Dupilumab treatment improves signs, symptoms, quality of life, and work productivity in patients with atopic hand and foot dermatitis: Results from a phase 3, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Despite high disease burden, systemic treatment options for patients with atopic hand and/or foot dermatitis (H/F AD) are limited. OBJECTIVES: To evaluate efficacy and safety of dupilumab in H/F AD using specific instruments for assessing disease severity on hands and feet. METHODS: In this multicenter phase 3 trial, adults and adolescents with moderate-to-severe H/F AD were randomized to dupilumab monotherapy (regimen approved for generalized AD), or matched placebo. The primary endpoint was proportion of patients achieving Hand and Foot Investigator's Global Assessment score 0 or 1 at week 16. Secondary prespecified endpoints assessed the severity and extent of signs, symptom intensity (itch, pain), quality of life, and sleep. RESULTS: A total of 133 patients (adults = 106, adolescents = 27) were randomized to dupilumab (n = 67) or placebo (n = 66). At week 16, significantly more patients receiving dupilumab (n = 27) than placebo (n = 11) achieved Hand and Foot Investigator's Global Assessment score 0 or 1 (40.3% vs 16.7%; P = .003). All other prespecified endpoints were met. Safety was consistent with the known AD dupilumab profile. LIMITATIONS: Short-term, 16-week treatment period. CONCLUSION: Dupilumab monotherapy resulted in significant improvements across different domains of H/F AD with acceptable safety, supporting dupilumab as a systemic treatment approach for this often difficult to treat condition.

Photoallergy.

Abstract Photoallergic contact dermatitis (PACD) is a hypersensitivity reaction mounting from skin exposure to generally harmless amounts of ultraviolet and/or visible light in the presence of a photoreactive allergen. These reactions are typically delayed type (Gell and Coombs type IV) reactions and require pre-sensitization to photoallergens. Phototoxic reactions are clinically similar and often difficult to differentiate from photoallergies, but they are caused by interaction of light with photoirritants and do not require sensitization. The main investigative technique to diagnose PACD is photopatch testing, which is not commonly used; therefore, PACD may be overlooked in many patients. Currently, leading contact photosensitizers are sunscreens and topical non-steroidal anti-inflammatory drugs. This article provides an overview on photocontact allergies.

The Skin and Lewy Body Disease.

This manuscript reviews the significant skin manifestations of Lewy body disease, including Parkinson's disease and dementia with Lewy bodies, and the diagnostic utility of skin biopsy. Besides classic motor and cognitive symptoms, non-motor manifestations, particularly dermatologic disorders, can play a crucial role in disease presentation and diagnosis. This review explores the intricate relationship between the skin and Lewy body disease. Seborrheic dermatitis, autoimmune blistering diseases (bullous pemphigoid and pemphigus), rosacea, and melanoma are scrutinized for their unique associations with Parkinson's disease, revealing potential links through shared pathophysiological mechanisms. Advances in diagnostic techniques allow the identification of promising biomarkers such as α-synuclein in samples obtained by skin punch biopsy. Understanding the dermatologic aspects of Lewy body disease not only contributes to its holistic characterization but also holds implications for innovative diagnostic approaches.

Vitamin D Combined with Aminolevulinate (ALA)-Mediated Photodynamic Therapy (PDT) for Human Psoriasis: A Proof-of-Principle Study.

We previously showed that select agents (methotrexate or Vitamin D), when administered as a preconditioning regimen, are capable of promoting cellular differentiation of epithelial cancer cells while simultaneously enhancing the efficacy of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT). In solid tumors, pretreatment with Vitamin D simultaneously promotes cellular differentiation and leads to selective accumulation of target porphyrins (mainly protoporphyrin IX, PpIX) within diseased tissue. However, questions of whether or not the effects upon cellular differentiation are inexorably linked to PpIX accumulation, and whether these effects might occur in hyperproliferative noncancerous tissues, have remained unanswered. In this paper, we reasoned that psoriasis, a human skin disease in which abnormal cellular proliferation and differentiation plays a major role, could serve as a useful model to test the effects of pro-differentiating agents upon PpIX levels in a non-neoplastic setting. In particular, Vitamin D, a treatment for psoriasis that restores (increases) differentiation, might increase PpIX levels in psoriatic lesions and facilitate their responsiveness to ALA-PDT. This concept was tested in a pilot study of 7 patients with bilaterally-matched psoriatic plaques. A regimen in which calcipotriol 0.005% ointment was applied for 3 days prior to ALA-PDT with blue light, led to preferential increases in PpIX (~130%), and reductions in thickness, redness, scaling, and itching in the pretreated plaques. The results suggest that a larger clinical trial is warranted to confirm a role for combination treatments with Vitamin D and ALA-PDT for psoriasis.

