Hydroxychloroquine-induced generalized myopathy in a patient with lupus tumidus: a case report.

A subtype of cutaneous lupus erythematosus known as lupus erythematosus tumidus (LET) is characterized by sun-exposed areas that typically display urticaria-like papules and plaques. For LET, systemic therapy with antimalarials - particularly hydroxychloroquine (HCQ) - is the first line of treatment. Even though the safety profile of these medications appears to be high, there have been very few reports of side effects in the literature, including hemolytic anemia, retinal toxicity, maculopapular rash, gastrointestinal disturbance, and blue-gray discoloration of the skin or mucous membranes. Here, we report a unique instance of a 46-year-old LET smoker who, following HCQ treatment, developed a generalized myopathy.

Environmental factors in autoimmune bullous diseases with a focus on seasonality: new insights.

Autoimmune bullous diseases are a heterogeneous group of rare conditions clinically characterized by the presence of blisters and/or erosions on the skin and the mucous membranes. Practically, they can be divided into two large groups: the pemphigoid group and the pemphigus group, depending on the depth of the autoimmune process on the skin. A family history of autoimmune diseases can often be found, demonstrating that genetic predisposition is crucial for their development. Moreover, numerous environmental risk factors, such as solar radiation, drugs, and infections, are known. This study aimed to evaluate how seasonality can affect the trend of bullous pemphigoid and pemphigus vulgaris, especially considering the number of hospitalizations recorded over the course of individual months. The total number of hospitalizations in the twelve months of the year was evaluated. Moreover, blood chemistry assay and, for some patients, enzyme-linked immunosorbent assay were executed to evaluate antibodies. Regarding the severity of the disease, the bullous pemphigoid area index and the pemphigus disease area index score systems were used. Results showed a complex interplay between environmental factors such as seasons and autoimmune conditions.

Case Report: Resolution of Lichen Planus Pemphigoides as an unexpected outcome of SARS-CoV-2 infection.

It is well known that viral infections play a relevant role in inducing or protecting from autoimmune diseases, thus representing a major environmental factor in the disruption of the immune system in genetically susceptible individuals. Since the beginning of the Covid-19 pandemic a great number of clinical and epidemiological studies have demonstrated that SARS-CoV-2 infection is no exception to the rule by interfering on many different levels in the normal functioning of our immune system. Even though a growing number of case series and case reports has been cited in the literature linking the infection to the new onset of autoimmune diseases, to date very little has been reported concerning a possible correlation between the virus and the clinical resolution of any kind of autoimmune pathology. Here we describe an interesting case of abrupt and unexpected resolution of Lichen planus pemphigoides mucocutaneous lesions in a fully vaccinated patient after a mildly symptomatic SARS-CoV-2 respiratory infection and we speculate on the possible underlying mechanisms correlating the two events.

Skin gluten-related disorders: new and old cutaneous manifestations to be considered.

The term gluten-related disorders (GRD) refer to a spectrum of different clinical manifestations triggered by the ingestion of gluten in genetically susceptible individuals, including coeliac disease (CD), wheat allergy and non-celiac gluten sensitivity (NCGS). GRD are characterized by a large variety of clinical presentations with both intestinal and extra-intestinal manifestations. The latter may affect almost every organ of the body, including the skin. Besides the well-known association between CD and dermatitis herpetiformis, considered as the cutaneous specific manifestation of CD, many other muco-cutaneous disorders have been associated to GRD. In this review, we analyzed the main features of dermatological diseases with a proven association with GRD and those that improve after a gluten-free diet, focusing on the newly described cutaneous manifestations associated with NCGS. Our main hypothesis is that a "cutaneous-gluten sensitivity," as specific cutaneous manifestation of NCGS, may exist and could represent a diagnostic marker of NCGS.

S2k guidelines on the management of paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome initiated by the European Academy of Dermatology and Venereology (EADV).

BACKGROUND: Paraneoplastic pemphigus (PNP), also called paraneoplastic autoimmune multiorgan syndrome (PAMS), is a rare autoimmune disease with mucocutaneous and multi-organ involvement. PNP/PAMS is typically associated with lymphoproliferative or haematological malignancies, and less frequently with solid malignancies. The mortality rate of PNP/PAMS is elevated owing to the increased risk of severe infections and disease-associated complications, such as bronchiolitis obliterans. OBJECTIVES: These guidelines summarize evidence-based and expert-based recommendations (S2k level) for the clinical characterization, diagnosis and management of PNP/PAMS. They have been initiated by the Task Force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology with the contribution of physicians from all relevant disciplines. The degree of consent among all task force members was included. RESULTS: Chronic severe mucositis and polymorphic skin lesions are clue clinical characteristics of PNP/PAMS. A complete assessment of the patient with suspected PNP/PAMS, requiring histopathological study and immunopathological investigations, including direct and indirect immunofluorescence, ELISA and, where available, immunoblotting/immunoprecipitation, is recommended to achieve a diagnosis of PNP/PAMS. Detection of anti-envoplakin antibodies and/or circulating antibodies binding to the rat bladder epithelium at indirect immunofluorescence is the most specific tool for the diagnosis of PNP/PAMS in a patient with compatible clinical and anamnestic features. Treatment of PNP/PAMS is highly challenging. Systemic steroids up to 1.5 mg/kg/day are recommended as first-line option. Rituximab is also recommended in patients with PNP/PAMS secondary to lymphoproliferative conditions but might also be considered in cases of PNP/PAMS associated with solid tumours. A multidisciplinary approach involving pneumologists, ophthalmologists and onco-haematologists is recommended for optimal management of the patients. CONCLUSIONS: These are the first European guidelines for the diagnosis and management of PNP/PAMS. Diagnostic criteria and therapeutic recommendations will require further validation by prospective studies.

