no longer appeared after starting isotretinoin therapy. To our knowledge, this is the first reported case of AWP resolving with isotretinoin use.

This case and photo were submitted by Mr. Birk, University of Texas, Austin, Texas; and Dr. Mamelak, Sanova Dermatology, in Austin. Donna Bilu Martin, MD, edited the column.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at MDedge.com/Dermatology. To submit a case for possible publication, send an email to [email protected].

References

1. Katz M, Ramot Y. CMAJ. 2015 Dec 8;187(18):E515.

2. Tolland JP et al. Dermatology. 2010;221(4):326-30.

3. Kabashima K et al. J Am Acad Dermatol. 2008 Aug;59(2 Suppl 1):S28-32.

4. Gild R et al. Br J Dermatol. 2010 Nov;163(5):1082-4.

5. Glatz M and Muellegger RR. BMJ Case Rep. 2014. doi: 10.1136/bcr-2014-203929.

Aquagenic wrinkling of the palms (AWP) is a condition characterized by excessive wrinkling and sudden appearance or aggravation of white papules and plaques localized to the palms upon exposure to water. This eruption can be accompanied by a mild burning or tingling sensation, which will subside with the rest of the symptoms in minutes to hours after drying.¹

AWP is most frequently associated with cystic fibrosis (CF).² It can be observed in up to 80% of CF patients and is considered a clinical sign of the disease. AWP can be present in CF carriers to a lesser extent,^2,4 and has also been associated with focal hyperhidrosis, atopic dermatitis, Raynaud phenomenon, and COX-2 inhibitor use.⁵

While a definitive cause is unknown, it is thought that AWP is caused by dysregulation of sweat glands in the palms through increased expression of aquaporin, a protein crucial in the transport of water between cells.³

AWP is quite rare and benign in nature. However, because of its strong association with CF, genetic screening should be considered in asymptomatic patients. Our patient had been screened in the past and is not a CF carrier. Often, the itching or burning associated with CF is mild and easily controlled. The patient was placed on low dose isotretinoin for treatment of her acne. Interestingly, the patient claimed her eruption no longer appeared after starting isotretinoin therapy. To our knowledge, this is the first reported case of AWP resolving with isotretinoin use.

This case and photo were submitted by Mr. Birk, University of Texas, Austin, Texas; and Dr. Mamelak, Sanova Dermatology, in Austin. Donna Bilu Martin, MD, edited the column.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at MDedge.com/Dermatology. To submit a case for possible publication, send an email to [email protected].

References

1. Katz M, Ramot Y. CMAJ. 2015 Dec 8;187(18):E515.

2. Tolland JP et al. Dermatology. 2010;221(4):326-30.

3. Kabashima K et al. J Am Acad Dermatol. 2008 Aug;59(2 Suppl 1):S28-32.

4. Gild R et al. Br J Dermatol. 2010 Nov;163(5):1082-4.

5. Glatz M and Muellegger RR. BMJ Case Rep. 2014. doi: 10.1136/bcr-2014-203929.

The constellation of symptoms was suggestive of Lyme disease, although connective tissue disease and syphilis were also considered. Two punch biopsies were performed in the office, and erythrocyte sedimentation rate (ESR), complete blood cell count (CBC), international normalized ratio (INR), comprehensive metabolic panel (CMP), Lyme enzyme-linked immunosorbent assay (ELISA) antibody panel, and rapid plasma reagin (RPR) laboratory tests were ordered.

Immediately available laboratory results included ESR, CBC, INR, and CMP. Findings were notable for elevated INR, as well as elevated alanine aminotransferase and aspartate transaminase. The transaminitis suggested myopathy and was consistent with clinical muscle weakness. RPR testing was negative.

Because of the confusion, severity of muscle weakness, and plausibility of early encephalopathy with Lyme disease, the patient was admitted to the hospital for further work-up. Lumbar puncture was delayed until his INR was reduced, but subsequently was found to be normal. He received intravenous (IV) ceftriaxone (2 g/d) empirically for possible early disseminated disease with neurologic complications. His confusion, muscle weakness, and transaminitis rapidly improved.

His Lyme antibody panel was positive for IgM after his third day of hospitalization. A reflexive confirmatory western blot for IgG was not positive on the initial set of labs but was positive when redrawn 4 weeks after this hospitalization, confirming Lyme disease.

Lyme disease is a vector-borne disease caused by the Borrelia genus of spirochete bacteria, most commonly Borrelia burgdorferi in North America. Transmission occurs through prolonged (typically 36-48 hours) attachment of a blacklegged tick.

The disease can be divided into 3 stages:

• localized (3-30 days): erythema migrans rash and flulike illness
• early disseminated (days to weeks; seen in this patient): multiple erythema migrans rashes, early neuroborreliosis, arthritis, carditis, and rarely hepatitis and uveitis
• late disseminated (months to years): chronic Lyme arthritis, chronic neurological disorders (eg, encephalopathy, radicular pain, and chronic neuropathy).

The initial erythema migrans rash is classically red and targetoid; it expands from the site of attachment. Early disseminated patches tend to be smaller and can occur on any body part. The rash is rarely itchy or painful but may be warm to the touch or sensitive. The rash resolves spontaneously within 3 to 4 weeks of onset.

Treatment of all early and early disseminated Lyme disease typically involves a 14- to 28-day course of doxycycline (100 mg bid for adults, 2.2 mg/kg bid [maximum 100 mg bid] for children). Patients with acute neurologic disease often can be treated with doxycycline, but patients who cannot tolerate doxycycline and those with parenchymal disease such as encephalitis should receive IV therapy with ceftriaxone 2 g/d.

In this case, the patient was discharged home on a 3-week course of doxycycline 100 mg bid and cleared without further symptoms.

‌

Text courtesy of Tristan Reynolds, DO, Maine Dartmouth Family Medicine Residency, and Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

The constellation of symptoms was suggestive of Lyme disease, although connective tissue disease and syphilis were also considered. Two punch biopsies were performed in the office, and erythrocyte sedimentation rate (ESR), complete blood cell count (CBC), international normalized ratio (INR), comprehensive metabolic panel (CMP), Lyme enzyme-linked immunosorbent assay (ELISA) antibody panel, and rapid plasma reagin (RPR) laboratory tests were ordered.

Immediately available laboratory results included ESR, CBC, INR, and CMP. Findings were notable for elevated INR, as well as elevated alanine aminotransferase and aspartate transaminase. The transaminitis suggested myopathy and was consistent with clinical muscle weakness. RPR testing was negative.

Because of the confusion, severity of muscle weakness, and plausibility of early encephalopathy with Lyme disease, the patient was admitted to the hospital for further work-up. Lumbar puncture was delayed until his INR was reduced, but subsequently was found to be normal. He received intravenous (IV) ceftriaxone (2 g/d) empirically for possible early disseminated disease with neurologic complications. His confusion, muscle weakness, and transaminitis rapidly improved.

His Lyme antibody panel was positive for IgM after his third day of hospitalization. A reflexive confirmatory western blot for IgG was not positive on the initial set of labs but was positive when redrawn 4 weeks after this hospitalization, confirming Lyme disease.

Lyme disease is a vector-borne disease caused by the Borrelia genus of spirochete bacteria, most commonly Borrelia burgdorferi in North America. Transmission occurs through prolonged (typically 36-48 hours) attachment of a blacklegged tick.

The disease can be divided into 3 stages:

• localized (3-30 days): erythema migrans rash and flulike illness
• early disseminated (days to weeks; seen in this patient): multiple erythema migrans rashes, early neuroborreliosis, arthritis, carditis, and rarely hepatitis and uveitis
• late disseminated (months to years): chronic Lyme arthritis, chronic neurological disorders (eg, encephalopathy, radicular pain, and chronic neuropathy).

The initial erythema migrans rash is classically red and targetoid; it expands from the site of attachment. Early disseminated patches tend to be smaller and can occur on any body part. The rash is rarely itchy or painful but may be warm to the touch or sensitive. The rash resolves spontaneously within 3 to 4 weeks of onset.

Treatment of all early and early disseminated Lyme disease typically involves a 14- to 28-day course of doxycycline (100 mg bid for adults, 2.2 mg/kg bid [maximum 100 mg bid] for children). Patients with acute neurologic disease often can be treated with doxycycline, but patients who cannot tolerate doxycycline and those with parenchymal disease such as encephalitis should receive IV therapy with ceftriaxone 2 g/d.

In this case, the patient was discharged home on a 3-week course of doxycycline 100 mg bid and cleared without further symptoms.

‌

Text courtesy of Tristan Reynolds, DO, Maine Dartmouth Family Medicine Residency, and Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

The constellation of symptoms was suggestive of Lyme disease, although connective tissue disease and syphilis were also considered. Two punch biopsies were performed in the office, and erythrocyte sedimentation rate (ESR), complete blood cell count (CBC), international normalized ratio (INR), comprehensive metabolic panel (CMP), Lyme enzyme-linked immunosorbent assay (ELISA) antibody panel, and rapid plasma reagin (RPR) laboratory tests were ordered.

Immediately available laboratory results included ESR, CBC, INR, and CMP. Findings were notable for elevated INR, as well as elevated alanine aminotransferase and aspartate transaminase. The transaminitis suggested myopathy and was consistent with clinical muscle weakness. RPR testing was negative.

Because of the confusion, severity of muscle weakness, and plausibility of early encephalopathy with Lyme disease, the patient was admitted to the hospital for further work-up. Lumbar puncture was delayed until his INR was reduced, but subsequently was found to be normal. He received intravenous (IV) ceftriaxone (2 g/d) empirically for possible early disseminated disease with neurologic complications. His confusion, muscle weakness, and transaminitis rapidly improved.

His Lyme antibody panel was positive for IgM after his third day of hospitalization. A reflexive confirmatory western blot for IgG was not positive on the initial set of labs but was positive when redrawn 4 weeks after this hospitalization, confirming Lyme disease.

Lyme disease is a vector-borne disease caused by the Borrelia genus of spirochete bacteria, most commonly Borrelia burgdorferi in North America. Transmission occurs through prolonged (typically 36-48 hours) attachment of a blacklegged tick.

The disease can be divided into 3 stages:

• localized (3-30 days): erythema migrans rash and flulike illness
• early disseminated (days to weeks; seen in this patient): multiple erythema migrans rashes, early neuroborreliosis, arthritis, carditis, and rarely hepatitis and uveitis
• late disseminated (months to years): chronic Lyme arthritis, chronic neurological disorders (eg, encephalopathy, radicular pain, and chronic neuropathy).

The initial erythema migrans rash is classically red and targetoid; it expands from the site of attachment. Early disseminated patches tend to be smaller and can occur on any body part. The rash is rarely itchy or painful but may be warm to the touch or sensitive. The rash resolves spontaneously within 3 to 4 weeks of onset.

Treatment of all early and early disseminated Lyme disease typically involves a 14- to 28-day course of doxycycline (100 mg bid for adults, 2.2 mg/kg bid [maximum 100 mg bid] for children). Patients with acute neurologic disease often can be treated with doxycycline, but patients who cannot tolerate doxycycline and those with parenchymal disease such as encephalitis should receive IV therapy with ceftriaxone 2 g/d.

In this case, the patient was discharged home on a 3-week course of doxycycline 100 mg bid and cleared without further symptoms.

‌

Text courtesy of Tristan Reynolds, DO, Maine Dartmouth Family Medicine Residency, and Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

A 15-year-old girl was brought to the Family Medicine Clinic in Somaliland, Africa, for evaluation of intermittent abdominal pain and watery diarrhea of 12 years’ duration. Over the previous 2 months, her symptoms had worsened and included vomiting and weight loss. She denied fever, melena, or hematemesis.

Physical examination revealed a thin female with a normal abdominal exam and numerous hyperpigmented macules on the lips, buccal mucosa, fingers, and toes (FIGURE 1). Her family reported that the black spots on her lips had been there since birth. There was no known family history of similar symptoms or black spots.

Her hemoglobin was 10 g/dL (reference range, 12–15 g/dL). A probable diagnosis was discussed with the family, and they elected to travel to India for further evaluation due to limited diagnostic resources in their location. In India, computed tomography (CT) and ultrasonography showed duodenojejunal intussusception. Upper gastrointestinal (GI) endoscopy revealed multiple polyps from the lower stomach to the jejunum of the small bowel; colonoscopy was normal.

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

Our patient was given a diagnosis of Peutz-Jeghers syndrome (PJS) based on the characteristic pigmented mucocutaneous macules and numerous polyps in the stomach and small bowel. PJS is an autosomal dominant syndrome characterized by mucocutaneous pigmentation, polyposis of the GI tract, and increased cancer risk. The prevalence is approximately 1 in 100,000.¹ Genetic testing for the STK11 gene mutation, which is found in 70% of familial cases and 30% to 67% of sporadic cases, is not required for diagnosis.¹

What you’ll see. The bluish brown to black spots of PJS often are apparent at birth or in early infancy. They are most common on the lips, buccal mucosa, perioral region, palms, and soles.

When PeutzJeghers syndrome is suspected, the entire GI tract should be investigated.

The polyps may cause bleeding, anemia, and abdominal pain due to intussusception, obstruction, or infarction.² Intussusception is the most frequent cause of morbidity in childhood for PJS patients.^3,4 Recurrent attacks of abdominal pain likely result from recurring transient episodes of incomplete intussusception. The polyps usually are benign, but patients are at increased risk of GI and non-GI malignancies such as breast, pancreas, lung, and reproductive tract cancers.¹ Most cancers associated with PJS occur during adulthood.²

Other possible causes of hyperpigmentation

PJS can be differentiated from other causes of hyperpigmentation by clinical presentation and/or genetic testing.

Laugier-Hunziker syndrome manifests with macular hyperpigmentation of the lips and buccal mucosa and pigmented bands on the nails in young or middle-aged adults. It is not associated with intestinal polyps.

