Summary

A Nonrandomized Controlled Trial

[Posted 17/Jan/2023]

AUDIENCE: Dermatology

KEY FINDINGS: These findings suggest that apremilast was a safe and efficacious add-on treatment in recalcitrant dermatomyositis, with an overall response rate of 87.5% and associations with downregulation of multiple inflammatory pathways.

BACKGROUND: Cutaneous disease in dermatomyositis has no standardized treatment approach and so presents a challenging task for patients and clinicians. Purpose of this trial was to study the efficacy and safety of apremilast as an add-on therapy in patients with recalcitrant cutaneous dermatomyositis.

DETAILS: This phase 2a, open-label, single-arm nonrandomized controlled trial was conducted at a single center from June 2018 to June 2021. Participants were 8 patients with recalcitrant cutaneous dermatomyositis, defined by a cutaneous disease activity severity index (CDASI) score greater than 5 despite treatment with steroids, steroid-sparing agents, or both. Data were analyzed from June 2018 to June 2021. The primary outcome was the overall response rate (ORR) at 3 months. Key secondary outcomes were the safety and toxicity of apremilast and the durability of response at 6 months. The CDASI, muscle score, dermatology life quality index (DLQI), and depression assessments were performed at baseline and regularly until month 7. Skin biopsies were performed at baseline and 3 months after apremilast (defined as 3 months into active apremilast therapy) and tested for gene expression profiling and immunohistochemical stains. Adverse events were assessed using the Common Terminology Criteria for Adverse Events version 5.0. Among 8 patients with recalcitrant cutaneous dermatomyositis (all women; mean [SD] age, 54 [15.9] years), a response was found at 3 months after apremilast among 7 patients (ORR, 87.5%). The mean (SD) decrease in CDASI was 12.9 (6.3) points at 3 months (P .001). Apremilast was well tolerated, with no grade 3 or higher adverse events. Sequencing of RNA was performed on skin biopsies taken from 7 patients at baseline and at 3 months after therapy. Appropriate negative (ie, no primary antibody) and positive (ie, tonsil and spleen) controls were stained in parallel with each set of slides studied. Of 39,076 expressed genes, there were 195 whose expression changed 2-fold or more at P < .01 (123 downregulated and 72 upregulated genes). Gene set enrichment analysis identified 13 pathways in which apremilast was associated with downregulated expression, notably signal transducers and activators of transcription 1 (STAT1), STAT3, interleukin 4 (IL-4), IL-6, IL-12, IL-23, interferon γ (IFNy), and tumor necrosis factor α (TNFα) pathways. In immunohistochemical staining, there was a mean (SD) decrease in phosphorylation levels STAT1 (22.3% [28.3%] positive cells) and STAT3 (13.4% [11.6%] positive cells) at the protein level, a downstream signaling pathway for the downregulated cytokines.

Copyright © American Medical Association. All Rights Reserved.

Source: Bitar, C., Ninh, T., Brag, K., et al. (2022). Apremilast in Recalcitrant Cutaneous Dermatomyositis: A Nonrandomized Controlled Trial. JAMA Dermatol. 2022;158(12): 1357-1366. Published: December, 2022. DOI: 0.1001/jamadermatol.2022.3917.

Summary

[Posted 7/Jul/2025]

AUDIENCE: Dermatologists, Gynecologists, Primary Care Physicians, and other healthcare professionals involved in women's health.

KEY FINDINGS:

• Vulvovaginal itching is a common, often under-recognized condition with diverse etiologies, necessitating a comprehensive diagnostic approach.
• Causes span infectious, inflammatory, hormonal, neoplastic, neuropathic, systemic, and genetic factors, often requiring a multidisciplinary assessment.
• Chronic vulvovaginal pruritus significantly impacts patients' physical and emotional quality of life, leading to embarrassment, frustration, and avoidance of care.
• Effective management involves a multimodal strategy, combining lifestyle modifications, topical therapies (e.g., corticosteroids, antifungals, calcineurin inhibitors), systemic treatments (e.g., oral corticosteroids, anticonvulsants, biologics for refractory cases), and non-pharmaceutical interventions.
• There remains a critical need for further research to develop comprehensive, evidence-based guidelines and understand the holistic impact of female-specific pruritus.

