The Psychosocial Impact of Atopic Dermatitis.

Atopic dermatitis is a chronic skin condition that has significant psychosocial and quality-of-life impact. The condition causes physical discomfort, emotional distress, embarrassment, social stigma, and daily activity limitation. In an effort to assess these aspects of disease burden, quality-of-life measurement tools were developed. Through use of these tools, we have expanded our knowledge of the psychosocial and quality-of-life burden of this condition. A variety of quality of assessment tools exist, yet there is no consensus on which tool is best suited to assess the quality-of-life impact of atopic dermatitis. Research studies assessing quality-of-life in atopic dermatitis patients utilize a variety of quality-of-life measurement tools; this complicates comparisons across research studies. Though comparison across studies is difficult, the data echoes tremendous overall burden of disease, especially pertaining to psychosocial status and life quality.

Hidradenitis Suppurativa: Molecular Etiology, Pathophysiology, and Management-A Systematic Review.

Hidradenitis suppurativa is a chronic inflammatory skin condition that affects the hair follicles in areas of the body with apocrine glands. The condition is characterized by recurrent, painful nodules, abscesses, and draining sinuses that can lead to scarring and disfigurement. In this present study, we provide a focused evaluation of recent developments in hidradenitis suppurativa research, including novel therapeutics and promising biomarkers that may facilitate clinical diagnosis and treatment. We conducted a systematic review of controlled trials, randomized controlled trials, meta-analyses, case reports, and Cochrane Review articles in accordance with the PRISMA guidelines. The Cochrane Library, PubMed, EMBASE, and Epistemonikos databases were queried via Title/Abstract screen. Eligibility criteria included the following: (1) has a primary focus on hidradenitis suppurativa, (2) includes measurable outcomes data with robust comparators, (3) details the sample population, (4) English language, and (5) archived as full-text journal articles. A total of 42 eligible articles were selected for review. Qualitative evaluation identified numerous developments in our understanding of the disease's multiple potential etiologies, pathophysiology, and treatment options. It is important for individuals with hidradenitis suppurativa to work closely with a healthcare provider to develop a comprehensive treatment plan that addresses their individual needs and goals. To meet this objective, providers must keep current with developments in the genetic, immunological, microbiological, and environmental factors contributing to the disease's development and progression.

Risk of melanoma and nonmelanoma skin cancer with immunosuppressants, part II: Methotrexate, alkylating agents, biologics, and small molecule inhibitors.

In solid organ transplant recipients, skin cancer risk associated with posttransplant immunosuppression has been well-described, and screening practices generally reflect these risks. In addition to agents used posttransplant, other classes of immunosuppressants also have the potential to raise the risk of nonmelanoma skin cancer (NMSC) or melanoma. In the present manuscript, the evidence for melanoma and NMSC risk associated with methotrexate, cyclophosphamide, biologic cytokine inhibitors including TNF (tumor necrosis factor)-alpha and interleukin inhibitors, costimulation blockers such as abatacept, integrin inhibitors such as natalizumab, targeted B-cell, and T-cell inhibitors including CD20 (cluster of differentiate 20), CD52, and BTK (Bruton's tyrosine kinase) inhibitors, and JAK (Janus kinase) inhibitors is reviewed. Based on the available data, we recommend regular skin cancer screening for select nontransplant patients receiving immunosuppressive regimens that are shown to raise the risk of NMSC or melanoma. We also offer suggestions for conscientious use of these therapies in high-risk patients. Finally, a comprehensive summary of the relative risk associated with each immunosuppressant class and associated recommendations is presented.

Risk of melanoma and nonmelanoma skin cancer with immunosuppressants, part I: Calcineurin inhibitors, thiopurines, IMDH inhibitors, mTOR inhibitors, and corticosteroids.