Continue to: Cronkhite-Canada syndrome

Cronkhite-Canada syndrome consists of acral and oral pigmented macules and GI polyps as well as generalized darkening of the skin, extensive alopecia, loss of taste, and nail dystrophy.

Familial lentiginosis syndromes such as Noonan syndrome and NAME syndrome (nevi, atrial myxoma, myxoid neurofibroma, ephelides) have other systemic signs such as cardiac abnormalities, and the pigmentation is not as clearly perioral.

Albright syndrome manifests with oral pigmented macules but also is associated with precocious puberty and polyostotic fibrous dysplasia.

Addison disease may cause multiple hyperpigmented macules but has other systemic involvement; adrenocorticotropic hormone levels are elevated.

Juvenile polyposis syndrome manifests with GI polyps but is not associated with mucosal pigmentation.

Continue to: Use these 4 criteria to make the diagnosis

Use these 4 criteria to make the diagnosis

The diagnosis of PJS is made using the following criteria: (1) two or more histologically confirmed PJS polyps, (2) any number of PJS polyps and a family history of PJS, (3) characteristic mucocutaneous pigmentation and a family history of PJS, or (4) any number of PJS polyps and characteristic mucocutaneous pigmentation.²

When PJS is suspected, the entire GI tract should be investigated. The hamartomatous polyps may be found from the stomach to the anal canal, but the small bowel most commonly is involved. The polyps may occur in early childhood, with one study of 14 children reporting a median age of 4.5 years.⁵ Polyp biopsy will show smooth muscle arborization. When possible, those who meet clinical criteria for PJS should undergo genetic testing for a STK11 gene mutation. PJS may occur due to de novo mutations in patients with no family history.⁶

Long-term management involves surveillance for polyps and cancer

Screening guidelines for polyps vary. Some suggest starting screening at age 8 to 10 years with esophagogastroduodenoscopy or capsule endoscopy and if negative, colonoscopy at age 18. Others suggest starting screening at 4 to 5 years of age.⁵ The recommendation is to remove polyps if technically feasible.³ Surveillance for Sertoli cell tumors (sex cord stromal tumors) should be done before puberty, and evaluation of other organs at risk of malignancy should begin by the end of adolescence.

The pigmented macules do not require treatment. Macules on the lips may disappear with time, while those on the buccal mucosa persist. The lip lesions can be lightened with chemical peels or laser.

Our patient underwent laparotomy, which revealed a grossly dilated and gangrenous small bowel segment. Intussusception was not present and was thought to have spontaneously reduced. Resection and anastomosis of the affected small bowel was performed. The patient’s postoperative course was uneventful, and her diarrhea and abdominal pain resolved. We recommended follow-up in her home city with primary care and a GI specialist and explained the need for surveillance of her condition.

CORRESPONDENCE
Josette R. McMichael, MD, Department of Dermatology, Emory University, 1525 Clifton Road NE, 1st Floor, Atlanta, GA 30322; [email protected]

A 15-year-old girl was brought to the Family Medicine Clinic in Somaliland, Africa, for evaluation of intermittent abdominal pain and watery diarrhea of 12 years’ duration. Over the previous 2 months, her symptoms had worsened and included vomiting and weight loss. She denied fever, melena, or hematemesis.

Physical examination revealed a thin female with a normal abdominal exam and numerous hyperpigmented macules on the lips, buccal mucosa, fingers, and toes (FIGURE 1). Her family reported that the black spots on her lips had been there since birth. There was no known family history of similar symptoms or black spots.

Her hemoglobin was 10 g/dL (reference range, 12–15 g/dL). A probable diagnosis was discussed with the family, and they elected to travel to India for further evaluation due to limited diagnostic resources in their location. In India, computed tomography (CT) and ultrasonography showed duodenojejunal intussusception. Upper gastrointestinal (GI) endoscopy revealed multiple polyps from the lower stomach to the jejunum of the small bowel; colonoscopy was normal.

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

Our patient was given a diagnosis of Peutz-Jeghers syndrome (PJS) based on the characteristic pigmented mucocutaneous macules and numerous polyps in the stomach and small bowel. PJS is an autosomal dominant syndrome characterized by mucocutaneous pigmentation, polyposis of the GI tract, and increased cancer risk. The prevalence is approximately 1 in 100,000.¹ Genetic testing for the STK11 gene mutation, which is found in 70% of familial cases and 30% to 67% of sporadic cases, is not required for diagnosis.¹

What you’ll see. The bluish brown to black spots of PJS often are apparent at birth or in early infancy. They are most common on the lips, buccal mucosa, perioral region, palms, and soles.

When PeutzJeghers syndrome is suspected, the entire GI tract should be investigated.

The polyps may cause bleeding, anemia, and abdominal pain due to intussusception, obstruction, or infarction.² Intussusception is the most frequent cause of morbidity in childhood for PJS patients.^3,4 Recurrent attacks of abdominal pain likely result from recurring transient episodes of incomplete intussusception. The polyps usually are benign, but patients are at increased risk of GI and non-GI malignancies such as breast, pancreas, lung, and reproductive tract cancers.¹ Most cancers associated with PJS occur during adulthood.²

Other possible causes of hyperpigmentation

PJS can be differentiated from other causes of hyperpigmentation by clinical presentation and/or genetic testing.

Laugier-Hunziker syndrome manifests with macular hyperpigmentation of the lips and buccal mucosa and pigmented bands on the nails in young or middle-aged adults. It is not associated with intestinal polyps.

Continue to: Cronkhite-Canada syndrome

Cronkhite-Canada syndrome consists of acral and oral pigmented macules and GI polyps as well as generalized darkening of the skin, extensive alopecia, loss of taste, and nail dystrophy.

Familial lentiginosis syndromes such as Noonan syndrome and NAME syndrome (nevi, atrial myxoma, myxoid neurofibroma, ephelides) have other systemic signs such as cardiac abnormalities, and the pigmentation is not as clearly perioral.

Albright syndrome manifests with oral pigmented macules but also is associated with precocious puberty and polyostotic fibrous dysplasia.

Addison disease may cause multiple hyperpigmented macules but has other systemic involvement; adrenocorticotropic hormone levels are elevated.

Juvenile polyposis syndrome manifests with GI polyps but is not associated with mucosal pigmentation.

Continue to: Use these 4 criteria to make the diagnosis

Use these 4 criteria to make the diagnosis

The diagnosis of PJS is made using the following criteria: (1) two or more histologically confirmed PJS polyps, (2) any number of PJS polyps and a family history of PJS, (3) characteristic mucocutaneous pigmentation and a family history of PJS, or (4) any number of PJS polyps and characteristic mucocutaneous pigmentation.²

When PJS is suspected, the entire GI tract should be investigated. The hamartomatous polyps may be found from the stomach to the anal canal, but the small bowel most commonly is involved. The polyps may occur in early childhood, with one study of 14 children reporting a median age of 4.5 years.⁵ Polyp biopsy will show smooth muscle arborization. When possible, those who meet clinical criteria for PJS should undergo genetic testing for a STK11 gene mutation. PJS may occur due to de novo mutations in patients with no family history.⁶

Long-term management involves surveillance for polyps and cancer

Screening guidelines for polyps vary. Some suggest starting screening at age 8 to 10 years with esophagogastroduodenoscopy or capsule endoscopy and if negative, colonoscopy at age 18. Others suggest starting screening at 4 to 5 years of age.⁵ The recommendation is to remove polyps if technically feasible.³ Surveillance for Sertoli cell tumors (sex cord stromal tumors) should be done before puberty, and evaluation of other organs at risk of malignancy should begin by the end of adolescence.

The pigmented macules do not require treatment. Macules on the lips may disappear with time, while those on the buccal mucosa persist. The lip lesions can be lightened with chemical peels or laser.

Our patient underwent laparotomy, which revealed a grossly dilated and gangrenous small bowel segment. Intussusception was not present and was thought to have spontaneously reduced. Resection and anastomosis of the affected small bowel was performed. The patient’s postoperative course was uneventful, and her diarrhea and abdominal pain resolved. We recommended follow-up in her home city with primary care and a GI specialist and explained the need for surveillance of her condition.

CORRESPONDENCE
Josette R. McMichael, MD, Department of Dermatology, Emory University, 1525 Clifton Road NE, 1st Floor, Atlanta, GA 30322; [email protected]

A 15-year-old girl was brought to the Family Medicine Clinic in Somaliland, Africa, for evaluation of intermittent abdominal pain and watery diarrhea of 12 years’ duration. Over the previous 2 months, her symptoms had worsened and included vomiting and weight loss. She denied fever, melena, or hematemesis.

Physical examination revealed a thin female with a normal abdominal exam and numerous hyperpigmented macules on the lips, buccal mucosa, fingers, and toes (FIGURE 1). Her family reported that the black spots on her lips had been there since birth. There was no known family history of similar symptoms or black spots.

Her hemoglobin was 10 g/dL (reference range, 12–15 g/dL). A probable diagnosis was discussed with the family, and they elected to travel to India for further evaluation due to limited diagnostic resources in their location. In India, computed tomography (CT) and ultrasonography showed duodenojejunal intussusception. Upper gastrointestinal (GI) endoscopy revealed multiple polyps from the lower stomach to the jejunum of the small bowel; colonoscopy was normal.

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

Our patient was given a diagnosis of Peutz-Jeghers syndrome (PJS) based on the characteristic pigmented mucocutaneous macules and numerous polyps in the stomach and small bowel. PJS is an autosomal dominant syndrome characterized by mucocutaneous pigmentation, polyposis of the GI tract, and increased cancer risk. The prevalence is approximately 1 in 100,000.¹ Genetic testing for the STK11 gene mutation, which is found in 70% of familial cases and 30% to 67% of sporadic cases, is not required for diagnosis.¹

What you’ll see. The bluish brown to black spots of PJS often are apparent at birth or in early infancy. They are most common on the lips, buccal mucosa, perioral region, palms, and soles.

When PeutzJeghers syndrome is suspected, the entire GI tract should be investigated.

The polyps may cause bleeding, anemia, and abdominal pain due to intussusception, obstruction, or infarction.² Intussusception is the most frequent cause of morbidity in childhood for PJS patients.^3,4 Recurrent attacks of abdominal pain likely result from recurring transient episodes of incomplete intussusception. The polyps usually are benign, but patients are at increased risk of GI and non-GI malignancies such as breast, pancreas, lung, and reproductive tract cancers.¹ Most cancers associated with PJS occur during adulthood.²

Other possible causes of hyperpigmentation

PJS can be differentiated from other causes of hyperpigmentation by clinical presentation and/or genetic testing.

Laugier-Hunziker syndrome manifests with macular hyperpigmentation of the lips and buccal mucosa and pigmented bands on the nails in young or middle-aged adults. It is not associated with intestinal polyps.

Continue to: Cronkhite-Canada syndrome

Cronkhite-Canada syndrome consists of acral and oral pigmented macules and GI polyps as well as generalized darkening of the skin, extensive alopecia, loss of taste, and nail dystrophy.

Familial lentiginosis syndromes such as Noonan syndrome and NAME syndrome (nevi, atrial myxoma, myxoid neurofibroma, ephelides) have other systemic signs such as cardiac abnormalities, and the pigmentation is not as clearly perioral.

Albright syndrome manifests with oral pigmented macules but also is associated with precocious puberty and polyostotic fibrous dysplasia.

Addison disease may cause multiple hyperpigmented macules but has other systemic involvement; adrenocorticotropic hormone levels are elevated.

Juvenile polyposis syndrome manifests with GI polyps but is not associated with mucosal pigmentation.

Continue to: Use these 4 criteria to make the diagnosis

Use these 4 criteria to make the diagnosis

The diagnosis of PJS is made using the following criteria: (1) two or more histologically confirmed PJS polyps, (2) any number of PJS polyps and a family history of PJS, (3) characteristic mucocutaneous pigmentation and a family history of PJS, or (4) any number of PJS polyps and characteristic mucocutaneous pigmentation.²

When PJS is suspected, the entire GI tract should be investigated. The hamartomatous polyps may be found from the stomach to the anal canal, but the small bowel most commonly is involved. The polyps may occur in early childhood, with one study of 14 children reporting a median age of 4.5 years.⁵ Polyp biopsy will show smooth muscle arborization. When possible, those who meet clinical criteria for PJS should undergo genetic testing for a STK11 gene mutation. PJS may occur due to de novo mutations in patients with no family history.⁶

Long-term management involves surveillance for polyps and cancer

Screening guidelines for polyps vary. Some suggest starting screening at age 8 to 10 years with esophagogastroduodenoscopy or capsule endoscopy and if negative, colonoscopy at age 18. Others suggest starting screening at 4 to 5 years of age.⁵ The recommendation is to remove polyps if technically feasible.³ Surveillance for Sertoli cell tumors (sex cord stromal tumors) should be done before puberty, and evaluation of other organs at risk of malignancy should begin by the end of adolescence.

The pigmented macules do not require treatment. Macules on the lips may disappear with time, while those on the buccal mucosa persist. The lip lesions can be lightened with chemical peels or laser.

Our patient underwent laparotomy, which revealed a grossly dilated and gangrenous small bowel segment. Intussusception was not present and was thought to have spontaneously reduced. Resection and anastomosis of the affected small bowel was performed. The patient’s postoperative course was uneventful, and her diarrhea and abdominal pain resolved. We recommended follow-up in her home city with primary care and a GI specialist and explained the need for surveillance of her condition.

CORRESPONDENCE
Josette R. McMichael, MD, Department of Dermatology, Emory University, 1525 Clifton Road NE, 1st Floor, Atlanta, GA 30322; [email protected]

THE CASE

A 45-year-old man was admitted to the hospital with a fever and generalized rash. For the previous 2 weeks, he had been treated at a skilled nursing facility with IV vancomycin and cefepime for left calcaneal osteomyelitis. He reported that the rash was pruritic and started 2 days prior to hospital admission.