BACKGROUND: Vulvovaginal itching is a prevalent yet frequently under-recognized complaint affecting women across all age groups. Despite its commonality, many dermatologists receive limited training in vulvar diseases, contributing to delayed diagnoses and prolonged patient discomfort. Patients often attempt self-treatment with over-the-counter products, which can exacerbate symptoms and complicate accurate diagnosis. The complex nature of vulvovaginal pruritus often demands a multidisciplinary approach for effective diagnosis and treatment, highlighting the need for improved understanding and management strategies.

DETAILS:

Pathophysiology Vulvovaginal itching can arise from various mechanisms, including compromised skin barrier integrity, elevated skin pH activating proteases, and hormonal fluctuations impacting epithelial health and microflora. Psychogenic factors can also initiate or aggravate itch through an itch-scratch cycle.

Causes

• Infectious Common acute causes include fungal (e.g., *Candida albicans*), bacterial (e.g., bacterial vaginosis, Group A β-hemolytic streptococcus), parasitic (e.g., trichomoniasis, pinworms, scabies, pubic lice), and viral infections (e.g., HSV, HPV).
• Inflammatory Dermatological conditions like atopic dermatitis, irritant/allergic contact dermatitis (from hygiene products, fabrics), psoriasis, lichen simplex chronicus, lichen sclerosus, and lichen planus are frequent culprits.
• Neoplastic Though rare, vulvar malignancies (e.g., squamous cell carcinoma, melanoma, extramammary Paget's disease) can present with persistent itching, often as an early symptom. Benign tumors like syringomas can also be pruritic.
• Neuropathic Damage or dysfunction of nerve fibers in the vulvar region (e.g., from burns, scars, radiation, spinal nerve compression, small fiber polyneuropathy, vulvodynia) can lead to abnormal, often intense, sensory experiences.
• Systemic Conditions like diabetes (predisposing to infection and neurogenic itch), HIV, hepatic, and renal diseases can cause generalized or localized vulvar pruritus due to circulating pruritogens or altered immune responses.
• Genetic Rare genodermatoses such as Darier disease and Hailey-Hailey disease can cause itchy lesions in the vulvovaginal area. Genetic predispositions may also increase susceptibility to conditions like atopic dermatitis or recurrent candidiasis.

Evaluation A thorough history (onset, duration, severity, timing, aggravating/relieving factors, environmental exposures, hygiene, sexual history, medications, medical history) and physical examination are crucial. This includes inspecting the vulvovaginal area for lesions, discharge, and tissue changes. Diagnostic tools may include wet mount microscopy, STI testing, pH testing, vulvoscopy, and biopsy for persistent or suspicious lesions.

Treatment Strategies

• Lifestyle & Environment Wearing breathable cotton underwear, avoiding irritants (scented products, harsh soaps), gentle hygiene, proper toilet habits, and addressing psychological factors (stress, anxiety) are fundamental.
• Topical Therapies Corticosteroids (mid- to high-potency for acute inflammation, lower for maintenance), calcineurin inhibitors (tacrolimus, pimecrolimus) for chronic management, local estrogen for atrophy, antifungals for fungal infections, lactic acid products for pH balance, emollients for barrier support, and topical anesthetics (lidocaine, pramoxine) for symptomatic relief, especially in neuropathic itch. Novel topical agents like tofacitinib are emerging for inflammatory conditions.
• Systemic Treatments Oral corticosteroids for severe inflammation, anticonvulsants (gabapentin, pregabalin) and antidepressants (TCAs, SSRIs, SNRIs) for neuropathic/psychogenic itch, opiate receptor antagonists (naltrexone) for some cases, and systemic immunotherapies (methotrexate, mycophenolate mofetil) for refractory inflammatory conditions. Biologics (ixekizumab, dupilumab, tralokinumab) show promise for specific inflammatory and autoimmune causes. Antibiotics are used for bacterial infections.
• Non-pharmaceutical Sitz baths, cold compresses, Transcutaneous Electrical Nerve Stimulation (TENS), acupuncture, and physical therapy can offer symptomatic relief.

Copyright © [Your Name/Institution, if applicable]. All rights reserved.

Source: Mashoudy, K. D., Tomlinson, A.F., Kim, S. et al. Scratching the Surface: A Comprehensive Guide to Understanding and Managing Vulvovaginal Itching. Am J Clin Dermatol. 26: 361-378 (2025); Published: March 25, 2025. DOI: 10.1007/s40257-025-00939-7.

Summary

Results From an Observational Cross-Sectional Multicenter European Study in 17 Countries

[Posted 22/Apr/2025]

AUDIENCE: Dermatology, Family Medicine

KEY FINDINGS: CPG patients have high levels of perceived stress, perceived stigmatization and body dysmorphic, which are partly related to sociodemographic factors like younger age or lower income as well as to other psychological and disease-related factors.

