Dermatology

Nearly all Americans say that sun protection is important, but almost half don’t use sunscreen regularly and more than a third believe that tanning is healthy, according to the results of a recent survey commissioned by the American Academy of Dermatology.

With the pandemic seemingly behind it, the United States enters the summer months facing the paradox of sun protection. Four out of five adults know that sunscreen should be reapplied every 2 hours when they’re outdoors, but only one in three make the actual effort, and 77% are likely to use sunscreen at the beach or a pool, compared with 41% when they’re gardening or working outside on their homes, the AAD reported.

“These findings are surprising and seem to suggest that many people do not take skin cancer seriously or perhaps believe skin cancer won’t happen to them,” Robert T. Brodell, MD, professor of dermatology at the University of Mississippi Medical Center, Jackson, said in a written statement from the AAD, adding that “unprotected exposure to ultraviolet rays is the most preventable risk factor for skin cancer, including melanoma.”

A quarter of all survey respondents reported getting sunburned in 2020, with the youngest adults most likely to feel the wrath of the sun. Sunburn was reported by 43% of those aged 18-23 years, 37% of those aged 24-39, 25% of the 40- to 55-year-olds, 12% of the 56- to 74-year-olds, and 7% of those aged 75 and older. More than a quarter of those who got sunburned said that it was bad enough to make their clothes feel uncomfortable, the academy said.

“Americans see the damaging effects of the sun on their skin as they get older, and two out of three look back and wish they had been more careful. But when it comes to cancer, specifically, most feel unconcerned in spite of their own risk,” according to a statement from Versta Research, which conducted the poll on behalf of the AAD. The survey was conducted from Feb. 22 to March 10, 2021, and involved 1,056 respondents, with a ±3% margin of error.

The lack of concern for skin cancer looks like this: More than two-thirds of the respondents (69%) have at least one possible risk factor – lighter skin tone, blue or green eyes, more than 50 moles, family history – but only 36% expressed concern about developing it. “Indeed, half of survey respondents (49%) say they are more worried about avoiding sunburn than they are about preventing skin cancer, and a third (32%) are more worried about avoiding premature wrinkles than they are about preventing cancer,” the AAD said.

The AAD is considering the creation of a social media quiz or interactive tool, and if the results of this survey were recast as a potential “Knowledge and Awareness Quiz” and graded with a traditional scheme (A = 90%-100%, B = 80%-89%, etc.), then 34% of the respondents would have failed, 15% would have gotten a D, and only 5% would have earned an A, the academy noted.

rfranki@mdedge.com

Nearly all Americans say that sun protection is important, but almost half don’t use sunscreen regularly and more than a third believe that tanning is healthy, according to the results of a recent survey commissioned by the American Academy of Dermatology.

With the pandemic seemingly behind it, the United States enters the summer months facing the paradox of sun protection. Four out of five adults know that sunscreen should be reapplied every 2 hours when they’re outdoors, but only one in three make the actual effort, and 77% are likely to use sunscreen at the beach or a pool, compared with 41% when they’re gardening or working outside on their homes, the AAD reported.

“These findings are surprising and seem to suggest that many people do not take skin cancer seriously or perhaps believe skin cancer won’t happen to them,” Robert T. Brodell, MD, professor of dermatology at the University of Mississippi Medical Center, Jackson, said in a written statement from the AAD, adding that “unprotected exposure to ultraviolet rays is the most preventable risk factor for skin cancer, including melanoma.”

A quarter of all survey respondents reported getting sunburned in 2020, with the youngest adults most likely to feel the wrath of the sun. Sunburn was reported by 43% of those aged 18-23 years, 37% of those aged 24-39, 25% of the 40- to 55-year-olds, 12% of the 56- to 74-year-olds, and 7% of those aged 75 and older. More than a quarter of those who got sunburned said that it was bad enough to make their clothes feel uncomfortable, the academy said.

“Americans see the damaging effects of the sun on their skin as they get older, and two out of three look back and wish they had been more careful. But when it comes to cancer, specifically, most feel unconcerned in spite of their own risk,” according to a statement from Versta Research, which conducted the poll on behalf of the AAD. The survey was conducted from Feb. 22 to March 10, 2021, and involved 1,056 respondents, with a ±3% margin of error.

The lack of concern for skin cancer looks like this: More than two-thirds of the respondents (69%) have at least one possible risk factor – lighter skin tone, blue or green eyes, more than 50 moles, family history – but only 36% expressed concern about developing it. “Indeed, half of survey respondents (49%) say they are more worried about avoiding sunburn than they are about preventing skin cancer, and a third (32%) are more worried about avoiding premature wrinkles than they are about preventing cancer,” the AAD said.

The AAD is considering the creation of a social media quiz or interactive tool, and if the results of this survey were recast as a potential “Knowledge and Awareness Quiz” and graded with a traditional scheme (A = 90%-100%, B = 80%-89%, etc.), then 34% of the respondents would have failed, 15% would have gotten a D, and only 5% would have earned an A, the academy noted.

rfranki@mdedge.com

Nearly all Americans say that sun protection is important, but almost half don’t use sunscreen regularly and more than a third believe that tanning is healthy, according to the results of a recent survey commissioned by the American Academy of Dermatology.

With the pandemic seemingly behind it, the United States enters the summer months facing the paradox of sun protection. Four out of five adults know that sunscreen should be reapplied every 2 hours when they’re outdoors, but only one in three make the actual effort, and 77% are likely to use sunscreen at the beach or a pool, compared with 41% when they’re gardening or working outside on their homes, the AAD reported.

“These findings are surprising and seem to suggest that many people do not take skin cancer seriously or perhaps believe skin cancer won’t happen to them,” Robert T. Brodell, MD, professor of dermatology at the University of Mississippi Medical Center, Jackson, said in a written statement from the AAD, adding that “unprotected exposure to ultraviolet rays is the most preventable risk factor for skin cancer, including melanoma.”

A quarter of all survey respondents reported getting sunburned in 2020, with the youngest adults most likely to feel the wrath of the sun. Sunburn was reported by 43% of those aged 18-23 years, 37% of those aged 24-39, 25% of the 40- to 55-year-olds, 12% of the 56- to 74-year-olds, and 7% of those aged 75 and older. More than a quarter of those who got sunburned said that it was bad enough to make their clothes feel uncomfortable, the academy said.

“Americans see the damaging effects of the sun on their skin as they get older, and two out of three look back and wish they had been more careful. But when it comes to cancer, specifically, most feel unconcerned in spite of their own risk,” according to a statement from Versta Research, which conducted the poll on behalf of the AAD. The survey was conducted from Feb. 22 to March 10, 2021, and involved 1,056 respondents, with a ±3% margin of error.

The lack of concern for skin cancer looks like this: More than two-thirds of the respondents (69%) have at least one possible risk factor – lighter skin tone, blue or green eyes, more than 50 moles, family history – but only 36% expressed concern about developing it. “Indeed, half of survey respondents (49%) say they are more worried about avoiding sunburn than they are about preventing skin cancer, and a third (32%) are more worried about avoiding premature wrinkles than they are about preventing cancer,” the AAD said.

The AAD is considering the creation of a social media quiz or interactive tool, and if the results of this survey were recast as a potential “Knowledge and Awareness Quiz” and graded with a traditional scheme (A = 90%-100%, B = 80%-89%, etc.), then 34% of the respondents would have failed, 15% would have gotten a D, and only 5% would have earned an A, the academy noted.

rfranki@mdedge.com

A large proportion of initial Investigator Global Assessment (IGA) 0/1 or Eczema Area and Severity Index (EASI) 75 responders at week 16 maintained response with continued tralokinumab dosing every 2 weeks or every 4 weeks during a 36-week maintenance period without the use of rescue medication including topical corticosteroids, results from a pooled analysis of two trials found.

“The interesting thing here is that there weren’t major differences in the maintenance dosing, which really allows us some flexibility with maintenance dosing for this particular drug,” lead study investigator Andrew Blauvelt, MD, MBA, said during the Revolutionizing Atopic Dermatitis symposium.

Administered subcutaneously, tralokinumab is a fully human IgG4 monoclonal antibody that specifically binds to interleukin-13, a key driver of underlying inflammation in AD. In two of the drug’s pivotal phase 3 trials, ECZTRA 1 and ECZTRA 2, tralokinumab monotherapy was superior to placebo at week 16 for all primary and secondary endpoints.

The purpose of the current trial was to investigate the maintenance of efficacy after 16 weeks of tralokinumab in those who were initial responders and to assess the efficacy of reduced dosing frequency from 300 mg every 2 weeks to 300 mg every 4 weeks after a 36-week maintenance phase. Patients who used rescue medication, including topical corticosteroids, were considered to be nonresponders.

Dr. Blauvelt reported results from 1,596 adult patients with a mean age of 38 years who were randomized to tralokinumab 300 mg every 2 weeks or placebo in the initial treatment period. At baseline, the mean duration of AD was 28.2 years, 50% had severe disease based on their IGA score, and their mean Dermatology Life Quality Index score was 17.

Of these patients, 412 achieved an IGA score of 0 or 1 and/or an EASI 75 at week 16 with tralokinumab every 2 weeks and were rerandomized (2:2:1) to continue tralokinumab 300 mg every 2 weeks, tralokinumab 300 mg every 4 weeks, or placebo for 36 weeks.

The researchers found that 56%-57% of patients in the tralokinumab every 2-week dosing group maintained their IGA 0/1 and EASI 75 response at week 52, compared with 42%-50% of those who received the drug every 4 weeks. “So, there may be a population of patients who require drug every 4 weeks after initially receiving the drug every 2 weeks for the first 16 weeks,” said Dr. Blauvelt, a dermatologist who is president of Oregon Medical Research Center, Portland. “Interestingly, 26%-34% of patients on placebo maintained their IGA 0/1 and EASI 75 response a response to week 52. Perhaps those are patients who have more mild disease or more episodic disease when they started this trial.”

He also noted that time to relapse based on their IGA 0/1 and EASI 75 was prolonged with tralokinumab treatment, compared with placebo, and adverse event frequency was similar among all treatment groups (73% among those who received tralokinumab every 2 weeks, 66% among those who received tralokinumab every 4 weeks, and 70% in the placebo group).

Dr. Blauvelt concluded that a step-down in tralokinumab dosing to every 4 weeks may be an option for some patients achieving clear or almost clear skin after an initial dosing schedule of every 2 weeks.

LEO Pharma, which is developing tralokinumab, sponsored the analysis. Dr. Blauvelt reported that he is an investigator and a scientific adviser for LEO Pharma and for several other pharmaceutical companies developing treatments for AD.

dbrunk@mdedge.com

A large proportion of initial Investigator Global Assessment (IGA) 0/1 or Eczema Area and Severity Index (EASI) 75 responders at week 16 maintained response with continued tralokinumab dosing every 2 weeks or every 4 weeks during a 36-week maintenance period without the use of rescue medication including topical corticosteroids, results from a pooled analysis of two trials found.

“The interesting thing here is that there weren’t major differences in the maintenance dosing, which really allows us some flexibility with maintenance dosing for this particular drug,” lead study investigator Andrew Blauvelt, MD, MBA, said during the Revolutionizing Atopic Dermatitis symposium.

Administered subcutaneously, tralokinumab is a fully human IgG4 monoclonal antibody that specifically binds to interleukin-13, a key driver of underlying inflammation in AD. In two of the drug’s pivotal phase 3 trials, ECZTRA 1 and ECZTRA 2, tralokinumab monotherapy was superior to placebo at week 16 for all primary and secondary endpoints.

The purpose of the current trial was to investigate the maintenance of efficacy after 16 weeks of tralokinumab in those who were initial responders and to assess the efficacy of reduced dosing frequency from 300 mg every 2 weeks to 300 mg every 4 weeks after a 36-week maintenance phase. Patients who used rescue medication, including topical corticosteroids, were considered to be nonresponders.

Dr. Blauvelt reported results from 1,596 adult patients with a mean age of 38 years who were randomized to tralokinumab 300 mg every 2 weeks or placebo in the initial treatment period. At baseline, the mean duration of AD was 28.2 years, 50% had severe disease based on their IGA score, and their mean Dermatology Life Quality Index score was 17.

Of these patients, 412 achieved an IGA score of 0 or 1 and/or an EASI 75 at week 16 with tralokinumab every 2 weeks and were rerandomized (2:2:1) to continue tralokinumab 300 mg every 2 weeks, tralokinumab 300 mg every 4 weeks, or placebo for 36 weeks.

The researchers found that 56%-57% of patients in the tralokinumab every 2-week dosing group maintained their IGA 0/1 and EASI 75 response at week 52, compared with 42%-50% of those who received the drug every 4 weeks. “So, there may be a population of patients who require drug every 4 weeks after initially receiving the drug every 2 weeks for the first 16 weeks,” said Dr. Blauvelt, a dermatologist who is president of Oregon Medical Research Center, Portland. “Interestingly, 26%-34% of patients on placebo maintained their IGA 0/1 and EASI 75 response a response to week 52. Perhaps those are patients who have more mild disease or more episodic disease when they started this trial.”

He also noted that time to relapse based on their IGA 0/1 and EASI 75 was prolonged with tralokinumab treatment, compared with placebo, and adverse event frequency was similar among all treatment groups (73% among those who received tralokinumab every 2 weeks, 66% among those who received tralokinumab every 4 weeks, and 70% in the placebo group).

Dr. Blauvelt concluded that a step-down in tralokinumab dosing to every 4 weeks may be an option for some patients achieving clear or almost clear skin after an initial dosing schedule of every 2 weeks.

LEO Pharma, which is developing tralokinumab, sponsored the analysis. Dr. Blauvelt reported that he is an investigator and a scientific adviser for LEO Pharma and for several other pharmaceutical companies developing treatments for AD.

dbrunk@mdedge.com

A large proportion of initial Investigator Global Assessment (IGA) 0/1 or Eczema Area and Severity Index (EASI) 75 responders at week 16 maintained response with continued tralokinumab dosing every 2 weeks or every 4 weeks during a 36-week maintenance period without the use of rescue medication including topical corticosteroids, results from a pooled analysis of two trials found.

“The interesting thing here is that there weren’t major differences in the maintenance dosing, which really allows us some flexibility with maintenance dosing for this particular drug,” lead study investigator Andrew Blauvelt, MD, MBA, said during the Revolutionizing Atopic Dermatitis symposium.

Administered subcutaneously, tralokinumab is a fully human IgG4 monoclonal antibody that specifically binds to interleukin-13, a key driver of underlying inflammation in AD. In two of the drug’s pivotal phase 3 trials, ECZTRA 1 and ECZTRA 2, tralokinumab monotherapy was superior to placebo at week 16 for all primary and secondary endpoints.

The purpose of the current trial was to investigate the maintenance of efficacy after 16 weeks of tralokinumab in those who were initial responders and to assess the efficacy of reduced dosing frequency from 300 mg every 2 weeks to 300 mg every 4 weeks after a 36-week maintenance phase. Patients who used rescue medication, including topical corticosteroids, were considered to be nonresponders.

Dr. Blauvelt reported results from 1,596 adult patients with a mean age of 38 years who were randomized to tralokinumab 300 mg every 2 weeks or placebo in the initial treatment period. At baseline, the mean duration of AD was 28.2 years, 50% had severe disease based on their IGA score, and their mean Dermatology Life Quality Index score was 17.

Of these patients, 412 achieved an IGA score of 0 or 1 and/or an EASI 75 at week 16 with tralokinumab every 2 weeks and were rerandomized (2:2:1) to continue tralokinumab 300 mg every 2 weeks, tralokinumab 300 mg every 4 weeks, or placebo for 36 weeks.

The researchers found that 56%-57% of patients in the tralokinumab every 2-week dosing group maintained their IGA 0/1 and EASI 75 response at week 52, compared with 42%-50% of those who received the drug every 4 weeks. “So, there may be a population of patients who require drug every 4 weeks after initially receiving the drug every 2 weeks for the first 16 weeks,” said Dr. Blauvelt, a dermatologist who is president of Oregon Medical Research Center, Portland. “Interestingly, 26%-34% of patients on placebo maintained their IGA 0/1 and EASI 75 response a response to week 52. Perhaps those are patients who have more mild disease or more episodic disease when they started this trial.”

He also noted that time to relapse based on their IGA 0/1 and EASI 75 was prolonged with tralokinumab treatment, compared with placebo, and adverse event frequency was similar among all treatment groups (73% among those who received tralokinumab every 2 weeks, 66% among those who received tralokinumab every 4 weeks, and 70% in the placebo group).

Dr. Blauvelt concluded that a step-down in tralokinumab dosing to every 4 weeks may be an option for some patients achieving clear or almost clear skin after an initial dosing schedule of every 2 weeks.

LEO Pharma, which is developing tralokinumab, sponsored the analysis. Dr. Blauvelt reported that he is an investigator and a scientific adviser for LEO Pharma and for several other pharmaceutical companies developing treatments for AD.

dbrunk@mdedge.com

A 21-year-old man presented to the emergency department (ED) with a 2-month history of joint pain, swelling, and difficulty walking that began with swelling of his right knee (FIGURE 1A). The patient said that over the course of several weeks, the swelling and joint pain spread to his left knee, followed by bilateral elbows and ankles. Nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin produced only modest improvement.

Two weeks prior to presentation, the patient also experienced widespread pruritus and conjunctivitis. His past medical history was significant for a sexual encounter that resulted in urinary tract infection (UTI)–like symptoms approximately 1 month prior to the onset of his joint symptoms. He did not seek care for the UTI-like symptoms.

In the ED, the patient was febrile (102.1 °F) and tachycardic. Skin examination revealed erythematous papules, intact vesicles, and pustules with background hyperkeratosis and desquamation on his right foot (FIGURE 1B). The patient had spotty erythema on his palate and a 4-mm superficial erosion on the right penile shaft. Swelling and tenderness were noted over the elbows, knees, hands, and ankles. No inguinal lymphadenopathy was noted.

An arthrocentesis was performed on the right knee that demonstrated no organisms on Gram stain and a normal joint fluid cell count. A complete blood count (CBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and urinalysis were ordered. A punch biopsy was performed on a scaly patch on the right elbow.