His past medical history was significant for type 2 diabetes mellitus and polysubstance drug abuse. Medical and travel history were otherwise unremarkable. The patient was taking the following medications at the time of presentation: hydrocodone-acetaminophen, cyclobenzaprine, melatonin, and metformin.

Initial vital signs included a temperature of 102.9°F; respiratory rate, 22 breaths/min; heart rate, 97 beats/min; and blood pressure, 89/50 mm Hg. Physical exam was notable for left anterior cervical and axillary lymphadenopathy. The patient had no facial edema, but he did have a diffuse, morbilliform rash on his bilateral upper and lower extremities, encompassing about 54% of his body surface area (FIGURE 1).

Laboratory studies revealed a white blood cell count of 4.7/mcL, with 3.4% eosinophils and 10.9% monocytes; an erythrocyte sedimentation rate of 60 mm/h; and a C-reactive protein level of 1 mg/dL. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were both elevated (AST: 95 U/L [normal range, 8 - 48 U/L]; ALT: 115 U/L [normal range: 7 - 55 U/L]). A chest x-ray was obtained and showed new lung infiltrates (FIGURE 2).

Linezolid and meropenem were initiated for a presumed health care–associated pneumonia, and a sepsis work-up was initiated.

THE DIAGNOSIS

The patient’s rash and pruritus worsened after meropenem was introduced. A hepatitis panel was nonreactive except for prior hepatitis A exposure. Ultrasound of the liver and spleen was normal. Investigation of pneumonia pathogens including Legionella, Streptococcus, Mycoplasma, and Chlamydia psittaci did not reveal any causative agents. A skin biopsy revealed perivascular neutrophilic dermatitis with dyskeratosis.

The patient was diagnosed with DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome based on his fever, worsening morbilliform rash, lymphadenopathy, and elevated liver transaminase levels. Although he did not have marked eosinophilia, atypical lymphocytes were present. Serologies for human herpesvirus (HHV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) were all unremarkable.

Continue to: During discussions...

During discussions with an infectious disease specialist, it was concluded that the patient’s DRESS syndrome was likely secondary to beta-lactam antibiotics. The patient had been receiving cefepime prior to hospitalization. Meropenem was discontinued and aztreonam was started, with continued linezolid. This patient did not have a reactivation of a herpesvirus (HHV-6, HHV-7, EBV, or CMV), which has been previously reported in cases of DRESS syndrome.

DISCUSSION

DRESS syndrome is a challenging diagnosis to make due to the multiplicity of presenting symptoms. Skin rash, lymphadenopathy, hepatic involvement, and hypereosinophilia are characteristic findings.¹ Accurate diagnosis reduces fatal disease outcomes, which are estimated to occur in 5%-10% of cases.^1,2

Causative agents. DRESS syndrome typically occurs 2 to 6 weeks after the introduction of the causative agent, commonly an aromatic anticonvulsant or antibiotic.³ The incidence of DRESS syndrome in patients using carbamazepine and phenytoin is estimated to be 1 to 5 per 10,000 patients. The incidence of DRESS syndrome in patients using antibiotics is unknown. Frequently, the inducing antibiotic is a beta-lactam, as in this case.^4,5

The pathogenesis of DRESS syndrome is not well understood, although there appears to be an immune-mediated reaction that occurs in certain patients after viral reactivation, particularly with herpesviruses. In vitro studies have demonstrated that the culprit drug is able to induce viral reactivation leading to T-lymphocyte response and systemic inflammation, which occurs in multiple organs.^6,7 Reported long-term sequelae of DRESS syndrome include immune-mediated diseases such as thyroiditis and type 1 diabetes. In addition, it is hypothesized that there is a genetic predisposition involving human leukocyte antigens that increases the likelihood that individuals will develop DRESS syndrome.^5,8

Skin rash, lymphadenopathy, hepatic involvement, and hypereosinophilia are characteristic findings of DRESS syndrome.

Diagnosis. The Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) was developed to assist in the diagnosis of DRESS syndrome.⁹ Patients should be assessed for 11 criteria (outlined in the TABLE⁹), with points applied for the presence, absence, or unknown status of each. A total score of > 5 is consistent with definitive diagnosis of DRESS syndrome, while a score of > 2 indicates probable DRESS syndrome. Additionally, a skin biopsy may be contributory by revealing a dense infiltrate of eosinophils or lymphocytes in the papillary dermis, but this is not needed to make the diagnosis.^10,11

Continue to: Treatment

Treatment is aimed at stopping the causative agent and starting moderate- to high-dose systemic corticosteroids (from 0.5 to 2 mg/kg/d). If symptoms continue to progress, cyclosporine can be used. ­N-acetylcysteine may also be beneficial due to its ability to neutralize drug metabolites that can stimulate T-cell response.⁷ There has not been sufficient evidence to suggest that antiviral medication should be initiated.^1,7

Our patient was treated with 2 mg/kg/d of prednisone, along with triamcinolone cream, diphenhydramine, and ­N-acetylcysteine. His rash improved dramatically during his hospital stay and at the subsequent 1-month follow-up was completely resolved.

THE TAKEAWAY

DRESS syndrome should be suspected in patients presenting with fever, rash, lymphadenopathy, pulmonary infiltrates, and liver involvement after initiation of drugs commonly associated with this syndrome. Our case reinforces previous clinical evidence that beta-lactam antibiotics are a common cause of DRESS syndrome; patients taking these medications should be closely monitored. Cross-reactions are frequent, and it is imperative that patients avoid related drugs to prevent recurrence. Although glucocorticoids are the mainstay of treatment, further studies are needed to assess the benefits of N-acetylcysteine.

CORRESPONDENCE
W. Jacob Cobb, MD, JPS Health Network, 1500 South Main Street, Fort Worth, TX, 76104; [email protected]

THE CASE

A 45-year-old man was admitted to the hospital with a fever and generalized rash. For the previous 2 weeks, he had been treated at a skilled nursing facility with IV vancomycin and cefepime for left calcaneal osteomyelitis. He reported that the rash was pruritic and started 2 days prior to hospital admission.

His past medical history was significant for type 2 diabetes mellitus and polysubstance drug abuse. Medical and travel history were otherwise unremarkable. The patient was taking the following medications at the time of presentation: hydrocodone-acetaminophen, cyclobenzaprine, melatonin, and metformin.

Initial vital signs included a temperature of 102.9°F; respiratory rate, 22 breaths/min; heart rate, 97 beats/min; and blood pressure, 89/50 mm Hg. Physical exam was notable for left anterior cervical and axillary lymphadenopathy. The patient had no facial edema, but he did have a diffuse, morbilliform rash on his bilateral upper and lower extremities, encompassing about 54% of his body surface area (FIGURE 1).

Laboratory studies revealed a white blood cell count of 4.7/mcL, with 3.4% eosinophils and 10.9% monocytes; an erythrocyte sedimentation rate of 60 mm/h; and a C-reactive protein level of 1 mg/dL. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were both elevated (AST: 95 U/L [normal range, 8 - 48 U/L]; ALT: 115 U/L [normal range: 7 - 55 U/L]). A chest x-ray was obtained and showed new lung infiltrates (FIGURE 2).

Linezolid and meropenem were initiated for a presumed health care–associated pneumonia, and a sepsis work-up was initiated.

THE DIAGNOSIS

The patient’s rash and pruritus worsened after meropenem was introduced. A hepatitis panel was nonreactive except for prior hepatitis A exposure. Ultrasound of the liver and spleen was normal. Investigation of pneumonia pathogens including Legionella, Streptococcus, Mycoplasma, and Chlamydia psittaci did not reveal any causative agents. A skin biopsy revealed perivascular neutrophilic dermatitis with dyskeratosis.

The patient was diagnosed with DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome based on his fever, worsening morbilliform rash, lymphadenopathy, and elevated liver transaminase levels. Although he did not have marked eosinophilia, atypical lymphocytes were present. Serologies for human herpesvirus (HHV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) were all unremarkable.

Continue to: During discussions...

During discussions with an infectious disease specialist, it was concluded that the patient’s DRESS syndrome was likely secondary to beta-lactam antibiotics. The patient had been receiving cefepime prior to hospitalization. Meropenem was discontinued and aztreonam was started, with continued linezolid. This patient did not have a reactivation of a herpesvirus (HHV-6, HHV-7, EBV, or CMV), which has been previously reported in cases of DRESS syndrome.

DISCUSSION

DRESS syndrome is a challenging diagnosis to make due to the multiplicity of presenting symptoms. Skin rash, lymphadenopathy, hepatic involvement, and hypereosinophilia are characteristic findings.¹ Accurate diagnosis reduces fatal disease outcomes, which are estimated to occur in 5%-10% of cases.^1,2

Causative agents. DRESS syndrome typically occurs 2 to 6 weeks after the introduction of the causative agent, commonly an aromatic anticonvulsant or antibiotic.³ The incidence of DRESS syndrome in patients using carbamazepine and phenytoin is estimated to be 1 to 5 per 10,000 patients. The incidence of DRESS syndrome in patients using antibiotics is unknown. Frequently, the inducing antibiotic is a beta-lactam, as in this case.^4,5

The pathogenesis of DRESS syndrome is not well understood, although there appears to be an immune-mediated reaction that occurs in certain patients after viral reactivation, particularly with herpesviruses. In vitro studies have demonstrated that the culprit drug is able to induce viral reactivation leading to T-lymphocyte response and systemic inflammation, which occurs in multiple organs.^6,7 Reported long-term sequelae of DRESS syndrome include immune-mediated diseases such as thyroiditis and type 1 diabetes. In addition, it is hypothesized that there is a genetic predisposition involving human leukocyte antigens that increases the likelihood that individuals will develop DRESS syndrome.^5,8

Skin rash, lymphadenopathy, hepatic involvement, and hypereosinophilia are characteristic findings of DRESS syndrome.

Diagnosis. The Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) was developed to assist in the diagnosis of DRESS syndrome.⁹ Patients should be assessed for 11 criteria (outlined in the TABLE⁹), with points applied for the presence, absence, or unknown status of each. A total score of > 5 is consistent with definitive diagnosis of DRESS syndrome, while a score of > 2 indicates probable DRESS syndrome. Additionally, a skin biopsy may be contributory by revealing a dense infiltrate of eosinophils or lymphocytes in the papillary dermis, but this is not needed to make the diagnosis.^10,11

Continue to: Treatment

Treatment is aimed at stopping the causative agent and starting moderate- to high-dose systemic corticosteroids (from 0.5 to 2 mg/kg/d). If symptoms continue to progress, cyclosporine can be used. ­N-acetylcysteine may also be beneficial due to its ability to neutralize drug metabolites that can stimulate T-cell response.⁷ There has not been sufficient evidence to suggest that antiviral medication should be initiated.^1,7

Our patient was treated with 2 mg/kg/d of prednisone, along with triamcinolone cream, diphenhydramine, and ­N-acetylcysteine. His rash improved dramatically during his hospital stay and at the subsequent 1-month follow-up was completely resolved.

THE TAKEAWAY

DRESS syndrome should be suspected in patients presenting with fever, rash, lymphadenopathy, pulmonary infiltrates, and liver involvement after initiation of drugs commonly associated with this syndrome. Our case reinforces previous clinical evidence that beta-lactam antibiotics are a common cause of DRESS syndrome; patients taking these medications should be closely monitored. Cross-reactions are frequent, and it is imperative that patients avoid related drugs to prevent recurrence. Although glucocorticoids are the mainstay of treatment, further studies are needed to assess the benefits of N-acetylcysteine.

CORRESPONDENCE
W. Jacob Cobb, MD, JPS Health Network, 1500 South Main Street, Fort Worth, TX, 76104; [email protected]

THE CASE

A 45-year-old man was admitted to the hospital with a fever and generalized rash. For the previous 2 weeks, he had been treated at a skilled nursing facility with IV vancomycin and cefepime for left calcaneal osteomyelitis. He reported that the rash was pruritic and started 2 days prior to hospital admission.

His past medical history was significant for type 2 diabetes mellitus and polysubstance drug abuse. Medical and travel history were otherwise unremarkable. The patient was taking the following medications at the time of presentation: hydrocodone-acetaminophen, cyclobenzaprine, melatonin, and metformin.

Initial vital signs included a temperature of 102.9°F; respiratory rate, 22 breaths/min; heart rate, 97 beats/min; and blood pressure, 89/50 mm Hg. Physical exam was notable for left anterior cervical and axillary lymphadenopathy. The patient had no facial edema, but he did have a diffuse, morbilliform rash on his bilateral upper and lower extremities, encompassing about 54% of his body surface area (FIGURE 1).

Laboratory studies revealed a white blood cell count of 4.7/mcL, with 3.4% eosinophils and 10.9% monocytes; an erythrocyte sedimentation rate of 60 mm/h; and a C-reactive protein level of 1 mg/dL. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were both elevated (AST: 95 U/L [normal range, 8 - 48 U/L]; ALT: 115 U/L [normal range: 7 - 55 U/L]). A chest x-ray was obtained and showed new lung infiltrates (FIGURE 2).

Linezolid and meropenem were initiated for a presumed health care–associated pneumonia, and a sepsis work-up was initiated.

THE DIAGNOSIS

The patient’s rash and pruritus worsened after meropenem was introduced. A hepatitis panel was nonreactive except for prior hepatitis A exposure. Ultrasound of the liver and spleen was normal. Investigation of pneumonia pathogens including Legionella, Streptococcus, Mycoplasma, and Chlamydia psittaci did not reveal any causative agents. A skin biopsy revealed perivascular neutrophilic dermatitis with dyskeratosis.

The patient was diagnosed with DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome based on his fever, worsening morbilliform rash, lymphadenopathy, and elevated liver transaminase levels. Although he did not have marked eosinophilia, atypical lymphocytes were present. Serologies for human herpesvirus (HHV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) were all unremarkable.

Continue to: During discussions...

