Dermatology

MADRID – A growing recognition that atopic dermatitis (AD) patients on dupilumab are prone to develop a paradoxical head and neck erythema that’s clinically and histologically distinct from their background skin disease emerged as a hot topic of discussion at a meeting of the European Task Force on Atopic Dermatitis held in conjunction with the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

“During treatment with dupilumab, we saw something that is really different from the classic eczema that patients experienced prior to dupilumab, with no or minimal scaling, itch, or burning sensation. We do not believe this is a delayed effect of dupilumab on that specific region. We think this is a dupilumab-induced entity that we’re looking at. You should take home, in my opinion, that this is a common side effect that’s underreported in daily practice at this moment, and it’s not reported in clinical trials at all,” said Linde de Wijs, MD, of the department of dermatology, Erasmus University Medical Center in Rotterdam, the Netherlands.

She presented a detailed case series of seven affected patients which included histologic examination of lesional skin biopsies. The biopsies were characterized by a perivascular lymphohistiocytic infiltrate, an increase in ectatic capillaries in the papillary dermis, and a notable dearth of spongiosis, eosinophils, and neutrophils. Four patients had bulbous elongated rete ridges evocative of a psoriasiform dermatitis. The overall histologic picture was suggestive of a drug-induced skin reaction.

A striking finding was that, even though AD patients typically place high importance on achieving total clearing of disease on the head and neck, these seven closely studied patients nonetheless rated their treatment satisfaction as 9 out of a possible 10 points. Dr. de Wijs interpreted this as testimony to dupilumab’s potent efficacy and comparatively acceptable safety profile, especially the apparent side effect’s absence of scaling and itch.

“Remember, these are patients with really severe atopic dermatitis who’ve been treated with a lot of immunosuppressants prior to dupilumab,” she said.

Once the investigators began to suspect the existence of a novel dupilumab-induced skin reaction, they conducted a retrospective chart review of more than 150 patients treated with dupilumab (Dupixent) and determined that roughly 30% had developed this distinctive sharply demarcated patchy erythema on the head and neck characterized by absence of itch. The sequence involved clearance of the AD in response to dupilumab, followed by gradual development of the head and neck erythema 10-39 weeks after the start of treatment.

The erythema proved treatment refractory. Dr. de Wijs and her colleagues tried topical corticosteroids, including potent ones, as well as topical tacrolimus, antifungals, antibiotics, emollients, oral steroids, and antihistamines, to no avail. Patch testing to investigate allergic contact dermatitis as a possible etiology was unremarkable.

She hypothesized that, since dupilumab blocks the key signaling pathways for Th2 T-cell differentiation by targeting the interleukin-4 receptor alpha, it’s possible that the biologic promotes a shift towards activation of the Th17 pathway, which might explain the observed histologic findings.

The fact that this erythema wasn’t reported in the major randomized clinical trials of dupilumab underscores the enormous value of clinical practice registries, she said.

“We are not the only ones observing this phenomenon,” noted Dr. de Wijs, citing recently published reports by other investigators (J Am Acad Dermatol. 2020 Jan;82[1]:230-2; JAMA Dermatol. 2019 Jul 1;155[7]:850-2).

Indeed, her talk was immediately followed by a presentation by Sebastien Barbarot, MD, PhD, who reported on a French national retrospective study of head and neck dermatitis arising in patients on dupilumab that was conducted by the French Atopic Dermatitis Network using the organization’s GREAT database. Among 1,000 adult patients with AD treated with the biologic at 29 French centers, 10 developed a de novo head and neck dermatitis, and 32 others experienced more than 50% worsening of eczema signs on the head and neck from baseline beginning about 2 months after starting on dupilumab.

This 4.2% incidence is probably an underestimate, since dermatologists weren’t aware of the phenomenon and didn’t specifically ask patients about it, observed Dr. Barbarot, a dermatologist at the University of Nantes (France).

Among the key findings: No differences in clinical characteristics were found between the de novo and exacerbation groups, nearly half of affected patients had concomitant conjunctivitis, and seven patients discontinued dupilumab because of an intolerable burning sensation on the head/neck.

“I think this condition is quite different from rosacea,” Dr. Barbarot emphasized.

French dermatologists generally turned to topical corticosteroids or topical tacrolimus to treat the face and neck dermatitis, with mixed results; 22 of the 42 patients showed improvement and 8 worsened.

Bruce Jancin/MDedge News

[email protected]

MADRID – A growing recognition that atopic dermatitis (AD) patients on dupilumab are prone to develop a paradoxical head and neck erythema that’s clinically and histologically distinct from their background skin disease emerged as a hot topic of discussion at a meeting of the European Task Force on Atopic Dermatitis held in conjunction with the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

“During treatment with dupilumab, we saw something that is really different from the classic eczema that patients experienced prior to dupilumab, with no or minimal scaling, itch, or burning sensation. We do not believe this is a delayed effect of dupilumab on that specific region. We think this is a dupilumab-induced entity that we’re looking at. You should take home, in my opinion, that this is a common side effect that’s underreported in daily practice at this moment, and it’s not reported in clinical trials at all,” said Linde de Wijs, MD, of the department of dermatology, Erasmus University Medical Center in Rotterdam, the Netherlands.

She presented a detailed case series of seven affected patients which included histologic examination of lesional skin biopsies. The biopsies were characterized by a perivascular lymphohistiocytic infiltrate, an increase in ectatic capillaries in the papillary dermis, and a notable dearth of spongiosis, eosinophils, and neutrophils. Four patients had bulbous elongated rete ridges evocative of a psoriasiform dermatitis. The overall histologic picture was suggestive of a drug-induced skin reaction.

A striking finding was that, even though AD patients typically place high importance on achieving total clearing of disease on the head and neck, these seven closely studied patients nonetheless rated their treatment satisfaction as 9 out of a possible 10 points. Dr. de Wijs interpreted this as testimony to dupilumab’s potent efficacy and comparatively acceptable safety profile, especially the apparent side effect’s absence of scaling and itch.

“Remember, these are patients with really severe atopic dermatitis who’ve been treated with a lot of immunosuppressants prior to dupilumab,” she said.

Once the investigators began to suspect the existence of a novel dupilumab-induced skin reaction, they conducted a retrospective chart review of more than 150 patients treated with dupilumab (Dupixent) and determined that roughly 30% had developed this distinctive sharply demarcated patchy erythema on the head and neck characterized by absence of itch. The sequence involved clearance of the AD in response to dupilumab, followed by gradual development of the head and neck erythema 10-39 weeks after the start of treatment.

The erythema proved treatment refractory. Dr. de Wijs and her colleagues tried topical corticosteroids, including potent ones, as well as topical tacrolimus, antifungals, antibiotics, emollients, oral steroids, and antihistamines, to no avail. Patch testing to investigate allergic contact dermatitis as a possible etiology was unremarkable.

She hypothesized that, since dupilumab blocks the key signaling pathways for Th2 T-cell differentiation by targeting the interleukin-4 receptor alpha, it’s possible that the biologic promotes a shift towards activation of the Th17 pathway, which might explain the observed histologic findings.

The fact that this erythema wasn’t reported in the major randomized clinical trials of dupilumab underscores the enormous value of clinical practice registries, she said.

“We are not the only ones observing this phenomenon,” noted Dr. de Wijs, citing recently published reports by other investigators (J Am Acad Dermatol. 2020 Jan;82[1]:230-2; JAMA Dermatol. 2019 Jul 1;155[7]:850-2).

Indeed, her talk was immediately followed by a presentation by Sebastien Barbarot, MD, PhD, who reported on a French national retrospective study of head and neck dermatitis arising in patients on dupilumab that was conducted by the French Atopic Dermatitis Network using the organization’s GREAT database. Among 1,000 adult patients with AD treated with the biologic at 29 French centers, 10 developed a de novo head and neck dermatitis, and 32 others experienced more than 50% worsening of eczema signs on the head and neck from baseline beginning about 2 months after starting on dupilumab.

This 4.2% incidence is probably an underestimate, since dermatologists weren’t aware of the phenomenon and didn’t specifically ask patients about it, observed Dr. Barbarot, a dermatologist at the University of Nantes (France).

Among the key findings: No differences in clinical characteristics were found between the de novo and exacerbation groups, nearly half of affected patients had concomitant conjunctivitis, and seven patients discontinued dupilumab because of an intolerable burning sensation on the head/neck.

“I think this condition is quite different from rosacea,” Dr. Barbarot emphasized.

French dermatologists generally turned to topical corticosteroids or topical tacrolimus to treat the face and neck dermatitis, with mixed results; 22 of the 42 patients showed improvement and 8 worsened.

Bruce Jancin/MDedge News

[email protected]

MADRID – A growing recognition that atopic dermatitis (AD) patients on dupilumab are prone to develop a paradoxical head and neck erythema that’s clinically and histologically distinct from their background skin disease emerged as a hot topic of discussion at a meeting of the European Task Force on Atopic Dermatitis held in conjunction with the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

“During treatment with dupilumab, we saw something that is really different from the classic eczema that patients experienced prior to dupilumab, with no or minimal scaling, itch, or burning sensation. We do not believe this is a delayed effect of dupilumab on that specific region. We think this is a dupilumab-induced entity that we’re looking at. You should take home, in my opinion, that this is a common side effect that’s underreported in daily practice at this moment, and it’s not reported in clinical trials at all,” said Linde de Wijs, MD, of the department of dermatology, Erasmus University Medical Center in Rotterdam, the Netherlands.

She presented a detailed case series of seven affected patients which included histologic examination of lesional skin biopsies. The biopsies were characterized by a perivascular lymphohistiocytic infiltrate, an increase in ectatic capillaries in the papillary dermis, and a notable dearth of spongiosis, eosinophils, and neutrophils. Four patients had bulbous elongated rete ridges evocative of a psoriasiform dermatitis. The overall histologic picture was suggestive of a drug-induced skin reaction.