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

 

 

Dx: Keratoderma blenorrhagicum

The patient’s history, clinical findings, and lab results, including a positive Chlamydia trachomatis polymerase chain reaction (PCR) test from a urethral swab, pointed to a diagnosis of keratoderma blenorrhagicum in association with reactive arthritis (following infection with C trachomatis).

Reactive arthritis features a triad of conjunctivitis, urethritis, and arthritis that follows either gastrointestinal or urogenital infection.

Relevant diagnostic findings included an elevated CRP of 26.5 mg/L (normal range, < 10 mg/L), an elevated ESR of 116 mm/h (normal range, < 15 mm/h) and as noted, a positive C trachomatis PCR test. The patient’s white blood cell count was 9.7/μL (normal range, 4.5-11 μL) and the rest of the CBC was within normal limits. Urinalysis was positive for leukocytes and rare bacteria. A treponemal antibody test was negative.

Additionally, the punch biopsy from the right elbow revealed acanthosis, intercellular spongiosis, and subcorneal pustules consistent with localized pustular psoriasis or keratoderma blenorrhagicum. After the diagnosis was made, human leukocyte antigen B27 allele (HLA-B27) testing was conducted and was positive.

A predisposition exacerbates the infection

Reactive arthritis, a type of spondyloarthropathy, features a triad of conjunctivitis, urethritis, and arthritis that follows either gastrointestinal or urogenital infection.¹ Reactive arthritis occurs with a male predominance of 3:1, and the worldwide prevalence is 1 in 3000.¹ Causative bacteria include C trachomatis, Yersinia, Salmonella, ­Shigella, and Campylobacter, Escherichia coli, Clostridioides (formerly Clostridium) difficile, and C pneumoniae.² Patients with the HLA-B27 allele are 50 times more likely to develop reactive arthritis following infection with the aforementioned bacteria.¹

Findings consistent with a diagnosis of reactive arthritis include a recent history of gastrointestinal or urogenital illness, joint pain, conjunctivitis, oral lesions, cutaneous changes, and genital lesions.³ Diagnostic tests should include arthrocentesis with cultures or PCR and cell count, ESR, CRP, CBC, and urinalysis. HLA-B27 can be used to support the diagnosis but is not routinely recommended.²

Pustules and psoriasiform scaling characterize this diagnosis

The differential diagnosis for the signs and symptoms seen in this patient include disseminated gonococcal arthritis, psoriatic arthritis, rheumatoid arthritis, and secondary syphilis.

Gonococcal arthritis manifests with painful, sterile joints as well as pustules on the palms and soles, but not with the psoriasiform scaling and desquamation that was seen in this case. A culture or PCR from urethral discharge or pustules on the palms and soles could be used to confirm this diagnosis.³

Continue to: Psoriasis in association with psoriatic arthritis

Psoriasis in association with psoriatic arthritis and the psoriasiform rashing of reactive arthritis (keratoderma blenorrhagicum) show similar histopathology; however, patients with psoriatic arthritis generally exhibit fewer constitutional symptoms.⁴

Rheumatoid arthritis also manifests with joint pain and swelling, especially in the hands, wrists, and knees. This diagnosis was unlikely in this patient, where small joints were largely uninvolved.⁴

Secondary syphilis also manifests with papular, scaly, erythematous lesions on the palms and soles along with pityriasis rosea–like rashing on the trunk. However, it rarely produces pustules or hyperkeratotic keratoderma.⁵ As noted earlier, a treponemal antibody test in this patient was negative.

Drug therapy is the best option

First-line therapy for reactive arthritis consists of NSAIDs. If the patient exhibits an inadequate response after a 2-week trial, intra-­articular or systemic glucocorticoids may be considered.³ If the patient fails to respond to the steroids, disease-modifying antirheumatic drugs (DMARDs) may be considered. Reactive arthritis is considered chronic if the disease lasts longer than 6 months, at which point, DMARDs or tumor necrosis factor-α inhibitors may be utilized.³ For cutaneous manifestations, such as keratoderma blenorrhagicum, topical glucocorticoids twice daily may be used along with keratolytic agents.

Our patient received 2 doses of azithromycin (500 mg IV) and 1 dose of ceftriaxone (2 g IV) to treat his infection while in the ED. Over the course of his hospital stay, he received ceftriaxone (1 g IV daily) for 6 days and naproxen (500 mg tid po) which was tapered. Additionally, he received a week of methylprednisolone (60 mg IM daily) before tapering to oral prednisone. His taper consisted of 40 mg po for 1 week and was decreased by 10 mg each week. Augmented betamethasone dipropionate 0.05% cream and urea 20% cream were prescribed for twice-daily application for the hyperkeratotic scale on both of his feet.

A 21-year-old man presented to the emergency department (ED) with a 2-month history of joint pain, swelling, and difficulty walking that began with swelling of his right knee (FIGURE 1A). The patient said that over the course of several weeks, the swelling and joint pain spread to his left knee, followed by bilateral elbows and ankles. Nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin produced only modest improvement.

Two weeks prior to presentation, the patient also experienced widespread pruritus and conjunctivitis. His past medical history was significant for a sexual encounter that resulted in urinary tract infection (UTI)–like symptoms approximately 1 month prior to the onset of his joint symptoms. He did not seek care for the UTI-like symptoms.

In the ED, the patient was febrile (102.1 °F) and tachycardic. Skin examination revealed erythematous papules, intact vesicles, and pustules with background hyperkeratosis and desquamation on his right foot (FIGURE 1B). The patient had spotty erythema on his palate and a 4-mm superficial erosion on the right penile shaft. Swelling and tenderness were noted over the elbows, knees, hands, and ankles. No inguinal lymphadenopathy was noted.

An arthrocentesis was performed on the right knee that demonstrated no organisms on Gram stain and a normal joint fluid cell count. A complete blood count (CBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and urinalysis were ordered. A punch biopsy was performed on a scaly patch on the right elbow.

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

 

 

Dx: Keratoderma blenorrhagicum

The patient’s history, clinical findings, and lab results, including a positive Chlamydia trachomatis polymerase chain reaction (PCR) test from a urethral swab, pointed to a diagnosis of keratoderma blenorrhagicum in association with reactive arthritis (following infection with C trachomatis).

Reactive arthritis features a triad of conjunctivitis, urethritis, and arthritis that follows either gastrointestinal or urogenital infection.

Relevant diagnostic findings included an elevated CRP of 26.5 mg/L (normal range, < 10 mg/L), an elevated ESR of 116 mm/h (normal range, < 15 mm/h) and as noted, a positive C trachomatis PCR test. The patient’s white blood cell count was 9.7/μL (normal range, 4.5-11 μL) and the rest of the CBC was within normal limits. Urinalysis was positive for leukocytes and rare bacteria. A treponemal antibody test was negative.

Additionally, the punch biopsy from the right elbow revealed acanthosis, intercellular spongiosis, and subcorneal pustules consistent with localized pustular psoriasis or keratoderma blenorrhagicum. After the diagnosis was made, human leukocyte antigen B27 allele (HLA-B27) testing was conducted and was positive.

A predisposition exacerbates the infection

Reactive arthritis, a type of spondyloarthropathy, features a triad of conjunctivitis, urethritis, and arthritis that follows either gastrointestinal or urogenital infection.¹ Reactive arthritis occurs with a male predominance of 3:1, and the worldwide prevalence is 1 in 3000.¹ Causative bacteria include C trachomatis, Yersinia, Salmonella, ­Shigella, and Campylobacter, Escherichia coli, Clostridioides (formerly Clostridium) difficile, and C pneumoniae.² Patients with the HLA-B27 allele are 50 times more likely to develop reactive arthritis following infection with the aforementioned bacteria.¹

Findings consistent with a diagnosis of reactive arthritis include a recent history of gastrointestinal or urogenital illness, joint pain, conjunctivitis, oral lesions, cutaneous changes, and genital lesions.³ Diagnostic tests should include arthrocentesis with cultures or PCR and cell count, ESR, CRP, CBC, and urinalysis. HLA-B27 can be used to support the diagnosis but is not routinely recommended.²

Pustules and psoriasiform scaling characterize this diagnosis

The differential diagnosis for the signs and symptoms seen in this patient include disseminated gonococcal arthritis, psoriatic arthritis, rheumatoid arthritis, and secondary syphilis.

Gonococcal arthritis manifests with painful, sterile joints as well as pustules on the palms and soles, but not with the psoriasiform scaling and desquamation that was seen in this case. A culture or PCR from urethral discharge or pustules on the palms and soles could be used to confirm this diagnosis.³

Continue to: Psoriasis in association with psoriatic arthritis

Psoriasis in association with psoriatic arthritis and the psoriasiform rashing of reactive arthritis (keratoderma blenorrhagicum) show similar histopathology; however, patients with psoriatic arthritis generally exhibit fewer constitutional symptoms.⁴

Rheumatoid arthritis also manifests with joint pain and swelling, especially in the hands, wrists, and knees. This diagnosis was unlikely in this patient, where small joints were largely uninvolved.⁴

Secondary syphilis also manifests with papular, scaly, erythematous lesions on the palms and soles along with pityriasis rosea–like rashing on the trunk. However, it rarely produces pustules or hyperkeratotic keratoderma.⁵ As noted earlier, a treponemal antibody test in this patient was negative.

Drug therapy is the best option

First-line therapy for reactive arthritis consists of NSAIDs. If the patient exhibits an inadequate response after a 2-week trial, intra-­articular or systemic glucocorticoids may be considered.³ If the patient fails to respond to the steroids, disease-modifying antirheumatic drugs (DMARDs) may be considered. Reactive arthritis is considered chronic if the disease lasts longer than 6 months, at which point, DMARDs or tumor necrosis factor-α inhibitors may be utilized.³ For cutaneous manifestations, such as keratoderma blenorrhagicum, topical glucocorticoids twice daily may be used along with keratolytic agents.

Our patient received 2 doses of azithromycin (500 mg IV) and 1 dose of ceftriaxone (2 g IV) to treat his infection while in the ED. Over the course of his hospital stay, he received ceftriaxone (1 g IV daily) for 6 days and naproxen (500 mg tid po) which was tapered. Additionally, he received a week of methylprednisolone (60 mg IM daily) before tapering to oral prednisone. His taper consisted of 40 mg po for 1 week and was decreased by 10 mg each week. Augmented betamethasone dipropionate 0.05% cream and urea 20% cream were prescribed for twice-daily application for the hyperkeratotic scale on both of his feet.

A 21-year-old man presented to the emergency department (ED) with a 2-month history of joint pain, swelling, and difficulty walking that began with swelling of his right knee (FIGURE 1A). The patient said that over the course of several weeks, the swelling and joint pain spread to his left knee, followed by bilateral elbows and ankles. Nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin produced only modest improvement.

Two weeks prior to presentation, the patient also experienced widespread pruritus and conjunctivitis. His past medical history was significant for a sexual encounter that resulted in urinary tract infection (UTI)–like symptoms approximately 1 month prior to the onset of his joint symptoms. He did not seek care for the UTI-like symptoms.

In the ED, the patient was febrile (102.1 °F) and tachycardic. Skin examination revealed erythematous papules, intact vesicles, and pustules with background hyperkeratosis and desquamation on his right foot (FIGURE 1B). The patient had spotty erythema on his palate and a 4-mm superficial erosion on the right penile shaft. Swelling and tenderness were noted over the elbows, knees, hands, and ankles. No inguinal lymphadenopathy was noted.

An arthrocentesis was performed on the right knee that demonstrated no organisms on Gram stain and a normal joint fluid cell count. A complete blood count (CBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and urinalysis were ordered. A punch biopsy was performed on a scaly patch on the right elbow.

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

 

 

Dx: Keratoderma blenorrhagicum

The patient’s history, clinical findings, and lab results, including a positive Chlamydia trachomatis polymerase chain reaction (PCR) test from a urethral swab, pointed to a diagnosis of keratoderma blenorrhagicum in association with reactive arthritis (following infection with C trachomatis).

Reactive arthritis features a triad of conjunctivitis, urethritis, and arthritis that follows either gastrointestinal or urogenital infection.

Relevant diagnostic findings included an elevated CRP of 26.5 mg/L (normal range, < 10 mg/L), an elevated ESR of 116 mm/h (normal range, < 15 mm/h) and as noted, a positive C trachomatis PCR test. The patient’s white blood cell count was 9.7/μL (normal range, 4.5-11 μL) and the rest of the CBC was within normal limits. Urinalysis was positive for leukocytes and rare bacteria. A treponemal antibody test was negative.

Additionally, the punch biopsy from the right elbow revealed acanthosis, intercellular spongiosis, and subcorneal pustules consistent with localized pustular psoriasis or keratoderma blenorrhagicum. After the diagnosis was made, human leukocyte antigen B27 allele (HLA-B27) testing was conducted and was positive.

A predisposition exacerbates the infection

Reactive arthritis, a type of spondyloarthropathy, features a triad of conjunctivitis, urethritis, and arthritis that follows either gastrointestinal or urogenital infection.¹ Reactive arthritis occurs with a male predominance of 3:1, and the worldwide prevalence is 1 in 3000.¹ Causative bacteria include C trachomatis, Yersinia, Salmonella, ­Shigella, and Campylobacter, Escherichia coli, Clostridioides (formerly Clostridium) difficile, and C pneumoniae.² Patients with the HLA-B27 allele are 50 times more likely to develop reactive arthritis following infection with the aforementioned bacteria.¹

Findings consistent with a diagnosis of reactive arthritis include a recent history of gastrointestinal or urogenital illness, joint pain, conjunctivitis, oral lesions, cutaneous changes, and genital lesions.³ Diagnostic tests should include arthrocentesis with cultures or PCR and cell count, ESR, CRP, CBC, and urinalysis. HLA-B27 can be used to support the diagnosis but is not routinely recommended.²

Pustules and psoriasiform scaling characterize this diagnosis

The differential diagnosis for the signs and symptoms seen in this patient include disseminated gonococcal arthritis, psoriatic arthritis, rheumatoid arthritis, and secondary syphilis.

Gonococcal arthritis manifests with painful, sterile joints as well as pustules on the palms and soles, but not with the psoriasiform scaling and desquamation that was seen in this case. A culture or PCR from urethral discharge or pustules on the palms and soles could be used to confirm this diagnosis.³

Continue to: Psoriasis in association with psoriatic arthritis

Psoriasis in association with psoriatic arthritis and the psoriasiform rashing of reactive arthritis (keratoderma blenorrhagicum) show similar histopathology; however, patients with psoriatic arthritis generally exhibit fewer constitutional symptoms.⁴

Rheumatoid arthritis also manifests with joint pain and swelling, especially in the hands, wrists, and knees. This diagnosis was unlikely in this patient, where small joints were largely uninvolved.⁴

Secondary syphilis also manifests with papular, scaly, erythematous lesions on the palms and soles along with pityriasis rosea–like rashing on the trunk. However, it rarely produces pustules or hyperkeratotic keratoderma.⁵ As noted earlier, a treponemal antibody test in this patient was negative.

Drug therapy is the best option

First-line therapy for reactive arthritis consists of NSAIDs. If the patient exhibits an inadequate response after a 2-week trial, intra-­articular or systemic glucocorticoids may be considered.³ If the patient fails to respond to the steroids, disease-modifying antirheumatic drugs (DMARDs) may be considered. Reactive arthritis is considered chronic if the disease lasts longer than 6 months, at which point, DMARDs or tumor necrosis factor-α inhibitors may be utilized.³ For cutaneous manifestations, such as keratoderma blenorrhagicum, topical glucocorticoids twice daily may be used along with keratolytic agents.

Our patient received 2 doses of azithromycin (500 mg IV) and 1 dose of ceftriaxone (2 g IV) to treat his infection while in the ED. Over the course of his hospital stay, he received ceftriaxone (1 g IV daily) for 6 days and naproxen (500 mg tid po) which was tapered. Additionally, he received a week of methylprednisolone (60 mg IM daily) before tapering to oral prednisone. His taper consisted of 40 mg po for 1 week and was decreased by 10 mg each week. Augmented betamethasone dipropionate 0.05% cream and urea 20% cream were prescribed for twice-daily application for the hyperkeratotic scale on both of his feet.

Among the 51 patients with moderate to severe atopic dermatitis (AD) who developed COVID-19 while participating in an open-label clinical trial of tralokinumab, 96% of cases were mild or moderate and all patients continued tralokinumab treatment following their diagnosis.

“This is a great first look at COVID-19 outcomes in this population,” lead study investigator Andrew Blauvelt, MD, MBA, said during the Revolutionizing Atopic Dermatitis symposium. “This suggests that tralokinumab does not significantly impact the ability to respond to SARS-CoV-2, the virus that causes COVID-19. It’s encouraging and promising.”

Tralokinumab is a fully human IgG4 monoclonal antibody that specifically binds to interleukin-13, which is a key driver of underlying inflammation in AD. An ongoing, open-label extension trial called ECZTEND is investigating the long-term safety and efficacy of tralokinumab in patients with AD who participated in previous tralokinumab trials. The purpose of the current case series is to describe the outcomes of patients diagnosed with COVID-19 while participating in ECZTEND, which is a 5-year study.

“Patients are receiving tralokinumab 300 mg every 2 weeks,” said Dr. Blauvelt, a dermatologist who is president of Oregon Medical Research Center, Portland. “They’re allowed to use topical steroids, but they’re not allowed to use other AD treatments. We do regular clinical and safety assessments throughout the study.”

As of Feb. 26, 2021, there were 51 adults with moderate to severe AD who had confirmed COVID-19 infection during treatment with tralokinumab every 2 weeks. “Patients were not required to discontinue tralokinumab treatment following a COVID-19 diagnosis, if continuation was deemed appropriate by the investigator,” Dr. Blauvelt said. Of the 51 patients, 22 were male, 29 were female, their mean age was 38 years, and their baseline body mass index was 27.6 kg/m². Most of the patients (36, or 71%) were from Europe, 15 (29%) were from North America, and 30 (59%) had a history of asthma.

The average duration of COVID-19 infection was 15 days and severity of disease was mild in 35 patients (69%), moderate in 14 (27%), and severe in 2 (4%). According to the study abstract, those two patients had multiple risk factors and comorbidities, including obesity, chronic obstructive pulmonary disease, and cardiovascular disease. They were hospitalized for a mean of 7 days, but subsequently recovered – one with sequelae. None of the patients died.