Immunosuppression is a well-documented risk factor for skin cancer, as exemplified by the 65- to 250-fold higher squamous cell carcinoma risk, 10-fold higher basal cell carcinoma risk, and 0 to 8-fold higher melanoma risk in solid organ transplant recipients (SOTRs) receiving potent, prolonged courses of immunosuppressive therapies. Numerous immune system components have been shown to either suppress or promote tumor growth, and immunosuppressive drugs may have additional effects on proliferative pathways independent of the immune system. Thus, evaluation of the specific regimen by the dermatologist is key for assessing skin cancer risk in each patient. In the present manuscript, the immune-mediated mechanisms of skin cancer development and regression are first reviewed. Next, a synthesis of the evidence shows the differing effects of immunosuppressive agents commonly used in SOTRs on melanoma and nonmelanoma skin cancer risk. These include systemic calcineurin inhibitors, thiopurines, IMDH (inosine monophosphate dehydrogenase) inhibitors, mTOR (mammalian target of rapamycin) inhibitors, and systemic corticosteroids. Finally, recommendations for skin cancer screening in SOTRs are discussed. We further offer recommendations for select nontransplant patients who may benefit from routine skin cancer screening due to risks associated with specific immunosuppressant exposure, and we propose evidence-based strategies for minimizing high-risk immunosuppressant use in clinical practice.

Prolonged Antipruritic Effect of Botulinum Toxin Type A on Cowhage-induced Itch: A Randomized, Single-blind, Placebo-controlled Trial.

Botulinum toxin type A (Botox) is thought to have antipruritic effects through inhibition of pruritic factors, including acetylcholine, substance P, and glutamate. The aim of this randomized, single-blind, placebo-controlled trial was to test the effect of botulinum toxin type A on cowhage, a non-histaminergic model for chronic itch. Botulinum toxin type A was injected into the arm of 35 healthy subjects, with a saline control injected into the contralateral arm. Thermal sensory parameters (warmth and heat thresholds and heat pain intensity) and itch intensity after cowhage application were examined on test areas. Botulinum toxin type A reduced itch intensity, overall perceived itch (area under the curve (AUC); percentage change from baseline), and peak itch intensity compared with the control at 1 week, 1 month, and 3 months. Botulinum toxin type A had no effect on thermal thresholds or heat pain intensity. In conclusion, botulinum toxin type A reduced cowhage itch for at least 3 months, which suggests that botulinum toxin type A is a potential long-lasting treatment for localized, non-histaminergic itch.

INDIVIDUAL ARTICLE: Management of Prurigo Nodularis.

BACKGROUND: Prurigo nodularis (PN) is a chronic disease characterized by intense pruritus and nodular lesions associated with reduced quality of life. Until recently, no US Food and Drug Administration (FDA)-approved therapies have been available for the management of PN. Treatment regimens have been highly variable and clinical management guidelines are lacking overall; formal treatment guidelines do not exist within the US. In 2022, dupilumab became the first FDA-approved medication for PN. Multiple novel agents that target the neuroimmune underpinnings of the disease are currently in development and show promise for this challenging disorder. OBJECTIVE: To review current treatments and emerging therapies for effective management of patients with PN. METHODS: We reviewed publications on PN management identified from PubMed, Embase, Web of Science, and the Cochrane Library. We also included publicly available data on clinical trials for PN therapies reported on the US National Library of Medicine ClinicalTrials.gov, the International Conference on Harmonisation-Good Clinical Practice (ICH-GCP) Database, and the European Clinical Trials (EudraCT) Database. RESULTS: The recommended management of PN begins with an assessment of disease severity, including disease burden and pruritus intensity, and evaluation of comorbid medical disorders. Treatment goals include resolution of itch, improvement in nodules or cutaneous lesions, and improvement in quality of life. Therapies should be selected based on a patient’s clinical presentation and comorbidities. Treatment should simultaneously address the neural and immunologic components of PN. Combination therapy, particularly with conventional agents, may be beneficial. LIMITATIONS: Data on most conventional PN treatments are limited to anecdotal reports, small clinical trials, or expert consensus recommendations. No head-to-head comparative trials have evaluated the relative efficacy of conventional and/or emerging agents, or combination therapy. CONCLUSION: An effective treatment approach for patients with PN should reduce pruritus, allow nodular lesions to heal, and improve individual quality of life. The treatment landscape for PN is rapidly evolving with one FDA-approved agent and several new promising therapies on the horizon. J Drugs Dermatol. 2023;22:12(Suppl 2):s15-22.

