Rachel Daher

Pemphigus vulgaris (PV) is a chronic autoimmune blistering disease characterized by intraepidermal flaccid blisters of the skin and mucous membranes. Although typically chronic and relapsing, rare fulminant variants have been described. We report a life-threatening case of PV in a previously healthy 55-year-old woman who developed a rapidly progressive, Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)-like phenotype with extensive epidermal detachment and mucocutaneous involvement. Histopathological analysis demonstrated suprabasal acantholysis, and direct immunofluorescence showed intercellular IgG and C3 deposition. Serology revealed markedly elevated anti–Desmoglein-1 (107.5 IU/mL) and modest anti–Desmoglein-3 titers (9.6 IU/mL). The clinical course was complicated by Cytomegalovirus reactivation, while malignancy screening remained negative. Treatment with rituximab and intravenous immunoglobulin led to rapid re-epithelialization and clinical stabilization. This case expands the clinical spectrum of PV and underscores diagnostic and therapeutic challenges posed by fulminant autoimmune blistering disease exhibiting overlapping features. As rat-bladder indirect immunofluorescence and extended plakin serology were not available, a paraneoplastic pemphigus (PNP)-spectrum disorder could not be formally excluded, although the clinical, histological, and serological picture strongly favored PV. We propose that markedly elevated anti-Dsg1 antibodies, complement activation, and CMV reactivation may each have contributed to this severe phenotype.

Pruritus is a common and burdensome symptom in inflammatory, autoimmune, and connective tissue skin diseases, significantly impairing quality of life, sleep, and psychological well-being. Pruritus arises from a complex interplay between skin barrier dysfunction, immune activation, and neuronal sensitization involving cytokines, alarmins, neuropeptides, and sensory pathways. Increasing evidence indicates that both biological sex and gender-related factors influence itch perception, severity, and clinical expression, although these differences remain insufficiently explored. This review provides a comprehensive analysis of current evidence on sex- and gender-related differences in pruritus across dermatological diseases, with particular attention to the neuroimmune mechanisms underlying chronic itch. Available studies suggest that women more frequently report greater itch intensity, enhanced psychological burden, and higher impairment in daily activities and sleep, whereas men may exhibit different clinical and sensory profiles. However, findings remain heterogeneous because of methodological limitations, small cohorts, and the lack of standardized itch assessment tools. In addition to biological determinants, psychosocial and behavioral factors likely contribute to sex- and gender-specific differences in chronic pruritus. Overall, the available evidence highlights the need for more standardized and sex-informed research approaches to improve the understanding and management of pruritus in dermatological diseases.

Dercum’s disease (DD) is a rare chronic disorder characterized by painful subcutaneous lipomas, mostly affecting overweight or obese middle-aged women. The etiology remains unclear, and evidence for medical treatments is limited. Surgical approaches may reduce pain but are associated with frequent relapses and are difficult to implement in extensive clinical pictures. We investigated the outcomes of multiple medical and surgical therapeutic strategies. Particularly, we explored immunomodulators (methotrexate and infliximab), used alone or combined with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) such as semaglutide, as well as the dual GIP (glucose-dependent insulinotropic polypeptide)/GLP-1 RAs tirzepatide. Five patients with DD were included in this retrospective single-center case series. Baseline clinical data, medical history, and longitudinal information on Dermatology Life Quality Index (DLQI), Visual Analogue Scale (VAS) for pain, and body mass index (BMI) were collected from existing medical records and scheduled follow-up visits conducted since 2021. Clinical trajectories differed across patients and regimens. Methotrexate and infliximab coincided with variable and often transient improvements in pain and quality of life. Combination regimens including GLP-1 RAs were accompanied by weight reduction and, in selected patients, by sustained improvements in pain and DLQI. In other cases, the benefit was limited or absent. Adverse events were manageable and consistent with the known safety profiles of these drugs. In this small real-world case series, therapeutic responses in DD were highly individualized, underscoring the absence of standardized medical treatment and the need for patient-tailored strategies. The observed patterns suggest that immunomodulatory and incretin-based therapies may represent exploratory options in selected patients, especially when surgery is not feasible. However, controlled studies are needed to clarify their role.

Dercum’s disease (DD) is a rare condition characterized by intense, asymmetrical, chronic burning pain localized in adipose tissue, often accompanied by subcutaneous fat nodules, leading to a significant reduction in quality of life. It typically affects overweight or obese adults between 35 and 50 years of age, with a marked female predominance. Despite numerous hypotheses proposed over time, the pathophysiology of DD remains poorly understood. Diagnosis is particularly challenging, as it relies solely on clinical evaluation. Given the overlapping features with other conditions, including symptoms, clinical course and inheritance pattern, a differential, accurate, and timely diagnosis is essential for the effective management of DD. Current treatment strategies focus primarily on pain relief, reflecting the still uncomplete understanding of DD etiopathogenesis. This review provides an updated overview of the current knowledge on DD, with particular emphasis on recent advances in pharmacological treatment strategies.

Biologic therapies have revolutionized the treatment of inflammatory skin conditions. Omalizumab is a biologic used for the treatment of asthma and chronic idiopathic urticaria (CIU), while Dupilumab is used for the treatment of Th2 pathway mediated diseases like atopic dermatitis (AD). Patients can present with concurrent immune-mediated conditions requiring the use of dual biologic therapy; however, there is no robust data to support this. We conducted a retrospective review of outpatient charts between January 2018– July 2024 at a large academic center to find patients with concurrent use of Omalizumab and Dupilumab. Diagnoses and indications for treatments, prior therapies, therapy regimen, therapy duration, adverse events, and new medications were recorded. There were 23 patients prescribed dual biologic therapy. The most common indication for omalizumab was CIU (n = 14) while for dupilumab was AD (n = 20). The median duration of dual therapy was 7 months, with a range of 1 to 41 months. The patient with the longest record of dual therapy was 41 months, with no severe adverse events and a robust clinical response. Of the 23 patients, 65% (n = 15) are currently continuing treatment. Of the 8 patients who discontinued therapy, the reasons included adverse events (n = 2), lack of response (n = 2), insurance issues (n = 1), and switch to monotherapy after improvement (n = 2). Most patients treated with dual therapy were able to obtain improvement for both conditions prescribed. This study showed real-world safety and efficacy of combination of Omalizumab and Dupilumab. Limitations of our study include a small sample size, a one-year average follow-up period, and its retrospective nature.