Long-Term Drug Survival and Effectiveness of Secukinumab in Patients with Moderate to Severe Chronic Plaque Psoriasis: 42-Month Results from the SUPREME 2.0 Study.

Purpose: SUPREME, a phase IIIb study conducted in Italy, demonstrated safety and high efficacy of secukinumab for up to 72 weeks in patients with moderate-to-severe plaque-type psoriasis. SUPREME 2.0 study aimed to provide real-world data on the long-term drug survival and effectiveness of secukinumab beyond 72 weeks. Patients and Methods: SUPREME 2.0 is a retrospective observational chart review study conducted in patients previously enrolled in SUPREME study. After the end of the SUPREME study, eligible patients continued treatment as per clinical practice, and their effectiveness and drug survival data were retrieved from medical charts. Results: Of the 415 patients enrolled in the SUPREME study, 297 were included in SUPREME 2.0; of which, 210 (70.7%) continued secukinumab treatment throughout the 42-month observation period. Patients in the biologic-naïve cohort had higher drug survival than those in the biologic-experienced cohort (74.9% vs 61.7%), while HLA-Cw6-positive and HLA-Cw6-negative patients showed similar drug survival (69.3% and 71.9%). After 42 months, Psoriasis Area and Severity Index (PASI) 90 was achieved by 79.6% of patients overall; with a similar proportion of biologic-naïve and biologic-experienced patients achieving PASI90 (79.8% and 79.1%). The mean absolute PASI score reduced from 21.94 to 1.38 in the overall population, 21.90 to 1.24 in biologic-naïve and 22.03 to 1.77 in biologic-experienced patients after 42 months. The decrease in the absolute PASI score was comparable between HLA-Cw6-positive and HLA-Cw6-negative patients. The baseline Dermatology Life Quality Index scores also decreased in the overall patients (10.5 to 2.32) and across all study sub-groups after 42 months. Safety was consistent with the known profile of secukinumab, with no new findings. Conclusion: In this real-world cohort study, secukinumab showed consistently high long-term drug survival and effectiveness with a favourable safety profile.

Autoimmune bullous dermatoses in cancer patients treated by immunotherapy: a literature review and Italian multicentric experience.

Cutaneous immune-related adverse events are frequently associated with immune checkpoint inhibitors (ICIs) administration in cancer patients. In fact, these monoclonal antibodies bind the cytotoxic T-lymphocyte antigen-4 and programmed cell death-1/ligand 1 leading to a non-specific activation of the immune system against both tumoral cells and self-antigens. The skin is the most frequently affected organ system appearing involved especially by inflammatory manifestations such as maculopapular, lichenoid, psoriatic, and eczematous eruptions. Although less common, ICI-induced autoimmune blistering diseases have also been reported, with an estimated overall incidence of less than 5%. Bullous pemphigoid-like eruption is the predominant phenotype, while lichen planus pemphigoides, pemphigus vulgaris, and mucous membrane pemphigoid have been described anecdotally. Overall, they have a wide range of clinical presentations and often overlap with each other leading to a delayed diagnosis. Achieving adequate control of skin toxicity in these cases often requires immunosuppressive systemic therapies and/or interruption of ICI treatment, presenting a therapeutic challenge in the context of cancer management. In this study, we present a case series from Italy based on a multicenter, retrospective, observational study, which included 45 patients treated with ICIs who developed ICI-induced bullous pemphigoid. In addition, we performed a comprehensive review to identify the cases reported in the literature on ICI-induced autoimmune bullous diseases. Several theories seeking their underlying pathogenesis have been reported and this work aims to better understand what is known so far on this issue.

Clinical Challenges in Primary Erythromelalgia: a Real-Life Experience from a Single Center and a Diagnostic-Therapeutic Flow-Chart Proposal.