A striking finding was that, even though AD patients typically place high importance on achieving total clearing of disease on the head and neck, these seven closely studied patients nonetheless rated their treatment satisfaction as 9 out of a possible 10 points. Dr. de Wijs interpreted this as testimony to dupilumab’s potent efficacy and comparatively acceptable safety profile, especially the apparent side effect’s absence of scaling and itch.

“Remember, these are patients with really severe atopic dermatitis who’ve been treated with a lot of immunosuppressants prior to dupilumab,” she said.

Once the investigators began to suspect the existence of a novel dupilumab-induced skin reaction, they conducted a retrospective chart review of more than 150 patients treated with dupilumab (Dupixent) and determined that roughly 30% had developed this distinctive sharply demarcated patchy erythema on the head and neck characterized by absence of itch. The sequence involved clearance of the AD in response to dupilumab, followed by gradual development of the head and neck erythema 10-39 weeks after the start of treatment.

The erythema proved treatment refractory. Dr. de Wijs and her colleagues tried topical corticosteroids, including potent ones, as well as topical tacrolimus, antifungals, antibiotics, emollients, oral steroids, and antihistamines, to no avail. Patch testing to investigate allergic contact dermatitis as a possible etiology was unremarkable.

She hypothesized that, since dupilumab blocks the key signaling pathways for Th2 T-cell differentiation by targeting the interleukin-4 receptor alpha, it’s possible that the biologic promotes a shift towards activation of the Th17 pathway, which might explain the observed histologic findings.

The fact that this erythema wasn’t reported in the major randomized clinical trials of dupilumab underscores the enormous value of clinical practice registries, she said.

“We are not the only ones observing this phenomenon,” noted Dr. de Wijs, citing recently published reports by other investigators (J Am Acad Dermatol. 2020 Jan;82[1]:230-2; JAMA Dermatol. 2019 Jul 1;155[7]:850-2).

Indeed, her talk was immediately followed by a presentation by Sebastien Barbarot, MD, PhD, who reported on a French national retrospective study of head and neck dermatitis arising in patients on dupilumab that was conducted by the French Atopic Dermatitis Network using the organization’s GREAT database. Among 1,000 adult patients with AD treated with the biologic at 29 French centers, 10 developed a de novo head and neck dermatitis, and 32 others experienced more than 50% worsening of eczema signs on the head and neck from baseline beginning about 2 months after starting on dupilumab.

This 4.2% incidence is probably an underestimate, since dermatologists weren’t aware of the phenomenon and didn’t specifically ask patients about it, observed Dr. Barbarot, a dermatologist at the University of Nantes (France).

Among the key findings: No differences in clinical characteristics were found between the de novo and exacerbation groups, nearly half of affected patients had concomitant conjunctivitis, and seven patients discontinued dupilumab because of an intolerable burning sensation on the head/neck.

“I think this condition is quite different from rosacea,” Dr. Barbarot emphasized.

French dermatologists generally turned to topical corticosteroids or topical tacrolimus to treat the face and neck dermatitis, with mixed results; 22 of the 42 patients showed improvement and 8 worsened.

Bruce Jancin/MDedge News

[email protected]

Patients with moderate to severe atopic dermatitis who responded well to the approved dupilumab regimen of 300 mg every 2 weeks in pivotal phase 3 monotherapy trials were more likely to have a continued response over the longer term if they maintained this regimen rather than switching to longer dosing intervals or discontinuing the medication.

This finding comes from a 36-week, randomized, double-blind, placebo-controlled trial that enrolled 422 patients who were previously successfully treated for 16 weeks with 300 mg of dupilumab weekly or every 2 weeks in two identically designed studies – SOLO 1 and SOLO 2.

The new international study – SOLO-CONTINUE – randomized these patients to continue the original regimen (weekly or every 2 weeks), to receive 300 mg of the biologic medication every 4 or 8 weeks, or to receive placebo.

Patients who continued the original regimen had the most consistent maintenance of treatment effect, while patients on longer dosage intervals or placebo had a dose-dependent reduction in response and no safety advantage. The incidence of treatment-emergent antidrug antibody was lowest with dupilumab weekly or every 2 weeks, and slightly higher with less-frequent dosing intervals, reported Margitta Worm, MD, of the Charité Universitätsmedizin Berlin, and coinvestigators.

“Because administration every 4 weeks or every 8 weeks did not provide an additional safety advantage and was numerically outperformed by administration weekly or every 2 weeks, we believe that it is prudent to adhere to the approved every 2 weeks regimen for adults and avoid less frequent treatment regimens (every 4 weeks or every 8 weeks) for long-term maintenance of efficacy,” they wrote in JAMA Dermatology.

Treatment success in the original SOLO trials was defined as having achieved an Investigator’s Global Assessment score of 0-1, or 75% improvement in Eczema Area and Severity Index Scores (EASI-75). As primary endpoints, SOLO-CONTINUE looked at the mean percentage change in EASI score over the course of the trial, and the percentage of patients who maintained EASI-75 at week 36.

Patients in the SOLO-CONTINUE trial who were randomized to receive dupilumab weekly or every 2 weeks had a mean percent change in EASI score of –0.06%. In contrast, patients assigned to the placebo group had a 21.7% decrease, and those taking the medication at 4- and 8-week intervals had mean changes of –3.84% and –6.84%, respectively. Post hoc analyses showed no apparent difference between dupilumab weekly and every 2 weeks in the maintenance of clinical response, the investigators reported.

Among patients with EASI-75 response at baseline, significantly more patients maintained this response at week 36 than patients receiving placebo, and there was again an apparent dose-dependent response. The percentage with EASI-75 at week 36 was 71.6% with the weekly or every-2-weeks regimen, 58.3% with the 4-week regimen, 54.9% with the 8-week regimen, and 30.4% in the placebo group.

Continuing treatment with 300 mg weekly or every 2 weeks resulted in greater maintenance of response across multiple other clinical endpoints and patient-reported outcomes as well (such as pruritus, atopic dermatitis symptoms, sleep, pain or discomfort, quality of life, and symptoms of anxiety and depression).

The more-frequent regimens also conferred no greater risk than less-frequent administration, and there were no new safety signals over the 36-week trial. Treatment-emergent adverse events (the most common were headache, nasopharyngitis, injection-site reactions, and herpes simplex virus infection) occurred in 70.7% of patients in the weekly or every-2-weeks group, 73.6% in the 4-week group, 75% in the 8-week group, and 81.7% in the placebo group.

Unlike earlier studies, the incidence of conjunctivitis was low (less than 6%) across all treatment groups, possibly because patients in the SOLO-CONTINUE trial were all high-level responders who tend to have conjunctivitis less frequently, the authors wrote.

Patients receiving less-frequent doses of dupilumab, particularly every 8 weeks, had greater rates of skin infections, flares, and rescue medication use than patients receiving doses weekly or every 2 weeks, the investigators reported. Treatment-emergent antidrug antibody incidence was slightly higher with less-frequent doses (11.7% and 6% in the 8-week and 4-week groups, respectively, compared with 4.3% and 1.2% in the every-2-weeks and weekly groups), which indicates a “higher incidence of immunogenicity with less-frequent dosage intervals” and is “consistent with other biologics,” they wrote.

Dupilumab is a human monoclonal antibody against the interleukin-4 receptor alpha that inhibits signaling of IL-4 and IL-13. The study was conducted at 185 sites in North America, Europe, Asia, and Japan. Patients had a mean age of 38.2 years; 53.8% were male.

While the trial suggests that the approved regimen of 300 mg every 2 weeks is best for long-term treatment, “therapeutic decisions are often influenced by cost-benefit considerations, in which case practitioners and other stakeholders involved in these decisions should carefully balance potential savings against suboptimal efficacy and long-term risks associated with discontinuous treatment regimens,” the investigators wrote.

The SOLO-CONTINUE trial was funded by Sanofi and Regeneron, the companies that market dupilumab. Dr. Worm reported receiving honoraria for consulting and lecture activity from Regeneron and Sanofi during and outside the conduct of the study, among other disclosures. The other authors had multiple disclosures related to these and multiple other pharmaceutical companies, or were employees of Sanofi or Regeneron.

SOURCE: Worm M et al. JAMA Dermatol. 2019 Dec 26. doi: 10.1001/jamadermatol.2019.3617.

Patients with moderate to severe atopic dermatitis who responded well to the approved dupilumab regimen of 300 mg every 2 weeks in pivotal phase 3 monotherapy trials were more likely to have a continued response over the longer term if they maintained this regimen rather than switching to longer dosing intervals or discontinuing the medication.

This finding comes from a 36-week, randomized, double-blind, placebo-controlled trial that enrolled 422 patients who were previously successfully treated for 16 weeks with 300 mg of dupilumab weekly or every 2 weeks in two identically designed studies – SOLO 1 and SOLO 2.

The new international study – SOLO-CONTINUE – randomized these patients to continue the original regimen (weekly or every 2 weeks), to receive 300 mg of the biologic medication every 4 or 8 weeks, or to receive placebo.

Patients who continued the original regimen had the most consistent maintenance of treatment effect, while patients on longer dosage intervals or placebo had a dose-dependent reduction in response and no safety advantage. The incidence of treatment-emergent antidrug antibody was lowest with dupilumab weekly or every 2 weeks, and slightly higher with less-frequent dosing intervals, reported Margitta Worm, MD, of the Charité Universitätsmedizin Berlin, and coinvestigators.

“Because administration every 4 weeks or every 8 weeks did not provide an additional safety advantage and was numerically outperformed by administration weekly or every 2 weeks, we believe that it is prudent to adhere to the approved every 2 weeks regimen for adults and avoid less frequent treatment regimens (every 4 weeks or every 8 weeks) for long-term maintenance of efficacy,” they wrote in JAMA Dermatology.

Treatment success in the original SOLO trials was defined as having achieved an Investigator’s Global Assessment score of 0-1, or 75% improvement in Eczema Area and Severity Index Scores (EASI-75). As primary endpoints, SOLO-CONTINUE looked at the mean percentage change in EASI score over the course of the trial, and the percentage of patients who maintained EASI-75 at week 36.

