A case of febrile ulceronecrotic Mucha-Habermann disease responsive to systemic corticosteroids.

Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is a rare, potentially fatal subtype of pityriasis lichenoides et varioliformis acuta (PLEVA). Herein, we present a rare case of a 14-year-old male without significant past medical history who was diagnosed with FUMHD without a clear inciting factor. He was effectively treated with systemic corticosteroids with complete resolution of symptoms.

Pruritus in Black Skin: Unique Molecular Characteristics and Clinical Features.

BACKGROUND: Chronic pruritus dramatically disrupts quality of life, impairs sleep, and is difficult to treat. The pathogenesis and severity of chronic itch can vary significantly with race. Black skin has inherent structural and molecular characteristics that exacerbates pruritus, leading to unique presentations of pruritic conditions and added challenges in finding effective therapies. The aim of this review is to discuss structural variances in black skin, the subsequent epidemiological disparities in chronic pruritic conditions, and clinical management pearls for the management of itch in black patients. METHODS: Current literature including mechanistic, translational, and epidemiological data on racial differences in pruritus focusing on black skin were reviewed in Pubmed. FINDINGS: Black skin has several unique structural properties related to the pathogenesis of pruritus, including increased trans-epidermal water loss, decreased ceramide levels, lower pH in the stratum corneum, and increased size of mast cells. Black patients consequently are disproportionately affected by chronic pruritic disorders including atopic dermatitis, prurigo nodularis, HIV-related pruritic dermatoses, and cutaneous T-cell lymphoma. CONCLUSION: Pruritus and chronic pruritus disorders disproportionately affects black patients. Management of pruritus of special importance in black patients includes low pH skin care products to protect the skin barrier along with emollients to diminish trans-epidermal water loss. Further mechanistic studies are needed to characterize racial differences in biomarkers and therapeutic targets of chronic itch.

Proteomic and Phosphoproteomic Analysis Reveals that Neurokinin-1 Receptor (NK1R) Blockade with Aprepitant in Human Keratinocytes Activates a Distinct Subdomain of EGFR Signaling: Implications for the Anti-Pruritic Activity of NK1R Antagonists.

Background: Epidermal growth factor receptor (EGFR) inhibitors can cause serious cutaneous toxicities, including pruritus and papulopustular acneiform skin eruptions. Increasingly, the neurokinin-1 receptor (NK1R) antagonist aprepitant is being utilized as an anti-pruritic agent in the treatment of EGFR-inhibitor induced pruritus. Aprepitant is believed to reduce itching by blocking NK1R on the surface of dermal mast cells. However, the effects of aprepitant on human keratinocytes remains unexplored. Methods: Herein, we examine the effects of aprepitant on EGFR stimulation in HaCaT cells using a phosphoproteomic approach including reverse phase protein arrays and Ingenuity Pathway Analysis. Changes in EGFR phosphorylation were visualized using Western blotting and the effect of EGF and aprepitant on the growth of HaCaT cells was determined using the WST-1 Cell Proliferation Assay System. Results: We found that aprepitant increased the phosphorylation of EGFR, as well as 10 of the 23 intracellular proteins phosphorylated by EGF. Analysis of phosphoproteomic data using Ingenuity Pathway Analysis software revealed that 5 of the top 10 pathways activated by EGF and aprepitant are shared. Conclusions: We propose that aprepitant produces its antipruritic effects by partially activating EGFR. Activation of EGFR by aprepitant was also seen in primary human keratinocytes. In addition to itch reduction through partial activation of shared EGFR pathways, aprepitant exerts a dose-dependent cytotoxicity to epithelial cells, which may contribute to its antitumor effects.

Mirtazapine for the Treatment of Chronic Pruritus.

Background: Chronic pruritus is a debilitating condition associated with a wide range of dermatologic, systemic and psychogenic etiologies. In patients with chronic pruritus that is refractory to conventional therapy, symptoms can significantly decrease quality of life by contributing to anxiety, sleep disturbances, and in many cases depression. Recent studies have demonstrated the effectiveness of mirtazapine in relieving chronic itch that is refractory to standard first-line therapies. Methods: We searched PubMed for English-language articles containing the words ("pruritus" or "itch") AND "antidepressant" and then conducted a systematic review of the current literature to summarize the efficacy of mirtazapine in treating chronic itch. Results: All studies reported a reduction in itch intensity following the administration of mirtazapine. Conclusion: Collectively, these studies suggest the potential for mirtazapine to relieve chronic itch attributed to dermatological causes and malignancies. As, such mirtazapine may be an option for patients with chronic pruritus that is refractory to typical first-line treatments.

Itching at night: A review on reducing nocturnal pruritus in children.

The most common causes of chronic nocturnal itching in children are atopic dermatitis and psoriasis, with lichen simplex chronicus and prurigo nodularis contributing to lesser degrees. Despite the prevalence of nocturnal itching, its pathophysiology remains poorly understood. The most troubling consequence of itching at night is poor quality of sleep. Poor sleep quality in children with nocturnal itching has been linked to adverse neurocognitive, behavioral, and physiologic outcomes, including poor performance in school, attention deficit hyperactivity disorder, short stature, hypertension, obesity, and impaired immune function. There is no consensus on the best management of nocturnal itching in children. We conducted a review of the literature evaluating the efficacy of various treatment options for children with chronic nocturnal pruritus. Our review found three recently conducted randomized controlled trials and one case report demonstrating the efficacy of topical corticosteroids, oral melatonin, and clonidine in reducing nocturnal itching or improving sleep quality in children with nocturnal pruritus. Future research is needed to elucidate the pathophysiology of nocturnal itching to best develop targeted, effective treatment strategies.