During discussions with an infectious disease specialist, it was concluded that the patient’s DRESS syndrome was likely secondary to beta-lactam antibiotics. The patient had been receiving cefepime prior to hospitalization. Meropenem was discontinued and aztreonam was started, with continued linezolid. This patient did not have a reactivation of a herpesvirus (HHV-6, HHV-7, EBV, or CMV), which has been previously reported in cases of DRESS syndrome.

DISCUSSION

DRESS syndrome is a challenging diagnosis to make due to the multiplicity of presenting symptoms. Skin rash, lymphadenopathy, hepatic involvement, and hypereosinophilia are characteristic findings.¹ Accurate diagnosis reduces fatal disease outcomes, which are estimated to occur in 5%-10% of cases.^1,2

Causative agents. DRESS syndrome typically occurs 2 to 6 weeks after the introduction of the causative agent, commonly an aromatic anticonvulsant or antibiotic.³ The incidence of DRESS syndrome in patients using carbamazepine and phenytoin is estimated to be 1 to 5 per 10,000 patients. The incidence of DRESS syndrome in patients using antibiotics is unknown. Frequently, the inducing antibiotic is a beta-lactam, as in this case.^4,5

The pathogenesis of DRESS syndrome is not well understood, although there appears to be an immune-mediated reaction that occurs in certain patients after viral reactivation, particularly with herpesviruses. In vitro studies have demonstrated that the culprit drug is able to induce viral reactivation leading to T-lymphocyte response and systemic inflammation, which occurs in multiple organs.^6,7 Reported long-term sequelae of DRESS syndrome include immune-mediated diseases such as thyroiditis and type 1 diabetes. In addition, it is hypothesized that there is a genetic predisposition involving human leukocyte antigens that increases the likelihood that individuals will develop DRESS syndrome.^5,8

Skin rash, lymphadenopathy, hepatic involvement, and hypereosinophilia are characteristic findings of DRESS syndrome.

Diagnosis. The Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) was developed to assist in the diagnosis of DRESS syndrome.⁹ Patients should be assessed for 11 criteria (outlined in the TABLE⁹), with points applied for the presence, absence, or unknown status of each. A total score of > 5 is consistent with definitive diagnosis of DRESS syndrome, while a score of > 2 indicates probable DRESS syndrome. Additionally, a skin biopsy may be contributory by revealing a dense infiltrate of eosinophils or lymphocytes in the papillary dermis, but this is not needed to make the diagnosis.^10,11

Continue to: Treatment

Treatment is aimed at stopping the causative agent and starting moderate- to high-dose systemic corticosteroids (from 0.5 to 2 mg/kg/d). If symptoms continue to progress, cyclosporine can be used. ­N-acetylcysteine may also be beneficial due to its ability to neutralize drug metabolites that can stimulate T-cell response.⁷ There has not been sufficient evidence to suggest that antiviral medication should be initiated.^1,7

Our patient was treated with 2 mg/kg/d of prednisone, along with triamcinolone cream, diphenhydramine, and ­N-acetylcysteine. His rash improved dramatically during his hospital stay and at the subsequent 1-month follow-up was completely resolved.

THE TAKEAWAY

DRESS syndrome should be suspected in patients presenting with fever, rash, lymphadenopathy, pulmonary infiltrates, and liver involvement after initiation of drugs commonly associated with this syndrome. Our case reinforces previous clinical evidence that beta-lactam antibiotics are a common cause of DRESS syndrome; patients taking these medications should be closely monitored. Cross-reactions are frequent, and it is imperative that patients avoid related drugs to prevent recurrence. Although glucocorticoids are the mainstay of treatment, further studies are needed to assess the benefits of N-acetylcysteine.

CORRESPONDENCE
W. Jacob Cobb, MD, JPS Health Network, 1500 South Main Street, Fort Worth, TX, 76104; [email protected]

Nasal papules that resemble angiofibromas are rarely described in the literature as a sequela of acne, but researchers believe the condition could be an underrecognized problem, affecting patients with skin of color in particular, according to the authors of a case series published in Pediatric Dermatology.

Courtesy Dr. Jorge Roman

Jorge Roman, MD, and coauthors in the department of dermatology at New York (N.Y.) University identified 20 patients with a history of acne who had nasal papules, in a retrospective review of electronic medical records at NYU over 1 year (April 2018 to April 2019). The presentation ranged from “a few, small skin-colored papules to large, dome-shaped papulonodules, to more extensive rhinophymatous-like” changes with some patients having papular lesions on the chin in addition to the nose, they wrote in the report.

These papules greatly resembled angiofibromas, but appear to be a sequela of acne, according to the authors. In five patients who had biopsies, the results showed “a dome-shaped proliferation of spindle and stellate-shaped cells with thickened collagen bundles and dilated thin-walled blood vessels,” the authors wrote. “The histopathological findings of these nasal papules were indistinguishable from those of a conventional angiofibroma.”

In addition, the patients did not have evidence of underlying genetic conditions that could explain the angiofibroma-like lesions. “Although acne has not previously been implicated in the development of angiofibromas, based on the data available for our patients, it seems extremely unlikely that the lesions would be related to anything else,” Dr. Roman, a dermatology resident at New York University, said in an interview.

He said he first recognized the nasal papules in clinic as a first-year resident, but was surprised to find a lack of information on the condition. “Dermatology has a name for just about every skin disease imaginable, so I found it very odd when I couldn’t find much describing this condition,” he said. “There was a large disparity between what we were seeing in clinic and what was reported in the literature.”

Nearly all the patients were Hispanic (17 of 20) and adolescent males (17 patients), with a median age of 16 years at the time of presentation. There were two Black patients and one Asian patient. Race and ethnicity were not mentioned in two previous reports describing papular acne scarring, but Dr. Roman and colleagues noted that in their clinic, the condition appeared to affect adolescent patients with skin of color predominantly.

Reasons why nasal papules may be underreported are unclear, Dr. Roman noted. One possible explanation is lower use of dermatologic care among patients with skin of color. “Interestingly, previous research has shown that racial minorities are lower utilizers of dermatologic care. It is possible that the patient demographic most afflicted by this condition face significant barriers when seeking care,” he said.

Due to a low level of awareness of acne-related nasal papules, “clinicians may not recognize it as an acne-related scarring process. This is significant, as early recognition and treatment can prevent the development or progression of these potentially disfiguring sequelae,” Dr. Roman said.

Although the results are from a small case series at a single center, Dr. Roman said this condition may be more prevalent than realized. “Having been raised in a predominately Latino community in Texas, I can easily recall seeing people with these papules growing up. I don’t think it would be surprising for dermatologists reading our paper to say, ‘I’ve seen this in clinic before,’ ” he said.

Regarding treatment, there is an ongoing investigation into what treatments are effective for the acne-related nasal papules. “Physical treatment modalities such as ablative laser or surgical removal seem to be the most efficacious,” Dr. Roman said. “In the future, a prospective clinical study will help to better define the prevalence and risk factors for the condition,” he said.

He and coauthors reported no conflicts of interest. No funding source was listed.

SOURCE: Roman J et al. Pediatr Dermatol. 2020 Aug 7. doi: 10.1111/pde.14319.

Nasal papules that resemble angiofibromas are rarely described in the literature as a sequela of acne, but researchers believe the condition could be an underrecognized problem, affecting patients with skin of color in particular, according to the authors of a case series published in Pediatric Dermatology.

Courtesy Dr. Jorge Roman

Jorge Roman, MD, and coauthors in the department of dermatology at New York (N.Y.) University identified 20 patients with a history of acne who had nasal papules, in a retrospective review of electronic medical records at NYU over 1 year (April 2018 to April 2019). The presentation ranged from “a few, small skin-colored papules to large, dome-shaped papulonodules, to more extensive rhinophymatous-like” changes with some patients having papular lesions on the chin in addition to the nose, they wrote in the report.

These papules greatly resembled angiofibromas, but appear to be a sequela of acne, according to the authors. In five patients who had biopsies, the results showed “a dome-shaped proliferation of spindle and stellate-shaped cells with thickened collagen bundles and dilated thin-walled blood vessels,” the authors wrote. “The histopathological findings of these nasal papules were indistinguishable from those of a conventional angiofibroma.”

In addition, the patients did not have evidence of underlying genetic conditions that could explain the angiofibroma-like lesions. “Although acne has not previously been implicated in the development of angiofibromas, based on the data available for our patients, it seems extremely unlikely that the lesions would be related to anything else,” Dr. Roman, a dermatology resident at New York University, said in an interview.

He said he first recognized the nasal papules in clinic as a first-year resident, but was surprised to find a lack of information on the condition. “Dermatology has a name for just about every skin disease imaginable, so I found it very odd when I couldn’t find much describing this condition,” he said. “There was a large disparity between what we were seeing in clinic and what was reported in the literature.”

Nearly all the patients were Hispanic (17 of 20) and adolescent males (17 patients), with a median age of 16 years at the time of presentation. There were two Black patients and one Asian patient. Race and ethnicity were not mentioned in two previous reports describing papular acne scarring, but Dr. Roman and colleagues noted that in their clinic, the condition appeared to affect adolescent patients with skin of color predominantly.

Reasons why nasal papules may be underreported are unclear, Dr. Roman noted. One possible explanation is lower use of dermatologic care among patients with skin of color. “Interestingly, previous research has shown that racial minorities are lower utilizers of dermatologic care. It is possible that the patient demographic most afflicted by this condition face significant barriers when seeking care,” he said.

Due to a low level of awareness of acne-related nasal papules, “clinicians may not recognize it as an acne-related scarring process. This is significant, as early recognition and treatment can prevent the development or progression of these potentially disfiguring sequelae,” Dr. Roman said.

Although the results are from a small case series at a single center, Dr. Roman said this condition may be more prevalent than realized. “Having been raised in a predominately Latino community in Texas, I can easily recall seeing people with these papules growing up. I don’t think it would be surprising for dermatologists reading our paper to say, ‘I’ve seen this in clinic before,’ ” he said.

Regarding treatment, there is an ongoing investigation into what treatments are effective for the acne-related nasal papules. “Physical treatment modalities such as ablative laser or surgical removal seem to be the most efficacious,” Dr. Roman said. “In the future, a prospective clinical study will help to better define the prevalence and risk factors for the condition,” he said.

He and coauthors reported no conflicts of interest. No funding source was listed.

SOURCE: Roman J et al. Pediatr Dermatol. 2020 Aug 7. doi: 10.1111/pde.14319.

Nasal papules that resemble angiofibromas are rarely described in the literature as a sequela of acne, but researchers believe the condition could be an underrecognized problem, affecting patients with skin of color in particular, according to the authors of a case series published in Pediatric Dermatology.

Courtesy Dr. Jorge Roman

Jorge Roman, MD, and coauthors in the department of dermatology at New York (N.Y.) University identified 20 patients with a history of acne who had nasal papules, in a retrospective review of electronic medical records at NYU over 1 year (April 2018 to April 2019). The presentation ranged from “a few, small skin-colored papules to large, dome-shaped papulonodules, to more extensive rhinophymatous-like” changes with some patients having papular lesions on the chin in addition to the nose, they wrote in the report.

These papules greatly resembled angiofibromas, but appear to be a sequela of acne, according to the authors. In five patients who had biopsies, the results showed “a dome-shaped proliferation of spindle and stellate-shaped cells with thickened collagen bundles and dilated thin-walled blood vessels,” the authors wrote. “The histopathological findings of these nasal papules were indistinguishable from those of a conventional angiofibroma.”

In addition, the patients did not have evidence of underlying genetic conditions that could explain the angiofibroma-like lesions. “Although acne has not previously been implicated in the development of angiofibromas, based on the data available for our patients, it seems extremely unlikely that the lesions would be related to anything else,” Dr. Roman, a dermatology resident at New York University, said in an interview.

He said he first recognized the nasal papules in clinic as a first-year resident, but was surprised to find a lack of information on the condition. “Dermatology has a name for just about every skin disease imaginable, so I found it very odd when I couldn’t find much describing this condition,” he said. “There was a large disparity between what we were seeing in clinic and what was reported in the literature.”

Nearly all the patients were Hispanic (17 of 20) and adolescent males (17 patients), with a median age of 16 years at the time of presentation. There were two Black patients and one Asian patient. Race and ethnicity were not mentioned in two previous reports describing papular acne scarring, but Dr. Roman and colleagues noted that in their clinic, the condition appeared to affect adolescent patients with skin of color predominantly.

Reasons why nasal papules may be underreported are unclear, Dr. Roman noted. One possible explanation is lower use of dermatologic care among patients with skin of color. “Interestingly, previous research has shown that racial minorities are lower utilizers of dermatologic care. It is possible that the patient demographic most afflicted by this condition face significant barriers when seeking care,” he said.

Due to a low level of awareness of acne-related nasal papules, “clinicians may not recognize it as an acne-related scarring process. This is significant, as early recognition and treatment can prevent the development or progression of these potentially disfiguring sequelae,” Dr. Roman said.

Although the results are from a small case series at a single center, Dr. Roman said this condition may be more prevalent than realized. “Having been raised in a predominately Latino community in Texas, I can easily recall seeing people with these papules growing up. I don’t think it would be surprising for dermatologists reading our paper to say, ‘I’ve seen this in clinic before,’ ” he said.

Regarding treatment, there is an ongoing investigation into what treatments are effective for the acne-related nasal papules. “Physical treatment modalities such as ablative laser or surgical removal seem to be the most efficacious,” Dr. Roman said. “In the future, a prospective clinical study will help to better define the prevalence and risk factors for the condition,” he said.

He and coauthors reported no conflicts of interest. No funding source was listed.

SOURCE: Roman J et al. Pediatr Dermatol. 2020 Aug 7. doi: 10.1111/pde.14319.

Potassium hydroxide preparation of expressed contents revealed no molluscum bodies, but rather, small-caliber, trapped, and coiled hairs consistent with eruptive vellus hair cysts (EVHCs).

