Catherine Maari

A randomized, double-blind, placebo-controlled, phase I study of MEDI-545, an anti–interferon-alfa monoclonal antibody, in subjects with chronic psoriasis

BACKGROUND Interferon-alfa (IFN-alpha) has been implicated in the pathogenesis of psoriasis. OBJECTIVE To evaluate the safety profile of MEDI-545, a fully human anti-IFN-alpha monoclonal antibody and to explore its effect on the involvement of type I IFN-alpha activity in the maintenance of established plaque psoriasis. METHODS We conducted an 18-week, randomized, double-blind, placebo-controlled, dose-escalating study in 36 subjects with chronic plaque psoriasis. Subjects received one intravenous dose of MEDI-545 (0.3-30.0 mg/kg) or placebo. Study outcomes were safety profile, pharmacokinetics, immunogenicity, and clinical effects. RESULTS There was no difference in adverse events between MEDI-545 and placebo. Two serious adverse events were reported; one drug-related hypotensive infusion reaction occurred in one subject in the 30.0 mg/kg MEDI-545 dose group, causing discontinuation of study drug in that subject and study dismissal of the other subjects in the same cohort; and a myocardial infarction occurred in one subject in the 10 mg/kg MEDI-545 dose group, which was considered to be unrelated to treatment. MEDI-545 was nonimmunogenic, had a half-life of 21 days, showed no significant inhibition of the type I IFN gene signature, and had no clinical activity. LIMITATIONS The study addressed only IFN-alpha and chronic psoriatic lesions. CONCLUSION The safety profile of MEDI-545 supports further clinical development. IFN-alpha does not appear to be significantly involved in the maintenance of established plaque psoriasis.

Large congenital melanocytic nevi and neurocutaneous melanocytosis: One pediatric center's experience

BACKGROUND Large congenital melanocytic nevi (LCMN) predispose to neurocutaneous melanocytosis (NCM), which is associated with significant morbidity and mortality. OBJECTIVE To identify risk factors for NCM in patients with LCMN and suggest guidelines for their management. METHODS Medical records of patients with LCMN were reviewed at Sainte-Justine Hospital between 1980 and 2006. Presence of multiple satellite nevi and posterior midline location were evaluated as risk factors for NCM using chi-square test. Magnetic resonance imaging scans were reviewed by a neuroradiologist. RESULTS Twenty-six of 52 patients underwent radiologic investigation. Six of 26 (23%) had NCM. Patients with this condition are more likely to have multiple satellite nevi (100% vs 50%, P = .03) and have a trend to posterior midline location of their LCMN (100% vs 60%, P = .08). Patients with NCM are more likely to have both multiple satellite nevi and posterior midline location (100% vs 25%, P = .002). Radiologic findings are also presented. LIMITATIONS This was a retrospective case series with imprecise chart data in 38% of cases. CONCLUSION The presence of multiple satellite nevi alone or with associated posterior midline location of LCMN is associated with a higher risk of NCM. We recommend magnetic resonance imaging testing before 4 months of age in patients with these features.

Efficacy and safety of adalimumab in patients with plaque psoriasis who have shown an unsatisfactory response to etanercept

BACKGROUND The safety and efficacy of adalimumab in patients who have shown an unsatisfactory response to etanercept are unknown. OBJECTIVE We sought to evaluate the safety and efficacy of adalimumab in patients who failed to show a satisfactory response or lost their satisfactory response to etanercept. METHODS This multicenter study enrolled patients who either failed to reach a physician global assessment (PGA) score of 0 or 1 after 12 weeks of etanercept (group A; 50 patients) or who lost their PGA score of 0 or 1 at any time after etanercept dose decrease from 50 mg twice a week to 50 mg every week (group B; 35 patients). Patients received adalimumab 40 mg every other week without loading dose for 12 weeks followed by 40 mg every week for an additional 12 weeks if they did not reach a PGA score of 0 or 1. RESULTS After 12 weeks of adalimumab, 34.0% (n = 17; 95% confidence interval [CI] 20.4-47.6) and 31.4% (n = 11; 95% CI 15.2-47.6) of patients from groups A and B, respectively, reached a PGA score of 0 or 1. A total of 46.0% (n = 23; 95% CI 31.7-60.3) and 45.7% (n = 16; 95% CI 28.4-63.1) of patients from group A and B, respectively, achieved a PGA score of 0 or 1 after 24 weeks of adalimumab. Adalimumab was well tolerated and no serious adverse events were reported. LIMITATIONS This was an open-label uncontrolled study. CONCLUSIONS Adalimumab should be considered as an alternative in patients with psoriasis who have not shown an adequate response or who lost their response to etanercept after a dose decrease.

Effect of adalimumab on sleep parameters in patients with psoriasis and obstructive sleep apnea: a randomized controlled trial

Introduction: Obstructive sleep apnea (OSA) is frequently seen in patients with psoriasis vulgaris. The effect of adalimumab, a TNF-α antagonist, on OSA is unknown. Methods: Patients with at least 5% of their body surface area covered with psoriasis and a sleep apnea defined as an apnea/hypopnea index (AHI) of at least 15 were recruited. They were randomized to either adalimumab 80 mg followed by adalimumab 40 mg every other week for 7 weeks or placebo. Patients were evaluated by polysomnography at baseline and day 56. The objective of this trial was to study the efficacy of adalimumab on sleep parameters in patients with psoriasis and OSA. The primary end point of this double-blind study was the change in AHI between baseline and day 56. Results: A total of 20 patients who were randomized completed the trial. There was no significant difference (p = 0.485) (95% CI = –21.07–42.73) at day 56 in the change from baseline in AHI between groups. Conclusions: Adalimumab used for 8 weeks at 40 mg every other week for the treatment of psoriasis did not improve OSA in this 20-patient study.