Allergic Contact Dermatitis of the Scalp Associated With Scalp Applied Products: A Systematic Review of Topical Allergens.

ABSTRACT: Hair products are commonly used to maintain hair health or cosmesis. Products applied to the scalp and hair contain multiple active and inactive ingredients that can potentially cause irritant and/or allergic contact dermatitis. The objectives of this study were to identify and to discuss the most common allergens in scalp and hair applied products causing scalp allergic contact dermatitis (ACD). A PubMed search identified 99 studies, with 3185 patients and 31 categories of scalp products. Hair products reportedly associated with scalp ACD were hair dyes (41%), shampoos (28%), and conditioners (22%). The most commonly reported patch test-positive allergens were p -phenylenediamine (23%), nickel (15%), fragrance mix (13%), balsam of Peru (10%), cocamidopropyl betaine/3-dimethylaminopropylamine (7%), and methylchloroisothiazolinone/methylisothiazolinone (6%). Common symptoms and signs include eczematous lesions, pruritus, and a burning sensation. Medical practitioners should be aware of causative agents to provide appropriate patient education, counseling, and/or treatment.

Assessment of Comorbidities Associated With Allergic Contact Dermatitis in the United States: A Retrospective Claims-Based Study.

BACKGROUND: Allergic contact dermatitis (ACD) is a common dermatologic disease. Patch testing remains the criterion standard for diagnosis. In clinical practice, avoidance may be limited by patient occupation or noncompliance, the pervasive nature of the culprit agent, or barriers to expert care because of socioeconomic, cultural, or geographic factors. Thus, ACD is frequently chronic and/or recurrent; however, the comorbidities associated with ACD are not well characterized. OBJECTIVE: The aim of the study is to identify associations between ACD and psychiatric, sleep health, cardiovascular, and infectious conditions. METHODS: In this study, we used a large US claims database to identify comorbidities associated with ACD diagnosed after patch testing, including psychiatric, sleep health, cardiovascular, and infectious conditions. We also stratified these associations by chronicity of disease. RESULTS: We identified associations between ACD and psychiatric, sleep-related, cardiovascular, and infectious comorbidities. We also found that more chronic ACD was associated with more infectious comorbidities. All of these associations remained significant on further subanalysis when patients with AD and venous stasis were excluded. CONCLUSIONS: Allergic contact dermatitis is associated with multiple comorbidities. Further study is required to corroborate these findings, determine causality, and to explore the impact of possible interventions in the workup and management of this common and often debilitating disease.

Post-implantation erythema in 3 patients and a review of reticular telangiectatic erythema.

BACKGROUND: The appearance of erythematous, blanchable patches or plaques overlying an implant suggests possible reticular telangiectatic erythema (RTE). RTE is a benign reactive cutaneous manifestation that can present following the implantation of a cardiac pacemaker, defibrillator or intrathecal infusion pump in an otherwise asymptomatic, non-infectious patient. OBJECTIVE: To demonstrate the variety in clinical presentation of patients presenting with RTE or similar patch test-negative post-implantation erythema. PATIENTS/MATERIALS/METHODS: After institutional board approval had been obtained, patient information was obtained from electronic medical record files, which included surgical reports, pathology reports, and notes from outpatient encounters. RESULTS: We report post-implantation erythema following insertion of an elbow prosthesis, a knee prosthesis, and a spinal cord stimulator, which have not previously been cited as aetiologies of RTE. CONCLUSION: Owing to the delayed onset and variable recovery, RTE remains a diagnostic challenge. RTE should be included in the differential diagnosis of any patient presenting with erythema over the site of a previously implanted device.

Facial Personal Protective Equipment: Materials, Resterilization Methods, and Management of Occupation-Related Dermatoses.

BACKGROUND: The coronavirus infectious disease 2019 pandemic has resulted in health care workers donning personal protective equipment (PPE) for extended periods. OBJECTIVES: The aims of the study were to review facial PPE (surgical masks and N95 respirators) ingredients, to identify facial PPE resterilization techniques, and to recommend strategies for prevention and management of facial PPE-related dermatoses. METHODS: Twenty-one facial PPE (11 N95 respirators, 10 surgical masks) were reviewed. Resterilization techniques were identified. Personal protective equipment-induced occupational dermatoses and management strategies were explored. RESULTS: Polypropylene is the most common chemical identified in facial PPE. Most masks contain aluminum at the nosepiece. Two surgical masks released nickel. Facial PPE dermatoses include irritant contact dermatitis, allergic contact dermatitis, acne, and contact urticaria. Strategies for prevention and management of facial PPE occupational dermatoses are discussed. CONCLUSIONS: There are increasing reports of occupational dermatoses associated with facial PPE. This review discusses the components of facial PPE, mask resterilization methods, and strategies for prevention and management of facial PPE dermatoses.