BACKGROUND: Anxiety, depression and suicidal ideation are frequent in patients with chronic prurigo (CPG). Purpose of the study is to analyze perceived stress, stigmatization, body dysmorphia, anxiety, depression and itch-related quality of life in CPG patients and compare them to controls, and then to identify variables/predictors of them. This study is part of a cross-sectional multicenter study in 17 European countries including 5487 consecutive patients and 2808 controls. CPG patients were older than controls and had significantly more comorbidities. However, multivariate analysis allowed controlling for these differences by including them as a covariate.

DETAILS: One hundred twenty-seven individuals with prurigo were included in the analyses. They reported higher levels of stress, stigmatization, and body dysmorphia than controls. In the patient group, stigmatization was associated with higher stress and having a severe disease, stress with younger age and lower income, depression and anxiety with lower income and higher itch intensity, body dysmorphia with younger age, and dissatisfaction with appearance.

Copyright © Published by Elsevier Inc. on behalf of the American Academy of Dermatology, Inc. All rights reserved.

Source: Ficheux, A., Brenaut, E., Schut, C., et al. (20245). Predictors of Perceived Stress, Perceived Stigmatization, and Body Dysmorphia in Patients With Chronic Prurigo/Prurigo Nodularis: Results From an Observational Cross-Sectional Multicenter European Study in 17 Countries. Journal of the American Academy of Dermatology. 2025; 92(5): 1056-1063. Published: May, 2025. DOI: 10.1016/j.jaad.2024.12.043.

Summary

Results From a Phase 2b Extension Study

[Posted 8/Apr/2025]

AUDIENCE: Dermatology, Family Medicine

KEY FINDINGS: Ritlecitinib alone and with nbUVB therapy improved facial and total body repigmentation and was well tolerated. Adding nbUVB may improve ritlecitinib efficacy.

BACKGROUND: Purpose of this study is to evaluate the efficacy and tolerability of ritlecitinib with add-on narrow-band ultraviolet B (nbUVB) phototherapy in patients with nonsegmental vitiligo.

DETAILS: Following a 24-week, placebo-controlled, dose-ranging period, patients received ritlecitinib 200 mg for 4 weeks then 50 mg for 20 weeks, with or without nbUVB phototherapy 2x/week. Missing data were handled using last observation carried forward and observed case (OC). Forty-three patients received ritlecitinib + nbUVB and 187 received ritlecitinib-monotherapy. Nine patients receiving ritlecitinib + nbUVB discontinued due to nbUVB group-specific efficacy criteria requiring >10% improvement in % change from baseline (% change from baseline) in Total-Vitiligo Area Scoring Index at week 12. At week 24, mean % change from baseline in Facial-VASI score was -57.0 vs -51.5 (last observation carried forward; P = .158) and -69.6 vs -55.1 (OC; P = .009), for ritlecitinib + nbUVB vs ritlecitinib-monotherapy, respectively. Mean % change from baseline in Total-Vitiligo Area Scoring Index at week 24 was -29.4 vs -21.2 (last observation carried forward; P = .043) and -46.8 vs -24.5 (OC; P < .001), respectively. nbUVB addition to ritlecitinib was well tolerated with no new safety signals.

Copyright © American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Source: Yamaguchi, Y., Peeva, E., Adiri, R., et al. (2025). Response to Ritlecitinib With or Without Narrow-Band Ultraviolet B Add-On Therapy in Patients With Active Nonsegmental Vitiligo: Results From a Phase 2b Extension Study. Journal of the American Academy of Dermatology. 2025; 92(4): 781-789. Published: April, 2025. DOI: 10.1016/j.jaad.2024.11.064.

Summary

16-Week Results of a Randomized Clinical Trial

[Posted 18/Sep/2024]

AUDIENCE: Dermatology, Family Medicine

KEY FINDINGS: Brodalumab SC 210 mg Q2W demonstrated efficacy in Japanese PPP patients. The most common TEAEs were mild infectious events.

BACKGROUND: Palmoplantar pustulosis (PPP), a refractory skin disease characterized by repeated eruptions of sterile pustules and vesicles on palms and/or soles, involves interleukin-17 pathway activation. Brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, is being investigated for use in PPP treatment. The aim was to assess the efficacy and safety of brodalumab in Japanese PPP patients with moderate or severe pustules/vesicles.