Patients in the SOLO-CONTINUE trial who were randomized to receive dupilumab weekly or every 2 weeks had a mean percent change in EASI score of –0.06%. In contrast, patients assigned to the placebo group had a 21.7% decrease, and those taking the medication at 4- and 8-week intervals had mean changes of –3.84% and –6.84%, respectively. Post hoc analyses showed no apparent difference between dupilumab weekly and every 2 weeks in the maintenance of clinical response, the investigators reported.

Among patients with EASI-75 response at baseline, significantly more patients maintained this response at week 36 than patients receiving placebo, and there was again an apparent dose-dependent response. The percentage with EASI-75 at week 36 was 71.6% with the weekly or every-2-weeks regimen, 58.3% with the 4-week regimen, 54.9% with the 8-week regimen, and 30.4% in the placebo group.

Continuing treatment with 300 mg weekly or every 2 weeks resulted in greater maintenance of response across multiple other clinical endpoints and patient-reported outcomes as well (such as pruritus, atopic dermatitis symptoms, sleep, pain or discomfort, quality of life, and symptoms of anxiety and depression).

The more-frequent regimens also conferred no greater risk than less-frequent administration, and there were no new safety signals over the 36-week trial. Treatment-emergent adverse events (the most common were headache, nasopharyngitis, injection-site reactions, and herpes simplex virus infection) occurred in 70.7% of patients in the weekly or every-2-weeks group, 73.6% in the 4-week group, 75% in the 8-week group, and 81.7% in the placebo group.

Unlike earlier studies, the incidence of conjunctivitis was low (less than 6%) across all treatment groups, possibly because patients in the SOLO-CONTINUE trial were all high-level responders who tend to have conjunctivitis less frequently, the authors wrote.

Patients receiving less-frequent doses of dupilumab, particularly every 8 weeks, had greater rates of skin infections, flares, and rescue medication use than patients receiving doses weekly or every 2 weeks, the investigators reported. Treatment-emergent antidrug antibody incidence was slightly higher with less-frequent doses (11.7% and 6% in the 8-week and 4-week groups, respectively, compared with 4.3% and 1.2% in the every-2-weeks and weekly groups), which indicates a “higher incidence of immunogenicity with less-frequent dosage intervals” and is “consistent with other biologics,” they wrote.

Dupilumab is a human monoclonal antibody against the interleukin-4 receptor alpha that inhibits signaling of IL-4 and IL-13. The study was conducted at 185 sites in North America, Europe, Asia, and Japan. Patients had a mean age of 38.2 years; 53.8% were male.

While the trial suggests that the approved regimen of 300 mg every 2 weeks is best for long-term treatment, “therapeutic decisions are often influenced by cost-benefit considerations, in which case practitioners and other stakeholders involved in these decisions should carefully balance potential savings against suboptimal efficacy and long-term risks associated with discontinuous treatment regimens,” the investigators wrote.

The SOLO-CONTINUE trial was funded by Sanofi and Regeneron, the companies that market dupilumab. Dr. Worm reported receiving honoraria for consulting and lecture activity from Regeneron and Sanofi during and outside the conduct of the study, among other disclosures. The other authors had multiple disclosures related to these and multiple other pharmaceutical companies, or were employees of Sanofi or Regeneron.

SOURCE: Worm M et al. JAMA Dermatol. 2019 Dec 26. doi: 10.1001/jamadermatol.2019.3617.

Patients with moderate to severe atopic dermatitis who responded well to the approved dupilumab regimen of 300 mg every 2 weeks in pivotal phase 3 monotherapy trials were more likely to have a continued response over the longer term if they maintained this regimen rather than switching to longer dosing intervals or discontinuing the medication.

This finding comes from a 36-week, randomized, double-blind, placebo-controlled trial that enrolled 422 patients who were previously successfully treated for 16 weeks with 300 mg of dupilumab weekly or every 2 weeks in two identically designed studies – SOLO 1 and SOLO 2.

The new international study – SOLO-CONTINUE – randomized these patients to continue the original regimen (weekly or every 2 weeks), to receive 300 mg of the biologic medication every 4 or 8 weeks, or to receive placebo.

Patients who continued the original regimen had the most consistent maintenance of treatment effect, while patients on longer dosage intervals or placebo had a dose-dependent reduction in response and no safety advantage. The incidence of treatment-emergent antidrug antibody was lowest with dupilumab weekly or every 2 weeks, and slightly higher with less-frequent dosing intervals, reported Margitta Worm, MD, of the Charité Universitätsmedizin Berlin, and coinvestigators.

“Because administration every 4 weeks or every 8 weeks did not provide an additional safety advantage and was numerically outperformed by administration weekly or every 2 weeks, we believe that it is prudent to adhere to the approved every 2 weeks regimen for adults and avoid less frequent treatment regimens (every 4 weeks or every 8 weeks) for long-term maintenance of efficacy,” they wrote in JAMA Dermatology.

Treatment success in the original SOLO trials was defined as having achieved an Investigator’s Global Assessment score of 0-1, or 75% improvement in Eczema Area and Severity Index Scores (EASI-75). As primary endpoints, SOLO-CONTINUE looked at the mean percentage change in EASI score over the course of the trial, and the percentage of patients who maintained EASI-75 at week 36.

Patients in the SOLO-CONTINUE trial who were randomized to receive dupilumab weekly or every 2 weeks had a mean percent change in EASI score of –0.06%. In contrast, patients assigned to the placebo group had a 21.7% decrease, and those taking the medication at 4- and 8-week intervals had mean changes of –3.84% and –6.84%, respectively. Post hoc analyses showed no apparent difference between dupilumab weekly and every 2 weeks in the maintenance of clinical response, the investigators reported.

Among patients with EASI-75 response at baseline, significantly more patients maintained this response at week 36 than patients receiving placebo, and there was again an apparent dose-dependent response. The percentage with EASI-75 at week 36 was 71.6% with the weekly or every-2-weeks regimen, 58.3% with the 4-week regimen, 54.9% with the 8-week regimen, and 30.4% in the placebo group.

Continuing treatment with 300 mg weekly or every 2 weeks resulted in greater maintenance of response across multiple other clinical endpoints and patient-reported outcomes as well (such as pruritus, atopic dermatitis symptoms, sleep, pain or discomfort, quality of life, and symptoms of anxiety and depression).

The more-frequent regimens also conferred no greater risk than less-frequent administration, and there were no new safety signals over the 36-week trial. Treatment-emergent adverse events (the most common were headache, nasopharyngitis, injection-site reactions, and herpes simplex virus infection) occurred in 70.7% of patients in the weekly or every-2-weeks group, 73.6% in the 4-week group, 75% in the 8-week group, and 81.7% in the placebo group.

Unlike earlier studies, the incidence of conjunctivitis was low (less than 6%) across all treatment groups, possibly because patients in the SOLO-CONTINUE trial were all high-level responders who tend to have conjunctivitis less frequently, the authors wrote.

Patients receiving less-frequent doses of dupilumab, particularly every 8 weeks, had greater rates of skin infections, flares, and rescue medication use than patients receiving doses weekly or every 2 weeks, the investigators reported. Treatment-emergent antidrug antibody incidence was slightly higher with less-frequent doses (11.7% and 6% in the 8-week and 4-week groups, respectively, compared with 4.3% and 1.2% in the every-2-weeks and weekly groups), which indicates a “higher incidence of immunogenicity with less-frequent dosage intervals” and is “consistent with other biologics,” they wrote.

Dupilumab is a human monoclonal antibody against the interleukin-4 receptor alpha that inhibits signaling of IL-4 and IL-13. The study was conducted at 185 sites in North America, Europe, Asia, and Japan. Patients had a mean age of 38.2 years; 53.8% were male.

While the trial suggests that the approved regimen of 300 mg every 2 weeks is best for long-term treatment, “therapeutic decisions are often influenced by cost-benefit considerations, in which case practitioners and other stakeholders involved in these decisions should carefully balance potential savings against suboptimal efficacy and long-term risks associated with discontinuous treatment regimens,” the investigators wrote.

The SOLO-CONTINUE trial was funded by Sanofi and Regeneron, the companies that market dupilumab. Dr. Worm reported receiving honoraria for consulting and lecture activity from Regeneron and Sanofi during and outside the conduct of the study, among other disclosures. The other authors had multiple disclosures related to these and multiple other pharmaceutical companies, or were employees of Sanofi or Regeneron.

SOURCE: Worm M et al. JAMA Dermatol. 2019 Dec 26. doi: 10.1001/jamadermatol.2019.3617.

Dermatopathologic evaluation of the tissue sample indicated that the lesion was a neurofibroma, and clinical correlation fine-tuned the diagnosis to segmental neurofibromatosis (NF). The diagnosis of segmental NF is clinical, with biopsy to confirm that the lesions are neurofibromas. Segmental NF is a mosaic form of neurofibromatosis type 1 (NF1) that results from a postzygotic mutation of the NF1 gene. While NF1 is a relatively common neurocutaneous disorder that occurs with a frequency of 1 in 3000, segmental NF is uncommon, with an estimated prevalence of 1 in 40,000.

NF1 often follows an autosomal dominant inheritance pattern, although up to 50% of patients with NF1 arise de novo from spontaneous mutations. NF1 is characterized by multiple café-au-lait macules, axillary freckling, neurofibromas, and Lisch nodules (pigmented iris hamartomas). Systemic findings associated with NF1 include malignant peripheral nerve sheath tumors, optic gliomas, and vasculopathy. While patients with segmental NF may exhibit some of these same findings, the distribution of the neurofibromas is often limited to a single dermatome. Additionally, patients with segmental NF typically do not exhibit extracutaneous lesions, systemic involvement, or a family history of NF. Segmental NF treatment typically focuses on symptomatic management or cosmetic concerns.

This patient did not have any of the systemic complications that occasionally occur with segmental NF, so no medical treatment was required. The patient was advised that cutaneous and subcutaneous neurofibromas do not require removal unless there is pain, bleeding, disfigurement, or signs of malignant transformation. The patient was not interested in removal of the nodules for cosmetic reasons, so he was encouraged to seek follow-up care, as needed. 
 