Low-dose methotrexate enhances aminolevulinate-based photodynamic therapy in skin carcinoma cells in vitro and in vivo.

PURPOSE: To improve treatment efficacy and tumor cell selectivity of delta-aminolevulinic acid (ALA)-based photodynamic therapy (PDT) via pretreatment of cells and tumors with methotrexate to enhance intracellular photosensitizer levels. EXPERIMENTAL DESIGN: Skin carcinoma cells, in vitro and in vivo, served as the model system. Cultured human SCC13 and HEK1 cells, normal keratinocytes, and in vivo skin tumor models were preconditioned with methotrexate for 72 h and then incubated with ALA for 4 h. Changes in protoporphyrin IX (PpIX) levels and cell survival after light exposure were assessed. RESULTS: Methotrexate preconditioning of monolayer cultures preferentially increased intracellular PpIX levels 2- to 4-fold in carcinoma cells versus normal keratinocytes. Photodynamic killing was synergistically enhanced by the combined therapy compared with PDT alone. Methotrexate enhancement of PpIX levels was achieved over a broad methotrexate concentration range (0.0003-1.0 mg/L; 0.6 nmol/L-2 mmol/L). PpIX enhancement correlated with changes in protein expression of key porphyrin pathway enzymes, approximately 4-fold increase in coproporphyrinogen oxidase and stable or slightly decreased expression of ferrochelatase. Differentiation markers (E-cadherin, involucrin, and filaggrin) were also selectively induced by methotrexate in carcinoma cells. In vivo relevance was established by showing that methotrexate preconditioning enhances PpIX accumulation in three models: (a) organotypic cultures of immortalized keratinocytes, (b) chemically induced skin tumors in mice; and (c) human A431 squamous cell tumors implanted subcutaneously in mice. CONCLUSION: Combination therapy using short-term exposure to low-dose methotrexate followed by ALA-PDT should be further investigated as a new combination modality to enhance efficacy and selectivity of PDT for epithelial carcinomas.

Photopatch Testing Among Members of the American Contact Dermatitis Society.

BACKGROUND: Photopatch testing is an important diagnostic tool in evaluating patients with suspected photoallergic contact dermatitis. Although protocols for photopatch testing have been described, there are no consensus recommendations by the American Contact Dermatitis Society (ACDS). OBJECTIVES: The aims of this study were to examine the common practices of photopatch testing among ACDS members and to review and compare commonly used photoallergen series. METHODS: We conducted a questionnaire-based survey among ACDS members via e-mail to inquire about their photopatch test methods. We compared the results with the European consensus methodology and reviewed photoallergen series reported by the respondents. RESULTS: Of the 791 members contacted, 112 members (14%) responded to the survey. Among these, 50 respondents (45%) perform photopatch testing, approximately half of whom (48%) determine minimal erythema dose before the test using UVA with or without UVB irradiation. Respondents use a total of 13 photoallergen series, alone or in any combination, as well as customized series. CONCLUSIONS: These results have potential to aid clinicians in identifying photoallergen series best suited for their patients and suggest a need for consensus recommendations by the ACDS.

Parental E-Cigarette Use and Pediatric Atopic Dermatitis.

This cross-sectional study uses data from the 2014-2018 National Health Interview Survey to assess whether there is an association between parental e-cigarette use and atopic dermatitis in children.

Hypersensitivity reactions associated with endovascular devices.

Allergic reactions to endoprostheses are uncommon and reported in association with orthopaedic, dental, endovascular and other implanted devices. Hypersensitivity reactions to the biomaterials used in endovascular prostheses are among the infrequent reactions that may lead to local or systemic complications following cardiovascular therapeutic interventions. This article reviews potential immunotoxic effects of commonly used biomaterials. Reports of putative hypersensitivity reactions to endovascular devices, including coronary stents, perforated foramen occluders, pacemakers and implantable cardioverter defibrillators are also reviewed.

Association of Intraoperative Antibiotic Irrigation With Systemic Contact Dermatitis.

This case series describes the development of morbilliform drug eruption after breast surgery.