Skin IL-17A and IFN-γ Production Correlate with Disease Severity in Patients with Psoriasis and Streptococcal Infection.

Psoriasis is a multisystemic inflammatory disorder mainly involving the skin and joints, whose etiopathogenesis is still not completely understood. An association with streptococcal throat infection has been suggested. We aim to investigate a correlation between IL-17A and IFN-γ production by T cells infiltrating skin lesions and PASI in 313 patients with psoriasis, compared with that in 252 healthy controls. The phenotype of ß-hemolytic Streptococci-specific infiltrating T cells in skin lesions was evaluated and characterized for IFN-γ, IL-4, and IL-17A production. In addition, PBMCs were tested by ELISpot for IFN-γ and IL-17A after streptococcal antigen exposure. A total of 64 of 313 (20.4%) patients with psoriasis had throat streptococcal infection. Of the 3,868 skin-derived T-cell clones from psoriasis with streptococcal infection, 66% proliferated in response to ß-hemolytic Streptococci antigens. Most ß-hemolytic Streptococci-specific T cells displayed T helper 17 and T helper 1 phenotypes. The levels of IFN-γ and IL-17A secreted by skin-infiltrating T cells of patients with psoriasis significantly correlated with PASI score. In ß-hemolytic Streptococci-positive patients, IFN-γ and IL-17A production by peripheral blood T cells after stimulation with streptococcal antigens was quantified by ELISpot. The results obtained may suggest ELISpot as a useful diagnostic tool to identify patients with psoriasis that may deserve antibiotic treatment.

Five cases of new-onset pemphigus following vaccinations against coronavirus disease 2019.

Pemphigus is a group of blistering disorders characterized by the formation of intraepithelial blisters in skin and mucous membranes induced by the binding of circulating autoantibodies to intercellular adhesion molecules. The pathogenesis is complex and not fully understood; however, genetic predisposition and various triggers are widely accepted as key factors in pemphigus development. A few cases of new-onset pemphigus following coronavirus disease 2019 (COVID-19) vaccination have already been published. The present paper reports a total of two cases of pemphigus foliaceous and three cases of pemphigus vulgaris that occurred following vaccinations against COVID-19, with anamnestic, clinical, and diagnostic data collection suggesting assumptions over a possible causal correlation.

Cutaneous vasculitis: Lessons from COVID-19 and COVID-19 vaccination.

Cutaneous vasculitis (CV) is an inflammatory skin-limited vascular disease affecting the dermal and/or hypodermal vessel wall. From the pathogenetic point of view, idiopathic forms are described as well as the induction from various triggers, such as drugs, infections, and vaccines. Following SARS-CoV-2 pandemic outbreak, cases of CV induced by both COVID-19 and COVID-19 vaccinations have been reported in literature. The aim of our work was to collect multiple cases available in the literature and analyze the frequency of the different forms of induced vasculitis, as well as their histological and immunopathological features. Although rare, CV induced by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and vaccines may provide interesting insights into the pathogenesis of these inflammatory processes that may in the future be useful to understand the mechanisms underlying cutaneous and systemic vasculitis.

Multicentric Reticulohistiocytosis Associated with an Early Form of Systemic Lupus Erythematosus: A Case Report of a Rare Disease, with Mini Review of the Literature.

Multicentric reticulohistiocytosis (MRH) is the most frequently described form of reticulohistiocytosis (RH), and it is classified as a class IIb non-Langerhans cell histiocytosis. It has been designated as multicentric, being characterized by multisystemic involvement. In fact, although mainly involving the skin, along with the joints, it is a systemic inflammatory condition potentially involving every internal organ. As MRH-related skin findings can mimic rheumatoid nodules or Gottron papules, the histopathology of the cutaneous lesions is often necessary for the correct diagnosis. Approximately one-third of MRH patients have confirmed concomitant autoimmune disorders. A wide variety of autoimmune disorders associated with the disease have been reported in the literature, suggesting immune dysfunction as a factor in the pathophysiology of MRH. A case of MRH associated with autoimmune manifestation is reported in the context of a mini review of the literature, with a focus on clinical presentation, treatments, and treatment outcomes. Moreover, eight cases of MRH associated with autoimmune diseases are briefly discussed.