Of the 51 COVID-19 cases, 2 were deemed to be possibly related to tralokinumab treatment by the investigator, Dr. Blauvelt said. Both were mild or moderate cases that occurred in patients younger than age 30. “Interestingly, 75% of the COVID-19 patients had no dose interruption; they continued dosing their tralokinumab every 2 weeks during and around the time they had COVID-19,” he said. “However, 25% of patients did interrupt their dosing during COVID-19 infection. That means that they either delayed or stopped dosing while they were sick.”

Of the 51 patients, 19 (37%) had received their first dose of the COVID-19 vaccine and 6 (12%) had received their second dose. “So, 12% of patients were fully vaccinated,” Dr. Blauvelt said. “We do know that the mRNA vaccines are about 95% effective in preventing COVID-19. Currently in Oregon, about 98% of our cases are in unvaccinated patients and about 2% of COVID-19 patients are fully vaccinated.”

In addition, the recently published ECZTRA5 vaccine study showed that nonlive vaccines (tetanus, diphtheria, and pertussis; and meningococcal vaccines) could be safely administered and can elicit normal immune responses in patients treated with tralokinumab.

“We sorely need COVID-19–related safety data for all of our current and emerging systemic and biologic therapies used to treat atopic dermatitis,” said Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research in the division of dermatology at George Washington University, Washington, who was asked to comment about these results. “This study is important because it shows that tralokinumab was not associated with any obvious safety signals with respect to COVID-19 infections. The major limitation is that it is not a prospective study designed to assess tralokinumab efficacy in COVID-19 patients per se. However, this post hoc study provides reassuring data. We need similar or even more robust studies for other systemic therapies in AD.”

Dr. Blauvelt reported that he is an investigator and a scientific advisor for LEO Pharma, which is developing tralokinumab, and for several other pharmaceutical companies developing treatments for AD. Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies, including LEO Pharma.

dbrunk@mdedge.com

Among the 51 patients with moderate to severe atopic dermatitis (AD) who developed COVID-19 while participating in an open-label clinical trial of tralokinumab, 96% of cases were mild or moderate and all patients continued tralokinumab treatment following their diagnosis.

“This is a great first look at COVID-19 outcomes in this population,” lead study investigator Andrew Blauvelt, MD, MBA, said during the Revolutionizing Atopic Dermatitis symposium. “This suggests that tralokinumab does not significantly impact the ability to respond to SARS-CoV-2, the virus that causes COVID-19. It’s encouraging and promising.”

Tralokinumab is a fully human IgG4 monoclonal antibody that specifically binds to interleukin-13, which is a key driver of underlying inflammation in AD. An ongoing, open-label extension trial called ECZTEND is investigating the long-term safety and efficacy of tralokinumab in patients with AD who participated in previous tralokinumab trials. The purpose of the current case series is to describe the outcomes of patients diagnosed with COVID-19 while participating in ECZTEND, which is a 5-year study.

“Patients are receiving tralokinumab 300 mg every 2 weeks,” said Dr. Blauvelt, a dermatologist who is president of Oregon Medical Research Center, Portland. “They’re allowed to use topical steroids, but they’re not allowed to use other AD treatments. We do regular clinical and safety assessments throughout the study.”

As of Feb. 26, 2021, there were 51 adults with moderate to severe AD who had confirmed COVID-19 infection during treatment with tralokinumab every 2 weeks. “Patients were not required to discontinue tralokinumab treatment following a COVID-19 diagnosis, if continuation was deemed appropriate by the investigator,” Dr. Blauvelt said. Of the 51 patients, 22 were male, 29 were female, their mean age was 38 years, and their baseline body mass index was 27.6 kg/m². Most of the patients (36, or 71%) were from Europe, 15 (29%) were from North America, and 30 (59%) had a history of asthma.

The average duration of COVID-19 infection was 15 days and severity of disease was mild in 35 patients (69%), moderate in 14 (27%), and severe in 2 (4%). According to the study abstract, those two patients had multiple risk factors and comorbidities, including obesity, chronic obstructive pulmonary disease, and cardiovascular disease. They were hospitalized for a mean of 7 days, but subsequently recovered – one with sequelae. None of the patients died.

Of the 51 COVID-19 cases, 2 were deemed to be possibly related to tralokinumab treatment by the investigator, Dr. Blauvelt said. Both were mild or moderate cases that occurred in patients younger than age 30. “Interestingly, 75% of the COVID-19 patients had no dose interruption; they continued dosing their tralokinumab every 2 weeks during and around the time they had COVID-19,” he said. “However, 25% of patients did interrupt their dosing during COVID-19 infection. That means that they either delayed or stopped dosing while they were sick.”

Of the 51 patients, 19 (37%) had received their first dose of the COVID-19 vaccine and 6 (12%) had received their second dose. “So, 12% of patients were fully vaccinated,” Dr. Blauvelt said. “We do know that the mRNA vaccines are about 95% effective in preventing COVID-19. Currently in Oregon, about 98% of our cases are in unvaccinated patients and about 2% of COVID-19 patients are fully vaccinated.”

In addition, the recently published ECZTRA5 vaccine study showed that nonlive vaccines (tetanus, diphtheria, and pertussis; and meningococcal vaccines) could be safely administered and can elicit normal immune responses in patients treated with tralokinumab.

“We sorely need COVID-19–related safety data for all of our current and emerging systemic and biologic therapies used to treat atopic dermatitis,” said Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research in the division of dermatology at George Washington University, Washington, who was asked to comment about these results. “This study is important because it shows that tralokinumab was not associated with any obvious safety signals with respect to COVID-19 infections. The major limitation is that it is not a prospective study designed to assess tralokinumab efficacy in COVID-19 patients per se. However, this post hoc study provides reassuring data. We need similar or even more robust studies for other systemic therapies in AD.”

Dr. Blauvelt reported that he is an investigator and a scientific advisor for LEO Pharma, which is developing tralokinumab, and for several other pharmaceutical companies developing treatments for AD. Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies, including LEO Pharma.

dbrunk@mdedge.com

Among the 51 patients with moderate to severe atopic dermatitis (AD) who developed COVID-19 while participating in an open-label clinical trial of tralokinumab, 96% of cases were mild or moderate and all patients continued tralokinumab treatment following their diagnosis.

“This is a great first look at COVID-19 outcomes in this population,” lead study investigator Andrew Blauvelt, MD, MBA, said during the Revolutionizing Atopic Dermatitis symposium. “This suggests that tralokinumab does not significantly impact the ability to respond to SARS-CoV-2, the virus that causes COVID-19. It’s encouraging and promising.”

Tralokinumab is a fully human IgG4 monoclonal antibody that specifically binds to interleukin-13, which is a key driver of underlying inflammation in AD. An ongoing, open-label extension trial called ECZTEND is investigating the long-term safety and efficacy of tralokinumab in patients with AD who participated in previous tralokinumab trials. The purpose of the current case series is to describe the outcomes of patients diagnosed with COVID-19 while participating in ECZTEND, which is a 5-year study.

“Patients are receiving tralokinumab 300 mg every 2 weeks,” said Dr. Blauvelt, a dermatologist who is president of Oregon Medical Research Center, Portland. “They’re allowed to use topical steroids, but they’re not allowed to use other AD treatments. We do regular clinical and safety assessments throughout the study.”

As of Feb. 26, 2021, there were 51 adults with moderate to severe AD who had confirmed COVID-19 infection during treatment with tralokinumab every 2 weeks. “Patients were not required to discontinue tralokinumab treatment following a COVID-19 diagnosis, if continuation was deemed appropriate by the investigator,” Dr. Blauvelt said. Of the 51 patients, 22 were male, 29 were female, their mean age was 38 years, and their baseline body mass index was 27.6 kg/m². Most of the patients (36, or 71%) were from Europe, 15 (29%) were from North America, and 30 (59%) had a history of asthma.

The average duration of COVID-19 infection was 15 days and severity of disease was mild in 35 patients (69%), moderate in 14 (27%), and severe in 2 (4%). According to the study abstract, those two patients had multiple risk factors and comorbidities, including obesity, chronic obstructive pulmonary disease, and cardiovascular disease. They were hospitalized for a mean of 7 days, but subsequently recovered – one with sequelae. None of the patients died.

Of the 51 COVID-19 cases, 2 were deemed to be possibly related to tralokinumab treatment by the investigator, Dr. Blauvelt said. Both were mild or moderate cases that occurred in patients younger than age 30. “Interestingly, 75% of the COVID-19 patients had no dose interruption; they continued dosing their tralokinumab every 2 weeks during and around the time they had COVID-19,” he said. “However, 25% of patients did interrupt their dosing during COVID-19 infection. That means that they either delayed or stopped dosing while they were sick.”

Of the 51 patients, 19 (37%) had received their first dose of the COVID-19 vaccine and 6 (12%) had received their second dose. “So, 12% of patients were fully vaccinated,” Dr. Blauvelt said. “We do know that the mRNA vaccines are about 95% effective in preventing COVID-19. Currently in Oregon, about 98% of our cases are in unvaccinated patients and about 2% of COVID-19 patients are fully vaccinated.”

In addition, the recently published ECZTRA5 vaccine study showed that nonlive vaccines (tetanus, diphtheria, and pertussis; and meningococcal vaccines) could be safely administered and can elicit normal immune responses in patients treated with tralokinumab.

“We sorely need COVID-19–related safety data for all of our current and emerging systemic and biologic therapies used to treat atopic dermatitis,” said Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research in the division of dermatology at George Washington University, Washington, who was asked to comment about these results. “This study is important because it shows that tralokinumab was not associated with any obvious safety signals with respect to COVID-19 infections. The major limitation is that it is not a prospective study designed to assess tralokinumab efficacy in COVID-19 patients per se. However, this post hoc study provides reassuring data. We need similar or even more robust studies for other systemic therapies in AD.”

Dr. Blauvelt reported that he is an investigator and a scientific advisor for LEO Pharma, which is developing tralokinumab, and for several other pharmaceutical companies developing treatments for AD. Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies, including LEO Pharma.

dbrunk@mdedge.com

Lupus images in medical resource materials underrepresent patients with skin of color, based on data from a review of more than 1,400 images published between 2014 and 2019 in materials from a university’s online medical library.

Courtesy Dr. Catalina Matiz

Patients with skin of color who develop lupus tend to present earlier and with more severe cases, and often experience worse outcomes, compared with other populations, wrote Amaad Rana, MD, of Washington University, St. Louis, and colleagues. Medical resources in general have historically underrepresented patients of color, and the researchers reviewed lupus materials for a similar publication bias.

In a study published in Arthritis Care & Research, the investigators identified 1,417 images in rheumatology, dermatology, and internal medicine resources, including 119 medical textbooks, 15 medical journals, 2 online image libraries, and the online image collections of Google and UpToDate. An additional 24 images came from skin of color atlases.

Excluding the skin of color atlases, 56.4% of the images represented light skin, 35.1% showed medium skin, and 8.5% showed dark skin. Overall, publishers were more than twice as likely to portray light skin tones and were significantly less likely to portray dark skin tones (odds ratios, 2.59 and 0.19, respectively), compared with an equal representation of skin tones; however, the difference was not significant for portrayal of medium skin tones (OR, 1.08).

By specialty, dermatology was more inclusive of skin of color images than rheumatology or internal medicine, although the internal medicine sample size was too small for comparable analysis, the researchers noted. Dermatology textbooks were 2.42 times more likely and rheumatology textbooks were 4.87 times more likely to depict light skin tones than an equal representation of light, medium, and dark skin tones.

The researchers rated the skin color in the images using the New Immigrant Survey Skin Color Scale and categorized the images as representing light (NISSCS scores, 1-2), medium (NISSCS scores, 3-5), or dark skin (NISSCS scores, 6-10). Medical journals had the most images of dark skin, excluding skin of color atlases. In a comparison of specialties, dermatology materials included the most images of medium and darker skin tones.

The underrepresentation of skin of color patients can contribute to a limited knowledge of lupus presentation that could lead to disparate health outcomes, the researchers noted.

The study findings were limited by several factors, including the review of only the online textbooks and journals available through the medical library of a single university, the researchers noted. In addition, definitions of light, medium, and dark skin tones were variable among studies, and the researchers did not distinguish among lupus pathologies.

“Further research is needed to quantitatively assess the influence these materials have on healthcare providers’ ability to care for patients with lupus and SOC, and new material and strategies will be required to correct this disparity and promote equitable representation,” the researchers emphasized. “Ultimately, this will arm practitioners with the resources to competently treat patients with any skin color and work towards reducing disparities in health outcomes.”

The study received no outside funding. The researchers had no financial conflicts to disclose.

Lupus images in medical resource materials underrepresent patients with skin of color, based on data from a review of more than 1,400 images published between 2014 and 2019 in materials from a university’s online medical library.

Courtesy Dr. Catalina Matiz

Patients with skin of color who develop lupus tend to present earlier and with more severe cases, and often experience worse outcomes, compared with other populations, wrote Amaad Rana, MD, of Washington University, St. Louis, and colleagues. Medical resources in general have historically underrepresented patients of color, and the researchers reviewed lupus materials for a similar publication bias.

In a study published in Arthritis Care & Research, the investigators identified 1,417 images in rheumatology, dermatology, and internal medicine resources, including 119 medical textbooks, 15 medical journals, 2 online image libraries, and the online image collections of Google and UpToDate. An additional 24 images came from skin of color atlases.

Excluding the skin of color atlases, 56.4% of the images represented light skin, 35.1% showed medium skin, and 8.5% showed dark skin. Overall, publishers were more than twice as likely to portray light skin tones and were significantly less likely to portray dark skin tones (odds ratios, 2.59 and 0.19, respectively), compared with an equal representation of skin tones; however, the difference was not significant for portrayal of medium skin tones (OR, 1.08).

By specialty, dermatology was more inclusive of skin of color images than rheumatology or internal medicine, although the internal medicine sample size was too small for comparable analysis, the researchers noted. Dermatology textbooks were 2.42 times more likely and rheumatology textbooks were 4.87 times more likely to depict light skin tones than an equal representation of light, medium, and dark skin tones.

The researchers rated the skin color in the images using the New Immigrant Survey Skin Color Scale and categorized the images as representing light (NISSCS scores, 1-2), medium (NISSCS scores, 3-5), or dark skin (NISSCS scores, 6-10). Medical journals had the most images of dark skin, excluding skin of color atlases. In a comparison of specialties, dermatology materials included the most images of medium and darker skin tones.

The underrepresentation of skin of color patients can contribute to a limited knowledge of lupus presentation that could lead to disparate health outcomes, the researchers noted.

The study findings were limited by several factors, including the review of only the online textbooks and journals available through the medical library of a single university, the researchers noted. In addition, definitions of light, medium, and dark skin tones were variable among studies, and the researchers did not distinguish among lupus pathologies.

“Further research is needed to quantitatively assess the influence these materials have on healthcare providers’ ability to care for patients with lupus and SOC, and new material and strategies will be required to correct this disparity and promote equitable representation,” the researchers emphasized. “Ultimately, this will arm practitioners with the resources to competently treat patients with any skin color and work towards reducing disparities in health outcomes.”

The study received no outside funding. The researchers had no financial conflicts to disclose.

Lupus images in medical resource materials underrepresent patients with skin of color, based on data from a review of more than 1,400 images published between 2014 and 2019 in materials from a university’s online medical library.

Courtesy Dr. Catalina Matiz

Patients with skin of color who develop lupus tend to present earlier and with more severe cases, and often experience worse outcomes, compared with other populations, wrote Amaad Rana, MD, of Washington University, St. Louis, and colleagues. Medical resources in general have historically underrepresented patients of color, and the researchers reviewed lupus materials for a similar publication bias.

In a study published in Arthritis Care & Research, the investigators identified 1,417 images in rheumatology, dermatology, and internal medicine resources, including 119 medical textbooks, 15 medical journals, 2 online image libraries, and the online image collections of Google and UpToDate. An additional 24 images came from skin of color atlases.

Excluding the skin of color atlases, 56.4% of the images represented light skin, 35.1% showed medium skin, and 8.5% showed dark skin. Overall, publishers were more than twice as likely to portray light skin tones and were significantly less likely to portray dark skin tones (odds ratios, 2.59 and 0.19, respectively), compared with an equal representation of skin tones; however, the difference was not significant for portrayal of medium skin tones (OR, 1.08).

By specialty, dermatology was more inclusive of skin of color images than rheumatology or internal medicine, although the internal medicine sample size was too small for comparable analysis, the researchers noted. Dermatology textbooks were 2.42 times more likely and rheumatology textbooks were 4.87 times more likely to depict light skin tones than an equal representation of light, medium, and dark skin tones.

The researchers rated the skin color in the images using the New Immigrant Survey Skin Color Scale and categorized the images as representing light (NISSCS scores, 1-2), medium (NISSCS scores, 3-5), or dark skin (NISSCS scores, 6-10). Medical journals had the most images of dark skin, excluding skin of color atlases. In a comparison of specialties, dermatology materials included the most images of medium and darker skin tones.

The underrepresentation of skin of color patients can contribute to a limited knowledge of lupus presentation that could lead to disparate health outcomes, the researchers noted.

The study findings were limited by several factors, including the review of only the online textbooks and journals available through the medical library of a single university, the researchers noted. In addition, definitions of light, medium, and dark skin tones were variable among studies, and the researchers did not distinguish among lupus pathologies.

“Further research is needed to quantitatively assess the influence these materials have on healthcare providers’ ability to care for patients with lupus and SOC, and new material and strategies will be required to correct this disparity and promote equitable representation,” the researchers emphasized. “Ultimately, this will arm practitioners with the resources to competently treat patients with any skin color and work towards reducing disparities in health outcomes.”

The study received no outside funding. The researchers had no financial conflicts to disclose.

Large, firm, erythematous, nodular lesions with central keratin plugs that arise rapidly are the hallmark of keratoacanthomas (KAs).