Vellus hairs are fine, light-colored (nonterminal) hairs that normally are found on the face, trunk, and limbs. EVHCs are typically asymptomatic papules containing an entrapped vellus hair. They form from entrapment of the hair follicle just proximal to the infundibulum, leading to hair bulb atrophy and dilation of the follicle. EVHCs typically are dome-shaped, flesh-colored soft papules that are 2 to 3 mm in size.

Diagnostic confusion can arise with molluscum contagiosum because those lesions also tend to be umbilicated and flesh colored. EVHCs can appear at any age but are more common in the first 3 decades of life. Familial types exist, presenting earlier in life than sporadic types. The differential diagnosis includes molluscum contagiosum, folliculitis, and steatocystoma multiplex. Rare genodermatoses have been associated with EVHCs, including autosomal dominant familial keratin gene mutation, anhidrotic and hidrotic ectodermal dysplasia, and pachyonychia congenita.

Up to 25% of cases spontaneously resolve, so patients can be counseled to observe the lesions. Alternative options including topical emollients or various topical keratolytics, including ammonium lactate 20% once to twice daily, topical urea, or topical salicylic acid until the lesions are flat and smooth. Topical and systemic retinoids have been reported to have limited success. Individual lesions of concern may be removed surgically by excision, curettage, cryotherapy, or laser but will likely leave a minor scar.

The patient and his family were reassured of the benign nature of the lesions and instructed to treat the papules with topical ammonium lactate 20% twice daily until the next appointment in 12 weeks. At follow-up, many, but not all, of the lesions had resolved.

‌

Text courtesy of Tristan Reynolds, DO, Maine Dartmouth Family Medicine Residency, and Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

Potassium hydroxide preparation of expressed contents revealed no molluscum bodies, but rather, small-caliber, trapped, and coiled hairs consistent with eruptive vellus hair cysts (EVHCs).

Vellus hairs are fine, light-colored (nonterminal) hairs that normally are found on the face, trunk, and limbs. EVHCs are typically asymptomatic papules containing an entrapped vellus hair. They form from entrapment of the hair follicle just proximal to the infundibulum, leading to hair bulb atrophy and dilation of the follicle. EVHCs typically are dome-shaped, flesh-colored soft papules that are 2 to 3 mm in size.

Diagnostic confusion can arise with molluscum contagiosum because those lesions also tend to be umbilicated and flesh colored. EVHCs can appear at any age but are more common in the first 3 decades of life. Familial types exist, presenting earlier in life than sporadic types. The differential diagnosis includes molluscum contagiosum, folliculitis, and steatocystoma multiplex. Rare genodermatoses have been associated with EVHCs, including autosomal dominant familial keratin gene mutation, anhidrotic and hidrotic ectodermal dysplasia, and pachyonychia congenita.

Up to 25% of cases spontaneously resolve, so patients can be counseled to observe the lesions. Alternative options including topical emollients or various topical keratolytics, including ammonium lactate 20% once to twice daily, topical urea, or topical salicylic acid until the lesions are flat and smooth. Topical and systemic retinoids have been reported to have limited success. Individual lesions of concern may be removed surgically by excision, curettage, cryotherapy, or laser but will likely leave a minor scar.

The patient and his family were reassured of the benign nature of the lesions and instructed to treat the papules with topical ammonium lactate 20% twice daily until the next appointment in 12 weeks. At follow-up, many, but not all, of the lesions had resolved.

‌

Text courtesy of Tristan Reynolds, DO, Maine Dartmouth Family Medicine Residency, and Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

Potassium hydroxide preparation of expressed contents revealed no molluscum bodies, but rather, small-caliber, trapped, and coiled hairs consistent with eruptive vellus hair cysts (EVHCs).

Vellus hairs are fine, light-colored (nonterminal) hairs that normally are found on the face, trunk, and limbs. EVHCs are typically asymptomatic papules containing an entrapped vellus hair. They form from entrapment of the hair follicle just proximal to the infundibulum, leading to hair bulb atrophy and dilation of the follicle. EVHCs typically are dome-shaped, flesh-colored soft papules that are 2 to 3 mm in size.

Diagnostic confusion can arise with molluscum contagiosum because those lesions also tend to be umbilicated and flesh colored. EVHCs can appear at any age but are more common in the first 3 decades of life. Familial types exist, presenting earlier in life than sporadic types. The differential diagnosis includes molluscum contagiosum, folliculitis, and steatocystoma multiplex. Rare genodermatoses have been associated with EVHCs, including autosomal dominant familial keratin gene mutation, anhidrotic and hidrotic ectodermal dysplasia, and pachyonychia congenita.

Up to 25% of cases spontaneously resolve, so patients can be counseled to observe the lesions. Alternative options including topical emollients or various topical keratolytics, including ammonium lactate 20% once to twice daily, topical urea, or topical salicylic acid until the lesions are flat and smooth. Topical and systemic retinoids have been reported to have limited success. Individual lesions of concern may be removed surgically by excision, curettage, cryotherapy, or laser but will likely leave a minor scar.

The patient and his family were reassured of the benign nature of the lesions and instructed to treat the papules with topical ammonium lactate 20% twice daily until the next appointment in 12 weeks. At follow-up, many, but not all, of the lesions had resolved.

‌

Text courtesy of Tristan Reynolds, DO, Maine Dartmouth Family Medicine Residency, and Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

Malignant melanomas in children and adolescents are thankfully rare, but they can be challenging to diagnose, and fatal disease can manifest itself in any of several different ways, results of a retrospective multicenter study showed.

“The most striking thing that we learned from this study is that pediatric melanoma can present in so many different ways, and it’s distinct from the adult population in that we see more presentations associated with congenital nevi, or spitz melanoma, which is a special class of pigmented lesions that looks a little different under the microscope,” Elena B. Hawryluk, MD, PhD, of the department of dermatology at Massachusetts General Hospital (MGH) and Harvard University, Boston, said in an interview. Dr. Hawryluk is lead author of the study, which was published online ahead of print in the Journal of the American Academy of Dermatology.

Dr. Hawryluk and colleagues at MGH and 11 other centers conducted a retrospective review of all cases of fatal pediatric melanoma among patients younger than 20 years diagnosed from late 1994 through early 2017.

They identified a total of 38 fatal cases over more than 2 decades. The cases were distinguished primarily by their heterogeneous clinical presentation and by the diversity of the patients, their precursor lesions, and the tumor histopathology, she said in an interview.

“We were surprised to find that patients with each of these presentations could end up with a fatal course, it wasn’t just all the adolescents, or all the patients with giant congenital nevi; it really presented quite diversely.”
 

Rare malignancy

Melanoma is far less common in the pediatric population than in adults, with an annual incidence of 18 per 1 million among adolescents aged 15-18 years, and 1 per 1 million in children under 10 years, the authors noted.

“Melanoma in children and adolescents often has distinct clinical presentations such as association with a congenital melanocytic nevus (CMN), spitzoid melanoma, or amelanotic melanoma, which are more rarely observed in adult melanoma patients. Unique pediatric-specific clinical detection criteria have been proposed to highlight these differences, such as a tendency to present amelanotically,” they wrote.

Factors associated with worse prognosis, such as higher Breslow thickness and mitotic index, are more frequently present at the time of diagnosis in children compared with adults, particularly those diagnosed before age 11 years.

“It is unclear if this difference is secondary to diagnostic delays due to low clinical suspicion, atypical clinical presentations, or more rapid tumor growth rate, as many childhood melanomas are of nodular or spitzoid subtypes,” Dr. Hawryluk and her coauthors wrote.
 

Study details

The investigators sought to characterize the clinical and histopathologic features of fatal pediatric melanomas.

They found that 21 of the 38 patients (57%) were of White heritage, 7 (19%) were of Hispanic or Latino background, 1 (3%) was of Asian lineage, and 1 each were of Black African American or Black Hispanic background. The remaining children were classified as “other” or did not have their ethnic backgrounds recorded.

The “striking prevalence” of Hispanic patients observed in the study is consistent with surveillance reports of an increasing incidence of melanoma among children of Hispanic background, they noted.

The mean age at diagnosis was 12.7 years, and the mean age at death was 15.6 years.

Of the 16 cases with known identifiable disease subtypes, 8 (50%) were nodular, 5 (31%) were superficial spreading, and 3 (19%) were spitzoid melanomas. Of the 38 fatal melanomas, 10 were thought to have originated from congenital melanocytic nevi.
 

Outlook improving

Recent therapeutic breakthroughs such as targeted agents and immunotherapy with checkpoint inhibitors augur well for children diagnosed with melanoma, Dr. Hawryluk said.

“Fortunately, it’s not superaggressive in children at high frequency, so we generally use adult algorithms to inform treatment decisions,” she said. “It’s just important to note that melanomas that arise in congenital nevi tend to have different driver mutations than those that arise in older patients who may have lots of sun exposure.”

“Nowadays, we’re lucky to have a lot of extra tests and workups so that, if a patient does have metastatic or advance disease, they can have a better genetic profile that would guide our choice of medications,” she added.

The study was supported by a Pediatric Dermatology Research Alliance Study Support grant and Society for Pediatric Dermatology, Pediatric Dermatology Research Alliance Pilot award. Dr. Hawryluk is supported by the Dermatology Foundation and the Harvard Medical School Eleanor and Miles Shore Fellowship award. The authors reported no conflicts of interest.

SOURCE: Hawryluk EB et al. J Am Acad Dermatol. 2020 Jul 1. doi: 10.1016/j.jaad.2020.06.1010.

Malignant melanomas in children and adolescents are thankfully rare, but they can be challenging to diagnose, and fatal disease can manifest itself in any of several different ways, results of a retrospective multicenter study showed.

“The most striking thing that we learned from this study is that pediatric melanoma can present in so many different ways, and it’s distinct from the adult population in that we see more presentations associated with congenital nevi, or spitz melanoma, which is a special class of pigmented lesions that looks a little different under the microscope,” Elena B. Hawryluk, MD, PhD, of the department of dermatology at Massachusetts General Hospital (MGH) and Harvard University, Boston, said in an interview. Dr. Hawryluk is lead author of the study, which was published online ahead of print in the Journal of the American Academy of Dermatology.

Dr. Hawryluk and colleagues at MGH and 11 other centers conducted a retrospective review of all cases of fatal pediatric melanoma among patients younger than 20 years diagnosed from late 1994 through early 2017.

They identified a total of 38 fatal cases over more than 2 decades. The cases were distinguished primarily by their heterogeneous clinical presentation and by the diversity of the patients, their precursor lesions, and the tumor histopathology, she said in an interview.

“We were surprised to find that patients with each of these presentations could end up with a fatal course, it wasn’t just all the adolescents, or all the patients with giant congenital nevi; it really presented quite diversely.”
 

Rare malignancy

Melanoma is far less common in the pediatric population than in adults, with an annual incidence of 18 per 1 million among adolescents aged 15-18 years, and 1 per 1 million in children under 10 years, the authors noted.

“Melanoma in children and adolescents often has distinct clinical presentations such as association with a congenital melanocytic nevus (CMN), spitzoid melanoma, or amelanotic melanoma, which are more rarely observed in adult melanoma patients. Unique pediatric-specific clinical detection criteria have been proposed to highlight these differences, such as a tendency to present amelanotically,” they wrote.

Factors associated with worse prognosis, such as higher Breslow thickness and mitotic index, are more frequently present at the time of diagnosis in children compared with adults, particularly those diagnosed before age 11 years.

“It is unclear if this difference is secondary to diagnostic delays due to low clinical suspicion, atypical clinical presentations, or more rapid tumor growth rate, as many childhood melanomas are of nodular or spitzoid subtypes,” Dr. Hawryluk and her coauthors wrote.
 

Study details

The investigators sought to characterize the clinical and histopathologic features of fatal pediatric melanomas.

They found that 21 of the 38 patients (57%) were of White heritage, 7 (19%) were of Hispanic or Latino background, 1 (3%) was of Asian lineage, and 1 each were of Black African American or Black Hispanic background. The remaining children were classified as “other” or did not have their ethnic backgrounds recorded.

The “striking prevalence” of Hispanic patients observed in the study is consistent with surveillance reports of an increasing incidence of melanoma among children of Hispanic background, they noted.

The mean age at diagnosis was 12.7 years, and the mean age at death was 15.6 years.

Of the 16 cases with known identifiable disease subtypes, 8 (50%) were nodular, 5 (31%) were superficial spreading, and 3 (19%) were spitzoid melanomas. Of the 38 fatal melanomas, 10 were thought to have originated from congenital melanocytic nevi.
 

Outlook improving

Recent therapeutic breakthroughs such as targeted agents and immunotherapy with checkpoint inhibitors augur well for children diagnosed with melanoma, Dr. Hawryluk said.

“Fortunately, it’s not superaggressive in children at high frequency, so we generally use adult algorithms to inform treatment decisions,” she said. “It’s just important to note that melanomas that arise in congenital nevi tend to have different driver mutations than those that arise in older patients who may have lots of sun exposure.”

“Nowadays, we’re lucky to have a lot of extra tests and workups so that, if a patient does have metastatic or advance disease, they can have a better genetic profile that would guide our choice of medications,” she added.

The study was supported by a Pediatric Dermatology Research Alliance Study Support grant and Society for Pediatric Dermatology, Pediatric Dermatology Research Alliance Pilot award. Dr. Hawryluk is supported by the Dermatology Foundation and the Harvard Medical School Eleanor and Miles Shore Fellowship award. The authors reported no conflicts of interest.

SOURCE: Hawryluk EB et al. J Am Acad Dermatol. 2020 Jul 1. doi: 10.1016/j.jaad.2020.06.1010.

Malignant melanomas in children and adolescents are thankfully rare, but they can be challenging to diagnose, and fatal disease can manifest itself in any of several different ways, results of a retrospective multicenter study showed.

“The most striking thing that we learned from this study is that pediatric melanoma can present in so many different ways, and it’s distinct from the adult population in that we see more presentations associated with congenital nevi, or spitz melanoma, which is a special class of pigmented lesions that looks a little different under the microscope,” Elena B. Hawryluk, MD, PhD, of the department of dermatology at Massachusetts General Hospital (MGH) and Harvard University, Boston, said in an interview. Dr. Hawryluk is lead author of the study, which was published online ahead of print in the Journal of the American Academy of Dermatology.