INTRODUCTION: Primary erythromelalgia (EM) is a rare clinical syndrome characterized by recurrent erythema, burning pain and warmth of the extremities. The symptoms greatly compromise the patients' quality of life leading to severe disability. SCN9A mutations can be the cause of the disease. Dermatologists are often the specialists these patients turn to for assistance. OBJECTIVES: To describe the demographic and clinical characteristics of patients with primary EM, to assess the presence and mutation types in the SCN9A gene, to evaluate the effectiveness of several therapeutic approaches, and to propose a diagnostic algorithm with therapeutic implications. METHODS: A monocentric retrospective study using the database of patients with a discharge diagnosis of primary EM of our Center. Demographic, clinical, instrumental and laboratory data of patients were reviewed. RESULTS: Eleven female patients (age range 16 to 57) were selected. All patients were affected in both the lower and upper extremities. Follow-up ranged from 2 to 9 years. Four patients had four different heterozygous variants of the SCN9A gene. Two patients, although genetically negative, had a suggestive family history. A variety of medications were tried in all our patients to alleviate symptoms, but their efficacy was variable, partial and/or transitory. The most effective therapies were antihistamines, venlafaxine, and mexiletine. CONCLUSIONS: The diagnosis and treatment of EM remain challenging. Patients with this condition display a wide spectrum of clinical manifestations and severity, as well as a paucity of resources and structures to support them. Mutations in the SCN9A gene are not always detected.

Eosinophilic dermatosis of hematologic malignancy in patients with chronic lymphocytic leukemia/non-Hodgkin's B lymphoma: a single center prospective clinico-pathological study.

Background: The pathogenesis of eosinophilic dermatosis of hematologic malignancy (EDHM) is poorly understood. Previously thought to be a hypersensitivity reaction to insect bites, immune dysregulation and cytokine imbalance are now thought to be responsible. Its prognostic significance is unclear. Objective: To describe the clinical, pathological and immunological findings in a series of oncohematological patients with EDHM. Methods: An observational prospective cohort study of oncohematological patients receiving a diagnosis of EDHM between April 2017 and December 2018. Results: A total of 15 patients with EDHM (10 females and 5 males) were identified among 422 oncohematological patients. Disease presentation varied from firm erythematous papules to more polymorphic presentations. The lesions were most prevalent on the exposed sites, 8/15 patients recalled an insect bite. Lesion seasonality was reported in 13/15 patients. IgE levels were elevated in six patients, circulating IL-4 and IL-5 were within a normal range. Twelve out of 15 patients developed skin manifestations after chemotherapy. The infiltrate could be eosinophil-rich or lymphocytic-rich. Interestingly, the histopathologic findings were in accordance with arthropod bites. Conclusion: A role for insect bites in EDHM is supported by our findings. EDHM may be related to aggressive hematologic disease.

Atypical exanthem with acral involvement in adult patients associated with human herpesvirus 7 active replication: A case series.

An "atypical exanthem" (AE) is an eruptive skin eruption that differs in morphology and etiology from classical exanthems and is often a reason for urgent medical evaluation. The most frequent cause of AEs is a viral infection, but an accurate etiology cannot be established basing on the sole clinical features. Human herpesviruses (HHV) have been often suspected as etiologic agents or cofactors in atypical rashes. We performed a retrospective analysis of adult patients presenting an atypical exanthem associated with HHV-7 active replication in our center. The charts of patients were reviewed and the demographic, clinical and laboratory data collected. Nine patients (six males and three females) were included in the study, with a mean age of 43 years for men and of 26 years for women. All patients presented active HHV-7 replication in plasma during the rash, which turned negative after the exanthem resolved. The exanthem displayed a maculopapular pattern involving the trunk, limbs and, notably, the acral regions, in six patients. In three cases the exanthem was confined to only the acral sites. In most cases, there was no fever and the inflammatory indices remained unchanged. Antihistamines, topical and systemic corticosteroids were used as treatment, with excellent symptom control. We propose adding skin manifestation associated with HHV-7 to the concept of atypical exanthems, in particular those localized to the acral regions.

A monolateral pigmented lesion of the nipple.

Pigmented mammary Paget's disease is a very rare variant of mammary Paget's disease linked to an underlying carcinoma in almost all cases. We present the case of a 62-year-old female patient who came to our attention for the evaluation of a monolateral asymptomatic pigmented lesion of the right nipple, which turned out to be a pigmented mammary Paget's disease unassociated to an underlying malignancy - an extremely rare entity only anecdotally reported in literature. The two main peculiarities of our patient's lesion, the importance of immunohistochemistry in the differential diagnosis and the theories on its pathogenesis are discussed. Further studies are necessary to establish the best treatment options. Click here for the corresponding questions to this CME article.

Omalizumab as a corticosteroid-sparing agent in the treatment of bullous pemphigoid.