Multifactorial causes of chronic itch in diabetes: More than just neuropathy.

BACKGROUND: Chronic pruritus is common in patients with diabetes though its pathophysiology is unknown and difficult to pinpoint given the multi-system manifestations of diabetes. Herein, we aim to evaluate the severity of chronic itch in patients with diabetes and its association with glycaemic control, microvascular complications and quality of life. METHODS: We conducted a retrospective study of 105 adults with diabetes evaluated by a dermatologist at a tertiary care centre in Mexico City. Degree of chronic pruritus and its impact on quality of life as well as laboratory, clinical and demographic data were collected. Patients without chronic pruritus (n = 62) were compared to those with chronic pruritus (n = 43). The latter cohort was further stratified by itch severity, and characteristics of their itch were quantified. RESULTS: Neuropathy and loss of protective sensation were more common in patients with chronic pruritus, compared to those without chronic pruritus (p = 0.007 and p = 0.001, respectively). Anxiety and depression were more common in individuals with chronic pruritus (p = 0.009), and these group reported higher effect of pruritus on their quality of life (p < 0.0001). The most common sites of itch were the head, back and arms. Among patients with chronic itch, increasing itch severity was associated with decreasing eGFR (p = 0.080). CONCLUSIONS: The underlying cause of chronic itch in patients with diabetes is likely multifactorial and owing to microvascular complications such as neuropathy and nephropathy. Better understanding of the causes of itch in these patients can allow for more targeted treatment, leading to improved quality of life.

PRAME immunohistochemistry as an adjunct for diagnosis and histological margin assessment in lentigo maligna.

AIMS: Lentigo maligna (LM), the most common type of melanoma in situ, is a diagnostically challenging lesion for pathologists due to abundant background melanocytic hyperplasia in sun-damaged skin. Currently, no laboratory methods reliably distinguish benign from malignant melanocytes. However, preferentially expressed antigen in melanoma (PRAME) has shown promise in this regard, and could potentially be applied to diagnosis and margin assessment in difficult cases of LM. METHODS AND RESULTS: Ninety-six cases with a diagnosis of LM (n = 77) or no residual LM (n = 19) following initial biopsy were identified and stained with an antibody directed towards PRAME. Immunohistochemistry (IHC) was scored as positive or negative, and measurement of histological margins by PRAME was performed and compared to the measurement of histological margins using conventional methods [haematoxylin and eosin (H&E) and/or sex-determining region Y-box 10 (SOX10) and/or Melan-A]. Of cases with LM, 93.5% (72 of 77) were PRAME+ and 94.7% (18 of 19) of cases with no residual LM were PRAME- . Of the 35 cases with no margin involvement by PRAME or conventional assessment, 14 cases (40.0%) had no difference in measurement, 17 (48.6%) had a difference of 1 mm or less and four (11.4%) differed by between 1 and 3.5 mm. There was a high correlation between margin assessment methods (r = 0.97, P < 0.0001). CONCLUSIONS: PRAME IHC is a sensitive (93.5%) and specific (94.7%) method for diagnosing LM on biopsy and excision, and measurement of histological margins by PRAME shows a high correlation with conventional methods for margin assessment. Furthermore, the nuclear expression of PRAME makes it a good target for use in dual-colour IHC stains.

Extreme winter weather: A force to be remembered in dermatopathology.

It is important for the dermatopathologist to be adept in differentiating tissue artifacts from normal tissue variants and pathologies. Numerous tissue artifacts have been described to date; however, once we are familiar with the common artifacts that appear in our practice, we may not immediately recognize other confounders. For example, dermatopathologists in more temperate regions of the country may not be familiar with freezing artifact. In this case series, we present three common diagnoses in dermatopathology that were obscured by the extreme winter weather that severely impacted the Southern United States in February 2021 and discuss methods to prevent these artifacts.