This case was adapted from: Laurent KJ, Beachkofsky TM, Loyd A, et al. Segmental distribution of nodules on trunk. J Fam Pract. 2017;66: 765-767.

Dermatopathologic evaluation of the tissue sample indicated that the lesion was a neurofibroma, and clinical correlation fine-tuned the diagnosis to segmental neurofibromatosis (NF). The diagnosis of segmental NF is clinical, with biopsy to confirm that the lesions are neurofibromas. Segmental NF is a mosaic form of neurofibromatosis type 1 (NF1) that results from a postzygotic mutation of the NF1 gene. While NF1 is a relatively common neurocutaneous disorder that occurs with a frequency of 1 in 3000, segmental NF is uncommon, with an estimated prevalence of 1 in 40,000.

NF1 often follows an autosomal dominant inheritance pattern, although up to 50% of patients with NF1 arise de novo from spontaneous mutations. NF1 is characterized by multiple café-au-lait macules, axillary freckling, neurofibromas, and Lisch nodules (pigmented iris hamartomas). Systemic findings associated with NF1 include malignant peripheral nerve sheath tumors, optic gliomas, and vasculopathy. While patients with segmental NF may exhibit some of these same findings, the distribution of the neurofibromas is often limited to a single dermatome. Additionally, patients with segmental NF typically do not exhibit extracutaneous lesions, systemic involvement, or a family history of NF. Segmental NF treatment typically focuses on symptomatic management or cosmetic concerns.

This patient did not have any of the systemic complications that occasionally occur with segmental NF, so no medical treatment was required. The patient was advised that cutaneous and subcutaneous neurofibromas do not require removal unless there is pain, bleeding, disfigurement, or signs of malignant transformation. The patient was not interested in removal of the nodules for cosmetic reasons, so he was encouraged to seek follow-up care, as needed. 
 

This case was adapted from: Laurent KJ, Beachkofsky TM, Loyd A, et al. Segmental distribution of nodules on trunk. J Fam Pract. 2017;66: 765-767.

Dermatopathologic evaluation of the tissue sample indicated that the lesion was a neurofibroma, and clinical correlation fine-tuned the diagnosis to segmental neurofibromatosis (NF). The diagnosis of segmental NF is clinical, with biopsy to confirm that the lesions are neurofibromas. Segmental NF is a mosaic form of neurofibromatosis type 1 (NF1) that results from a postzygotic mutation of the NF1 gene. While NF1 is a relatively common neurocutaneous disorder that occurs with a frequency of 1 in 3000, segmental NF is uncommon, with an estimated prevalence of 1 in 40,000.

NF1 often follows an autosomal dominant inheritance pattern, although up to 50% of patients with NF1 arise de novo from spontaneous mutations. NF1 is characterized by multiple café-au-lait macules, axillary freckling, neurofibromas, and Lisch nodules (pigmented iris hamartomas). Systemic findings associated with NF1 include malignant peripheral nerve sheath tumors, optic gliomas, and vasculopathy. While patients with segmental NF may exhibit some of these same findings, the distribution of the neurofibromas is often limited to a single dermatome. Additionally, patients with segmental NF typically do not exhibit extracutaneous lesions, systemic involvement, or a family history of NF. Segmental NF treatment typically focuses on symptomatic management or cosmetic concerns.

This patient did not have any of the systemic complications that occasionally occur with segmental NF, so no medical treatment was required. The patient was advised that cutaneous and subcutaneous neurofibromas do not require removal unless there is pain, bleeding, disfigurement, or signs of malignant transformation. The patient was not interested in removal of the nodules for cosmetic reasons, so he was encouraged to seek follow-up care, as needed. 
 

This case was adapted from: Laurent KJ, Beachkofsky TM, Loyd A, et al. Segmental distribution of nodules on trunk. J Fam Pract. 2017;66: 765-767.

MADRID – Adults with atopic dermatitis (AD) face significantly increased risks of osteoporosis and major osteoporotic fractures – even if they’ve never taken systemic corticosteroids, according to a large observational Danish national registry study.

Bruce Jancin/MDedge News

A key study finding was that these elevated risks were concentrated in the patients who used potent or superpotent topical corticosteroids. Adult AD patients who used mild- or moderate-potency topical steroids were not at significantly increased risk. Neither were patients on topical calcineurin inhibitors, Jacob P. Thyssen, MD, PhD, reported at a meeting of the European Task Force on Atopic Dermatitis held in conjunction with the annual congress of the European Academy of Dermatology and Venereology.

“The absolute risk is low, but it’s real,” commented Dr. Thyssen, professor of dermatology at the University of Copenhagen.

His advice to colleagues: “Dermatologists should consider alternative treatments in the chronic excessive users of topical corticosteroids, or use them in combination with prophylactic treatment to preserve bone homeostasis in such patients.”

He presented the results of a retrospective case-control study of 10,636 Danish adults with AD and 87,989 matched controls. At baseline in this study, which featured a maximum of 20 years of follow-up starting in 1997, participants had no history of osteoporosis.

Dr. Thyssen expressed the absolute risk of being diagnosed with osteoporosis in the study as follows: If 10,000 adult AD patients were followed for 1 year, on average 23.5 of them would be diagnosed with osteoporosis, a rate more than double the 10.3 per 10,000 in the general population. Moreover, on average, 42.6 out of 10,000 adult AD patients would incur a major osteoporotic fracture during a year of follow-up, compared with 32.3 individuals in the general population.

In the subgroup of patients who never used systemic corticosteroids, the risk of being diagnosed with osteoporosis was 12.8 per 10,000 per year, significantly higher than the 7.4 per 10,000 rate in the general population. Similarly, the 1-year rate of major osteoporotic fractures was 33.1 per 10,000 among the AD group and 29.6 in matched controls.

In a Cox regression analysis adjusted for age, sex, socioeconomic status, body mass index, asthma, and the use of a variety of medications thought to potentially have a negative effect upon bone metabolism, the risk of osteoporosis in the entire group of 10,636 adult AD patients was 51% greater than in matched controls, and their risk of major osteoporotic fractures was 18% greater. In the subgroup of AD patients who never used systemic steroids, the risks of osteoporosis and major osteoporotic fractures were 82% and 14% greater than in controls. The medications adjusted for in the regression analysis included proton pump inhibitors, thiazide diuretics, H₂ receptor blockers, statins, cyclosporine, hormone therapy, contraceptives, and psychotropic medications.

Scoring Atopic Dermatitis (SCORAD) ratings were available on roughly 4,000 of the adult AD patients. In an analysis of this large subgroup, disease severity as reflected in SCORAD scores did not explain the increased osteoporosis and fracture risks. However, the use of potent or superpotent topical corticosteroids did. Patients who used potent topical steroids had a statistically significant 16% increased risk of being diagnosed with osteoporosis than nonusers, as well as a 7% increased risk of major osteoporotic fractures. Patients who applied superpotent topical steroids had 42% and 18% increased risks of those two adverse outcomes.

In contrast, neither the use of topical calcineurin inhibitors nor mild- or mid-potency topical steroids was associated with increased risk of bone events in a Cox regression analysis adjusted for potential confounders.

A relationship between the use of high-potency topical corticosteroids and adverse bone events is biologically plausible, according to Dr. Thyssen. He and his coinvestigators have previously documented a 100%-400% increased rate of chemical penetration through atopic skin, which is notoriously barrier damaged.

“We find it very likely that, if you put topical steroids on atopic skin in high amounts and for a very long time, you may have systemic effects,” he said.

A great many adult AD patients do exactly that. When Dr. Thyssen and coworkers analyzed Danish national prescription drug registry data for their patient cohort, they found that roughly one-third of the elderly subgroup had filled prescriptions totaling greater than 2 kg of mometasone or other similar-potency steroids over the previous 10 years.

“So we know that a significant proportion of our atopic dermatitis patients are really high users of topical corticosteroids,” the dermatologist noted.

Dr. Thyssen’s national osteoporosis and fracture study was funded with a government research grant. He reported serving as an advisor to and/or recipient of research grants from AbbVie, Pfizer, Leo Pharma, Eli Lilly, Regeneron, Sanofi Genzyme, and Union Therapeutics.

[email protected]

MADRID – Adults with atopic dermatitis (AD) face significantly increased risks of osteoporosis and major osteoporotic fractures – even if they’ve never taken systemic corticosteroids, according to a large observational Danish national registry study.

Bruce Jancin/MDedge News

A key study finding was that these elevated risks were concentrated in the patients who used potent or superpotent topical corticosteroids. Adult AD patients who used mild- or moderate-potency topical steroids were not at significantly increased risk. Neither were patients on topical calcineurin inhibitors, Jacob P. Thyssen, MD, PhD, reported at a meeting of the European Task Force on Atopic Dermatitis held in conjunction with the annual congress of the European Academy of Dermatology and Venereology.

“The absolute risk is low, but it’s real,” commented Dr. Thyssen, professor of dermatology at the University of Copenhagen.

His advice to colleagues: “Dermatologists should consider alternative treatments in the chronic excessive users of topical corticosteroids, or use them in combination with prophylactic treatment to preserve bone homeostasis in such patients.”

He presented the results of a retrospective case-control study of 10,636 Danish adults with AD and 87,989 matched controls. At baseline in this study, which featured a maximum of 20 years of follow-up starting in 1997, participants had no history of osteoporosis.

Dr. Thyssen expressed the absolute risk of being diagnosed with osteoporosis in the study as follows: If 10,000 adult AD patients were followed for 1 year, on average 23.5 of them would be diagnosed with osteoporosis, a rate more than double the 10.3 per 10,000 in the general population. Moreover, on average, 42.6 out of 10,000 adult AD patients would incur a major osteoporotic fracture during a year of follow-up, compared with 32.3 individuals in the general population.

In the subgroup of patients who never used systemic corticosteroids, the risk of being diagnosed with osteoporosis was 12.8 per 10,000 per year, significantly higher than the 7.4 per 10,000 rate in the general population. Similarly, the 1-year rate of major osteoporotic fractures was 33.1 per 10,000 among the AD group and 29.6 in matched controls.