KAs commonly manifest on the hands and face and can alarm patients who are unfamiliar with their rapid growth. Since KAs can involute spontaneously after their growth and scarring phase, they were previously regarded as a benign lesion. KAs have a characteristic central keratin plug; this contrasts with basal cell carcinomas, which have central ulceration or scabbing. Currently, KAs are considered a subtype of squamous cell carcinoma (SCC). KAs tend to grow much faster and are raised, unlike SCCs, which normally have scale surrounding macular or slightly raised erythematous tissue.

Treatments include surgical excision, cryosurgery, curettage with electrodesiccation, topical 5-fluorouracil, imiquimod, intralesional methotrexate, or bleomycin.¹ The isolated form of KAs is most common, but there are syndromes of multiple KAs that can be treated with systemic retinoids.

For this patient, the KA was transected across the base level with the surrounding skin and sent for pathology. At the same visit, the base was curetted down to the dermis and treated with electrodesiccation. This was followed by a repeat cycle of curettage and electrodesiccation. The patient was advised that if the pathology report showed invasive SCC, excision with margins would be recommended; otherwise, she would be followed clinically. Pathology did confirm a KA type of SCC. At the 6-week follow-up, the area was healing well, with no evidence of recurrence.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque

Large, firm, erythematous, nodular lesions with central keratin plugs that arise rapidly are the hallmark of keratoacanthomas (KAs).

KAs commonly manifest on the hands and face and can alarm patients who are unfamiliar with their rapid growth. Since KAs can involute spontaneously after their growth and scarring phase, they were previously regarded as a benign lesion. KAs have a characteristic central keratin plug; this contrasts with basal cell carcinomas, which have central ulceration or scabbing. Currently, KAs are considered a subtype of squamous cell carcinoma (SCC). KAs tend to grow much faster and are raised, unlike SCCs, which normally have scale surrounding macular or slightly raised erythematous tissue.

Treatments include surgical excision, cryosurgery, curettage with electrodesiccation, topical 5-fluorouracil, imiquimod, intralesional methotrexate, or bleomycin.¹ The isolated form of KAs is most common, but there are syndromes of multiple KAs that can be treated with systemic retinoids.

For this patient, the KA was transected across the base level with the surrounding skin and sent for pathology. At the same visit, the base was curetted down to the dermis and treated with electrodesiccation. This was followed by a repeat cycle of curettage and electrodesiccation. The patient was advised that if the pathology report showed invasive SCC, excision with margins would be recommended; otherwise, she would be followed clinically. Pathology did confirm a KA type of SCC. At the 6-week follow-up, the area was healing well, with no evidence of recurrence.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque

Large, firm, erythematous, nodular lesions with central keratin plugs that arise rapidly are the hallmark of keratoacanthomas (KAs).

KAs commonly manifest on the hands and face and can alarm patients who are unfamiliar with their rapid growth. Since KAs can involute spontaneously after their growth and scarring phase, they were previously regarded as a benign lesion. KAs have a characteristic central keratin plug; this contrasts with basal cell carcinomas, which have central ulceration or scabbing. Currently, KAs are considered a subtype of squamous cell carcinoma (SCC). KAs tend to grow much faster and are raised, unlike SCCs, which normally have scale surrounding macular or slightly raised erythematous tissue.

Treatments include surgical excision, cryosurgery, curettage with electrodesiccation, topical 5-fluorouracil, imiquimod, intralesional methotrexate, or bleomycin.¹ The isolated form of KAs is most common, but there are syndromes of multiple KAs that can be treated with systemic retinoids.

For this patient, the KA was transected across the base level with the surrounding skin and sent for pathology. At the same visit, the base was curetted down to the dermis and treated with electrodesiccation. This was followed by a repeat cycle of curettage and electrodesiccation. The patient was advised that if the pathology report showed invasive SCC, excision with margins would be recommended; otherwise, she would be followed clinically. Pathology did confirm a KA type of SCC. At the 6-week follow-up, the area was healing well, with no evidence of recurrence.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque

THE COMPARISON

A Pink scaling plaques and erythematous erosions in the antecubital fossae of a 6-year-old White boy.

B Violaceous, hyperpigmented, nummular plaques on the back and extensor surface of the right arm of a 16-month-old Black girl.

C Atopic dermatitis and follicular prominence/accentuation on the neck of a young Black girl.

Epidemiology

People of African descent have the highest atopic dermatitis prevalence and severity.

Key clinical features in people with darker skin tones include:

• follicular prominence
• papular morphology
• prurigo nodules
• hyperpigmented, violaceous-brown or gray plaques instead of erythematous plaques
• lichenification
• treatment resistant.^1,2

Worth noting

Postinflammatory hyperpigmentation and postinflammatory hypopigmentation may be more distressing to the patient/family than the atopic dermatitis itself.

Health disparity highlight

In the United States, patients with skin of color are more likely to be hospitalized with severe atopic dermatitis, have more substantial out-of-pocket costs, be underinsured, and have an increased number of missed days of work. Limited access to outpatient health care plays a role in exacerbating this health disparity.^3,4

THE COMPARISON

A Pink scaling plaques and erythematous erosions in the antecubital fossae of a 6-year-old White boy.

B Violaceous, hyperpigmented, nummular plaques on the back and extensor surface of the right arm of a 16-month-old Black girl.

C Atopic dermatitis and follicular prominence/accentuation on the neck of a young Black girl.

Epidemiology

People of African descent have the highest atopic dermatitis prevalence and severity.

Key clinical features in people with darker skin tones include:

• follicular prominence
• papular morphology
• prurigo nodules
• hyperpigmented, violaceous-brown or gray plaques instead of erythematous plaques
• lichenification
• treatment resistant.^1,2

Worth noting

Postinflammatory hyperpigmentation and postinflammatory hypopigmentation may be more distressing to the patient/family than the atopic dermatitis itself.

Health disparity highlight

In the United States, patients with skin of color are more likely to be hospitalized with severe atopic dermatitis, have more substantial out-of-pocket costs, be underinsured, and have an increased number of missed days of work. Limited access to outpatient health care plays a role in exacerbating this health disparity.^3,4

THE COMPARISON

A Pink scaling plaques and erythematous erosions in the antecubital fossae of a 6-year-old White boy.

B Violaceous, hyperpigmented, nummular plaques on the back and extensor surface of the right arm of a 16-month-old Black girl.

C Atopic dermatitis and follicular prominence/accentuation on the neck of a young Black girl.

Epidemiology

People of African descent have the highest atopic dermatitis prevalence and severity.

Key clinical features in people with darker skin tones include:

• follicular prominence
• papular morphology
• prurigo nodules
• hyperpigmented, violaceous-brown or gray plaques instead of erythematous plaques
• lichenification
• treatment resistant.^1,2

Worth noting

Postinflammatory hyperpigmentation and postinflammatory hypopigmentation may be more distressing to the patient/family than the atopic dermatitis itself.

Health disparity highlight

In the United States, patients with skin of color are more likely to be hospitalized with severe atopic dermatitis, have more substantial out-of-pocket costs, be underinsured, and have an increased number of missed days of work. Limited access to outpatient health care plays a role in exacerbating this health disparity.^3,4

Skin and soft-tissue infections, frequently encountered in primary care, range from the uncomplicated erysipelas to the life-threatening necrotizing fasciitis. This review draws from the latest evidence and guidelines to help guide the care you provide to patients with cellulitis, orbital cellulitis, erysipelas, folliculitis, furuncles, carbuncles, abscesses, and necrotizing fasciitis.

Cellulitis

Cellulitis, an infection of the deep dermal and subcutaneous layers of the skin, has become increasingly common in recent years, with both incidence and hospitalization rates rising.¹ Cellulitis occurs when pathogens enter the dermis through breaks in the skin barrier due to cutaneous fungal infections, trauma, pressure sores, venous stasis, or inflammation. The diagnosis is often made clinically based on characteristic skin findings—classically an acute, poorly demarcated area of erythema, warmth, swelling, and tenderness. Lymphangitic streaking and local lymphadenopathy may also be present. Infection often occurs on an extremity (although it can be found on other areas of the body) and is usually unilateral. Fever may or may not be present.²

Likely responsible microorganisms. Staphylococcus aureus and Group A streptococci (often Streptococcus pyogenes) are common culprits. One systematic review that examined cultures taken of intact skin in cellulitis patients found S aureus to be about twice as common as S pyogenes, with both bacteria accounting for a little more than 70% of cases. Of the remaining positive cultures, the most common organisms were alpha-­hemolytic streptococcus, group B streptococcus, Pseudomonas aeruginosa, Clostridium perfringens, Escherichia coli, Pasteurella multocida, and Proteus mirabilis.³ Similarly, a systematic review of bacteremia in patients with cellulitis and erysipelas found that S pyogenes, other beta-hemolytic strep, and S aureus account for about 70% of cases (although S aureus was responsible for just 14%), with the remainder of cases caused by gram-negative organisms such as E coli and P aeruginosa.⁴

Treatment considerations. Strict treatment guidelines for cellulitis are lacking, but general consensus encourages the use of antibiotics and occasionally surgery. For mild and moderate cases of cellulitis, prescribe oral and parenteral antibiotics to cover for streptococci and methicillin-susceptible S aureus, respectively. Expand coverage to include vancomycin if nasal colonization shows methicillin-resistant S aureus (MRSA) or if you otherwise suspect prior MRSA exposure. Expanded coverage will also be needed if there is severe nonpurulent infection associated with penetrating trauma or a history of intravenous drug use, or the patient meets criteria for systemic inflammatory response syndrome. If patients are severely compromised (eg, neutropenic), it is reasonable to further add broad-spectrum coverage (eg, intravenous piperacillin-­tazobactam or carbapenem). Typical duration of treatment is 5 to 7 days, although this should be extended if there is no clinical improvement.

For orbital cellulitis, choose antibiotics effective against sinusitis-related pathogens (eg, S pneumoniae, H influenzae, M catarrhalis), S aureus, and anaerobes.

Generally, cellulitis can be managed in the outpatient setting, although hospitalization is recommended if there are concerns for deep or necrotizing infection, if patients are nonadherent to therapy or are immunocompromised, or if outpatient therapy has failed.⁵ Furthermore, in an observational study of 606 adult patients, prior episodes of cellulitis, venous insufficiency, and immunosuppression were all independently associated with poorer clinical outcomes.² Also treat underlying predisposing factors such as edema, obesity, eczema, venous insufficiency, and toe web abnormalities such as fissures, scaling, or maceration.⁵ Consider the use of prophylactic antibiotics for patients who have had 3 to 4 episodes of cellulitis despite attempts to treat predisposing conditions. Prophylactic antibiotic regimens include penicillin or erythromycin orally and penicillin G benzathine intramuscularly.⁵ Antibiotic regimens are summarized in the TABLE.⁵

Orbital cellulitis

Orbital cellulitis is an infection of the tissues posterior to the orbital septum.^6,7 Periorbital, or preseptal, cellulitis occurs anterior to the orbital septum and is the more common of the 2 infections—84% compared with 16% for orbital cellulitis.⁶ However, orbital cellulitis, which affects mainly children at a median age of 7 years,⁶ must be detected and treated early due to the potential for serious complications such as cavernous sinus thrombosis, meningitis, intracranial abscess, and vision loss.⁷ Chemosis (conjunctival edema) and diplopia are more commonly associated with orbital cellulitis and are seldom seen with preseptal cellulitis.

Predominant causative organisms are S pneumoniae, Moraxella catarrhalis, non-typeable Haemophilus influenzae, and group A streptococcus. The most common mechanism of infection is tracking from periorbital structures (eg, paranasal and ethmoid sinusitis). Other causes include orbital trauma/fracture, periorbital surgery, and bacterial endocarditis. Clinically, patients present with limited ocular motility and proptosis associated with inflamed conjunctiva, orbital pain, headache, malaise, fever, eyelid edema, and possible decrease in visual acuity. The diagnosis is often made clinically and confirmed with orbital computed tomography (CT) with contrast, which can assist in ruling out intracranial involvement such as abscess.

Continue to: Antibiotic therapy

Antibiotic therapy, generally administered intravenously, is recommended for at least 3 days or until orbital symptoms begin to resolve. Choose antibiotics effective against sinusitis-related pathogens (eg, S pneumoniae, H influenzae, M catarrhalis), S aureus, and anaerobes.⁸ For instance, a regimen may include vancomycin for MRSA coverage, a third-generation cephalosporin, or metronidazole for anaerobic coverage if there is concern about intracranial involvement. Surgical intervention is often reserved for patients with inadequate response to antibiotic therapy, necessitating biopsy for pathogen identification, as well as drainage of large abscesses refractory to antibiotics.

Erysipelas

Erysipelas, a related yet distinct form of cellulitis, is a bacterial infection of the superficial dermis and hypodermis and is commonly caused by group A streptococcus.^5,9 Other less common organisms include S aureus, P aeruginosa, and enterobacteria. Erysipelas predominantly affects the lower extremities unilaterally (~90%); the arms and the face are the next most common locations. In addition to the rapid onset of well-demarcated erythema, pain, and swelling, patients may have fever and regional lymphadenopathy. Risk factors include portal of entry (eg, tinea pedis, ulceration), lymphedema, and diabetes. Complications of erysipelas include bullae from edema, abscess formation, and, rarely, bacteremia.

When clinical exam alone is inconclusive when evaluating skin and softtissue infections in children and adolescents, consider using ultrasound to improve diagnostic accuracy.

Antibiotic treatment regimens include penicillin G, macrolides (reserved for those with penicillin allergies), fluoroquinolones, and cephalosporins, with duration of treatment ranging from 10 to 14 days depending on infection severity. Fever, pain, and erythema generally improve within 48 to 72 hours of antibiotic therapy. If there is no improvement, consider alternative diagnoses, such as necrotizing fasciitis. Recurrence rates following the initial episode of erysipelas are estimated at 10% of patients at 6 months and 30% at 3 years.¹⁰

Folliculitis

Inflammation of hair follicles is characterized by superficial inflammation with the development of perifollicular papules or pustules on an erythematous base.^11,12 Folliculitis most commonly affects the face, scalp, thighs, buttocks, axillae, and inguinal areas.¹³ It may be caused by infection, an inflammatory reaction, or physical injury. Diagnosis is typically based on the patient’s history and physical examination.

Bacteria are the most common cause of infection, although fungi, viruses, and other entities can cause folliculitis. S aureus (methicillin sensitive or methicillin resistant) is the most common pathogen; in the past, superficial pustular folliculitis attributed to S aureus was referred to as Bockhart impetigo. Folliculitis secondary to P aeruginosa, often seen after exposure to contaminated water or hot tubs, is frequently referred to as “hot tub folliculitis.” Malassezia, a reported cause of fungal folliculitis, tends to occur in adolescents of either sex and men with high sebum production, is common in tropical climates, and can be associated with HIV or immunosuppression.^11,12,14

Continue to: Differential diagnosis...

Differential diagnosis of folliculitis includes pseudofolliculitis barbae, eosinophilic folliculitis, keratosis pilaris, acne vulgaris, candidiasis, contact dermatitis, impetigo, and miliaria.¹³ Pseudofolliculitis barbae is an inflammatory reaction to shaving, more commonly seen in darkly pigmented skin. Pseudofolliculitis develops when the hair shaft penetrates the wall of the follicle or directly enters the epidermis.

Initial treatment for mild disease includes the elimination of predisposing factors such as occlusion, moisture, and abrasion. The area should be kept clean and dry, avoiding friction. For localized disease, prescribe topical clindamycin, mupirocin ointment, or benzoyl peroxide. If symptoms fail to respond, prescribe a 7-day course of antibiotic that targets methicillin-sensitive S aureus—eg, cephalexin or dicloxacillin. Also consider doxycycline, which has anti-inflammatory effects and is effective against MRSA. For refractory lesions, ­trimethoprim-sulfamethoxazole, clindamycin, or minocycline may be useful. If you suspect pseudomonas, consider giving ciprofloxacin for 10 to 14 days for persistent lesions or if the patient is immunocompromised.^13,15 Consider obtaining bacterial, fungal, or viral cultures for lesions that fail to respond to initial treatment.

Do not routinely order cultures or prescribe antibiotics for uncomplicated abscesses.

Furuncles/carbuncles/abscesses

A furuncle, commonly referred to as a boil, is an infected hair follicle that becomes enclosed, creating a collection of pus. A carbuncle is a collection of furuncles that converge and drain through a single opening. An abscess is a localized collection of pus arising from within the dermis that can extend within deeper tissues.⁵ Furuncles, carbuncles, and abscesses are managed similarly with drainage and consideration for MRSA risk factors.

S aureus is the most common cause of these infections; 59% of skin abscesses are due to community-acquired MRSA.¹⁶ Anaerobes may contribute to the polymicrobial flora of skin abscesses.¹⁷ Risk factors for MRSA infection include a history of previous MRSA infection, diabetes, dialysis or renal failure, placement of an indwelling catheter or medical device, injection drug use, incarceration, close contact with a person with known MRSA infection or colonization, long-term care residence, hospitalization or surgery within the past 12 months, and high prevalence of MRSA in the community.⁵

Ultrasound improves diagnostic accuracy. One study showed that when a clinical exam alone was inconclusive in evaluating skin and soft-tissue infections in children and adolescents, an ultrasound-assisted examination improved diagnostic accuracy.¹⁸ Sensitivity of the clinical examination was 43.7%, compared with 77.6% for the clinical examination plus ultrasound.¹⁸

Continue to: Incision and drainage first

Incision and drainage first. Ultrasound-guided needle aspiration, however, has not improved treatment efficacy compared with incision and drainage,¹⁹ the mainstay approach for abscesses.¹⁷ The procedure to drain a furuncle, carbuncle, or abscess should include the expression of all purulent material and the removal of all loculations if possible. Wound culture is recommended during incision and drainage per current guidelines.⁵ Simple dry dressings are convenient and effective, although some wounds may require packing. Tap water (that is potable) is suitable for wound cleansing. However, there is no strong evidence that irrigating wounds increases healing or reduces infection.²⁰

Routine use of antibiotics is not recommended for simple cutaneous abscesses.^5,17,21 Evidence has been conflicting regarding empiric antibiotic coverage of MRSA following incision and drainage.^22-25 Guidelines recommend considering the initiation of antibiotics if there are multiple abscesses, gangrene, surrounding cellulitis, or systemic signs of infection, or if the host is immunocompromised.⁵

If MRSA is suspected, recommended antibiotic coverage includes trimethoprim-­sulfamethoxazole, clindamycin, doxycycline, or minocycline.⁵ If MRSA is identified, treatment options include dicloxacillin or cephalexin. For severe infections persisting after incision and drainage, in addition to oral antibiotic therapy, consider intravenous antibiotic options for MRSA: cefazolin, clindamycin, linezolid, nafcillin, telavancin, or vancomycin.⁵

Necrotizing fasciitis

Necrotizing fasciitis is a rare but potentially deadly infection of the skin and soft tissue. It progresses rapidly and spreads along fascial planes, leading to the necrosis of the superficial fascia. The infection often is more extensive than is indicated by superficial signs. Prompt diagnosis is imperative as necrotizing fasciitis is a surgical emergency.^5,26 In the United States, 500 to 1500 cases of necrotizing fasciitis occur each year.²⁷ Risk factors for necrotizing fasciitis include diabetes, peripheral vascular disease, malignancy, obesity, cirrhosis, renal failure, injection drug use, chronic corticosteroid therapy, alcohol abuse, malnutrition, and iatrogenic immunosuppression.^26,28

Monomicrobial infections, which account for 20% to 30% of cases of necrotizing fasciitis, are community acquired.