Dr. Hawryluk and colleagues at MGH and 11 other centers conducted a retrospective review of all cases of fatal pediatric melanoma among patients younger than 20 years diagnosed from late 1994 through early 2017.

They identified a total of 38 fatal cases over more than 2 decades. The cases were distinguished primarily by their heterogeneous clinical presentation and by the diversity of the patients, their precursor lesions, and the tumor histopathology, she said in an interview.

“We were surprised to find that patients with each of these presentations could end up with a fatal course, it wasn’t just all the adolescents, or all the patients with giant congenital nevi; it really presented quite diversely.”
 

Rare malignancy

Melanoma is far less common in the pediatric population than in adults, with an annual incidence of 18 per 1 million among adolescents aged 15-18 years, and 1 per 1 million in children under 10 years, the authors noted.

“Melanoma in children and adolescents often has distinct clinical presentations such as association with a congenital melanocytic nevus (CMN), spitzoid melanoma, or amelanotic melanoma, which are more rarely observed in adult melanoma patients. Unique pediatric-specific clinical detection criteria have been proposed to highlight these differences, such as a tendency to present amelanotically,” they wrote.

Factors associated with worse prognosis, such as higher Breslow thickness and mitotic index, are more frequently present at the time of diagnosis in children compared with adults, particularly those diagnosed before age 11 years.

“It is unclear if this difference is secondary to diagnostic delays due to low clinical suspicion, atypical clinical presentations, or more rapid tumor growth rate, as many childhood melanomas are of nodular or spitzoid subtypes,” Dr. Hawryluk and her coauthors wrote.
 

Study details

The investigators sought to characterize the clinical and histopathologic features of fatal pediatric melanomas.

They found that 21 of the 38 patients (57%) were of White heritage, 7 (19%) were of Hispanic or Latino background, 1 (3%) was of Asian lineage, and 1 each were of Black African American or Black Hispanic background. The remaining children were classified as “other” or did not have their ethnic backgrounds recorded.

The “striking prevalence” of Hispanic patients observed in the study is consistent with surveillance reports of an increasing incidence of melanoma among children of Hispanic background, they noted.

The mean age at diagnosis was 12.7 years, and the mean age at death was 15.6 years.

Of the 16 cases with known identifiable disease subtypes, 8 (50%) were nodular, 5 (31%) were superficial spreading, and 3 (19%) were spitzoid melanomas. Of the 38 fatal melanomas, 10 were thought to have originated from congenital melanocytic nevi.
 

Outlook improving

Recent therapeutic breakthroughs such as targeted agents and immunotherapy with checkpoint inhibitors augur well for children diagnosed with melanoma, Dr. Hawryluk said.

“Fortunately, it’s not superaggressive in children at high frequency, so we generally use adult algorithms to inform treatment decisions,” she said. “It’s just important to note that melanomas that arise in congenital nevi tend to have different driver mutations than those that arise in older patients who may have lots of sun exposure.”

“Nowadays, we’re lucky to have a lot of extra tests and workups so that, if a patient does have metastatic or advance disease, they can have a better genetic profile that would guide our choice of medications,” she added.

The study was supported by a Pediatric Dermatology Research Alliance Study Support grant and Society for Pediatric Dermatology, Pediatric Dermatology Research Alliance Pilot award. Dr. Hawryluk is supported by the Dermatology Foundation and the Harvard Medical School Eleanor and Miles Shore Fellowship award. The authors reported no conflicts of interest.

SOURCE: Hawryluk EB et al. J Am Acad Dermatol. 2020 Jul 1. doi: 10.1016/j.jaad.2020.06.1010.

With an average age of diagnosis of 28 years, and one of two incidence peaks occurring at 15-30 years, psoriasis affects many women in the midst of their reproductive years. The prospect of pregnancy – or the reality of a surprise pregnancy – drives questions about heritability of the disease in offspring, the impact of the disease on pregnancy outcomes and breastfeeding, and how to best balance risks of treatments with risks of uncontrolled psoriasis and/or psoriatic arthritis (PsA).

shironosov/Getty Images

While answers to these questions are not always clear, discussions about pregnancy and psoriasis management “shouldn’t be scary,” said Jenny E. Murase, MD, a dermatologist who speaks and writes widely about her research and experience with psoriasis and pregnancy. “We have access to information and data and educational resources to [work with] and reassure our patients – we just need to use it. Right now, there’s unnecessary suffering [with some patients unnecessarily stopping all treatment].”

Much has been learned in the past 2 decades about the course of psoriasis in pregnancy, and pregnancy outcomes data on the safety of biologics during pregnancy are increasingly emerging – particularly for tumor necrosis factor (TNF)–alpha inhibitors.

Ideally, since half of all pregnancies are unplanned, the implications of therapeutic options should be discussed with all women with psoriasis who are of reproductive age, whether they are sexually active or not. “The onus is on us to make sure that we’re considering the possibility [that our patient] could become pregnant without consulting us first,” said Dr. Murase, associate professor of dermatology at the University of California, San Francisco, and director of medical consultative dermatology for the Palo Alto Foundation Medical Group in Mountain View, Calif.

Lisa R. Sammaritano, MD, associate professor of clinical medicine at Weill Cornell Medicine and a rheumatologist at the Hospital for Special Surgery, both in New York, urges similar attention for PsA. “Pregnancy is best planned while patients have quiescent disease on pregnancy-compatible medications,” she said. “We encourage [more] rheumatologists to be actively involved in pregnancy planning [in order] to guide therapy.”

The impact of estrogen

Dr. Murase was inspired to study psoriasis and pregnancy in part by a patient she met as a medical student. “She had severe psoriasis covering her body, and she said that the only times her psoriasis cleared was during her three pregnancies,” Dr. Murase recalled. “I wondered: What about the pregnancies resulted in such a substantial reduction of her psoriasis?”

She subsequently led a study, published in 2005, of 47 pregnant and 27 nonpregnant patients with psoriasis. More than half of the patients – 55% – reported improvements in their psoriasis during pregnancy, 21% reported no change, and 23% reported worsening. Among the 16 patients who had 10% or greater psoriatic body surface area (BSA) involvement and reported improvements, lesions decreased by 84%.

In the postpartum period, only 9% reported improvement, 26% reported no change, and 65% reported worsening. The increased BSA values observed 6 weeks postpartum did not exceed those of the first trimester, suggesting a return to the patients’ baseline status.

Earlier and smaller retrospective studies had also shown that approximately half of patients improve during pregnancy, and it was believed that progesterone was most likely responsible for this improvement. Dr. Murase’s study moved the needle in that it examined BSA in pregnancy and the postpartum period. It also turned the spotlight on estrogen: Patients who had higher levels of improvement also had higher levels of estradiol, estrone, and the ratio of estrogen to progesterone. However, there was no correlation between psoriatic change and levels of progesterone.

To promote fetal survival, pregnancy triggers a shift from Th1 cell–mediated immunity – and Th17 immunity – to Th2 immunity. While there’s no proof of a causative effect, increased estrogen appears to play a role in this shift and in the reduced production of Th1 and Th17 cytokines. Psoriasis is believed to be primarily a Th17-mediated disease, with some Th1 involvement, so this down-regulation can result in improved disease status, Dr. Murase said. (A host of other autoimmune diseases categorized as Th1 mediated similarly tend to improve during pregnancy, she added.)

Information on the effect of pregnancy on PsA is “conflicting,” Dr. Sammaritano said. “Some [of a limited number of studies] suggest a beneficial effect as is generally seen for rheumatoid arthritis. Others, however, have found an increased risk of disease activity during pregnancy ... It may be that psoriatic arthritis can be quite variable from patient to patient in its clinical presentation.”

At least one study, Dr. Sammaritano added, “has shown that the arthritis in pregnancy patients with PsA did not improve, compared to control nonpregnant patients, while the psoriasis rash did improve.”

The mixed findings don’t surprise Dr. Murase. “It harder to quantify joint disease in general,” she said. “And during pregnancy, physiologic changes relating to the pregnancy itself can cause discomfort – your joints ache. The numbers [of improved] cases aren’t as high with PsA, but it’s a more complex question.”

In the postpartum period, however, research findings “all suggest an increased risk of flare” of PsA, Dr. Sammaritano said, just as with psoriasis.
 

Assessing risk of treatment

Understanding the immunologic effects of pregnancy on psoriasis and PsA – and appreciating the concept of a hormonal component – is an important part of treatment decision making. So is understanding pregnancy outcomes data.

Researchers have looked at a host of pregnancy outcomes – including congenital malformations, preterm birth, spontaneous abortion, low birth weight, macrosomia, and gestational diabetes and hypertension – in women with psoriasis or psoriasis/PsA, compared with control groups. Some studies have suggested a link between disease activity and pregnancy complications or adverse pregnancy outcomes, “just as a result of having moderate to severe disease,” while others have found no evidence of increased risk, Dr. Murase said.

“It’s a bit unclear and a difficult question to answer; it depends on what study you look at and what data you believe. It would be nice to have some clarity, but basically the jury is still out,” said Dr. Murase, who, with coauthors Alice B. Gottlieb, MD, PhD, of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and Caitriona Ryan, MD, of the Blackrock Clinic and Charles Institute of Dermatology, University College Dublin, discussed the pregnancy outcomes data in a recently published review of psoriasis in women.

“In my opinion, because we have therapies that are so low risk and well tolerated, it’s better to make sure that the inflammatory cascade and inflammation created by psoriasis is under control,” she said. “So whether or not the pregnancy itself causes the patient to go into remission, or whether you have to use therapy to help the patient stay in remission, it’s important to control the inflammation.”

Contraindicated in pregnancy are oral psoralen, methotrexate, and acitretin, the latter of which should be avoided for several years before pregnancy and “therefore shouldn’t be used in a woman of childbearing age,” said Dr. Murase. Methotrexate, said Dr. Sammaritano, should generally be stopped 1-3 months prior to conception.

For psoriasis, the therapy that’s “classically considered the safest in pregnancy is UVB light therapy, specifically the 300-nm wavelength of light, which works really well as an anti-inflammatory,” Dr. Murase said. Because of the potential for maternal folate degradation with phototherapy and the long-known association of folate deficiency with neural tube defects, women of childbearing age who are receiving light therapy should take daily folic acid supplementation. (She prescribes a daily prenatal vitamin containing at least 1 mg of folic acid for women who are utilizing light therapy.)

Many topical agents can be used during pregnancy, Dr. Murase said. Topical corticosteroids, she noted, have the most safety-affirming data of any topical medication.

Regarding oral therapies, Dr. Murase recommends against the use of apremilast (Otezla) for her patients. “It’s not contraindicated, but the animal studies don’t look promising, so I don’t use that one in women of childbearing age just in case. There’s just very little data to support the safety of this medication [in pregnancy].”

There are no therapeutic guidelines in the United States for guiding the management of psoriasis in women who are considering pregnancy. In 2012, the medical board of the National Psoriasis Foundation published a review of treatment options for psoriasis in pregnant or lactating women, the “closest thing to guidelines that we’ve had,” said Dr. Murase. (Now almost a decade old, the review addresses TNF inhibitors but does not cover the anti-interleukin agents more recently approved for moderate to severe psoriasis and PsA.)

For treating PsA, rheumatologists now have the American College of Rheumatology’s first guideline for the management of reproductive health in rheumatic and musculoskeletal diseases to reference. The 2020 guideline does not address PsA specifically, but its section on pregnancy and lactation includes recommendations on biologic and other therapies used to treat the disease.

Guidelines aside, physician-patient discussions over drug safety have the potential to be much more meaningful now that drug labels offer clinical summaries, data, and risk summaries regarding potential use in pregnancy. The labels have “more of a narrative, which is a more useful way to counsel patients and make risk-benefit decisions” than the former system of five-letter categories, said Dr. Murase. (The changes were made per the Pregnancy and Lactation Labeling Rule of 2015.)

MothertoBaby, a service of the nonprofit Organization of Teratology Information Specialists, also provides good evidence-based information to physicians and mothers, Dr. Sammaritano noted.

The use of biologic therapies

In a 2017 review of biologic safety for patients with psoriasis during pregnancy, Alexa B. Kimball, MD, MPH, professor of dermatology at Harvard Medical School, Boston; Martina L. Porter, MD, currently with the department of dermatology at Beth Israel Deaconess Medical Center, Boston; and Stephen J. Lockwood, MD, MPH, of the department of dermatology at Harvard Medical School, concluded that an increasing body of literature suggests that biologic agents can be used during pregnancy and breastfeeding. Anti-TNF agents “should be considered over IL-12/23 and IL-17 inhibitors due to the increased availability of long-term data,” they wrote.

“In general,” said Dr. Murase, “there’s more and more data coming out from gastroenterology and rheumatology to reassure patients and prescribing physicians that the TNF-blocker class is likely safe to use in pregnancy,” particularly during the first trimester and early second trimester, when the transport of maternal antibodies across the placenta is “essentially nonexistent.” In the third trimester, the active transport of IgG antibodies increases rapidly.

If possible, said Dr. Sammaritano, who served as lead author of the ACR’s reproductive health guideline, TNF inhibitors “will be stopped prior to the third trimester to avoid [the possibility of] high drug levels in the infant at birth, which raises concern for immunosuppression in the newborn. If disease is very active, however, they can be continued throughout the pregnancy.”

The TNF inhibitor certolizumab pegol (Cimzia) has the advantage of being transported only minimally across the placenta, if at all, she and Dr. Murase both explained. “To be actively carried across, antibodies need what’s called an Fc region for the placenta to grab onto,” Dr. Murase said. Certolizumab – a pegylated anti–binding fragment antibody – lacks this Fc region.