In a Cox regression analysis adjusted for age, sex, socioeconomic status, body mass index, asthma, and the use of a variety of medications thought to potentially have a negative effect upon bone metabolism, the risk of osteoporosis in the entire group of 10,636 adult AD patients was 51% greater than in matched controls, and their risk of major osteoporotic fractures was 18% greater. In the subgroup of AD patients who never used systemic steroids, the risks of osteoporosis and major osteoporotic fractures were 82% and 14% greater than in controls. The medications adjusted for in the regression analysis included proton pump inhibitors, thiazide diuretics, H₂ receptor blockers, statins, cyclosporine, hormone therapy, contraceptives, and psychotropic medications.

Scoring Atopic Dermatitis (SCORAD) ratings were available on roughly 4,000 of the adult AD patients. In an analysis of this large subgroup, disease severity as reflected in SCORAD scores did not explain the increased osteoporosis and fracture risks. However, the use of potent or superpotent topical corticosteroids did. Patients who used potent topical steroids had a statistically significant 16% increased risk of being diagnosed with osteoporosis than nonusers, as well as a 7% increased risk of major osteoporotic fractures. Patients who applied superpotent topical steroids had 42% and 18% increased risks of those two adverse outcomes.

In contrast, neither the use of topical calcineurin inhibitors nor mild- or mid-potency topical steroids was associated with increased risk of bone events in a Cox regression analysis adjusted for potential confounders.

A relationship between the use of high-potency topical corticosteroids and adverse bone events is biologically plausible, according to Dr. Thyssen. He and his coinvestigators have previously documented a 100%-400% increased rate of chemical penetration through atopic skin, which is notoriously barrier damaged.

“We find it very likely that, if you put topical steroids on atopic skin in high amounts and for a very long time, you may have systemic effects,” he said.

A great many adult AD patients do exactly that. When Dr. Thyssen and coworkers analyzed Danish national prescription drug registry data for their patient cohort, they found that roughly one-third of the elderly subgroup had filled prescriptions totaling greater than 2 kg of mometasone or other similar-potency steroids over the previous 10 years.

“So we know that a significant proportion of our atopic dermatitis patients are really high users of topical corticosteroids,” the dermatologist noted.

Dr. Thyssen’s national osteoporosis and fracture study was funded with a government research grant. He reported serving as an advisor to and/or recipient of research grants from AbbVie, Pfizer, Leo Pharma, Eli Lilly, Regeneron, Sanofi Genzyme, and Union Therapeutics.

[email protected]

MADRID – Adults with atopic dermatitis (AD) face significantly increased risks of osteoporosis and major osteoporotic fractures – even if they’ve never taken systemic corticosteroids, according to a large observational Danish national registry study.

Bruce Jancin/MDedge News

A key study finding was that these elevated risks were concentrated in the patients who used potent or superpotent topical corticosteroids. Adult AD patients who used mild- or moderate-potency topical steroids were not at significantly increased risk. Neither were patients on topical calcineurin inhibitors, Jacob P. Thyssen, MD, PhD, reported at a meeting of the European Task Force on Atopic Dermatitis held in conjunction with the annual congress of the European Academy of Dermatology and Venereology.

“The absolute risk is low, but it’s real,” commented Dr. Thyssen, professor of dermatology at the University of Copenhagen.

His advice to colleagues: “Dermatologists should consider alternative treatments in the chronic excessive users of topical corticosteroids, or use them in combination with prophylactic treatment to preserve bone homeostasis in such patients.”

He presented the results of a retrospective case-control study of 10,636 Danish adults with AD and 87,989 matched controls. At baseline in this study, which featured a maximum of 20 years of follow-up starting in 1997, participants had no history of osteoporosis.

Dr. Thyssen expressed the absolute risk of being diagnosed with osteoporosis in the study as follows: If 10,000 adult AD patients were followed for 1 year, on average 23.5 of them would be diagnosed with osteoporosis, a rate more than double the 10.3 per 10,000 in the general population. Moreover, on average, 42.6 out of 10,000 adult AD patients would incur a major osteoporotic fracture during a year of follow-up, compared with 32.3 individuals in the general population.

In the subgroup of patients who never used systemic corticosteroids, the risk of being diagnosed with osteoporosis was 12.8 per 10,000 per year, significantly higher than the 7.4 per 10,000 rate in the general population. Similarly, the 1-year rate of major osteoporotic fractures was 33.1 per 10,000 among the AD group and 29.6 in matched controls.

In a Cox regression analysis adjusted for age, sex, socioeconomic status, body mass index, asthma, and the use of a variety of medications thought to potentially have a negative effect upon bone metabolism, the risk of osteoporosis in the entire group of 10,636 adult AD patients was 51% greater than in matched controls, and their risk of major osteoporotic fractures was 18% greater. In the subgroup of AD patients who never used systemic steroids, the risks of osteoporosis and major osteoporotic fractures were 82% and 14% greater than in controls. The medications adjusted for in the regression analysis included proton pump inhibitors, thiazide diuretics, H₂ receptor blockers, statins, cyclosporine, hormone therapy, contraceptives, and psychotropic medications.

Scoring Atopic Dermatitis (SCORAD) ratings were available on roughly 4,000 of the adult AD patients. In an analysis of this large subgroup, disease severity as reflected in SCORAD scores did not explain the increased osteoporosis and fracture risks. However, the use of potent or superpotent topical corticosteroids did. Patients who used potent topical steroids had a statistically significant 16% increased risk of being diagnosed with osteoporosis than nonusers, as well as a 7% increased risk of major osteoporotic fractures. Patients who applied superpotent topical steroids had 42% and 18% increased risks of those two adverse outcomes.

In contrast, neither the use of topical calcineurin inhibitors nor mild- or mid-potency topical steroids was associated with increased risk of bone events in a Cox regression analysis adjusted for potential confounders.

A relationship between the use of high-potency topical corticosteroids and adverse bone events is biologically plausible, according to Dr. Thyssen. He and his coinvestigators have previously documented a 100%-400% increased rate of chemical penetration through atopic skin, which is notoriously barrier damaged.

“We find it very likely that, if you put topical steroids on atopic skin in high amounts and for a very long time, you may have systemic effects,” he said.

A great many adult AD patients do exactly that. When Dr. Thyssen and coworkers analyzed Danish national prescription drug registry data for their patient cohort, they found that roughly one-third of the elderly subgroup had filled prescriptions totaling greater than 2 kg of mometasone or other similar-potency steroids over the previous 10 years.

“So we know that a significant proportion of our atopic dermatitis patients are really high users of topical corticosteroids,” the dermatologist noted.

Dr. Thyssen’s national osteoporosis and fracture study was funded with a government research grant. He reported serving as an advisor to and/or recipient of research grants from AbbVie, Pfizer, Leo Pharma, Eli Lilly, Regeneron, Sanofi Genzyme, and Union Therapeutics.

[email protected]

The first known case of contamination of skin-lightening cream with methylmercury was identified in July 2019 in a Mexican American woman in Sacramento, Calif., according to Anita Mudan, MD, of the department of emergency medicine at the University of California, San Francisco, and associates.

The woman, aged 47 years, sought medical care for dysesthesias and weakness in the upper extremities, the investigators wrote in a report published in Morbidity and Mortality Weekly Report.

This progressed to dysarthria, blurry vision, and unsteady gait over a 2-week period, leading to her hospitalization. Over the next 2 weeks, she declined into an agitated delirium; screening blood and urine tests detected levels of mercury exceeding the upper limit of quantification.

Oral dimercaptosuccinic acid at 10 mg/kg every 8 hours was administered via feeding tube. The California Department of Public Health (CDPH) conducted interviews with the patient’s family, discovering that the patient had used a skin-lightening cream obtained from Mexico for the past 7 years. The cream was analyzed and found to contain mercury at a concentration of 12,000 ppm. A Raman spectral analysis showed that the sample contained the organic compound methylmercury iodide.

Typically, contaminated skin-lightening creams contain inorganic mercury at levels up to 200,000 ppm; the significantly lower mercury content of the cream in this case “underscores the far higher toxicity of organic mercury compounds,” the investigators wrote.

The patient has undergone extensive chelation therapy, but remains unable to verbalize or care for herself, requiring continued tube feeding for nutritional support, Dr. Mudan and associates noted.

“CDPH is actively working to warn the public of this health risk, actively screening other skin lightening cream samples for mercury, and is investigating the case of a family member with likely exposure but less severe illness,” the investigators concluded.

The study authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Mudan A et al. MMWR Morb Mortal Wkly Rep. 2019 Dec 20. doi: 10.15585/mmwr.mm6850a4.

The first known case of contamination of skin-lightening cream with methylmercury was identified in July 2019 in a Mexican American woman in Sacramento, Calif., according to Anita Mudan, MD, of the department of emergency medicine at the University of California, San Francisco, and associates.

The woman, aged 47 years, sought medical care for dysesthesias and weakness in the upper extremities, the investigators wrote in a report published in Morbidity and Mortality Weekly Report.

This progressed to dysarthria, blurry vision, and unsteady gait over a 2-week period, leading to her hospitalization. Over the next 2 weeks, she declined into an agitated delirium; screening blood and urine tests detected levels of mercury exceeding the upper limit of quantification.

Oral dimercaptosuccinic acid at 10 mg/kg every 8 hours was administered via feeding tube. The California Department of Public Health (CDPH) conducted interviews with the patient’s family, discovering that the patient had used a skin-lightening cream obtained from Mexico for the past 7 years. The cream was analyzed and found to contain mercury at a concentration of 12,000 ppm. A Raman spectral analysis showed that the sample contained the organic compound methylmercury iodide.

Typically, contaminated skin-lightening creams contain inorganic mercury at levels up to 200,000 ppm; the significantly lower mercury content of the cream in this case “underscores the far higher toxicity of organic mercury compounds,” the investigators wrote.

The patient has undergone extensive chelation therapy, but remains unable to verbalize or care for herself, requiring continued tube feeding for nutritional support, Dr. Mudan and associates noted.

“CDPH is actively working to warn the public of this health risk, actively screening other skin lightening cream samples for mercury, and is investigating the case of a family member with likely exposure but less severe illness,” the investigators concluded.