Necrotizing fasciitis may be polymicrobial or monomicrobial. Polymicrobial infection, also referred to as type I, is often due to multiple bacteria that originate from the bowel flora, typically including a mix of anaerobic and aerobic organisms. On average, there can be 5 infecting organisms identified per wound, although in some cases up to 15 organisms have been identified in a single wound.⁵ Type I infection is often associated with tissue injury, abscess, or abdominal surgery. The majority of cases of necrotizing fasciitis are polymicrobial.^27,28

Continue to: Monomicrobial infection...

Monomicrobial infection, also referred to as type II, is often due to group A streptococcus, S aureus, vibrio spp, Aeromonas hyrophilio, or an anaerobic streptococci like peptostreptococcus spp. Typically monomicrobial infections, which account for 20% to 30% of cases of necrotizing fasciitis, are community acquired.^5,26,29,30

Clinical presentation. In the early stages of disease, patients commonly complain of flu-like symptoms and extreme pain that is out of proportion to findings on the exam. Additional warning signs include fevers and other symptoms of toxicity such as tachycardia, hypotension, nausea, vomiting, and diarrhea. Later in the course, symptoms may localize to the affected area and include erythema, tense swelling, development of blisters or bullae, blackish blue discoloration of the skin, severe pain, and loss of sensation. In some cases involving gas-forming bacteria, tissue crepitus may be noted on exam.^5,27-31

Rely on clinical judgment to hasten surgical intervention. Laboratory or imaging findings may augment clinical judgment. But if you suspect necrotizing fasciitis, obtaining blood tests and imaging should not delay surgery. Blood tests that may aid in the diagnosis of necrotizing fasciitis include a complete blood count with differential; coagulation studies; a comprehensive metabolic panel; assays of lactate, C-reactive protein (CRP), and creatinine kinase; and blood cultures. Most often, patients with necrotizing fasciitis will have leukocytosis or leukopenia, evidence of hemolysis, thrombocytopenia, acute renal failure, and significantly elevated CRP.

If you suspect necrotizing fasciitis, obtaining blood tests and imaging should not delay surgery.

On any imaging modality, indications of necrotizing fasciitis are inflammatory infiltration of the deep fascia on the affected side that is absent on the contralateral side, and the presence of subcutaneous air (which is a specific but rare finding). Imaging modalities may include CT or magnetic resonance imaging. A definitive diagnosis can only be made with surgical exploration of the involved area. Definitive microbiologic diagnosis will require culture of organisms from affected tissue or blood.^5,26,30,31

First address any hemodynamic instability (hypotension is frequently encountered), followed by urgent surgical exploration, debridement of the wound, and antimicrobial therapy. Antibiotic treatment should align with probable pathogens and treatment should be continued until repeated surgical debridement is no longer necessary, clinical improvement is evident, and 48 to 72 hours have passed since defervescence. A reasonable initial empiric regimen in adults would include an agent that is effective against group A streptococcus, gram-negative pathogens, and anaerobes, such as a carbapenem or a beta-lactam-­beta-lactamase inhibitor such as piperacillin-­tazobactam. Additionally, include an agent that targets MRSA, such as vancomycin, linezolid, or clindamycin.⁵

CORRESPONDENCE
Karl T. Clebak, MD, Department of Family and Community Medicine Residency Program, Penn State Health M.S. Hershey Medical Center, 500 University Drive, H154/C1613, Hershey, PA 17033; kclebak@pennstatehealth.psu.edu

Skin and soft-tissue infections, frequently encountered in primary care, range from the uncomplicated erysipelas to the life-threatening necrotizing fasciitis. This review draws from the latest evidence and guidelines to help guide the care you provide to patients with cellulitis, orbital cellulitis, erysipelas, folliculitis, furuncles, carbuncles, abscesses, and necrotizing fasciitis.

Cellulitis

Cellulitis, an infection of the deep dermal and subcutaneous layers of the skin, has become increasingly common in recent years, with both incidence and hospitalization rates rising.¹ Cellulitis occurs when pathogens enter the dermis through breaks in the skin barrier due to cutaneous fungal infections, trauma, pressure sores, venous stasis, or inflammation. The diagnosis is often made clinically based on characteristic skin findings—classically an acute, poorly demarcated area of erythema, warmth, swelling, and tenderness. Lymphangitic streaking and local lymphadenopathy may also be present. Infection often occurs on an extremity (although it can be found on other areas of the body) and is usually unilateral. Fever may or may not be present.²

Likely responsible microorganisms. Staphylococcus aureus and Group A streptococci (often Streptococcus pyogenes) are common culprits. One systematic review that examined cultures taken of intact skin in cellulitis patients found S aureus to be about twice as common as S pyogenes, with both bacteria accounting for a little more than 70% of cases. Of the remaining positive cultures, the most common organisms were alpha-­hemolytic streptococcus, group B streptococcus, Pseudomonas aeruginosa, Clostridium perfringens, Escherichia coli, Pasteurella multocida, and Proteus mirabilis.³ Similarly, a systematic review of bacteremia in patients with cellulitis and erysipelas found that S pyogenes, other beta-hemolytic strep, and S aureus account for about 70% of cases (although S aureus was responsible for just 14%), with the remainder of cases caused by gram-negative organisms such as E coli and P aeruginosa.⁴

Treatment considerations. Strict treatment guidelines for cellulitis are lacking, but general consensus encourages the use of antibiotics and occasionally surgery. For mild and moderate cases of cellulitis, prescribe oral and parenteral antibiotics to cover for streptococci and methicillin-susceptible S aureus, respectively. Expand coverage to include vancomycin if nasal colonization shows methicillin-resistant S aureus (MRSA) or if you otherwise suspect prior MRSA exposure. Expanded coverage will also be needed if there is severe nonpurulent infection associated with penetrating trauma or a history of intravenous drug use, or the patient meets criteria for systemic inflammatory response syndrome. If patients are severely compromised (eg, neutropenic), it is reasonable to further add broad-spectrum coverage (eg, intravenous piperacillin-­tazobactam or carbapenem). Typical duration of treatment is 5 to 7 days, although this should be extended if there is no clinical improvement.

For orbital cellulitis, choose antibiotics effective against sinusitis-related pathogens (eg, S pneumoniae, H influenzae, M catarrhalis), S aureus, and anaerobes.

Generally, cellulitis can be managed in the outpatient setting, although hospitalization is recommended if there are concerns for deep or necrotizing infection, if patients are nonadherent to therapy or are immunocompromised, or if outpatient therapy has failed.⁵ Furthermore, in an observational study of 606 adult patients, prior episodes of cellulitis, venous insufficiency, and immunosuppression were all independently associated with poorer clinical outcomes.² Also treat underlying predisposing factors such as edema, obesity, eczema, venous insufficiency, and toe web abnormalities such as fissures, scaling, or maceration.⁵ Consider the use of prophylactic antibiotics for patients who have had 3 to 4 episodes of cellulitis despite attempts to treat predisposing conditions. Prophylactic antibiotic regimens include penicillin or erythromycin orally and penicillin G benzathine intramuscularly.⁵ Antibiotic regimens are summarized in the TABLE.⁵

Orbital cellulitis

Orbital cellulitis is an infection of the tissues posterior to the orbital septum.^6,7 Periorbital, or preseptal, cellulitis occurs anterior to the orbital septum and is the more common of the 2 infections—84% compared with 16% for orbital cellulitis.⁶ However, orbital cellulitis, which affects mainly children at a median age of 7 years,⁶ must be detected and treated early due to the potential for serious complications such as cavernous sinus thrombosis, meningitis, intracranial abscess, and vision loss.⁷ Chemosis (conjunctival edema) and diplopia are more commonly associated with orbital cellulitis and are seldom seen with preseptal cellulitis.

Predominant causative organisms are S pneumoniae, Moraxella catarrhalis, non-typeable Haemophilus influenzae, and group A streptococcus. The most common mechanism of infection is tracking from periorbital structures (eg, paranasal and ethmoid sinusitis). Other causes include orbital trauma/fracture, periorbital surgery, and bacterial endocarditis. Clinically, patients present with limited ocular motility and proptosis associated with inflamed conjunctiva, orbital pain, headache, malaise, fever, eyelid edema, and possible decrease in visual acuity. The diagnosis is often made clinically and confirmed with orbital computed tomography (CT) with contrast, which can assist in ruling out intracranial involvement such as abscess.

Continue to: Antibiotic therapy

Antibiotic therapy, generally administered intravenously, is recommended for at least 3 days or until orbital symptoms begin to resolve. Choose antibiotics effective against sinusitis-related pathogens (eg, S pneumoniae, H influenzae, M catarrhalis), S aureus, and anaerobes.⁸ For instance, a regimen may include vancomycin for MRSA coverage, a third-generation cephalosporin, or metronidazole for anaerobic coverage if there is concern about intracranial involvement. Surgical intervention is often reserved for patients with inadequate response to antibiotic therapy, necessitating biopsy for pathogen identification, as well as drainage of large abscesses refractory to antibiotics.

Erysipelas

Erysipelas, a related yet distinct form of cellulitis, is a bacterial infection of the superficial dermis and hypodermis and is commonly caused by group A streptococcus.^5,9 Other less common organisms include S aureus, P aeruginosa, and enterobacteria. Erysipelas predominantly affects the lower extremities unilaterally (~90%); the arms and the face are the next most common locations. In addition to the rapid onset of well-demarcated erythema, pain, and swelling, patients may have fever and regional lymphadenopathy. Risk factors include portal of entry (eg, tinea pedis, ulceration), lymphedema, and diabetes. Complications of erysipelas include bullae from edema, abscess formation, and, rarely, bacteremia.

When clinical exam alone is inconclusive when evaluating skin and softtissue infections in children and adolescents, consider using ultrasound to improve diagnostic accuracy.

Antibiotic treatment regimens include penicillin G, macrolides (reserved for those with penicillin allergies), fluoroquinolones, and cephalosporins, with duration of treatment ranging from 10 to 14 days depending on infection severity. Fever, pain, and erythema generally improve within 48 to 72 hours of antibiotic therapy. If there is no improvement, consider alternative diagnoses, such as necrotizing fasciitis. Recurrence rates following the initial episode of erysipelas are estimated at 10% of patients at 6 months and 30% at 3 years.¹⁰

Folliculitis

Inflammation of hair follicles is characterized by superficial inflammation with the development of perifollicular papules or pustules on an erythematous base.^11,12 Folliculitis most commonly affects the face, scalp, thighs, buttocks, axillae, and inguinal areas.¹³ It may be caused by infection, an inflammatory reaction, or physical injury. Diagnosis is typically based on the patient’s history and physical examination.

Bacteria are the most common cause of infection, although fungi, viruses, and other entities can cause folliculitis. S aureus (methicillin sensitive or methicillin resistant) is the most common pathogen; in the past, superficial pustular folliculitis attributed to S aureus was referred to as Bockhart impetigo. Folliculitis secondary to P aeruginosa, often seen after exposure to contaminated water or hot tubs, is frequently referred to as “hot tub folliculitis.” Malassezia, a reported cause of fungal folliculitis, tends to occur in adolescents of either sex and men with high sebum production, is common in tropical climates, and can be associated with HIV or immunosuppression.^11,12,14

Continue to: Differential diagnosis...

Differential diagnosis of folliculitis includes pseudofolliculitis barbae, eosinophilic folliculitis, keratosis pilaris, acne vulgaris, candidiasis, contact dermatitis, impetigo, and miliaria.¹³ Pseudofolliculitis barbae is an inflammatory reaction to shaving, more commonly seen in darkly pigmented skin. Pseudofolliculitis develops when the hair shaft penetrates the wall of the follicle or directly enters the epidermis.

Initial treatment for mild disease includes the elimination of predisposing factors such as occlusion, moisture, and abrasion. The area should be kept clean and dry, avoiding friction. For localized disease, prescribe topical clindamycin, mupirocin ointment, or benzoyl peroxide. If symptoms fail to respond, prescribe a 7-day course of antibiotic that targets methicillin-sensitive S aureus—eg, cephalexin or dicloxacillin. Also consider doxycycline, which has anti-inflammatory effects and is effective against MRSA. For refractory lesions, ­trimethoprim-sulfamethoxazole, clindamycin, or minocycline may be useful. If you suspect pseudomonas, consider giving ciprofloxacin for 10 to 14 days for persistent lesions or if the patient is immunocompromised.^13,15 Consider obtaining bacterial, fungal, or viral cultures for lesions that fail to respond to initial treatment.

Do not routinely order cultures or prescribe antibiotics for uncomplicated abscesses.

Furuncles/carbuncles/abscesses

A furuncle, commonly referred to as a boil, is an infected hair follicle that becomes enclosed, creating a collection of pus. A carbuncle is a collection of furuncles that converge and drain through a single opening. An abscess is a localized collection of pus arising from within the dermis that can extend within deeper tissues.⁵ Furuncles, carbuncles, and abscesses are managed similarly with drainage and consideration for MRSA risk factors.

S aureus is the most common cause of these infections; 59% of skin abscesses are due to community-acquired MRSA.¹⁶ Anaerobes may contribute to the polymicrobial flora of skin abscesses.¹⁷ Risk factors for MRSA infection include a history of previous MRSA infection, diabetes, dialysis or renal failure, placement of an indwelling catheter or medical device, injection drug use, incarceration, close contact with a person with known MRSA infection or colonization, long-term care residence, hospitalization or surgery within the past 12 months, and high prevalence of MRSA in the community.⁵

Ultrasound improves diagnostic accuracy. One study showed that when a clinical exam alone was inconclusive in evaluating skin and soft-tissue infections in children and adolescents, an ultrasound-assisted examination improved diagnostic accuracy.¹⁸ Sensitivity of the clinical examination was 43.7%, compared with 77.6% for the clinical examination plus ultrasound.¹⁸

Continue to: Incision and drainage first

Incision and drainage first. Ultrasound-guided needle aspiration, however, has not improved treatment efficacy compared with incision and drainage,¹⁹ the mainstay approach for abscesses.¹⁷ The procedure to drain a furuncle, carbuncle, or abscess should include the expression of all purulent material and the removal of all loculations if possible. Wound culture is recommended during incision and drainage per current guidelines.⁵ Simple dry dressings are convenient and effective, although some wounds may require packing. Tap water (that is potable) is suitable for wound cleansing. However, there is no strong evidence that irrigating wounds increases healing or reduces infection.²⁰

Routine use of antibiotics is not recommended for simple cutaneous abscesses.^5,17,21 Evidence has been conflicting regarding empiric antibiotic coverage of MRSA following incision and drainage.^22-25 Guidelines recommend considering the initiation of antibiotics if there are multiple abscesses, gangrene, surrounding cellulitis, or systemic signs of infection, or if the host is immunocompromised.⁵

If MRSA is suspected, recommended antibiotic coverage includes trimethoprim-­sulfamethoxazole, clindamycin, doxycycline, or minocycline.⁵ If MRSA is identified, treatment options include dicloxacillin or cephalexin. For severe infections persisting after incision and drainage, in addition to oral antibiotic therapy, consider intravenous antibiotic options for MRSA: cefazolin, clindamycin, linezolid, nafcillin, telavancin, or vancomycin.⁵

Necrotizing fasciitis

Necrotizing fasciitis is a rare but potentially deadly infection of the skin and soft tissue. It progresses rapidly and spreads along fascial planes, leading to the necrosis of the superficial fascia. The infection often is more extensive than is indicated by superficial signs. Prompt diagnosis is imperative as necrotizing fasciitis is a surgical emergency.^5,26 In the United States, 500 to 1500 cases of necrotizing fasciitis occur each year.²⁷ Risk factors for necrotizing fasciitis include diabetes, peripheral vascular disease, malignancy, obesity, cirrhosis, renal failure, injection drug use, chronic corticosteroid therapy, alcohol abuse, malnutrition, and iatrogenic immunosuppression.^26,28

Monomicrobial infections, which account for 20% to 30% of cases of necrotizing fasciitis, are community acquired.

Necrotizing fasciitis may be polymicrobial or monomicrobial. Polymicrobial infection, also referred to as type I, is often due to multiple bacteria that originate from the bowel flora, typically including a mix of anaerobic and aerobic organisms. On average, there can be 5 infecting organisms identified per wound, although in some cases up to 15 organisms have been identified in a single wound.⁵ Type I infection is often associated with tissue injury, abscess, or abdominal surgery. The majority of cases of necrotizing fasciitis are polymicrobial.^27,28

Continue to: Monomicrobial infection...