Therapy of ulcerated hemangiomas.

Background: Cutaneous ulceration is the most common complication of infantile hemangiomas (IHs) seen in a pediatric dermatology practice. Objective: The most effective treatments in our experience are compared to those in the current literature. Methods: The study was a retrospective chart review of therapy of 169 ulcerated IHs at a tertiary care pediatric hospital and a literature review. Results: Combination therapy was the rule. Local wound care was required in all, pain management in 72%, pulsed dye laser in 42%, infection control in 38%, diminution of the hemangioma through systemic therapy in 36%, and suppression of bleeding in 2%. Limitations: A retrospective review compared to a case-control study has inherent bias. In addition, our cases were all at a tertiary referral center. Conclusion: All ulcerated IHs benefit from local barrier creams or dressings. Pulsed dye laser, antibiotics, topical morphine 0.1% in hydrogel, topical becaplermin, and, most importantly, systemic therapy (especially propranolol) to reduce the hemangioma may be useful.

Treatment of notalgia paresthetica with botulinum toxin A: A double-blind randomized controlled trial

To the Editor: Notalgia paresthetica (NP) is a chronic sensory neuropathy affecting the interscapular area, especially the T2-T6 dermatomes and characterized by pruritus on the upper back with cutaneous signs associated with rubbing and scratching. Botulinum toxin A (BTX-A) could have beneficial effects on localized pruritus, possibly by preventing the release of substance P, a mediator involved in pain and itch. One publication reports complete resolution of pruritus in 2 patients with NP treated with BTX-A. We conducted a randomized, placebocontrolled, double-blind clinical trial to study the efficacy and safety of BTX-A in patients with NP in a Canadian dermatology research clinic between July 2010 and November 2011. After signing informed consent, 20 patients with NP for at least 1 year, stable for 3 months before baseline and resistant to topical therapy, were randomized (1:1) to either BTX-A (Xeomin, Merz Pharmaceuticals, Frankfurt, Germany) in saline or saline alone ( placebo) (Fig 1). Baseline characteristics are shown in Table I. A sample size of 20 had a power of 0.8 to detect a difference in change from baseline of 1.7 in visual analogue score (VAS) for pruritus between the two groups, assuming a mean baseline VAS of 8 and

Open-label exploratory study of acitretin for the treatment of severe chronic hand dermatitis.

Abstract Introduction: Acitretin is a retinoid approved for the treatment of psoriasis that has good efficacy for palmoplantar psoriasis. The safety and efficacy of acitretin in severe chronic hand dermatitis (CHD) is unknown. Methods: A total of nine patients with severe CHD were enrolled and treated with acitretin 10 mg once daily which could be increased to 30 mg daily if well-tolerated. Patients were treated for up to 24 or 12 weeks if the physician global assessment (PGA) was clear or almost clear at that time. CHD severity was evaluated using a 5-grade PGA scale and the modified total lesion symptom score (mTLSS). Results: The proportion of patients achieving PGA of clear or almost clear was 33.3% (95% CI: 9–69%) and the proportion achieving PGA of clear, almost clear or mild was 44% (95% CI: 15–77%). The mTLSS decreased by 45% (−6.3 ± 4.7; p = 0.02). Three patients did not complete the study: one due to an increase in facial dermatitis, one due to lack of efficacy and one who withdrew consent. Conclusions: This pilot study suggests that acitretin could improve severe CHD. Further studies are needed to better assess the efficacy and safety of acitretin in patients with severe CHD.

Short incubation photodynamic therapy with methylaminolevulinate and no occlusion for the treatment of actinic keratoses.

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Palmoplantar pustular psoriasis (PPPP) is characterized by activation of the IL-17A pathway

BACKGROUND Palmoplantar pustular psoriasis (PPPP) is a variant of psoriasis, which has significant negative impact on quality of life. The cellular and molecular inflammatory pathways involved in PPPP have not been well studied. OBJECTIVE Study the expression of cytokines and chemokines involved in the IL-17/IL-23 axis in palmoplantar pustular psoriasis and other difficult to treat psoriasis areas (palms, scalp, elbows and lower legs). METHODS Skin biopsies were performed on a total of 80 patients with PPPP, non-pustular palmoplantar psoriasis (NPPPP), or psoriasis located on elbows, knees and scalp as well as 10 healthy subjects. RT-PCR, immunohistochemistry and flow cytometry on cells extracted from skin biopsies were used to compare PPPP to other forms of psoriasis. RESULTS There was a significant (p<0.05) increase in the expression of IL-1β, IL-6, LL-37, IL-19, IL-17A, CXCL1 and CXCL2 in PPPP as compared to NPPPP. However, there was no significant difference in expression of IL-23 in PPPP as compared to NPPPP and other forms of psoriasis. The proportion of IL-22+ but not IL-17A+ mast cells was higher in PPPP as compared to NPPPP (p<0.05). CONCLUSION These results suggest that the IL-17A pathway may play a more important role in PPPP than in NPPPP.

Use of capsule endoscopy to identify lesions suggestive of Crohn's disease in patients with moderate to severe psoriasis

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