The study authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Mudan A et al. MMWR Morb Mortal Wkly Rep. 2019 Dec 20. doi: 10.15585/mmwr.mm6850a4.

The first known case of contamination of skin-lightening cream with methylmercury was identified in July 2019 in a Mexican American woman in Sacramento, Calif., according to Anita Mudan, MD, of the department of emergency medicine at the University of California, San Francisco, and associates.

The woman, aged 47 years, sought medical care for dysesthesias and weakness in the upper extremities, the investigators wrote in a report published in Morbidity and Mortality Weekly Report.

This progressed to dysarthria, blurry vision, and unsteady gait over a 2-week period, leading to her hospitalization. Over the next 2 weeks, she declined into an agitated delirium; screening blood and urine tests detected levels of mercury exceeding the upper limit of quantification.

Oral dimercaptosuccinic acid at 10 mg/kg every 8 hours was administered via feeding tube. The California Department of Public Health (CDPH) conducted interviews with the patient’s family, discovering that the patient had used a skin-lightening cream obtained from Mexico for the past 7 years. The cream was analyzed and found to contain mercury at a concentration of 12,000 ppm. A Raman spectral analysis showed that the sample contained the organic compound methylmercury iodide.

Typically, contaminated skin-lightening creams contain inorganic mercury at levels up to 200,000 ppm; the significantly lower mercury content of the cream in this case “underscores the far higher toxicity of organic mercury compounds,” the investigators wrote.

The patient has undergone extensive chelation therapy, but remains unable to verbalize or care for herself, requiring continued tube feeding for nutritional support, Dr. Mudan and associates noted.

“CDPH is actively working to warn the public of this health risk, actively screening other skin lightening cream samples for mercury, and is investigating the case of a family member with likely exposure but less severe illness,” the investigators concluded.

The study authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Mudan A et al. MMWR Morb Mortal Wkly Rep. 2019 Dec 20. doi: 10.15585/mmwr.mm6850a4.

The groove in the patient’s nail, and associated splitting, was due to a digital mucous cyst seen in the photo proximal to the cuticle.

In spite of the name, these cysts do not contain mucus. Instead, they contain synovial fluid and represent an outpouching of the distal interphalangeal joint of the index finger. This same process is called a ganglion cyst when it is seen at the wrist and a Baker’s cyst when it is behind the knee. These cysts typically form from an increase in synovial fluid, often due to underlying osteoarthritis, injury, or degenerative changes of the joint capsule. If the patient is asymptomatic, no treatment is required. Half of the lesions spontaneously resolve. If the patient is symptomatic, treatment options include a steroid injection; aspirating the cyst and then using a compressive cryosurgery tip to freeze the superficial and deep aspects of the cyst to scar it down; and surgical resection of the cyst.

In this case, the patient was in pain because the abnormally shaped nail was breaking. She elected to have a steroid injection into the cyst—0.25 ml of triamcinolone 20 mg/ml. The family physician (FP) advised her that this would reduce the inflammation in the distal interphalangeal joint, hopefully reducing the size of the digital mucous cyst. The FP also indicated that she might require several injections to achieve a positive outcome and that it would take 6 months for her fingernail to return to normal.

‌

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

The groove in the patient’s nail, and associated splitting, was due to a digital mucous cyst seen in the photo proximal to the cuticle.

In spite of the name, these cysts do not contain mucus. Instead, they contain synovial fluid and represent an outpouching of the distal interphalangeal joint of the index finger. This same process is called a ganglion cyst when it is seen at the wrist and a Baker’s cyst when it is behind the knee. These cysts typically form from an increase in synovial fluid, often due to underlying osteoarthritis, injury, or degenerative changes of the joint capsule. If the patient is asymptomatic, no treatment is required. Half of the lesions spontaneously resolve. If the patient is symptomatic, treatment options include a steroid injection; aspirating the cyst and then using a compressive cryosurgery tip to freeze the superficial and deep aspects of the cyst to scar it down; and surgical resection of the cyst.

In this case, the patient was in pain because the abnormally shaped nail was breaking. She elected to have a steroid injection into the cyst—0.25 ml of triamcinolone 20 mg/ml. The family physician (FP) advised her that this would reduce the inflammation in the distal interphalangeal joint, hopefully reducing the size of the digital mucous cyst. The FP also indicated that she might require several injections to achieve a positive outcome and that it would take 6 months for her fingernail to return to normal.

‌

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

The groove in the patient’s nail, and associated splitting, was due to a digital mucous cyst seen in the photo proximal to the cuticle.

In spite of the name, these cysts do not contain mucus. Instead, they contain synovial fluid and represent an outpouching of the distal interphalangeal joint of the index finger. This same process is called a ganglion cyst when it is seen at the wrist and a Baker’s cyst when it is behind the knee. These cysts typically form from an increase in synovial fluid, often due to underlying osteoarthritis, injury, or degenerative changes of the joint capsule. If the patient is asymptomatic, no treatment is required. Half of the lesions spontaneously resolve. If the patient is symptomatic, treatment options include a steroid injection; aspirating the cyst and then using a compressive cryosurgery tip to freeze the superficial and deep aspects of the cyst to scar it down; and surgical resection of the cyst.

In this case, the patient was in pain because the abnormally shaped nail was breaking. She elected to have a steroid injection into the cyst—0.25 ml of triamcinolone 20 mg/ml. The family physician (FP) advised her that this would reduce the inflammation in the distal interphalangeal joint, hopefully reducing the size of the digital mucous cyst. The FP also indicated that she might require several injections to achieve a positive outcome and that it would take 6 months for her fingernail to return to normal.

‌

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

MADRID – A parental history of asthma or allergic rhinitis significantly increases the risk that a child will develop atopic dermatitis, and that risk doubles if a parent has a history of atopic dermatitis rather than another atopic disease, Nina H. Ravn reported at a meeting of the European Task Force on Atopic Dermatitis held in conjunction with the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

She presented a comprehensive meta-analysis of 149 published studies addressing the risk of developing atopic dermatitis according to parental history of atopic disease. The studies included more than 656,000 participants. The picture that emerged from the meta-analysis was one of a stepwise increase in the risk of pediatric atopic dermatitis according to the type and number of parental atopic diseases present.

“This is something that hopefully can be useful when you talk with parents or parents-to-be with atopic diseases and they want to know how their disease might affect their child,” explained Ms. Ravn of the University of Copenhagen.

It’s also information that clinicians will find helpful in appropriately targeting primary prevention interventions if and when methods of proven efficacy become available. That’s a likely prospect, as this is now an extremely active field of research, she noted.

Bruce Jancin/MDedge News

“An interesting result that was new to me what that fathers’ and mothers’ contribution to risk is equal,” said session cochair Andreas Wollenberg, MD, professor of dermatology at Ludwig Maximilian University of Munich. “For the past 2 decades we were always taught that the mother would have a greater impact on that risk.”

“I was also surprised by our findings,” Ms. Ravn replied. “But when we pooled all the data there really was no difference, nor in any of our subanalyses.”

She reported having no financial conflicts regarding her study.

[email protected]

SOURCE: Ravn NH. THE EADV CONGRESS.

MADRID – A parental history of asthma or allergic rhinitis significantly increases the risk that a child will develop atopic dermatitis, and that risk doubles if a parent has a history of atopic dermatitis rather than another atopic disease, Nina H. Ravn reported at a meeting of the European Task Force on Atopic Dermatitis held in conjunction with the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

She presented a comprehensive meta-analysis of 149 published studies addressing the risk of developing atopic dermatitis according to parental history of atopic disease. The studies included more than 656,000 participants. The picture that emerged from the meta-analysis was one of a stepwise increase in the risk of pediatric atopic dermatitis according to the type and number of parental atopic diseases present.

“This is something that hopefully can be useful when you talk with parents or parents-to-be with atopic diseases and they want to know how their disease might affect their child,” explained Ms. Ravn of the University of Copenhagen.

It’s also information that clinicians will find helpful in appropriately targeting primary prevention interventions if and when methods of proven efficacy become available. That’s a likely prospect, as this is now an extremely active field of research, she noted.

Bruce Jancin/MDedge News

“An interesting result that was new to me what that fathers’ and mothers’ contribution to risk is equal,” said session cochair Andreas Wollenberg, MD, professor of dermatology at Ludwig Maximilian University of Munich. “For the past 2 decades we were always taught that the mother would have a greater impact on that risk.”

“I was also surprised by our findings,” Ms. Ravn replied. “But when we pooled all the data there really was no difference, nor in any of our subanalyses.”

She reported having no financial conflicts regarding her study.

[email protected]

SOURCE: Ravn NH. THE EADV CONGRESS.

MADRID – A parental history of asthma or allergic rhinitis significantly increases the risk that a child will develop atopic dermatitis, and that risk doubles if a parent has a history of atopic dermatitis rather than another atopic disease, Nina H. Ravn reported at a meeting of the European Task Force on Atopic Dermatitis held in conjunction with the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

She presented a comprehensive meta-analysis of 149 published studies addressing the risk of developing atopic dermatitis according to parental history of atopic disease. The studies included more than 656,000 participants. The picture that emerged from the meta-analysis was one of a stepwise increase in the risk of pediatric atopic dermatitis according to the type and number of parental atopic diseases present.

“This is something that hopefully can be useful when you talk with parents or parents-to-be with atopic diseases and they want to know how their disease might affect their child,” explained Ms. Ravn of the University of Copenhagen.

It’s also information that clinicians will find helpful in appropriately targeting primary prevention interventions if and when methods of proven efficacy become available. That’s a likely prospect, as this is now an extremely active field of research, she noted.

Bruce Jancin/MDedge News

“An interesting result that was new to me what that fathers’ and mothers’ contribution to risk is equal,” said session cochair Andreas Wollenberg, MD, professor of dermatology at Ludwig Maximilian University of Munich. “For the past 2 decades we were always taught that the mother would have a greater impact on that risk.”

“I was also surprised by our findings,” Ms. Ravn replied. “But when we pooled all the data there really was no difference, nor in any of our subanalyses.”