DETAILS: A phase 3, randomized, double-blind, placebo-controlled trial was conducted between July 2019 and August 2022, at 41 centers in Japan. Patients aged 18-70 years with a diagnosis of PPP for >= 24 weeks, a PPP Area Severity Index (PPPASI) score of >= 12, a PPPASI subscore of pustules/vesicles of >= 2, and inadequate response to therapy were included. Participants were randomized 1:1 to receive brodalumab 210 mg or placebo, subcutaneously (SC) at baseline, weeks 1 and 2, and every 2 weeks (Q2W) thereafter until week 16. Changes from baseline to week 16 in the PPPASI total score (primary endpoint) and other secondary skin-related endpoints and safety endpoints were assessed. Of the 126 randomized patients, 50 of 63 in the brodalumab group and 62 of 63 in the placebo group completed the 16-week period. Reasons for discontinuation were adverse event (n = 6), withdrawal by patient/parent/guardian (n = 3), progressive disease (n = 3), and lost to follow-up (n = 1) in the brodalumab group and Good Clinical Practice deviation (n = 1) in the placebo group. Change from baseline in the PPPASI total score at week 16 was significantly higher (p = 0.0049) with brodalumab (least-squares mean [95% confidence interval {CI}] 13.73 [10.91-16.56]) versus placebo (8.45 [5.76-11.13]; difference [95% CI] 5.29 [1.64-8.94]). At week 16, brodalumab showed a trend of rapid improvement versus placebo for PPPASI-50/75/90 response (>= 50%/75%/90% improvement from baseline) and Physician’s Global Assessment 0/1 score: 54% versus 24.2%, 36.0% versus 8.1%, 16.0% versus 0.0%, and 32.0% versus 9.7%, respectively. Infection was the dominant treatment-emergent adverse event (TEAE); the commonly reported TEAEs were otitis externa (25.4%/1.6%), folliculitis (15.9%/3.2%), nasopharyngitis (14.3%/4.8%), and eczema (14.3%/12.9%) in the brodalumab/placebo groups, respectively. The severity of most TEAEs reported was Grade 1 or 2 and less frequently Grade >= 3.

Copyright © Springer Nature. All rights reserved.

Source: Okubo, Y., Kobayashi, S., Murakami, M., et al. (2024). Efficacy and Safety of Brodalumab, an Anti-interleukin-17 Receptor A Monoclonal Antibody, for Palmoplantar Pustulosis: 16-Week Results of a Randomized Clinical Trial. Am J Clin Dermatol. 2024; 25(5): 837-847. Published: September, 2024. DOI: 10.1007/s40257-024-00876-x.

Summary

A Critical Examination of Existing Knowledge

[Posted 29/Aug/2024]

AUDIENCE: Dermatology, Family Medicine

KEY FINDINGS: This review highlights the need for additional research because of the lack of standardized reporting of clinical effects in the studies under scrutiny. A deeper exploration of the pathophysiology focusing on dietary modifications and their potential associations with HS severity is essential. Furthermore, it is crucial to recognize that patients' willingness to experiment with new diets makes them vulnerable to fraudulent interventions, highlighting the importance of evidence-based dietary guidance.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic condition that can overwhelm patients, and the effectiveness of supplementary dietary treatments remains uncertain. The primary aim of this review is to explore the connection between diet and HS progression. However, it is imperative to note that the evidence supporting a substantial role of the diet in HS remains weak. Dietary alterations alone should not be considered independent solutions for managing HS.

DETAILS: Medical therapy continues to be indispensable for adequate treatment. Research indicates that the Mediterranean lifestyle and diet may provide cost-effective and beneficial adjustments when combined with traditional therapies. Conversely, foods with a high glycemic index and dairy could worsen HS symptoms, conceivably through mechanisms linked to insulin resistance and inflammation. Zinc, known for its antioxidant properties, shows promise as an adjunct therapy. Moreover, evidence suggests a connection between vitamin D deficiency and HS severity, although the findings are inconclusive. Brewer's yeast-free diet, B12 supplementation, intermittent fasting, and reducing the intake of refined sugar and dairy merit further investigation.

Copyright © John Wiley & Sons Ltd. All rights reserved.

Source: Vural, S., Baskurt, D., Yildirici, S., et al. (2024). Evaluating Dietary Considerations in Hidradenitis Suppurativa: A Critical Examination of Existing Knowledge. International Journal of Dermatology. 2024; 63(8): 987-998. Published: July, 2024. DOI: XX10.1111/ijd.17101XX.