Monomicrobial infection, also referred to as type II, is often due to group A streptococcus, S aureus, vibrio spp, Aeromonas hyrophilio, or an anaerobic streptococci like peptostreptococcus spp. Typically monomicrobial infections, which account for 20% to 30% of cases of necrotizing fasciitis, are community acquired.^5,26,29,30

Clinical presentation. In the early stages of disease, patients commonly complain of flu-like symptoms and extreme pain that is out of proportion to findings on the exam. Additional warning signs include fevers and other symptoms of toxicity such as tachycardia, hypotension, nausea, vomiting, and diarrhea. Later in the course, symptoms may localize to the affected area and include erythema, tense swelling, development of blisters or bullae, blackish blue discoloration of the skin, severe pain, and loss of sensation. In some cases involving gas-forming bacteria, tissue crepitus may be noted on exam.^5,27-31

Rely on clinical judgment to hasten surgical intervention. Laboratory or imaging findings may augment clinical judgment. But if you suspect necrotizing fasciitis, obtaining blood tests and imaging should not delay surgery. Blood tests that may aid in the diagnosis of necrotizing fasciitis include a complete blood count with differential; coagulation studies; a comprehensive metabolic panel; assays of lactate, C-reactive protein (CRP), and creatinine kinase; and blood cultures. Most often, patients with necrotizing fasciitis will have leukocytosis or leukopenia, evidence of hemolysis, thrombocytopenia, acute renal failure, and significantly elevated CRP.

If you suspect necrotizing fasciitis, obtaining blood tests and imaging should not delay surgery.

On any imaging modality, indications of necrotizing fasciitis are inflammatory infiltration of the deep fascia on the affected side that is absent on the contralateral side, and the presence of subcutaneous air (which is a specific but rare finding). Imaging modalities may include CT or magnetic resonance imaging. A definitive diagnosis can only be made with surgical exploration of the involved area. Definitive microbiologic diagnosis will require culture of organisms from affected tissue or blood.^5,26,30,31

First address any hemodynamic instability (hypotension is frequently encountered), followed by urgent surgical exploration, debridement of the wound, and antimicrobial therapy. Antibiotic treatment should align with probable pathogens and treatment should be continued until repeated surgical debridement is no longer necessary, clinical improvement is evident, and 48 to 72 hours have passed since defervescence. A reasonable initial empiric regimen in adults would include an agent that is effective against group A streptococcus, gram-negative pathogens, and anaerobes, such as a carbapenem or a beta-lactam-­beta-lactamase inhibitor such as piperacillin-­tazobactam. Additionally, include an agent that targets MRSA, such as vancomycin, linezolid, or clindamycin.⁵

CORRESPONDENCE
Karl T. Clebak, MD, Department of Family and Community Medicine Residency Program, Penn State Health M.S. Hershey Medical Center, 500 University Drive, H154/C1613, Hershey, PA 17033; kclebak@pennstatehealth.psu.edu

Skin and soft-tissue infections, frequently encountered in primary care, range from the uncomplicated erysipelas to the life-threatening necrotizing fasciitis. This review draws from the latest evidence and guidelines to help guide the care you provide to patients with cellulitis, orbital cellulitis, erysipelas, folliculitis, furuncles, carbuncles, abscesses, and necrotizing fasciitis.

Cellulitis

Cellulitis, an infection of the deep dermal and subcutaneous layers of the skin, has become increasingly common in recent years, with both incidence and hospitalization rates rising.¹ Cellulitis occurs when pathogens enter the dermis through breaks in the skin barrier due to cutaneous fungal infections, trauma, pressure sores, venous stasis, or inflammation. The diagnosis is often made clinically based on characteristic skin findings—classically an acute, poorly demarcated area of erythema, warmth, swelling, and tenderness. Lymphangitic streaking and local lymphadenopathy may also be present. Infection often occurs on an extremity (although it can be found on other areas of the body) and is usually unilateral. Fever may or may not be present.²

Likely responsible microorganisms. Staphylococcus aureus and Group A streptococci (often Streptococcus pyogenes) are common culprits. One systematic review that examined cultures taken of intact skin in cellulitis patients found S aureus to be about twice as common as S pyogenes, with both bacteria accounting for a little more than 70% of cases. Of the remaining positive cultures, the most common organisms were alpha-­hemolytic streptococcus, group B streptococcus, Pseudomonas aeruginosa, Clostridium perfringens, Escherichia coli, Pasteurella multocida, and Proteus mirabilis.³ Similarly, a systematic review of bacteremia in patients with cellulitis and erysipelas found that S pyogenes, other beta-hemolytic strep, and S aureus account for about 70% of cases (although S aureus was responsible for just 14%), with the remainder of cases caused by gram-negative organisms such as E coli and P aeruginosa.⁴

Treatment considerations. Strict treatment guidelines for cellulitis are lacking, but general consensus encourages the use of antibiotics and occasionally surgery. For mild and moderate cases of cellulitis, prescribe oral and parenteral antibiotics to cover for streptococci and methicillin-susceptible S aureus, respectively. Expand coverage to include vancomycin if nasal colonization shows methicillin-resistant S aureus (MRSA) or if you otherwise suspect prior MRSA exposure. Expanded coverage will also be needed if there is severe nonpurulent infection associated with penetrating trauma or a history of intravenous drug use, or the patient meets criteria for systemic inflammatory response syndrome. If patients are severely compromised (eg, neutropenic), it is reasonable to further add broad-spectrum coverage (eg, intravenous piperacillin-­tazobactam or carbapenem). Typical duration of treatment is 5 to 7 days, although this should be extended if there is no clinical improvement.

For orbital cellulitis, choose antibiotics effective against sinusitis-related pathogens (eg, S pneumoniae, H influenzae, M catarrhalis), S aureus, and anaerobes.

Generally, cellulitis can be managed in the outpatient setting, although hospitalization is recommended if there are concerns for deep or necrotizing infection, if patients are nonadherent to therapy or are immunocompromised, or if outpatient therapy has failed.⁵ Furthermore, in an observational study of 606 adult patients, prior episodes of cellulitis, venous insufficiency, and immunosuppression were all independently associated with poorer clinical outcomes.² Also treat underlying predisposing factors such as edema, obesity, eczema, venous insufficiency, and toe web abnormalities such as fissures, scaling, or maceration.⁵ Consider the use of prophylactic antibiotics for patients who have had 3 to 4 episodes of cellulitis despite attempts to treat predisposing conditions. Prophylactic antibiotic regimens include penicillin or erythromycin orally and penicillin G benzathine intramuscularly.⁵ Antibiotic regimens are summarized in the TABLE.⁵

Orbital cellulitis

Orbital cellulitis is an infection of the tissues posterior to the orbital septum.^6,7 Periorbital, or preseptal, cellulitis occurs anterior to the orbital septum and is the more common of the 2 infections—84% compared with 16% for orbital cellulitis.⁶ However, orbital cellulitis, which affects mainly children at a median age of 7 years,⁶ must be detected and treated early due to the potential for serious complications such as cavernous sinus thrombosis, meningitis, intracranial abscess, and vision loss.⁷ Chemosis (conjunctival edema) and diplopia are more commonly associated with orbital cellulitis and are seldom seen with preseptal cellulitis.

Predominant causative organisms are S pneumoniae, Moraxella catarrhalis, non-typeable Haemophilus influenzae, and group A streptococcus. The most common mechanism of infection is tracking from periorbital structures (eg, paranasal and ethmoid sinusitis). Other causes include orbital trauma/fracture, periorbital surgery, and bacterial endocarditis. Clinically, patients present with limited ocular motility and proptosis associated with inflamed conjunctiva, orbital pain, headache, malaise, fever, eyelid edema, and possible decrease in visual acuity. The diagnosis is often made clinically and confirmed with orbital computed tomography (CT) with contrast, which can assist in ruling out intracranial involvement such as abscess.

Continue to: Antibiotic therapy

Antibiotic therapy, generally administered intravenously, is recommended for at least 3 days or until orbital symptoms begin to resolve. Choose antibiotics effective against sinusitis-related pathogens (eg, S pneumoniae, H influenzae, M catarrhalis), S aureus, and anaerobes.⁸ For instance, a regimen may include vancomycin for MRSA coverage, a third-generation cephalosporin, or metronidazole for anaerobic coverage if there is concern about intracranial involvement. Surgical intervention is often reserved for patients with inadequate response to antibiotic therapy, necessitating biopsy for pathogen identification, as well as drainage of large abscesses refractory to antibiotics.

Erysipelas

Erysipelas, a related yet distinct form of cellulitis, is a bacterial infection of the superficial dermis and hypodermis and is commonly caused by group A streptococcus.^5,9 Other less common organisms include S aureus, P aeruginosa, and enterobacteria. Erysipelas predominantly affects the lower extremities unilaterally (~90%); the arms and the face are the next most common locations. In addition to the rapid onset of well-demarcated erythema, pain, and swelling, patients may have fever and regional lymphadenopathy. Risk factors include portal of entry (eg, tinea pedis, ulceration), lymphedema, and diabetes. Complications of erysipelas include bullae from edema, abscess formation, and, rarely, bacteremia.

When clinical exam alone is inconclusive when evaluating skin and softtissue infections in children and adolescents, consider using ultrasound to improve diagnostic accuracy.

Antibiotic treatment regimens include penicillin G, macrolides (reserved for those with penicillin allergies), fluoroquinolones, and cephalosporins, with duration of treatment ranging from 10 to 14 days depending on infection severity. Fever, pain, and erythema generally improve within 48 to 72 hours of antibiotic therapy. If there is no improvement, consider alternative diagnoses, such as necrotizing fasciitis. Recurrence rates following the initial episode of erysipelas are estimated at 10% of patients at 6 months and 30% at 3 years.¹⁰

Folliculitis

Inflammation of hair follicles is characterized by superficial inflammation with the development of perifollicular papules or pustules on an erythematous base.^11,12 Folliculitis most commonly affects the face, scalp, thighs, buttocks, axillae, and inguinal areas.¹³ It may be caused by infection, an inflammatory reaction, or physical injury. Diagnosis is typically based on the patient’s history and physical examination.

Bacteria are the most common cause of infection, although fungi, viruses, and other entities can cause folliculitis. S aureus (methicillin sensitive or methicillin resistant) is the most common pathogen; in the past, superficial pustular folliculitis attributed to S aureus was referred to as Bockhart impetigo. Folliculitis secondary to P aeruginosa, often seen after exposure to contaminated water or hot tubs, is frequently referred to as “hot tub folliculitis.” Malassezia, a reported cause of fungal folliculitis, tends to occur in adolescents of either sex and men with high sebum production, is common in tropical climates, and can be associated with HIV or immunosuppression.^11,12,14

Continue to: Differential diagnosis...

Differential diagnosis of folliculitis includes pseudofolliculitis barbae, eosinophilic folliculitis, keratosis pilaris, acne vulgaris, candidiasis, contact dermatitis, impetigo, and miliaria.¹³ Pseudofolliculitis barbae is an inflammatory reaction to shaving, more commonly seen in darkly pigmented skin. Pseudofolliculitis develops when the hair shaft penetrates the wall of the follicle or directly enters the epidermis.

Initial treatment for mild disease includes the elimination of predisposing factors such as occlusion, moisture, and abrasion. The area should be kept clean and dry, avoiding friction. For localized disease, prescribe topical clindamycin, mupirocin ointment, or benzoyl peroxide. If symptoms fail to respond, prescribe a 7-day course of antibiotic that targets methicillin-sensitive S aureus—eg, cephalexin or dicloxacillin. Also consider doxycycline, which has anti-inflammatory effects and is effective against MRSA. For refractory lesions, ­trimethoprim-sulfamethoxazole, clindamycin, or minocycline may be useful. If you suspect pseudomonas, consider giving ciprofloxacin for 10 to 14 days for persistent lesions or if the patient is immunocompromised.^13,15 Consider obtaining bacterial, fungal, or viral cultures for lesions that fail to respond to initial treatment.

Do not routinely order cultures or prescribe antibiotics for uncomplicated abscesses.

Furuncles/carbuncles/abscesses

A furuncle, commonly referred to as a boil, is an infected hair follicle that becomes enclosed, creating a collection of pus. A carbuncle is a collection of furuncles that converge and drain through a single opening. An abscess is a localized collection of pus arising from within the dermis that can extend within deeper tissues.⁵ Furuncles, carbuncles, and abscesses are managed similarly with drainage and consideration for MRSA risk factors.

S aureus is the most common cause of these infections; 59% of skin abscesses are due to community-acquired MRSA.¹⁶ Anaerobes may contribute to the polymicrobial flora of skin abscesses.¹⁷ Risk factors for MRSA infection include a history of previous MRSA infection, diabetes, dialysis or renal failure, placement of an indwelling catheter or medical device, injection drug use, incarceration, close contact with a person with known MRSA infection or colonization, long-term care residence, hospitalization or surgery within the past 12 months, and high prevalence of MRSA in the community.⁵

Ultrasound improves diagnostic accuracy. One study showed that when a clinical exam alone was inconclusive in evaluating skin and soft-tissue infections in children and adolescents, an ultrasound-assisted examination improved diagnostic accuracy.¹⁸ Sensitivity of the clinical examination was 43.7%, compared with 77.6% for the clinical examination plus ultrasound.¹⁸

Continue to: Incision and drainage first

Incision and drainage first. Ultrasound-guided needle aspiration, however, has not improved treatment efficacy compared with incision and drainage,¹⁹ the mainstay approach for abscesses.¹⁷ The procedure to drain a furuncle, carbuncle, or abscess should include the expression of all purulent material and the removal of all loculations if possible. Wound culture is recommended during incision and drainage per current guidelines.⁵ Simple dry dressings are convenient and effective, although some wounds may require packing. Tap water (that is potable) is suitable for wound cleansing. However, there is no strong evidence that irrigating wounds increases healing or reduces infection.²⁰

Routine use of antibiotics is not recommended for simple cutaneous abscesses.^5,17,21 Evidence has been conflicting regarding empiric antibiotic coverage of MRSA following incision and drainage.^22-25 Guidelines recommend considering the initiation of antibiotics if there are multiple abscesses, gangrene, surrounding cellulitis, or systemic signs of infection, or if the host is immunocompromised.⁵

If MRSA is suspected, recommended antibiotic coverage includes trimethoprim-­sulfamethoxazole, clindamycin, doxycycline, or minocycline.⁵ If MRSA is identified, treatment options include dicloxacillin or cephalexin. For severe infections persisting after incision and drainage, in addition to oral antibiotic therapy, consider intravenous antibiotic options for MRSA: cefazolin, clindamycin, linezolid, nafcillin, telavancin, or vancomycin.⁵

Necrotizing fasciitis

Necrotizing fasciitis is a rare but potentially deadly infection of the skin and soft tissue. It progresses rapidly and spreads along fascial planes, leading to the necrosis of the superficial fascia. The infection often is more extensive than is indicated by superficial signs. Prompt diagnosis is imperative as necrotizing fasciitis is a surgical emergency.^5,26 In the United States, 500 to 1500 cases of necrotizing fasciitis occur each year.²⁷ Risk factors for necrotizing fasciitis include diabetes, peripheral vascular disease, malignancy, obesity, cirrhosis, renal failure, injection drug use, chronic corticosteroid therapy, alcohol abuse, malnutrition, and iatrogenic immunosuppression.^26,28

Monomicrobial infections, which account for 20% to 30% of cases of necrotizing fasciitis, are community acquired.

Necrotizing fasciitis may be polymicrobial or monomicrobial. Polymicrobial infection, also referred to as type I, is often due to multiple bacteria that originate from the bowel flora, typically including a mix of anaerobic and aerobic organisms. On average, there can be 5 infecting organisms identified per wound, although in some cases up to 15 organisms have been identified in a single wound.⁵ Type I infection is often associated with tissue injury, abscess, or abdominal surgery. The majority of cases of necrotizing fasciitis are polymicrobial.^27,28

Continue to: Monomicrobial infection...

Monomicrobial infection, also referred to as type II, is often due to group A streptococcus, S aureus, vibrio spp, Aeromonas hyrophilio, or an anaerobic streptococci like peptostreptococcus spp. Typically monomicrobial infections, which account for 20% to 30% of cases of necrotizing fasciitis, are community acquired.^5,26,29,30

Clinical presentation. In the early stages of disease, patients commonly complain of flu-like symptoms and extreme pain that is out of proportion to findings on the exam. Additional warning signs include fevers and other symptoms of toxicity such as tachycardia, hypotension, nausea, vomiting, and diarrhea. Later in the course, symptoms may localize to the affected area and include erythema, tense swelling, development of blisters or bullae, blackish blue discoloration of the skin, severe pain, and loss of sensation. In some cases involving gas-forming bacteria, tissue crepitus may be noted on exam.^5,27-31

Rely on clinical judgment to hasten surgical intervention. Laboratory or imaging findings may augment clinical judgment. But if you suspect necrotizing fasciitis, obtaining blood tests and imaging should not delay surgery. Blood tests that may aid in the diagnosis of necrotizing fasciitis include a complete blood count with differential; coagulation studies; a comprehensive metabolic panel; assays of lactate, C-reactive protein (CRP), and creatinine kinase; and blood cultures. Most often, patients with necrotizing fasciitis will have leukocytosis or leukopenia, evidence of hemolysis, thrombocytopenia, acute renal failure, and significantly elevated CRP.

If you suspect necrotizing fasciitis, obtaining blood tests and imaging should not delay surgery.

On any imaging modality, indications of necrotizing fasciitis are inflammatory infiltration of the deep fascia on the affected side that is absent on the contralateral side, and the presence of subcutaneous air (which is a specific but rare finding). Imaging modalities may include CT or magnetic resonance imaging. A definitive diagnosis can only be made with surgical exploration of the involved area. Definitive microbiologic diagnosis will require culture of organisms from affected tissue or blood.^5,26,30,31

First address any hemodynamic instability (hypotension is frequently encountered), followed by urgent surgical exploration, debridement of the wound, and antimicrobial therapy. Antibiotic treatment should align with probable pathogens and treatment should be continued until repeated surgical debridement is no longer necessary, clinical improvement is evident, and 48 to 72 hours have passed since defervescence. A reasonable initial empiric regimen in adults would include an agent that is effective against group A streptococcus, gram-negative pathogens, and anaerobes, such as a carbapenem or a beta-lactam-­beta-lactamase inhibitor such as piperacillin-­tazobactam. Additionally, include an agent that targets MRSA, such as vancomycin, linezolid, or clindamycin.⁵

CORRESPONDENCE
Karl T. Clebak, MD, Department of Family and Community Medicine Residency Program, Penn State Health M.S. Hershey Medical Center, 500 University Drive, H154/C1613, Hershey, PA 17033; kclebak@pennstatehealth.psu.edu

Risankizumab (Skyrizi) was effective for treating psoriatic arthritis (PsA) in patients who did not respond to or who could not tolerate other biologics or standard disease-modifying antirheumatic drugs (DMARDs), according to a study presented at the annual European Congress of Rheumatology. It was also well tolerated.