Bullous pemphigoid (BP) is the most common autoimmune blistering skin disease, characterized by the development of autoantibodies against hemidesmosomal components BP180 and BP230. The mainstay of therapy is topical and systemic corticosteroids (CS) and immunosuppressors. As this pathology mainly involves the elderly, subjects often have numerous comorbidities that influence the clinical management. Omalizumab is a recombinant humanized monoclonal anti-IgE antibody which has recently emerged as a promising treatment for BP in patients for whom CS are contraindicated or conventional treatments have failed to control the disease. For this study, we selected five patients who presented with corticosteroid-dependent BP with a contraindication to the use of other immunosuppressive treatments. The objectives of our study were to evaluate the effectiveness of omalizumab in controlling BP and allowing to decrease the dosage of systemic CS, assessing the effects of omalizumab on the clinical manifestations and the titers of circulating anti-BP180 and BP230 antibodies, IgE and eosinophils. A reduction in the dose of systemic CS was possible in 100% of the patients and complete resolution of the clinical picture was seen in 100% for skin lesions and in 40% for pruritus. A reduction of circulating IgE was found in 40%, anti-BP180 and BP230 IgGs were decreased in 60% and eosinophils in 80%.

Anti-laminin 332 antibody detection using biochip immunofluorescence microscopy in a real-life cohort of Italian patients with mucous membrane pemphigoid

Background: Mucous membrane pemphigoid (MMP) with anti-laminin 332 autoantibodies may be associated with malignancies, however, current serological assays have considerable limitations. At present, no commercial test for anti-laminin 332 antibodies is available, restricting the diagnosis to specialized laboratories worldwide. Biochip immunofluorescence microscopy has shown promising results in selected cohorts of laminin 332-MMP patients. Objectives: To detect anti-laminin 332 antibodies by biochip immunofluorescence microscopy in a real-life cohort of MMP patients and compare the results with those from traditional immunoblotting. Materials & Methods: Sera were obtained from 31 patients with MMP, 28 with bullous pemphigoid, five with pemphigus vulgaris, five with paraneoplastic pemphigus, five with linear IgA bullous dermatosis, and 10 controls, and analysed by biochip immunofluorescence using human cells expressing laminin 332. Immunoblotting was performed using purified laminin 332. Results: MMP involved the oral mucosa in 65%, ocular mucosa in 9%, oral and ocular mucosae extensively in 13% as well as other mucosae in 13% of patients. Concomitant cutaneous involvement was reported in 35% of patients. Three MMP patients had an underlying malignancy. Anti-laminin 332 antibodies were detected in 2/31 (6%) cases by both methods. Based on immunoblotting, both laminin 332-positive sera reacted with α3 chain (in one case also with ß3 chain). Both patients with anti-laminin 332 antibodies had extensive mucosal involvement and only one had cancer. Anti-laminin 332 antibodies were not detected in control groups. Conclusion: Biochip immunofluorescence is an appropriate technique to detect anti-laminin 332 antibodies which should be tested in patients with MMP.

Erosive Pustular Dermatosis of the Scalp: A Clinicopathologic Study of Fifty Cases.

Erosive pustular dermatosis of the scalp (EPDS) is an uncommon, pustular, idiopathic disorder typically occurring on the scalp of the elderly, whose diagnosis requires close clinicopathologic correlations. Recently, the primary histopathologic characteristic of EPDS has been identified in some biopsies from hair-bearing scalp lesions as a sterile, vesiculo-pustule involving the infundibulum of hair follicles. To further delineate the clinicopathologic spectrum of the disease, we led a retrospective study of 50 patients (36 males and 14 females) with a diagnosis of EPDS between 2011 and 2021, reviewing clinical and histopathological data. Androgenetic alopecia was present in 32 patients. Triggering factors were present in 21 patients. The vertex was the most common location; one patient also had leg involvement. Two cases were familial. Disease presentation varied markedly from tiny, erosive, scaly lesions to crusted and hemorrhagic plaques, mimicking pustular pyoderma gangrenosum (PPG). Biopsies of patients with severe androgenetic or total baldness produced specimens showing nonspecific pathologic changes (39/50), while in 11 patients with a hair-bearing scalp histopathologic examination, changes were specific. The clinicopathologic similarities between EPDS and PPG suggest that EPDS should be included in the spectrum of autoinflammatory dermatoses. Clinicians could consider the possibility of associated disorders rather than managing EPDS as a sui generis skin disorder.