She reported having no financial conflicts regarding her study.

[email protected]

SOURCE: Ravn NH. THE EADV CONGRESS.

The use of ultrasound in screening for psoriatic arthritis in patients with psoriasis could reduce the number of unnecessary referrals to rheumatologists, according to a research letter published in the British Journal of Dermatology.

Bogdanhoda/Thinkstock

Up to one-third of patients with psoriasis have underlying psoriatic arthritis (PsA), but half of all patients with psoriasis experience nonspecific musculoskeletal complaints.

“Different screening tools have been developed for the dermatology practice to distinguish patients with a higher likelihood of having PsA; however, the low specificities of these tools limit their use in clinical practice,” wrote Dilek Solmaz, MD, and colleagues at the University of Ottawa.

In this prospective study, 51 patients with psoriasis were screened for referral to a rheumatologist using the Early Arthritis for Psoriatic Patients and Psoriasis Epidemiology Screening Tool questionnaires. They also underwent a limited ultrasound scanning of wrists, hands, feet, and the most painful joint, which was reviewed by experienced rheumatologists.

A dermatologist was asked to make a decision on referral based on the questionnaire data alone, then invited to revisit that decision after viewing the ultrasound results. When basing their decision on the questionnaires only, the dermatologist decided to refer 92% of patients to a rheumatologist. Of these patients, 40% were subsequently diagnosed with PsA, which represented a sensitivity of 95% but specificity of just 9%.

After reviewing the ultrasound data, the dermatologist revised their recommendations and only referred 43% of patients. Of these, 68% were later diagnosed with psoriatic arthritis. Among the patients who were not referred after the ultrasound review, five were diagnosed with PsA, but two had isolated axial involvement with no peripheral joint disease. Excluding these two cases, the sensitivity decreased to 88% but specificity increased to 77%.

“Screening tools in psoriasis that have high sensitivities usually have low specificities, which means a higher number of patients to be referred to rheumatology than needed,” the authors wrote. “Our study demonstrated that a musculoskeletal [ultrasound] based on a predefined protocol improves the referrals made to rheumatology.”

The authors did note that the ultrasounds were reviewed by experienced rheumatologists, so the results might not be generalizable to less-experienced sonographers without experience in musculoskeletal disorders.

The study was funded by AbbVie. One author declared receiving funding for a fellowship from UCB. Two authors declared honoraria and advisory consultancies with the pharmaceutical sector, including AbbVie.

SOURCE: Solmaz D et al. Br J Dermatol. 2019 Nov 28. doi: 10.1111/bjd.18515.

The use of ultrasound in screening for psoriatic arthritis in patients with psoriasis could reduce the number of unnecessary referrals to rheumatologists, according to a research letter published in the British Journal of Dermatology.

Bogdanhoda/Thinkstock

Up to one-third of patients with psoriasis have underlying psoriatic arthritis (PsA), but half of all patients with psoriasis experience nonspecific musculoskeletal complaints.

“Different screening tools have been developed for the dermatology practice to distinguish patients with a higher likelihood of having PsA; however, the low specificities of these tools limit their use in clinical practice,” wrote Dilek Solmaz, MD, and colleagues at the University of Ottawa.

In this prospective study, 51 patients with psoriasis were screened for referral to a rheumatologist using the Early Arthritis for Psoriatic Patients and Psoriasis Epidemiology Screening Tool questionnaires. They also underwent a limited ultrasound scanning of wrists, hands, feet, and the most painful joint, which was reviewed by experienced rheumatologists.

A dermatologist was asked to make a decision on referral based on the questionnaire data alone, then invited to revisit that decision after viewing the ultrasound results. When basing their decision on the questionnaires only, the dermatologist decided to refer 92% of patients to a rheumatologist. Of these patients, 40% were subsequently diagnosed with PsA, which represented a sensitivity of 95% but specificity of just 9%.

After reviewing the ultrasound data, the dermatologist revised their recommendations and only referred 43% of patients. Of these, 68% were later diagnosed with psoriatic arthritis. Among the patients who were not referred after the ultrasound review, five were diagnosed with PsA, but two had isolated axial involvement with no peripheral joint disease. Excluding these two cases, the sensitivity decreased to 88% but specificity increased to 77%.

“Screening tools in psoriasis that have high sensitivities usually have low specificities, which means a higher number of patients to be referred to rheumatology than needed,” the authors wrote. “Our study demonstrated that a musculoskeletal [ultrasound] based on a predefined protocol improves the referrals made to rheumatology.”

The authors did note that the ultrasounds were reviewed by experienced rheumatologists, so the results might not be generalizable to less-experienced sonographers without experience in musculoskeletal disorders.

The study was funded by AbbVie. One author declared receiving funding for a fellowship from UCB. Two authors declared honoraria and advisory consultancies with the pharmaceutical sector, including AbbVie.

SOURCE: Solmaz D et al. Br J Dermatol. 2019 Nov 28. doi: 10.1111/bjd.18515.

The use of ultrasound in screening for psoriatic arthritis in patients with psoriasis could reduce the number of unnecessary referrals to rheumatologists, according to a research letter published in the British Journal of Dermatology.

Bogdanhoda/Thinkstock

Up to one-third of patients with psoriasis have underlying psoriatic arthritis (PsA), but half of all patients with psoriasis experience nonspecific musculoskeletal complaints.

“Different screening tools have been developed for the dermatology practice to distinguish patients with a higher likelihood of having PsA; however, the low specificities of these tools limit their use in clinical practice,” wrote Dilek Solmaz, MD, and colleagues at the University of Ottawa.

In this prospective study, 51 patients with psoriasis were screened for referral to a rheumatologist using the Early Arthritis for Psoriatic Patients and Psoriasis Epidemiology Screening Tool questionnaires. They also underwent a limited ultrasound scanning of wrists, hands, feet, and the most painful joint, which was reviewed by experienced rheumatologists.

A dermatologist was asked to make a decision on referral based on the questionnaire data alone, then invited to revisit that decision after viewing the ultrasound results. When basing their decision on the questionnaires only, the dermatologist decided to refer 92% of patients to a rheumatologist. Of these patients, 40% were subsequently diagnosed with PsA, which represented a sensitivity of 95% but specificity of just 9%.

After reviewing the ultrasound data, the dermatologist revised their recommendations and only referred 43% of patients. Of these, 68% were later diagnosed with psoriatic arthritis. Among the patients who were not referred after the ultrasound review, five were diagnosed with PsA, but two had isolated axial involvement with no peripheral joint disease. Excluding these two cases, the sensitivity decreased to 88% but specificity increased to 77%.

“Screening tools in psoriasis that have high sensitivities usually have low specificities, which means a higher number of patients to be referred to rheumatology than needed,” the authors wrote. “Our study demonstrated that a musculoskeletal [ultrasound] based on a predefined protocol improves the referrals made to rheumatology.”

The authors did note that the ultrasounds were reviewed by experienced rheumatologists, so the results might not be generalizable to less-experienced sonographers without experience in musculoskeletal disorders.

The study was funded by AbbVie. One author declared receiving funding for a fellowship from UCB. Two authors declared honoraria and advisory consultancies with the pharmaceutical sector, including AbbVie.

SOURCE: Solmaz D et al. Br J Dermatol. 2019 Nov 28. doi: 10.1111/bjd.18515.

A skin biopsy of one of the lesions showed granulomatous inflammation composed of lymphocytes, macrophages, and giant cells around hair follicles with negative mycobacterium stains and fungal stains, consistent with granulomatous periorificial dermatitis. Tissue cultures from a skin biopsy for aerobic bacteria, mycobacteria, and fungus all were negative.

The patient initially was treated with erythromycin, but after 2 weeks, he reported abdominal pain and nausea and was unable to tolerate the medication. He was switched to clarithromycin, which he took for 6 weeks with clearance of the lesions.

A year later, some of the lesions recurred. He was treated again with clarithromycin and the lesions resolved.

Childhood granulomatous periorificial dermatitis (CGPD) is a benign skin eruption that occurs in prepubertal children. It also has been called facial Afro-Caribbean childhood eruption (FACE), and it tends to occur most commonly in children of darker skin types.¹CGPD is characterized by dome shape, monomorphous papules ranging from skin color to pink around the eyes, nose, and mouth, but there are some cases reported of extra facial involvement.² The lesions usually are not symptomatic, and they are more common in boys. The cause of this condition is not known, but possible triggers could include prior exposure to topical and systemic corticosteroids, as well as exposure to certain allergens such as formaldehyde.¹

In histopathology, the lesions are characterized by granulomatous infiltrates around the hair follicles and the upper dermis. The granulomas are formed of macrophages, lymphocytes, and giant cell, as were seen in our patient.³

Several conditions can look very similar to CGPD; these include sarcoidosis, lupus miliaris disseminatus faciei (LMDF), and granulomatous rosacea.

Sarcoidosis is a rare condition in children, and the lesions can be similar to the ones seen in our patient. Patients with sarcoidosis usually present with other systemic symptoms including fever, weight loss, respiratory symptoms, and fatigue; none of these were seen in our patient. Under the microscope, the lesions are characterized by “naked granulomas” instead of the inflammatory granulomas seen on our patient.

Lupus miliaris disseminatus faciei is a rare inflammatory skin condition commonly seen in young adults and is thought to be a variant of rosacea. It is characterized by skin-color to pink to yellow dome-shaped papules on the central face. Histologically, the lesions present as dermal epithelioid cell granulomas with central necrosis and surrounding lymphocytic infiltrate with multinucleate giant cells.⁴

Granulomatous rosacea and CGPD are considered two separate entities. Granulomatous rosacea tends to have a more chronic course, is not that common in children, and clinically presents with pustules, papules, and cysts around the eyes and cheeks.

Infectious processes like tuberculosis and fungal infections were ruled out in our patient with cultures and histopathology. Allergic contact dermatitis on the face can present with skin-color to pink papules, but they usually are very pruritic and improve with topical corticosteroids, while these medications can worsen CGPD.