Ethnic differences and comorbidities of 909 prurigo nodularis patients.

BACKGROUND: Prurigo nodularis (PN) is a poorly understood, understudied pruritic dermatosis that reduces quality of life. OBJECTIVE: To characterize the demographics and comorbidities associated with PN. METHODS: Cross-sectional study of patients 18 years and older who were seen at the Johns Hopkins Health System between December 6, 2012, and December 6, 2017. RESULTS: Over the past 5 years, 909 patients with PN were seen at Johns Hopkins Health System. African American patients were 3.4 times more likely to have PN than white patients were (odds ratio [OR], 3.4; 95% confidence interval [CI], 2.9-3.9; P < .001). A comparison of the study patients and race-matched controls revealed that PN was significantly associated with a variety of systemic, cardiovascular, and psychiatric comorbidities, including chronic kidney disease, chronic hepatitis C, chronic obstructive pulmonary disease, congestive heart failure, depression, and atopic dermatitis. Black patients with PN were 10.5 times more likely (OR, 10.5; 95% CI, 7.9-13.9; P < .001) to have HIV than were race-matched controls with atopic dermatitis, and 8 times more likely (OR, 8.0; 95% CI, 5.7-11.1; P < .001) to have HIV than were African American patients with psoriasis. LIMITATIONS: Our data describe patients seen by 1 hospital system. Our data identify associated conditions and comorbidities but are unable to support a causal relationship. CONCLUSION: PN disproportionately affects African Americans and is associated with several systemic conditions, including HIV, chronic kidney disease, and diabetes.

Clinical utility of marketing terms used for over-the-counter dermatologic products.

BACKGROUND: Cosmetic products are commonly marketed using dermatologic terms such as 'hypoallergenic', 'non-comedogenic', 'fragrance-free', etc. The clinical relevance of these claims can be confusing to both patients and clinicians. METHODS: A systematic review was performed via a PubMed search of published articles from January 1985 to October 2017 to further describe and elucidate the clinical utility of a predefined list of common dermatologic terms used by pharmaceutical companies to market over-the-counter products. RESULTS: The terms 'fragrance-free', 'hypoallergenic', 'non-comedogenic', and 'oil-free' on cosmetic product labels are not regulated by any governing body and provide varied clinical utility. Products labeled as having 'natural ingredients' are not necessarily safer or less irritating to patients with atopy or a history of allergic contact dermatitis. Despite the increasing popularity of 'paraben-free' cosmetics, parabens are safe for patients in the quantities used in cosmetic products and can be safely used in patients who do not exhibit contact dermatitis to this preservative. CONCLUSION: A working knowledge of common cosmetic ingredients may help dermatologists to counsel patients on which products to avoid for their specific dermatologic conditions.

Food and drug administration approval process for dermatology drugs in the United States.

AIM: The purpose of this review is to elucidate the steps involved in the FDA's approval of new dermatology drugs. METHODS: To help illustrate the process of drug approval, we use examples from the recent approval of dupilumab (REGN668; Regeneron Pharmaceuticals). RESULTS: In general, new dermatology drugs must undergo pre-clinical studies on non-human subjects and three phases of clinical trials in humans before undergoing review by the Food and Drug Administration (FDA). This review process involves an interdisciplinary team of scientists that determines if the drug should be brought to market based on its efficacy, risk-to-benefit ratio, and ability to be labeled. The team that specifically reviews dermatology drugs within the Center for Drug Evaluation and Research (CDER) at the FDA is the Division of Dermatologic and Dental Drug Products. CONCLUSIONS: The drug development process is enhanced by clinician input during all stages of development.

Oesophageal epidermal naevi as a feature of systematised epidermal naevus syndrome.

Systematised epidermal naevi are hamartomas developing from neural ectoderm that can be quite extensive, typically with involvement of the face, neck, scalp, arms, legs and trunk. Involvement of the gastrointestinal tract is rare. We report on a 38-year-old Caucasian woman with systematised epidermal naevus syndrome who presented with previously undescribed involvement of the oesophagus, as well as the right side of her scalp, forehead, cheeks, chin, oral mucosa, neck, arms and trunk.

Demographic characteristics of teenage boys with horizontal striae distensae of the lower back.

BACKGROUND: This study examines the clinical characteristics and demographics of teenage boys with horizontal striae distensae of the lower back in an outpatient setting. METHODS: Retrospective medical chart reviews and telephone survey studies were completed on an outpatient cohort of 12 boys 11 to 17 years of age with a clinical diagnosis of transverse striae distensae of the lower back at a single-center, university-based, pediatric dermatology practice. We evaluated the clinical features of the striae, participant demographic characteristics, and past medical history. A review of the literature concerning risk factors was conducted using PubMed and Google Scholar. RESULTS: Of the 14 patients we contacted, 12 agreed to participate. The average age of onset for the striae was 14.3 years. All boys were above the 50th percentile in height at the time of onset. Eight (66.7%) reported a significant growth spurt before the appearance of the stretch marks. Most were asymptomatic. None of the boys had a history of unmonitored exogenous steroid use or prior infection with Bartonella henselae or Borrelia burgdorferi. Only one (8.3%) had a chronic medical condition. Eleven (91.7%) had at least one first-degree relative with striae distensae. CONCLUSION: Our results indicate that horizontal striae distensae of the lower back in adolescent boys is associated with a rapid growth spurt, tall stature, and family history of striae distensae. There is no association between this type of striae distensae and any chronic medical condition, bacterial infection, or exogenous steroid use. Thus a careful review of systems and counseling without further medical testing is reasonable management.