“Treatment with risankizumab resulted in significantly greater improvements in signs and symptoms of psoriatic arthritis, including assessments of disease activity in joints and skin and patient-reported outcomes, compared with placebo, in patients who did not respond to or were intolerant to biologics or DMARDs,” reported Andrew Ostor, MD, of Monash University and Cabrini Hospital, both in Melbourne,. The safety profile was “consistent with that established for risankizumab in the treatment moderate to severe psoriasis,” he told attendees.

Risankizumab is approved in the United States for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. It is a humanized immunoglobulin G1 monoclonal antibody that selectively inhibits cytokine interleukin-23 by binding to its p19 subunit. IL-23 has been implicated in the development of PsA.

This was a phase 3 trial with “promising results in line with the ACR 20 response [at least 20% improvement in American College of Rheumatology response criteria] of other biologics in psoriatic arthritis,” according to Gaëlle Varkas, MD, PhD, of the Ghent (the Netherlands) University VIB Center for Inflammation Research and the department of rheumatology, Ghent University Hospital. “Especially in patients with severe and/or refractory skin disease or inadequate response at the level of the joint to other DMARDs or biologics, risankizumab is filling a void,” Dr. Varkas, who was not involved in the research, said in an interview.

There were no major safety problems, although long-term data, especially in regard to cancer and cardiovascular effects, “are always of interest, as they can be missed in randomized, controlled trials,” she said. In addition, “efficacy in concomitant axial disease, uveitis, and inflammatory bowel disease might favor one treatment over the other.” Another clinically significant takeaway was risankizumab’s “better effect on skin psoriasis while maintaining the effect on joint manifestations.”
 

Details of 24-week trial results

The phase 3, randomized, placebo-controlled, double-blind KEEPSAKE 2 trial involved 444 patients who had active PsA, defined as at least five swollen joints and at least five tender joints. All the patients either had an inadequate response to or were intolerant of one or two biologics or at least one conventional synthetic DMARD.

A total of 224 patients were randomly assigned to receive 150 mg of subcutaneous risankizumab at baseline and at 4 and 16 weeks after baseline; 220 participants received placebo injections. The primary endpoint was the proportion of patients who had at least 20% improvement in American College of Rheumatology response criteria at week 24.

Demographic and clinical characteristics were similar in both groups at baseline. Among the participants, the total mean number of swollen joints was 13.3, and the total mean number of tender joints was 22.6. The participants had PsA for an average of 8.2 years. The proportions of patients previously treated with biologics and DMARDs were similar in both groups, as were the proportions of patients currently taking glucocorticoids, NSAIDs, or methotrexate or another DMARD. At week 24, there remained 199 patients in the placebo group and 215 in the risankizumab group.

Just over half (51.3%) of patients who took risankizumab achieved at least 20% improvement in their ACR 20 score, compared with just over a quarter (26.5%) of those who received placebo (P < .001). All secondary endpoints also showed statistically significant improvements (P < .001 for all except P < .009 for the Fatigue Functional Assessment of Chronic Illness Therapy–Fatigue [FACIT-Fatigue] secondary endpoint).

Scores on the Health Assessment Questionnaire–Disability Index were –0.22 in the risankizumab group and –0.05 in the placebo group (P < .001). In the risankizumab group, 55% of patients achieved at least a 90% reduction in scores on the Psoriasis Area Severity Index, compared with 10.2% of patients who received placebo. Similarly, 25.6% of patients who took risankizumab and 11.4% of patients who received placebo had minimal disease activity 24 weeks after baseline.

In the 36-item Short Form Health Survey Physical Component Summary, the score change among risankizumab patients was 5.9, compared with 2 among the patients who received placebo. The change in FACIT-Fatigue score was 4.9 for patients who took risankizumab and 2.6 for patients who received placebo.

The researchers also assessed how many patients achieved higher levels of response to treatment. At least a 50% improvement in ACR response criteria occurred among 26.3% of patients taking risankizumab and 9.3% of patients taking placebo (P < .001). ACR 70 responses were seen in 12% of patients receiving risankizumab, compared with 5.9% of patients receiving placebo (P < .02). In the risankizumab group, 72.5% of patients had resolution of dactylitis and 42.9% had resolution of enthesitis, compared with 42.1% and 30.4%, respectively, in the placebo group.

Serious adverse events occurred in 4% of patients who received risankizumab and 5.5% of patients who received placebo. Serious infections occurred in 0.9% of those receiving risankizumab and 2.3% of those receiving placebo. Rates of treatment-emergent adverse events were also similar in the risankizumab (55.4%) and placebo (54.8%) groups.

In response to a question about whether it was possible to identify patients who might respond better to IL-23 inhibitors, compared with IL-17 inhibitors, Dr. Ostor acknowledged that rheumatologic practice is not yet proficient at using biomarkers to direct therapy, so the benefit from these drugs lay elsewhere.

“What I think is great is the luxury of choice these days,” Dr. Ostor told attendees. “We have these agents now, including risankizumab, that do work very effectively across the spectrum of the clinical features. It’s just lovely to have these agents available that can truly make a difference to the clinical picture of the individual.”

The trial was sponsored by AbbVie. Dr. Ostor has received research grants or speaking or consulting fees from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB. Dr. Varkas has received research grants or speaker fees from AbbVie and Pfizer.

A version of this article first appeared on Medscape.com.

Risankizumab (Skyrizi) was effective for treating psoriatic arthritis (PsA) in patients who did not respond to or who could not tolerate other biologics or standard disease-modifying antirheumatic drugs (DMARDs), according to a study presented at the annual European Congress of Rheumatology. It was also well tolerated.

“Treatment with risankizumab resulted in significantly greater improvements in signs and symptoms of psoriatic arthritis, including assessments of disease activity in joints and skin and patient-reported outcomes, compared with placebo, in patients who did not respond to or were intolerant to biologics or DMARDs,” reported Andrew Ostor, MD, of Monash University and Cabrini Hospital, both in Melbourne,. The safety profile was “consistent with that established for risankizumab in the treatment moderate to severe psoriasis,” he told attendees.

Risankizumab is approved in the United States for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. It is a humanized immunoglobulin G1 monoclonal antibody that selectively inhibits cytokine interleukin-23 by binding to its p19 subunit. IL-23 has been implicated in the development of PsA.

This was a phase 3 trial with “promising results in line with the ACR 20 response [at least 20% improvement in American College of Rheumatology response criteria] of other biologics in psoriatic arthritis,” according to Gaëlle Varkas, MD, PhD, of the Ghent (the Netherlands) University VIB Center for Inflammation Research and the department of rheumatology, Ghent University Hospital. “Especially in patients with severe and/or refractory skin disease or inadequate response at the level of the joint to other DMARDs or biologics, risankizumab is filling a void,” Dr. Varkas, who was not involved in the research, said in an interview.

There were no major safety problems, although long-term data, especially in regard to cancer and cardiovascular effects, “are always of interest, as they can be missed in randomized, controlled trials,” she said. In addition, “efficacy in concomitant axial disease, uveitis, and inflammatory bowel disease might favor one treatment over the other.” Another clinically significant takeaway was risankizumab’s “better effect on skin psoriasis while maintaining the effect on joint manifestations.”
 

Details of 24-week trial results

The phase 3, randomized, placebo-controlled, double-blind KEEPSAKE 2 trial involved 444 patients who had active PsA, defined as at least five swollen joints and at least five tender joints. All the patients either had an inadequate response to or were intolerant of one or two biologics or at least one conventional synthetic DMARD.

A total of 224 patients were randomly assigned to receive 150 mg of subcutaneous risankizumab at baseline and at 4 and 16 weeks after baseline; 220 participants received placebo injections. The primary endpoint was the proportion of patients who had at least 20% improvement in American College of Rheumatology response criteria at week 24.

Demographic and clinical characteristics were similar in both groups at baseline. Among the participants, the total mean number of swollen joints was 13.3, and the total mean number of tender joints was 22.6. The participants had PsA for an average of 8.2 years. The proportions of patients previously treated with biologics and DMARDs were similar in both groups, as were the proportions of patients currently taking glucocorticoids, NSAIDs, or methotrexate or another DMARD. At week 24, there remained 199 patients in the placebo group and 215 in the risankizumab group.

Just over half (51.3%) of patients who took risankizumab achieved at least 20% improvement in their ACR 20 score, compared with just over a quarter (26.5%) of those who received placebo (P < .001). All secondary endpoints also showed statistically significant improvements (P < .001 for all except P < .009 for the Fatigue Functional Assessment of Chronic Illness Therapy–Fatigue [FACIT-Fatigue] secondary endpoint).

Scores on the Health Assessment Questionnaire–Disability Index were –0.22 in the risankizumab group and –0.05 in the placebo group (P < .001). In the risankizumab group, 55% of patients achieved at least a 90% reduction in scores on the Psoriasis Area Severity Index, compared with 10.2% of patients who received placebo. Similarly, 25.6% of patients who took risankizumab and 11.4% of patients who received placebo had minimal disease activity 24 weeks after baseline.

In the 36-item Short Form Health Survey Physical Component Summary, the score change among risankizumab patients was 5.9, compared with 2 among the patients who received placebo. The change in FACIT-Fatigue score was 4.9 for patients who took risankizumab and 2.6 for patients who received placebo.

The researchers also assessed how many patients achieved higher levels of response to treatment. At least a 50% improvement in ACR response criteria occurred among 26.3% of patients taking risankizumab and 9.3% of patients taking placebo (P < .001). ACR 70 responses were seen in 12% of patients receiving risankizumab, compared with 5.9% of patients receiving placebo (P < .02). In the risankizumab group, 72.5% of patients had resolution of dactylitis and 42.9% had resolution of enthesitis, compared with 42.1% and 30.4%, respectively, in the placebo group.

Serious adverse events occurred in 4% of patients who received risankizumab and 5.5% of patients who received placebo. Serious infections occurred in 0.9% of those receiving risankizumab and 2.3% of those receiving placebo. Rates of treatment-emergent adverse events were also similar in the risankizumab (55.4%) and placebo (54.8%) groups.

In response to a question about whether it was possible to identify patients who might respond better to IL-23 inhibitors, compared with IL-17 inhibitors, Dr. Ostor acknowledged that rheumatologic practice is not yet proficient at using biomarkers to direct therapy, so the benefit from these drugs lay elsewhere.

“What I think is great is the luxury of choice these days,” Dr. Ostor told attendees. “We have these agents now, including risankizumab, that do work very effectively across the spectrum of the clinical features. It’s just lovely to have these agents available that can truly make a difference to the clinical picture of the individual.”

The trial was sponsored by AbbVie. Dr. Ostor has received research grants or speaking or consulting fees from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB. Dr. Varkas has received research grants or speaker fees from AbbVie and Pfizer.

A version of this article first appeared on Medscape.com.

Risankizumab (Skyrizi) was effective for treating psoriatic arthritis (PsA) in patients who did not respond to or who could not tolerate other biologics or standard disease-modifying antirheumatic drugs (DMARDs), according to a study presented at the annual European Congress of Rheumatology. It was also well tolerated.

“Treatment with risankizumab resulted in significantly greater improvements in signs and symptoms of psoriatic arthritis, including assessments of disease activity in joints and skin and patient-reported outcomes, compared with placebo, in patients who did not respond to or were intolerant to biologics or DMARDs,” reported Andrew Ostor, MD, of Monash University and Cabrini Hospital, both in Melbourne,. The safety profile was “consistent with that established for risankizumab in the treatment moderate to severe psoriasis,” he told attendees.

Risankizumab is approved in the United States for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. It is a humanized immunoglobulin G1 monoclonal antibody that selectively inhibits cytokine interleukin-23 by binding to its p19 subunit. IL-23 has been implicated in the development of PsA.

This was a phase 3 trial with “promising results in line with the ACR 20 response [at least 20% improvement in American College of Rheumatology response criteria] of other biologics in psoriatic arthritis,” according to Gaëlle Varkas, MD, PhD, of the Ghent (the Netherlands) University VIB Center for Inflammation Research and the department of rheumatology, Ghent University Hospital. “Especially in patients with severe and/or refractory skin disease or inadequate response at the level of the joint to other DMARDs or biologics, risankizumab is filling a void,” Dr. Varkas, who was not involved in the research, said in an interview.

There were no major safety problems, although long-term data, especially in regard to cancer and cardiovascular effects, “are always of interest, as they can be missed in randomized, controlled trials,” she said. In addition, “efficacy in concomitant axial disease, uveitis, and inflammatory bowel disease might favor one treatment over the other.” Another clinically significant takeaway was risankizumab’s “better effect on skin psoriasis while maintaining the effect on joint manifestations.”
 

Details of 24-week trial results

The phase 3, randomized, placebo-controlled, double-blind KEEPSAKE 2 trial involved 444 patients who had active PsA, defined as at least five swollen joints and at least five tender joints. All the patients either had an inadequate response to or were intolerant of one or two biologics or at least one conventional synthetic DMARD.

A total of 224 patients were randomly assigned to receive 150 mg of subcutaneous risankizumab at baseline and at 4 and 16 weeks after baseline; 220 participants received placebo injections. The primary endpoint was the proportion of patients who had at least 20% improvement in American College of Rheumatology response criteria at week 24.

Demographic and clinical characteristics were similar in both groups at baseline. Among the participants, the total mean number of swollen joints was 13.3, and the total mean number of tender joints was 22.6. The participants had PsA for an average of 8.2 years. The proportions of patients previously treated with biologics and DMARDs were similar in both groups, as were the proportions of patients currently taking glucocorticoids, NSAIDs, or methotrexate or another DMARD. At week 24, there remained 199 patients in the placebo group and 215 in the risankizumab group.

Just over half (51.3%) of patients who took risankizumab achieved at least 20% improvement in their ACR 20 score, compared with just over a quarter (26.5%) of those who received placebo (P < .001). All secondary endpoints also showed statistically significant improvements (P < .001 for all except P < .009 for the Fatigue Functional Assessment of Chronic Illness Therapy–Fatigue [FACIT-Fatigue] secondary endpoint).

Scores on the Health Assessment Questionnaire–Disability Index were –0.22 in the risankizumab group and –0.05 in the placebo group (P < .001). In the risankizumab group, 55% of patients achieved at least a 90% reduction in scores on the Psoriasis Area Severity Index, compared with 10.2% of patients who received placebo. Similarly, 25.6% of patients who took risankizumab and 11.4% of patients who received placebo had minimal disease activity 24 weeks after baseline.

In the 36-item Short Form Health Survey Physical Component Summary, the score change among risankizumab patients was 5.9, compared with 2 among the patients who received placebo. The change in FACIT-Fatigue score was 4.9 for patients who took risankizumab and 2.6 for patients who received placebo.

The researchers also assessed how many patients achieved higher levels of response to treatment. At least a 50% improvement in ACR response criteria occurred among 26.3% of patients taking risankizumab and 9.3% of patients taking placebo (P < .001). ACR 70 responses were seen in 12% of patients receiving risankizumab, compared with 5.9% of patients receiving placebo (P < .02). In the risankizumab group, 72.5% of patients had resolution of dactylitis and 42.9% had resolution of enthesitis, compared with 42.1% and 30.4%, respectively, in the placebo group.

Serious adverse events occurred in 4% of patients who received risankizumab and 5.5% of patients who received placebo. Serious infections occurred in 0.9% of those receiving risankizumab and 2.3% of those receiving placebo. Rates of treatment-emergent adverse events were also similar in the risankizumab (55.4%) and placebo (54.8%) groups.

In response to a question about whether it was possible to identify patients who might respond better to IL-23 inhibitors, compared with IL-17 inhibitors, Dr. Ostor acknowledged that rheumatologic practice is not yet proficient at using biomarkers to direct therapy, so the benefit from these drugs lay elsewhere.

“What I think is great is the luxury of choice these days,” Dr. Ostor told attendees. “We have these agents now, including risankizumab, that do work very effectively across the spectrum of the clinical features. It’s just lovely to have these agents available that can truly make a difference to the clinical picture of the individual.”

The trial was sponsored by AbbVie. Dr. Ostor has received research grants or speaking or consulting fees from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB. Dr. Varkas has received research grants or speaker fees from AbbVie and Pfizer.

A version of this article first appeared on Medscape.com.

A potassium hydroxide preparation (KOH) from skin scrapings from the scalp lesions demonstrated no fungal elements. Further laboratory work up revealed a normal blood cell count, normal liver enzymes, an antinuclear antibody (ANA) titer of less than 1:80, a positive anti–Sjögren’s syndrome type B (SSB) antibody but negative anti–Sjögren’s syndrome type A (SSA) antibody and anti-U1RNP antibody. An electrocardiogram revealed no abnormalities. Liver function tests were normal. The complete blood count showed mild thrombocytopenia. Given the typical skin lesions and the positive SSB test and associated thrombocytopenia, the baby was diagnosed with neonatal lupus erythematosus.

Because of the diagnosis of neonatal lupus the mother was also tested and was found to have an elevated ANA of 1:640, positive SSB and antiphospholipid antibodies. The mother was healthy and her review of systems was negative for any collagen vascular disease–related symptoms.
 

Discussion

Neonatal lupus erythematosus (NLE) is a rare form of systemic lupus erythematosus (SLE) believed to be caused by transplacental transfer of anti-Ro (Sjögren’s syndrome antigen A, SSA), or, less commonly, anti-La (Sjögren’s syndrome antigen B, SSB) from mothers who are positive for these antibodies. Approximately 95% of NLE is associated with maternal anti-SSA; of these cases, 40% are also associated with maternal anti-SSB.¹ Only about 2% of children of mothers who have anti-SSA or anti-SSB develop NLE, a finding that has led some researchers to postulate that maternal factors, fetal genetic factors, and environmental factors determine which children of anti-SSA or SSB positive mothers develop NLE.