CGPD can be a self-limiting condition. When mild, it can be treated with topical metronidazole, topical erythromycin, topical clindamycin solution, or pimecrolimus. Our patient failed treatment with pimecrolimus. For severe presentations, oral tetracyclines, erythromycin, and other macrolides, metronidazole, and oral isotretinoin can help clear the lesions.⁵
 

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. She said she had no relevant financial disclosures. Email her at [email protected].

References

1. Ann Dermatol. 2011 Aug;23(3):386-8.

2. Int J Dermatol. 2007 Feb;46(2):143-5.

3. J Cutan Med Surg. 2009 Feb 28;13(2):115-8.

4. An Bras Dermatol. 2017 Nov-Dec;92(6):851-3.

5. Indian Dermatol Online J. 2018 Jan-Feb; 9(1):68-70.

A skin biopsy of one of the lesions showed granulomatous inflammation composed of lymphocytes, macrophages, and giant cells around hair follicles with negative mycobacterium stains and fungal stains, consistent with granulomatous periorificial dermatitis. Tissue cultures from a skin biopsy for aerobic bacteria, mycobacteria, and fungus all were negative.

The patient initially was treated with erythromycin, but after 2 weeks, he reported abdominal pain and nausea and was unable to tolerate the medication. He was switched to clarithromycin, which he took for 6 weeks with clearance of the lesions.

A year later, some of the lesions recurred. He was treated again with clarithromycin and the lesions resolved.

Childhood granulomatous periorificial dermatitis (CGPD) is a benign skin eruption that occurs in prepubertal children. It also has been called facial Afro-Caribbean childhood eruption (FACE), and it tends to occur most commonly in children of darker skin types.¹CGPD is characterized by dome shape, monomorphous papules ranging from skin color to pink around the eyes, nose, and mouth, but there are some cases reported of extra facial involvement.² The lesions usually are not symptomatic, and they are more common in boys. The cause of this condition is not known, but possible triggers could include prior exposure to topical and systemic corticosteroids, as well as exposure to certain allergens such as formaldehyde.¹

In histopathology, the lesions are characterized by granulomatous infiltrates around the hair follicles and the upper dermis. The granulomas are formed of macrophages, lymphocytes, and giant cell, as were seen in our patient.³

Several conditions can look very similar to CGPD; these include sarcoidosis, lupus miliaris disseminatus faciei (LMDF), and granulomatous rosacea.

Sarcoidosis is a rare condition in children, and the lesions can be similar to the ones seen in our patient. Patients with sarcoidosis usually present with other systemic symptoms including fever, weight loss, respiratory symptoms, and fatigue; none of these were seen in our patient. Under the microscope, the lesions are characterized by “naked granulomas” instead of the inflammatory granulomas seen on our patient.

Lupus miliaris disseminatus faciei is a rare inflammatory skin condition commonly seen in young adults and is thought to be a variant of rosacea. It is characterized by skin-color to pink to yellow dome-shaped papules on the central face. Histologically, the lesions present as dermal epithelioid cell granulomas with central necrosis and surrounding lymphocytic infiltrate with multinucleate giant cells.⁴

Granulomatous rosacea and CGPD are considered two separate entities. Granulomatous rosacea tends to have a more chronic course, is not that common in children, and clinically presents with pustules, papules, and cysts around the eyes and cheeks.

Infectious processes like tuberculosis and fungal infections were ruled out in our patient with cultures and histopathology. Allergic contact dermatitis on the face can present with skin-color to pink papules, but they usually are very pruritic and improve with topical corticosteroids, while these medications can worsen CGPD.

CGPD can be a self-limiting condition. When mild, it can be treated with topical metronidazole, topical erythromycin, topical clindamycin solution, or pimecrolimus. Our patient failed treatment with pimecrolimus. For severe presentations, oral tetracyclines, erythromycin, and other macrolides, metronidazole, and oral isotretinoin can help clear the lesions.⁵
 

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. She said she had no relevant financial disclosures. Email her at [email protected].

References

1. Ann Dermatol. 2011 Aug;23(3):386-8.

2. Int J Dermatol. 2007 Feb;46(2):143-5.

3. J Cutan Med Surg. 2009 Feb 28;13(2):115-8.

4. An Bras Dermatol. 2017 Nov-Dec;92(6):851-3.

5. Indian Dermatol Online J. 2018 Jan-Feb; 9(1):68-70.

A skin biopsy of one of the lesions showed granulomatous inflammation composed of lymphocytes, macrophages, and giant cells around hair follicles with negative mycobacterium stains and fungal stains, consistent with granulomatous periorificial dermatitis. Tissue cultures from a skin biopsy for aerobic bacteria, mycobacteria, and fungus all were negative.

The patient initially was treated with erythromycin, but after 2 weeks, he reported abdominal pain and nausea and was unable to tolerate the medication. He was switched to clarithromycin, which he took for 6 weeks with clearance of the lesions.

A year later, some of the lesions recurred. He was treated again with clarithromycin and the lesions resolved.

Childhood granulomatous periorificial dermatitis (CGPD) is a benign skin eruption that occurs in prepubertal children. It also has been called facial Afro-Caribbean childhood eruption (FACE), and it tends to occur most commonly in children of darker skin types.¹CGPD is characterized by dome shape, monomorphous papules ranging from skin color to pink around the eyes, nose, and mouth, but there are some cases reported of extra facial involvement.² The lesions usually are not symptomatic, and they are more common in boys. The cause of this condition is not known, but possible triggers could include prior exposure to topical and systemic corticosteroids, as well as exposure to certain allergens such as formaldehyde.¹

In histopathology, the lesions are characterized by granulomatous infiltrates around the hair follicles and the upper dermis. The granulomas are formed of macrophages, lymphocytes, and giant cell, as were seen in our patient.³

Several conditions can look very similar to CGPD; these include sarcoidosis, lupus miliaris disseminatus faciei (LMDF), and granulomatous rosacea.

Sarcoidosis is a rare condition in children, and the lesions can be similar to the ones seen in our patient. Patients with sarcoidosis usually present with other systemic symptoms including fever, weight loss, respiratory symptoms, and fatigue; none of these were seen in our patient. Under the microscope, the lesions are characterized by “naked granulomas” instead of the inflammatory granulomas seen on our patient.

Lupus miliaris disseminatus faciei is a rare inflammatory skin condition commonly seen in young adults and is thought to be a variant of rosacea. It is characterized by skin-color to pink to yellow dome-shaped papules on the central face. Histologically, the lesions present as dermal epithelioid cell granulomas with central necrosis and surrounding lymphocytic infiltrate with multinucleate giant cells.⁴

Granulomatous rosacea and CGPD are considered two separate entities. Granulomatous rosacea tends to have a more chronic course, is not that common in children, and clinically presents with pustules, papules, and cysts around the eyes and cheeks.

Infectious processes like tuberculosis and fungal infections were ruled out in our patient with cultures and histopathology. Allergic contact dermatitis on the face can present with skin-color to pink papules, but they usually are very pruritic and improve with topical corticosteroids, while these medications can worsen CGPD.

CGPD can be a self-limiting condition. When mild, it can be treated with topical metronidazole, topical erythromycin, topical clindamycin solution, or pimecrolimus. Our patient failed treatment with pimecrolimus. For severe presentations, oral tetracyclines, erythromycin, and other macrolides, metronidazole, and oral isotretinoin can help clear the lesions.⁵
 

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. She said she had no relevant financial disclosures. Email her at [email protected].

References

1. Ann Dermatol. 2011 Aug;23(3):386-8.

2. Int J Dermatol. 2007 Feb;46(2):143-5.

3. J Cutan Med Surg. 2009 Feb 28;13(2):115-8.

4. An Bras Dermatol. 2017 Nov-Dec;92(6):851-3.

5. Indian Dermatol Online J. 2018 Jan-Feb; 9(1):68-70.

Dermoscopy was performed, which confirmed that this was a cherry angioma, also called a cherry hemangioma or Campbell de Morgan spot.

Cherry angiomas are benign proliferations that typically appear after age 30 as tiny bright erythematous macules that, over time, enlarge into papules. In their early, and smaller, stages they are typically maraschino cherry red, hence the name cherry angiomas. As they enlarge or become thrombosed, some lesions become darker red or even black in color. (The dermoscopy image shown here demonstrates the bright red globular red pattern that is classically seen with cherry angiomas.)

Cherry angiomas do not require treatment. If treatment is desired for cosmetic purposes, they can be treated with electrocautery, cryosurgery, or laser. The patient in this case was not worried about the appearance of the lesion and opted to leave it alone unless he developed symptoms.

‌

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

Dermoscopy was performed, which confirmed that this was a cherry angioma, also called a cherry hemangioma or Campbell de Morgan spot.

Cherry angiomas are benign proliferations that typically appear after age 30 as tiny bright erythematous macules that, over time, enlarge into papules. In their early, and smaller, stages they are typically maraschino cherry red, hence the name cherry angiomas. As they enlarge or become thrombosed, some lesions become darker red or even black in color. (The dermoscopy image shown here demonstrates the bright red globular red pattern that is classically seen with cherry angiomas.)

Cherry angiomas do not require treatment. If treatment is desired for cosmetic purposes, they can be treated with electrocautery, cryosurgery, or laser. The patient in this case was not worried about the appearance of the lesion and opted to leave it alone unless he developed symptoms.

‌

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

Dermoscopy was performed, which confirmed that this was a cherry angioma, also called a cherry hemangioma or Campbell de Morgan spot.

Cherry angiomas are benign proliferations that typically appear after age 30 as tiny bright erythematous macules that, over time, enlarge into papules. In their early, and smaller, stages they are typically maraschino cherry red, hence the name cherry angiomas. As they enlarge or become thrombosed, some lesions become darker red or even black in color. (The dermoscopy image shown here demonstrates the bright red globular red pattern that is classically seen with cherry angiomas.)

Cherry angiomas do not require treatment. If treatment is desired for cosmetic purposes, they can be treated with electrocautery, cryosurgery, or laser. The patient in this case was not worried about the appearance of the lesion and opted to leave it alone unless he developed symptoms.

‌

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