Two recent studies – CRIB and a UCB Pharma safety database analysis – showed “essentially no medication crossing – there were barely detectable levels,” Dr. Murase said. Certolizumab’s label contains this information and other clinical trial data as well as findings from safety database analyses/surveillance registries.

“Before we had much data for the biologics, I’d advise transitioning patients to light therapy from their biologics and a lot of times their psoriasis would improve, but it was more of a dance,” she said. “Now we tend to look at [certolizumab] when they’re of childbearing age and keep them on the treatment. I know that the baby is not being immunosuppressed.”

Consideration of the use of certolizumab when treatment with biologic agents is required throughout the pregnancy is a recommendation included in Dr. Kimball’s 2017 review.

As newer anti-interleukin agents – the IL-12/23 and IL-17 inhibitors – play a growing role in the treatment of psoriasis and PsA, questions loom about their safety profile. Dr. Murase and Dr. Sammaritano are waiting for more data. “In general,” Dr. Sammaritano said, “we recommend stopping them at the time pregnancy is detected, based on a lack of data at this time.”

Small-molecule drugs are also less well studied, she noted. “Because of their low molecular weight, we anticipate they will easily cross the placenta, so we recommend avoiding use during pregnancy until more information is available.”

Postpartum care

The good news, both experts say, is that the vast majority of medications, including biologics, are safe to use during breastfeeding. Methotrexate should be avoided, Dr. Sammaritano pointed out, and the impact of novel small-molecule therapies on breast milk has not been studied.

In her 2019 review of psoriasis in women, Dr. Murase and coauthors wrote that too many dermatologists believe that breastfeeding women should either not be on biologics or are uncertain about biologic use during breastfeeding. However, “biologics are considered compatible for use while breastfeeding due to their large molecular size and the proteolytic environment in the neonatal gastrointestinal tract,” they added.

Counseling and support for breastfeeding is especially important for women with psoriasis, Dr. Murase emphasized. “Breastfeeding is very traumatizing to the skin, and psoriasis can form in skin that’s injured. I have my patients set up an office visit very soon after the pregnancy to make sure they’re doing alright with their breastfeeding and that they’re coating their nipple area with some type of moisturizer and keeping the health of their nipples in good shape.”

Timely reviews of therapy and adjustments are also a priority, she said. “We need to prepare for 6 weeks post partum” when psoriasis will often flare without treatment.

Dr. Murase disclosed that she is a consultant for Dermira, UCB Pharma, Sanofi, Ferndale, and Regeneron. She is also coeditor in chief of the International Journal of Women’s Dermatology. Dr. Sammaritano reported that she has no disclosures relating to the treatment of PsA.

With an average age of diagnosis of 28 years, and one of two incidence peaks occurring at 15-30 years, psoriasis affects many women in the midst of their reproductive years. The prospect of pregnancy – or the reality of a surprise pregnancy – drives questions about heritability of the disease in offspring, the impact of the disease on pregnancy outcomes and breastfeeding, and how to best balance risks of treatments with risks of uncontrolled psoriasis and/or psoriatic arthritis (PsA).

shironosov/Getty Images

While answers to these questions are not always clear, discussions about pregnancy and psoriasis management “shouldn’t be scary,” said Jenny E. Murase, MD, a dermatologist who speaks and writes widely about her research and experience with psoriasis and pregnancy. “We have access to information and data and educational resources to [work with] and reassure our patients – we just need to use it. Right now, there’s unnecessary suffering [with some patients unnecessarily stopping all treatment].”

Much has been learned in the past 2 decades about the course of psoriasis in pregnancy, and pregnancy outcomes data on the safety of biologics during pregnancy are increasingly emerging – particularly for tumor necrosis factor (TNF)–alpha inhibitors.

Ideally, since half of all pregnancies are unplanned, the implications of therapeutic options should be discussed with all women with psoriasis who are of reproductive age, whether they are sexually active or not. “The onus is on us to make sure that we’re considering the possibility [that our patient] could become pregnant without consulting us first,” said Dr. Murase, associate professor of dermatology at the University of California, San Francisco, and director of medical consultative dermatology for the Palo Alto Foundation Medical Group in Mountain View, Calif.

Lisa R. Sammaritano, MD, associate professor of clinical medicine at Weill Cornell Medicine and a rheumatologist at the Hospital for Special Surgery, both in New York, urges similar attention for PsA. “Pregnancy is best planned while patients have quiescent disease on pregnancy-compatible medications,” she said. “We encourage [more] rheumatologists to be actively involved in pregnancy planning [in order] to guide therapy.”

The impact of estrogen

Dr. Murase was inspired to study psoriasis and pregnancy in part by a patient she met as a medical student. “She had severe psoriasis covering her body, and she said that the only times her psoriasis cleared was during her three pregnancies,” Dr. Murase recalled. “I wondered: What about the pregnancies resulted in such a substantial reduction of her psoriasis?”

She subsequently led a study, published in 2005, of 47 pregnant and 27 nonpregnant patients with psoriasis. More than half of the patients – 55% – reported improvements in their psoriasis during pregnancy, 21% reported no change, and 23% reported worsening. Among the 16 patients who had 10% or greater psoriatic body surface area (BSA) involvement and reported improvements, lesions decreased by 84%.

In the postpartum period, only 9% reported improvement, 26% reported no change, and 65% reported worsening. The increased BSA values observed 6 weeks postpartum did not exceed those of the first trimester, suggesting a return to the patients’ baseline status.

Earlier and smaller retrospective studies had also shown that approximately half of patients improve during pregnancy, and it was believed that progesterone was most likely responsible for this improvement. Dr. Murase’s study moved the needle in that it examined BSA in pregnancy and the postpartum period. It also turned the spotlight on estrogen: Patients who had higher levels of improvement also had higher levels of estradiol, estrone, and the ratio of estrogen to progesterone. However, there was no correlation between psoriatic change and levels of progesterone.

To promote fetal survival, pregnancy triggers a shift from Th1 cell–mediated immunity – and Th17 immunity – to Th2 immunity. While there’s no proof of a causative effect, increased estrogen appears to play a role in this shift and in the reduced production of Th1 and Th17 cytokines. Psoriasis is believed to be primarily a Th17-mediated disease, with some Th1 involvement, so this down-regulation can result in improved disease status, Dr. Murase said. (A host of other autoimmune diseases categorized as Th1 mediated similarly tend to improve during pregnancy, she added.)

Information on the effect of pregnancy on PsA is “conflicting,” Dr. Sammaritano said. “Some [of a limited number of studies] suggest a beneficial effect as is generally seen for rheumatoid arthritis. Others, however, have found an increased risk of disease activity during pregnancy ... It may be that psoriatic arthritis can be quite variable from patient to patient in its clinical presentation.”

At least one study, Dr. Sammaritano added, “has shown that the arthritis in pregnancy patients with PsA did not improve, compared to control nonpregnant patients, while the psoriasis rash did improve.”

The mixed findings don’t surprise Dr. Murase. “It harder to quantify joint disease in general,” she said. “And during pregnancy, physiologic changes relating to the pregnancy itself can cause discomfort – your joints ache. The numbers [of improved] cases aren’t as high with PsA, but it’s a more complex question.”

In the postpartum period, however, research findings “all suggest an increased risk of flare” of PsA, Dr. Sammaritano said, just as with psoriasis.
 

Assessing risk of treatment

Understanding the immunologic effects of pregnancy on psoriasis and PsA – and appreciating the concept of a hormonal component – is an important part of treatment decision making. So is understanding pregnancy outcomes data.

Researchers have looked at a host of pregnancy outcomes – including congenital malformations, preterm birth, spontaneous abortion, low birth weight, macrosomia, and gestational diabetes and hypertension – in women with psoriasis or psoriasis/PsA, compared with control groups. Some studies have suggested a link between disease activity and pregnancy complications or adverse pregnancy outcomes, “just as a result of having moderate to severe disease,” while others have found no evidence of increased risk, Dr. Murase said.

“It’s a bit unclear and a difficult question to answer; it depends on what study you look at and what data you believe. It would be nice to have some clarity, but basically the jury is still out,” said Dr. Murase, who, with coauthors Alice B. Gottlieb, MD, PhD, of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and Caitriona Ryan, MD, of the Blackrock Clinic and Charles Institute of Dermatology, University College Dublin, discussed the pregnancy outcomes data in a recently published review of psoriasis in women.

“In my opinion, because we have therapies that are so low risk and well tolerated, it’s better to make sure that the inflammatory cascade and inflammation created by psoriasis is under control,” she said. “So whether or not the pregnancy itself causes the patient to go into remission, or whether you have to use therapy to help the patient stay in remission, it’s important to control the inflammation.”

Contraindicated in pregnancy are oral psoralen, methotrexate, and acitretin, the latter of which should be avoided for several years before pregnancy and “therefore shouldn’t be used in a woman of childbearing age,” said Dr. Murase. Methotrexate, said Dr. Sammaritano, should generally be stopped 1-3 months prior to conception.

For psoriasis, the therapy that’s “classically considered the safest in pregnancy is UVB light therapy, specifically the 300-nm wavelength of light, which works really well as an anti-inflammatory,” Dr. Murase said. Because of the potential for maternal folate degradation with phototherapy and the long-known association of folate deficiency with neural tube defects, women of childbearing age who are receiving light therapy should take daily folic acid supplementation. (She prescribes a daily prenatal vitamin containing at least 1 mg of folic acid for women who are utilizing light therapy.)

Many topical agents can be used during pregnancy, Dr. Murase said. Topical corticosteroids, she noted, have the most safety-affirming data of any topical medication.

Regarding oral therapies, Dr. Murase recommends against the use of apremilast (Otezla) for her patients. “It’s not contraindicated, but the animal studies don’t look promising, so I don’t use that one in women of childbearing age just in case. There’s just very little data to support the safety of this medication [in pregnancy].”

There are no therapeutic guidelines in the United States for guiding the management of psoriasis in women who are considering pregnancy. In 2012, the medical board of the National Psoriasis Foundation published a review of treatment options for psoriasis in pregnant or lactating women, the “closest thing to guidelines that we’ve had,” said Dr. Murase. (Now almost a decade old, the review addresses TNF inhibitors but does not cover the anti-interleukin agents more recently approved for moderate to severe psoriasis and PsA.)

For treating PsA, rheumatologists now have the American College of Rheumatology’s first guideline for the management of reproductive health in rheumatic and musculoskeletal diseases to reference. The 2020 guideline does not address PsA specifically, but its section on pregnancy and lactation includes recommendations on biologic and other therapies used to treat the disease.

Guidelines aside, physician-patient discussions over drug safety have the potential to be much more meaningful now that drug labels offer clinical summaries, data, and risk summaries regarding potential use in pregnancy. The labels have “more of a narrative, which is a more useful way to counsel patients and make risk-benefit decisions” than the former system of five-letter categories, said Dr. Murase. (The changes were made per the Pregnancy and Lactation Labeling Rule of 2015.)

MothertoBaby, a service of the nonprofit Organization of Teratology Information Specialists, also provides good evidence-based information to physicians and mothers, Dr. Sammaritano noted.

The use of biologic therapies

In a 2017 review of biologic safety for patients with psoriasis during pregnancy, Alexa B. Kimball, MD, MPH, professor of dermatology at Harvard Medical School, Boston; Martina L. Porter, MD, currently with the department of dermatology at Beth Israel Deaconess Medical Center, Boston; and Stephen J. Lockwood, MD, MPH, of the department of dermatology at Harvard Medical School, concluded that an increasing body of literature suggests that biologic agents can be used during pregnancy and breastfeeding. Anti-TNF agents “should be considered over IL-12/23 and IL-17 inhibitors due to the increased availability of long-term data,” they wrote.

“In general,” said Dr. Murase, “there’s more and more data coming out from gastroenterology and rheumatology to reassure patients and prescribing physicians that the TNF-blocker class is likely safe to use in pregnancy,” particularly during the first trimester and early second trimester, when the transport of maternal antibodies across the placenta is “essentially nonexistent.” In the third trimester, the active transport of IgG antibodies increases rapidly.

If possible, said Dr. Sammaritano, who served as lead author of the ACR’s reproductive health guideline, TNF inhibitors “will be stopped prior to the third trimester to avoid [the possibility of] high drug levels in the infant at birth, which raises concern for immunosuppression in the newborn. If disease is very active, however, they can be continued throughout the pregnancy.”

The TNF inhibitor certolizumab pegol (Cimzia) has the advantage of being transported only minimally across the placenta, if at all, she and Dr. Murase both explained. “To be actively carried across, antibodies need what’s called an Fc region for the placenta to grab onto,” Dr. Murase said. Certolizumab – a pegylated anti–binding fragment antibody – lacks this Fc region.

Two recent studies – CRIB and a UCB Pharma safety database analysis – showed “essentially no medication crossing – there were barely detectable levels,” Dr. Murase said. Certolizumab’s label contains this information and other clinical trial data as well as findings from safety database analyses/surveillance registries.

“Before we had much data for the biologics, I’d advise transitioning patients to light therapy from their biologics and a lot of times their psoriasis would improve, but it was more of a dance,” she said. “Now we tend to look at [certolizumab] when they’re of childbearing age and keep them on the treatment. I know that the baby is not being immunosuppressed.”

Consideration of the use of certolizumab when treatment with biologic agents is required throughout the pregnancy is a recommendation included in Dr. Kimball’s 2017 review.

As newer anti-interleukin agents – the IL-12/23 and IL-17 inhibitors – play a growing role in the treatment of psoriasis and PsA, questions loom about their safety profile. Dr. Murase and Dr. Sammaritano are waiting for more data. “In general,” Dr. Sammaritano said, “we recommend stopping them at the time pregnancy is detected, based on a lack of data at this time.”

Small-molecule drugs are also less well studied, she noted. “Because of their low molecular weight, we anticipate they will easily cross the placenta, so we recommend avoiding use during pregnancy until more information is available.”

Postpartum care

The good news, both experts say, is that the vast majority of medications, including biologics, are safe to use during breastfeeding. Methotrexate should be avoided, Dr. Sammaritano pointed out, and the impact of novel small-molecule therapies on breast milk has not been studied.