A recent review found no association between the development of NLE and fetal birth weight, prematurity, or age.³ Over half of mothers of children who develop NLE are asymptomatic at the time of diagnosis of the neonate,³ though many become symptomatic in following years. Of mothers who are symptomatic, SLE and undifferentiated autoimmune syndrome are the most common diagnoses, though NLE has been rarely reported in the offspring of mothers with Sjögren’s syndrome, rheumatoid arthritis, and psoriasis.^4,5

Fetal genetics are not an absolute determinant of development of NLE, as discordance in the development of NLE in twins has been reported. However, certain genetic relationships have been established. Fetal mutations in tumor necrosis factor–alpha appear to increase the likelihood of cutaneous manifestations. Mutations in transforming growth factor beta appear to increase the likelihood of cardiac manifestations, and experiments in cultured mouse cardiocytes have shown anti-SSB antibodies to impair macrophage phagocytosis of apoptotic cells in the developing fetal heart. These observations taken together suggest a fibroblast-mediated response to unphagocytosed cardiocyte debris may account for conduction abnormalities in neonates with NLE-induced heart block.⁶

Cutaneous disease in NLE is possible at birth, but more skin findings develop upon exposure to the sun. Nearly 80% of neonates affected by NLE develop cutaneous manifestations in the first few months of life. The head, neck, and extensor surfaces of the arms are most commonly affected, presumably because they are most likely to be exposed to the sun. Erythematous, annular, or discoid lesions are most common, and periorbital erythema with or without scale (“raccoon eyes”) should prompt consideration of NLE. However, annular, or discoid lesions are sometimes not present in NLE; telangiectasias, bullae, atrophic divots (“ice-pick scars”) or ulcerations may be seen instead. Lesions in the genital area have been described in fewer than 5% of patients with NLE.

The differential diagnosis of annular, scaly lesions in neonates includes annular erythema of infancy, tinea corporis, and seborrheic dermatitis. Annular erythema of infancy is a rare skin condition characterized by a cyclical eruption of erythematous annular lesions with minimal scaling which resolve spontaneously within a few weeks to months without leaving scaring or pigment changes. There is no treatment needed as the lesions self-resolve.⁷ Acute urticaria can sometimes appear similar to NLE but these are not scaly and also the lesions will disappear within 24-36 hours, compared with NLE lesions, which may take weeks to months to go away. Seborrheic dermatitis is a common skin condition seen in newborns with in the first few weeks of life and can present as scaly annular erythematous plaques on the face, scalp, torso, and the diaper area. Seborrheic dermatitis usually responds well to a combination of an antiyeast cream and a low-potency topical corticosteroid medication.

When NLE is suspected, diagnostic testing for lupus antibodies (anti-SSA, anti-SSB, and anti-U1RNP) in both maternal and neonatal serum should be undertaken. The presence of a characteristic rash plus maternal or neonatal antibodies is sufficient to make the diagnosis. If the rash is less characteristic, a biopsy showing an interface dermatitis can help solidify the diagnosis. Neonates with cutaneous manifestations of lupus may also have systemic disease. The most common and serious complication is heart block, whose pathophysiology is described above. Neonates with evidence of first-, second-, or third-degree heart block should be referred to a pediatric cardiologist for careful monitoring and management. Hepatic involvement has been reported, but is usually mild. Hematologic abnormalities have also been described that include anemia, neutropenia, and thrombocytopenia, which resolve by 9 months of age. Central nervous system involvement may rarely occur. The mainstay of treatment for the rash in NLE is diligent sun avoidance and sun protection. Topical corticosteroids may be used, but are not needed as the rash typically resolves by 9 months to 1 year without treatment. Mothers who have one child with NLE should be advised that they are more likely to have another with NLE – the risk is as high as 30%-40% in the second child. Hydroxychloroquine taken during subsequent pregnancies can reduce the incidence of cardiac complications,⁸ as can the so-called “triple therapy” of plasmapheresis, steroids, and IVIg.⁹

The cutaneous manifestations of NLE are usually self-limiting. However, they can serve as important clues that can prompt diagnosis of SLE in the mother, investigation of cardiac complications in the infant, and appropriate preventative care in future pregnancies.

Dr. Matiz is with the department of dermatology, Southern California Permanente Medical Group, San Diego. Mr. Kusari is with the department of dermatology, University of California, San Francisco.

References

1. Moretti D et al. Int J Dermatol. 2014;53(12):1508-12.

2. Buyon JP et al. Nature Clin Prac Rheum. 2009;5(3):139-48.

3. Li Y-Q et al. Int J Rheum Dis. 2015;18(7):761-7.

4. Rivera TL et al. Annals Rheum Dis. 2009;68(6):828-35.

5. Li L et al. Zhonghua er ke za zhi 2011;49(2):146-50.

6. Izmirly PM et al. Clin Rheumatol. 2011;30(12):1641-5.

7. Toledo-Alberola F and Betlloch-Mas I. Actas Dermosifiliogr. 2010 Jul;101(6):473-84.

8. Izmirly PM et al. Circulation. 2012;126(1):76-82.

9. Martinez-Sanchez N et al. Autoimmun Rev. 2015;14(5):423-8.

A potassium hydroxide preparation (KOH) from skin scrapings from the scalp lesions demonstrated no fungal elements. Further laboratory work up revealed a normal blood cell count, normal liver enzymes, an antinuclear antibody (ANA) titer of less than 1:80, a positive anti–Sjögren’s syndrome type B (SSB) antibody but negative anti–Sjögren’s syndrome type A (SSA) antibody and anti-U1RNP antibody. An electrocardiogram revealed no abnormalities. Liver function tests were normal. The complete blood count showed mild thrombocytopenia. Given the typical skin lesions and the positive SSB test and associated thrombocytopenia, the baby was diagnosed with neonatal lupus erythematosus.

Because of the diagnosis of neonatal lupus the mother was also tested and was found to have an elevated ANA of 1:640, positive SSB and antiphospholipid antibodies. The mother was healthy and her review of systems was negative for any collagen vascular disease–related symptoms.
 

Discussion

Neonatal lupus erythematosus (NLE) is a rare form of systemic lupus erythematosus (SLE) believed to be caused by transplacental transfer of anti-Ro (Sjögren’s syndrome antigen A, SSA), or, less commonly, anti-La (Sjögren’s syndrome antigen B, SSB) from mothers who are positive for these antibodies. Approximately 95% of NLE is associated with maternal anti-SSA; of these cases, 40% are also associated with maternal anti-SSB.¹ Only about 2% of children of mothers who have anti-SSA or anti-SSB develop NLE, a finding that has led some researchers to postulate that maternal factors, fetal genetic factors, and environmental factors determine which children of anti-SSA or SSB positive mothers develop NLE.

A recent review found no association between the development of NLE and fetal birth weight, prematurity, or age.³ Over half of mothers of children who develop NLE are asymptomatic at the time of diagnosis of the neonate,³ though many become symptomatic in following years. Of mothers who are symptomatic, SLE and undifferentiated autoimmune syndrome are the most common diagnoses, though NLE has been rarely reported in the offspring of mothers with Sjögren’s syndrome, rheumatoid arthritis, and psoriasis.^4,5

Fetal genetics are not an absolute determinant of development of NLE, as discordance in the development of NLE in twins has been reported. However, certain genetic relationships have been established. Fetal mutations in tumor necrosis factor–alpha appear to increase the likelihood of cutaneous manifestations. Mutations in transforming growth factor beta appear to increase the likelihood of cardiac manifestations, and experiments in cultured mouse cardiocytes have shown anti-SSB antibodies to impair macrophage phagocytosis of apoptotic cells in the developing fetal heart. These observations taken together suggest a fibroblast-mediated response to unphagocytosed cardiocyte debris may account for conduction abnormalities in neonates with NLE-induced heart block.⁶

Cutaneous disease in NLE is possible at birth, but more skin findings develop upon exposure to the sun. Nearly 80% of neonates affected by NLE develop cutaneous manifestations in the first few months of life. The head, neck, and extensor surfaces of the arms are most commonly affected, presumably because they are most likely to be exposed to the sun. Erythematous, annular, or discoid lesions are most common, and periorbital erythema with or without scale (“raccoon eyes”) should prompt consideration of NLE. However, annular, or discoid lesions are sometimes not present in NLE; telangiectasias, bullae, atrophic divots (“ice-pick scars”) or ulcerations may be seen instead. Lesions in the genital area have been described in fewer than 5% of patients with NLE.

The differential diagnosis of annular, scaly lesions in neonates includes annular erythema of infancy, tinea corporis, and seborrheic dermatitis. Annular erythema of infancy is a rare skin condition characterized by a cyclical eruption of erythematous annular lesions with minimal scaling which resolve spontaneously within a few weeks to months without leaving scaring or pigment changes. There is no treatment needed as the lesions self-resolve.⁷ Acute urticaria can sometimes appear similar to NLE but these are not scaly and also the lesions will disappear within 24-36 hours, compared with NLE lesions, which may take weeks to months to go away. Seborrheic dermatitis is a common skin condition seen in newborns with in the first few weeks of life and can present as scaly annular erythematous plaques on the face, scalp, torso, and the diaper area. Seborrheic dermatitis usually responds well to a combination of an antiyeast cream and a low-potency topical corticosteroid medication.

When NLE is suspected, diagnostic testing for lupus antibodies (anti-SSA, anti-SSB, and anti-U1RNP) in both maternal and neonatal serum should be undertaken. The presence of a characteristic rash plus maternal or neonatal antibodies is sufficient to make the diagnosis. If the rash is less characteristic, a biopsy showing an interface dermatitis can help solidify the diagnosis. Neonates with cutaneous manifestations of lupus may also have systemic disease. The most common and serious complication is heart block, whose pathophysiology is described above. Neonates with evidence of first-, second-, or third-degree heart block should be referred to a pediatric cardiologist for careful monitoring and management. Hepatic involvement has been reported, but is usually mild. Hematologic abnormalities have also been described that include anemia, neutropenia, and thrombocytopenia, which resolve by 9 months of age. Central nervous system involvement may rarely occur. The mainstay of treatment for the rash in NLE is diligent sun avoidance and sun protection. Topical corticosteroids may be used, but are not needed as the rash typically resolves by 9 months to 1 year without treatment. Mothers who have one child with NLE should be advised that they are more likely to have another with NLE – the risk is as high as 30%-40% in the second child. Hydroxychloroquine taken during subsequent pregnancies can reduce the incidence of cardiac complications,⁸ as can the so-called “triple therapy” of plasmapheresis, steroids, and IVIg.⁹

The cutaneous manifestations of NLE are usually self-limiting. However, they can serve as important clues that can prompt diagnosis of SLE in the mother, investigation of cardiac complications in the infant, and appropriate preventative care in future pregnancies.

Dr. Matiz is with the department of dermatology, Southern California Permanente Medical Group, San Diego. Mr. Kusari is with the department of dermatology, University of California, San Francisco.

References

1. Moretti D et al. Int J Dermatol. 2014;53(12):1508-12.

2. Buyon JP et al. Nature Clin Prac Rheum. 2009;5(3):139-48.

3. Li Y-Q et al. Int J Rheum Dis. 2015;18(7):761-7.

4. Rivera TL et al. Annals Rheum Dis. 2009;68(6):828-35.

5. Li L et al. Zhonghua er ke za zhi 2011;49(2):146-50.

6. Izmirly PM et al. Clin Rheumatol. 2011;30(12):1641-5.

7. Toledo-Alberola F and Betlloch-Mas I. Actas Dermosifiliogr. 2010 Jul;101(6):473-84.

8. Izmirly PM et al. Circulation. 2012;126(1):76-82.

9. Martinez-Sanchez N et al. Autoimmun Rev. 2015;14(5):423-8.

A potassium hydroxide preparation (KOH) from skin scrapings from the scalp lesions demonstrated no fungal elements. Further laboratory work up revealed a normal blood cell count, normal liver enzymes, an antinuclear antibody (ANA) titer of less than 1:80, a positive anti–Sjögren’s syndrome type B (SSB) antibody but negative anti–Sjögren’s syndrome type A (SSA) antibody and anti-U1RNP antibody. An electrocardiogram revealed no abnormalities. Liver function tests were normal. The complete blood count showed mild thrombocytopenia. Given the typical skin lesions and the positive SSB test and associated thrombocytopenia, the baby was diagnosed with neonatal lupus erythematosus.

Because of the diagnosis of neonatal lupus the mother was also tested and was found to have an elevated ANA of 1:640, positive SSB and antiphospholipid antibodies. The mother was healthy and her review of systems was negative for any collagen vascular disease–related symptoms.
 

Discussion

Neonatal lupus erythematosus (NLE) is a rare form of systemic lupus erythematosus (SLE) believed to be caused by transplacental transfer of anti-Ro (Sjögren’s syndrome antigen A, SSA), or, less commonly, anti-La (Sjögren’s syndrome antigen B, SSB) from mothers who are positive for these antibodies. Approximately 95% of NLE is associated with maternal anti-SSA; of these cases, 40% are also associated with maternal anti-SSB.¹ Only about 2% of children of mothers who have anti-SSA or anti-SSB develop NLE, a finding that has led some researchers to postulate that maternal factors, fetal genetic factors, and environmental factors determine which children of anti-SSA or SSB positive mothers develop NLE.

A recent review found no association between the development of NLE and fetal birth weight, prematurity, or age.³ Over half of mothers of children who develop NLE are asymptomatic at the time of diagnosis of the neonate,³ though many become symptomatic in following years. Of mothers who are symptomatic, SLE and undifferentiated autoimmune syndrome are the most common diagnoses, though NLE has been rarely reported in the offspring of mothers with Sjögren’s syndrome, rheumatoid arthritis, and psoriasis.^4,5

Fetal genetics are not an absolute determinant of development of NLE, as discordance in the development of NLE in twins has been reported. However, certain genetic relationships have been established. Fetal mutations in tumor necrosis factor–alpha appear to increase the likelihood of cutaneous manifestations. Mutations in transforming growth factor beta appear to increase the likelihood of cardiac manifestations, and experiments in cultured mouse cardiocytes have shown anti-SSB antibodies to impair macrophage phagocytosis of apoptotic cells in the developing fetal heart. These observations taken together suggest a fibroblast-mediated response to unphagocytosed cardiocyte debris may account for conduction abnormalities in neonates with NLE-induced heart block.⁶

Cutaneous disease in NLE is possible at birth, but more skin findings develop upon exposure to the sun. Nearly 80% of neonates affected by NLE develop cutaneous manifestations in the first few months of life. The head, neck, and extensor surfaces of the arms are most commonly affected, presumably because they are most likely to be exposed to the sun. Erythematous, annular, or discoid lesions are most common, and periorbital erythema with or without scale (“raccoon eyes”) should prompt consideration of NLE. However, annular, or discoid lesions are sometimes not present in NLE; telangiectasias, bullae, atrophic divots (“ice-pick scars”) or ulcerations may be seen instead. Lesions in the genital area have been described in fewer than 5% of patients with NLE.

The differential diagnosis of annular, scaly lesions in neonates includes annular erythema of infancy, tinea corporis, and seborrheic dermatitis. Annular erythema of infancy is a rare skin condition characterized by a cyclical eruption of erythematous annular lesions with minimal scaling which resolve spontaneously within a few weeks to months without leaving scaring or pigment changes. There is no treatment needed as the lesions self-resolve.⁷ Acute urticaria can sometimes appear similar to NLE but these are not scaly and also the lesions will disappear within 24-36 hours, compared with NLE lesions, which may take weeks to months to go away. Seborrheic dermatitis is a common skin condition seen in newborns with in the first few weeks of life and can present as scaly annular erythematous plaques on the face, scalp, torso, and the diaper area. Seborrheic dermatitis usually responds well to a combination of an antiyeast cream and a low-potency topical corticosteroid medication.

When NLE is suspected, diagnostic testing for lupus antibodies (anti-SSA, anti-SSB, and anti-U1RNP) in both maternal and neonatal serum should be undertaken. The presence of a characteristic rash plus maternal or neonatal antibodies is sufficient to make the diagnosis. If the rash is less characteristic, a biopsy showing an interface dermatitis can help solidify the diagnosis. Neonates with cutaneous manifestations of lupus may also have systemic disease. The most common and serious complication is heart block, whose pathophysiology is described above. Neonates with evidence of first-, second-, or third-degree heart block should be referred to a pediatric cardiologist for careful monitoring and management. Hepatic involvement has been reported, but is usually mild. Hematologic abnormalities have also been described that include anemia, neutropenia, and thrombocytopenia, which resolve by 9 months of age. Central nervous system involvement may rarely occur. The mainstay of treatment for the rash in NLE is diligent sun avoidance and sun protection. Topical corticosteroids may be used, but are not needed as the rash typically resolves by 9 months to 1 year without treatment. Mothers who have one child with NLE should be advised that they are more likely to have another with NLE – the risk is as high as 30%-40% in the second child. Hydroxychloroquine taken during subsequent pregnancies can reduce the incidence of cardiac complications,⁸ as can the so-called “triple therapy” of plasmapheresis, steroids, and IVIg.⁹

The cutaneous manifestations of NLE are usually self-limiting. However, they can serve as important clues that can prompt diagnosis of SLE in the mother, investigation of cardiac complications in the infant, and appropriate preventative care in future pregnancies.

Dr. Matiz is with the department of dermatology, Southern California Permanente Medical Group, San Diego. Mr. Kusari is with the department of dermatology, University of California, San Francisco.

References

1. Moretti D et al. Int J Dermatol. 2014;53(12):1508-12.

2. Buyon JP et al. Nature Clin Prac Rheum. 2009;5(3):139-48.

3. Li Y-Q et al. Int J Rheum Dis. 2015;18(7):761-7.

4. Rivera TL et al. Annals Rheum Dis. 2009;68(6):828-35.

5. Li L et al. Zhonghua er ke za zhi 2011;49(2):146-50.

6. Izmirly PM et al. Clin Rheumatol. 2011;30(12):1641-5.

7. Toledo-Alberola F and Betlloch-Mas I. Actas Dermosifiliogr. 2010 Jul;101(6):473-84.

8. Izmirly PM et al. Circulation. 2012;126(1):76-82.

9. Martinez-Sanchez N et al. Autoimmun Rev. 2015;14(5):423-8.