Guttate leukoderma and acrokeratosis verruciformis of Hopf: a rare combination in Darier disease.

A distinct Darier phenotype presenting with confetti-like hypopigmented macules was first described in 1965. Designated as "guttate leukoderma," this skin finding is a rarely-reported presentation of Darier disease. It has been theorized that the mutation in ATP2A2 causes defective E-cadherin, which in turn disrupts the adhesion of melanocytes to keratinocytes, thus leading to impaired dendrite formation, hindered melanin transfer, and ultimately to melanocyte apoptosis. Herein, we contribute a case of a 56-year old woman who presented with the rarely-described guttate leukoderma of Darier disease and acrokeratosis verruciformis of Hopf.

Intravenous immunoglobulin G use in patients with chronic inflammatory demyelinating polyneuropathy: An uncommon cause of drug-induced discoid lupus erythematosus.

Drug-induced chronic cutaneous lupus erythematosus, or drug-induced discoid lupus erythematosus, is a rare cutaneous phenomenon. Various medications have been associated with drug-induced discoid lupus erythematosus including fluorouracile agents, especially tegafur and uraciltegafur, and TNF-α antagonists such as infliximab or etanercept. Recent literature has described a case series of six patients receiving IgG immunoglobulin for chronic inflammatory demyelinating polyneuropathy with subsequent presentations of discoid lupus erythematosus. We present a patient with chronic inflammatory demyelinating polyneuropathy who developed discoid lupus erythematosus secondary to IgG immunoglobulin.

MicroRNAs in cutaneous melanoma: Role as diagnostic and prognostic biomarkers.

Melanoma is the leading cause of skin cancer deaths in the United States, and its incidence has been rising steadily for the past 30 years (Aftab, Dinger, & Perera, 2014). A more complete understanding of the molecular mechanisms that drive melanomagenesis is crucial to improve diagnosis, prognostication, and treatment of this disease. Given that melanoma survival rates are better when the disease is detected early, precise diagnostic tests for early melanoma detection would be extremely useful. In addition, as survival rates decrease drastically when the disease becomes metastatic, improved tools to more precisely identify high-risk patients as well as to predict treatment response are necessary. The role of microRNAs (miRNAs) in melanoma biology could be the key. miRNA expression profiling has identified several miRNAs that play a crucial role in melanoma cell proliferation, migration, and invasion, as well as miRNAs involved in apoptosis and in the immune response. Here we review the most current data on the miRNAs involved in melanoma as well as their potential roles as diagnostic and prognostic biomarkers of this disease.

The Psychosocial Impact of Atopic Dermatitis.

Atopic dermatitis is a chronic skin condition which has significant psychosocial and quality of life impact. The condition causes physical discomfort, emotional distress, embarrassment, social stigma and daily activity limitation. In an effort to assess these aspects of disease burden, quality of life measurement tools were developed. Through use of these tools, we have expanded our knowledge of the psychosocial and quality of life burden of this condition. A variety of quality of life assessment tools exist, yet there is no consensus on which tool is best suited to assess the quality of life impact of atopic dermatitis. Research studies assessing quality of life in atopic dermatitis patients utilize a variety of quality of life measurement tools; this complicates comparisons across research studies. Though comparison across studies is difficult, the data echoes tremendous overall burden of disease, especially pertaining to psychosocial status and life quality.

Cutaneous metastatic pigmented breast carcinoma.

A 66-year-old woman presented with a 3 cm black, ulcerated nodule located on the skin of the upper abdomen, just below the breast. The lesion was painful to the touch, but the patient reported no other associated symptoms and was otherwise healthy. A 4-mm punch biopsy of the affected skin was obtained and the histological diagnosis was cutaneous metastatic pigmented breast carcinoma.