In her 2019 review of psoriasis in women, Dr. Murase and coauthors wrote that too many dermatologists believe that breastfeeding women should either not be on biologics or are uncertain about biologic use during breastfeeding. However, “biologics are considered compatible for use while breastfeeding due to their large molecular size and the proteolytic environment in the neonatal gastrointestinal tract,” they added.

Counseling and support for breastfeeding is especially important for women with psoriasis, Dr. Murase emphasized. “Breastfeeding is very traumatizing to the skin, and psoriasis can form in skin that’s injured. I have my patients set up an office visit very soon after the pregnancy to make sure they’re doing alright with their breastfeeding and that they’re coating their nipple area with some type of moisturizer and keeping the health of their nipples in good shape.”

Timely reviews of therapy and adjustments are also a priority, she said. “We need to prepare for 6 weeks post partum” when psoriasis will often flare without treatment.

Dr. Murase disclosed that she is a consultant for Dermira, UCB Pharma, Sanofi, Ferndale, and Regeneron. She is also coeditor in chief of the International Journal of Women’s Dermatology. Dr. Sammaritano reported that she has no disclosures relating to the treatment of PsA.

With an average age of diagnosis of 28 years, and one of two incidence peaks occurring at 15-30 years, psoriasis affects many women in the midst of their reproductive years. The prospect of pregnancy – or the reality of a surprise pregnancy – drives questions about heritability of the disease in offspring, the impact of the disease on pregnancy outcomes and breastfeeding, and how to best balance risks of treatments with risks of uncontrolled psoriasis and/or psoriatic arthritis (PsA).

shironosov/Getty Images

While answers to these questions are not always clear, discussions about pregnancy and psoriasis management “shouldn’t be scary,” said Jenny E. Murase, MD, a dermatologist who speaks and writes widely about her research and experience with psoriasis and pregnancy. “We have access to information and data and educational resources to [work with] and reassure our patients – we just need to use it. Right now, there’s unnecessary suffering [with some patients unnecessarily stopping all treatment].”

Much has been learned in the past 2 decades about the course of psoriasis in pregnancy, and pregnancy outcomes data on the safety of biologics during pregnancy are increasingly emerging – particularly for tumor necrosis factor (TNF)–alpha inhibitors.

Ideally, since half of all pregnancies are unplanned, the implications of therapeutic options should be discussed with all women with psoriasis who are of reproductive age, whether they are sexually active or not. “The onus is on us to make sure that we’re considering the possibility [that our patient] could become pregnant without consulting us first,” said Dr. Murase, associate professor of dermatology at the University of California, San Francisco, and director of medical consultative dermatology for the Palo Alto Foundation Medical Group in Mountain View, Calif.

Lisa R. Sammaritano, MD, associate professor of clinical medicine at Weill Cornell Medicine and a rheumatologist at the Hospital for Special Surgery, both in New York, urges similar attention for PsA. “Pregnancy is best planned while patients have quiescent disease on pregnancy-compatible medications,” she said. “We encourage [more] rheumatologists to be actively involved in pregnancy planning [in order] to guide therapy.”

The impact of estrogen

Dr. Murase was inspired to study psoriasis and pregnancy in part by a patient she met as a medical student. “She had severe psoriasis covering her body, and she said that the only times her psoriasis cleared was during her three pregnancies,” Dr. Murase recalled. “I wondered: What about the pregnancies resulted in such a substantial reduction of her psoriasis?”

She subsequently led a study, published in 2005, of 47 pregnant and 27 nonpregnant patients with psoriasis. More than half of the patients – 55% – reported improvements in their psoriasis during pregnancy, 21% reported no change, and 23% reported worsening. Among the 16 patients who had 10% or greater psoriatic body surface area (BSA) involvement and reported improvements, lesions decreased by 84%.

In the postpartum period, only 9% reported improvement, 26% reported no change, and 65% reported worsening. The increased BSA values observed 6 weeks postpartum did not exceed those of the first trimester, suggesting a return to the patients’ baseline status.

Earlier and smaller retrospective studies had also shown that approximately half of patients improve during pregnancy, and it was believed that progesterone was most likely responsible for this improvement. Dr. Murase’s study moved the needle in that it examined BSA in pregnancy and the postpartum period. It also turned the spotlight on estrogen: Patients who had higher levels of improvement also had higher levels of estradiol, estrone, and the ratio of estrogen to progesterone. However, there was no correlation between psoriatic change and levels of progesterone.

To promote fetal survival, pregnancy triggers a shift from Th1 cell–mediated immunity – and Th17 immunity – to Th2 immunity. While there’s no proof of a causative effect, increased estrogen appears to play a role in this shift and in the reduced production of Th1 and Th17 cytokines. Psoriasis is believed to be primarily a Th17-mediated disease, with some Th1 involvement, so this down-regulation can result in improved disease status, Dr. Murase said. (A host of other autoimmune diseases categorized as Th1 mediated similarly tend to improve during pregnancy, she added.)

Information on the effect of pregnancy on PsA is “conflicting,” Dr. Sammaritano said. “Some [of a limited number of studies] suggest a beneficial effect as is generally seen for rheumatoid arthritis. Others, however, have found an increased risk of disease activity during pregnancy ... It may be that psoriatic arthritis can be quite variable from patient to patient in its clinical presentation.”

At least one study, Dr. Sammaritano added, “has shown that the arthritis in pregnancy patients with PsA did not improve, compared to control nonpregnant patients, while the psoriasis rash did improve.”

The mixed findings don’t surprise Dr. Murase. “It harder to quantify joint disease in general,” she said. “And during pregnancy, physiologic changes relating to the pregnancy itself can cause discomfort – your joints ache. The numbers [of improved] cases aren’t as high with PsA, but it’s a more complex question.”

In the postpartum period, however, research findings “all suggest an increased risk of flare” of PsA, Dr. Sammaritano said, just as with psoriasis.
 

Assessing risk of treatment

Understanding the immunologic effects of pregnancy on psoriasis and PsA – and appreciating the concept of a hormonal component – is an important part of treatment decision making. So is understanding pregnancy outcomes data.

Researchers have looked at a host of pregnancy outcomes – including congenital malformations, preterm birth, spontaneous abortion, low birth weight, macrosomia, and gestational diabetes and hypertension – in women with psoriasis or psoriasis/PsA, compared with control groups. Some studies have suggested a link between disease activity and pregnancy complications or adverse pregnancy outcomes, “just as a result of having moderate to severe disease,” while others have found no evidence of increased risk, Dr. Murase said.

“It’s a bit unclear and a difficult question to answer; it depends on what study you look at and what data you believe. It would be nice to have some clarity, but basically the jury is still out,” said Dr. Murase, who, with coauthors Alice B. Gottlieb, MD, PhD, of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and Caitriona Ryan, MD, of the Blackrock Clinic and Charles Institute of Dermatology, University College Dublin, discussed the pregnancy outcomes data in a recently published review of psoriasis in women.

“In my opinion, because we have therapies that are so low risk and well tolerated, it’s better to make sure that the inflammatory cascade and inflammation created by psoriasis is under control,” she said. “So whether or not the pregnancy itself causes the patient to go into remission, or whether you have to use therapy to help the patient stay in remission, it’s important to control the inflammation.”

Contraindicated in pregnancy are oral psoralen, methotrexate, and acitretin, the latter of which should be avoided for several years before pregnancy and “therefore shouldn’t be used in a woman of childbearing age,” said Dr. Murase. Methotrexate, said Dr. Sammaritano, should generally be stopped 1-3 months prior to conception.

For psoriasis, the therapy that’s “classically considered the safest in pregnancy is UVB light therapy, specifically the 300-nm wavelength of light, which works really well as an anti-inflammatory,” Dr. Murase said. Because of the potential for maternal folate degradation with phototherapy and the long-known association of folate deficiency with neural tube defects, women of childbearing age who are receiving light therapy should take daily folic acid supplementation. (She prescribes a daily prenatal vitamin containing at least 1 mg of folic acid for women who are utilizing light therapy.)

Many topical agents can be used during pregnancy, Dr. Murase said. Topical corticosteroids, she noted, have the most safety-affirming data of any topical medication.

Regarding oral therapies, Dr. Murase recommends against the use of apremilast (Otezla) for her patients. “It’s not contraindicated, but the animal studies don’t look promising, so I don’t use that one in women of childbearing age just in case. There’s just very little data to support the safety of this medication [in pregnancy].”

There are no therapeutic guidelines in the United States for guiding the management of psoriasis in women who are considering pregnancy. In 2012, the medical board of the National Psoriasis Foundation published a review of treatment options for psoriasis in pregnant or lactating women, the “closest thing to guidelines that we’ve had,” said Dr. Murase. (Now almost a decade old, the review addresses TNF inhibitors but does not cover the anti-interleukin agents more recently approved for moderate to severe psoriasis and PsA.)

For treating PsA, rheumatologists now have the American College of Rheumatology’s first guideline for the management of reproductive health in rheumatic and musculoskeletal diseases to reference. The 2020 guideline does not address PsA specifically, but its section on pregnancy and lactation includes recommendations on biologic and other therapies used to treat the disease.

Guidelines aside, physician-patient discussions over drug safety have the potential to be much more meaningful now that drug labels offer clinical summaries, data, and risk summaries regarding potential use in pregnancy. The labels have “more of a narrative, which is a more useful way to counsel patients and make risk-benefit decisions” than the former system of five-letter categories, said Dr. Murase. (The changes were made per the Pregnancy and Lactation Labeling Rule of 2015.)

MothertoBaby, a service of the nonprofit Organization of Teratology Information Specialists, also provides good evidence-based information to physicians and mothers, Dr. Sammaritano noted.

The use of biologic therapies

In a 2017 review of biologic safety for patients with psoriasis during pregnancy, Alexa B. Kimball, MD, MPH, professor of dermatology at Harvard Medical School, Boston; Martina L. Porter, MD, currently with the department of dermatology at Beth Israel Deaconess Medical Center, Boston; and Stephen J. Lockwood, MD, MPH, of the department of dermatology at Harvard Medical School, concluded that an increasing body of literature suggests that biologic agents can be used during pregnancy and breastfeeding. Anti-TNF agents “should be considered over IL-12/23 and IL-17 inhibitors due to the increased availability of long-term data,” they wrote.

“In general,” said Dr. Murase, “there’s more and more data coming out from gastroenterology and rheumatology to reassure patients and prescribing physicians that the TNF-blocker class is likely safe to use in pregnancy,” particularly during the first trimester and early second trimester, when the transport of maternal antibodies across the placenta is “essentially nonexistent.” In the third trimester, the active transport of IgG antibodies increases rapidly.

If possible, said Dr. Sammaritano, who served as lead author of the ACR’s reproductive health guideline, TNF inhibitors “will be stopped prior to the third trimester to avoid [the possibility of] high drug levels in the infant at birth, which raises concern for immunosuppression in the newborn. If disease is very active, however, they can be continued throughout the pregnancy.”

The TNF inhibitor certolizumab pegol (Cimzia) has the advantage of being transported only minimally across the placenta, if at all, she and Dr. Murase both explained. “To be actively carried across, antibodies need what’s called an Fc region for the placenta to grab onto,” Dr. Murase said. Certolizumab – a pegylated anti–binding fragment antibody – lacks this Fc region.

Two recent studies – CRIB and a UCB Pharma safety database analysis – showed “essentially no medication crossing – there were barely detectable levels,” Dr. Murase said. Certolizumab’s label contains this information and other clinical trial data as well as findings from safety database analyses/surveillance registries.

“Before we had much data for the biologics, I’d advise transitioning patients to light therapy from their biologics and a lot of times their psoriasis would improve, but it was more of a dance,” she said. “Now we tend to look at [certolizumab] when they’re of childbearing age and keep them on the treatment. I know that the baby is not being immunosuppressed.”

Consideration of the use of certolizumab when treatment with biologic agents is required throughout the pregnancy is a recommendation included in Dr. Kimball’s 2017 review.

As newer anti-interleukin agents – the IL-12/23 and IL-17 inhibitors – play a growing role in the treatment of psoriasis and PsA, questions loom about their safety profile. Dr. Murase and Dr. Sammaritano are waiting for more data. “In general,” Dr. Sammaritano said, “we recommend stopping them at the time pregnancy is detected, based on a lack of data at this time.”

Small-molecule drugs are also less well studied, she noted. “Because of their low molecular weight, we anticipate they will easily cross the placenta, so we recommend avoiding use during pregnancy until more information is available.”

Postpartum care

The good news, both experts say, is that the vast majority of medications, including biologics, are safe to use during breastfeeding. Methotrexate should be avoided, Dr. Sammaritano pointed out, and the impact of novel small-molecule therapies on breast milk has not been studied.

In her 2019 review of psoriasis in women, Dr. Murase and coauthors wrote that too many dermatologists believe that breastfeeding women should either not be on biologics or are uncertain about biologic use during breastfeeding. However, “biologics are considered compatible for use while breastfeeding due to their large molecular size and the proteolytic environment in the neonatal gastrointestinal tract,” they added.

Counseling and support for breastfeeding is especially important for women with psoriasis, Dr. Murase emphasized. “Breastfeeding is very traumatizing to the skin, and psoriasis can form in skin that’s injured. I have my patients set up an office visit very soon after the pregnancy to make sure they’re doing alright with their breastfeeding and that they’re coating their nipple area with some type of moisturizer and keeping the health of their nipples in good shape.”

Timely reviews of therapy and adjustments are also a priority, she said. “We need to prepare for 6 weeks post partum” when psoriasis will often flare without treatment.

Dr. Murase disclosed that she is a consultant for Dermira, UCB Pharma, Sanofi, Ferndale, and Regeneron. She is also coeditor in chief of the International Journal of Women’s Dermatology. Dr. Sammaritano reported that she has no disclosures relating to the treatment of PsA.