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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. 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. 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 β3 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. Biochip immunofluorescence is an appropriate technique to detect anti-laminin 332 antibodies which should be tested in patients with MMP.

Background Syphilis is known as the “great imitator” because of its polymorphic clinical manifestations. Condyloma lata are an uncommon mucocutaneous manifestation of secondary syphilis, generally localized in intertriginous areas, such as the genitals and anus. Extragenital localization of condyloma lata is considered unusual. Methods A case study of extra-genital condylomata is presented. To contextualise the case, a literature review of extra-genital condylomata lata was subsequently undertaken. The authors searched MEDLINE/PubMed, Scopus and Excerpta Medica/EMBASE English-language sources using the following keywords: “condyloma lata”, “condylomata lata”, and “condyloma latum”. Results Thirty-five papers (from 1940 to 2021) describing an extra-anogenital localization of condyloma lata were found and are summarized in Table 1. Patients were mainly males (82.1%), with a mean age of 31.9 years. Most of them showed other manifestations of secondary syphilis (53.9%). In a minority of cases (39.0%), concomitant anogenital condyloma lata were present, thus making the diagnosis easier. The toe web localization was the most documented (26.2%) followed by the oral cavity (23.8%). Conclusion In the presence of extra-genital condyloma lata, the differential diagnosis is not always clear, especially when no other muco-cutaneous lesions are observed. In the case of eroded or wet lesions involving any cutaneous fold, associated or not with other cutaneous manifestations, a sexual history should be obtained, and syphilis must be considered.

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.

Background: COronaVIrus Disease 19 (COVID-19) is associated with a wide spectrum of skin manifestations, but SARS-CoV-2 RNA in lesional skin has been demonstrated only in few cases. Objective: To demonstrate SARS-CoV-2 presence in skin samples from patients with different COVID-19-related cutaneous phenotypes. Methods: Demographic and clinical data from 52 patients with COVID-19-associated cutaneous manifestations were collected. Immunohistochemistry and digital PCR (dPCR) were performed in all skin samples. RNA in situ hybridization (ISH) was used to confirm the presence of SARS-CoV-2 RNA. Results: Twenty out of 52 (38%) patients presented SARS-CoV-2 positivity in the skin. Among these, 10/52 (19%) patients tested positive for spike protein on immunohistochemistry, five of whom had also positive testing on dPCR. Of the latter, one tested positive both for ISH and ACE-2 on immunohistochemistry while another one tested positive for nucleocapsid protein. Twelve patients showed positivity only for nucleocapsid protein on immunohistochemistry. Conclusions: SARS-CoV-2 was detected only in 38% of patients, without any association with a specific cutaneous phenotype, suggesting that the pathophysiology of cutaneous lesions mostly depends on the activation of the immune system. The combination of spike and nucleocapsid immunohistochemistry has higher diagnostic yield than dPCR. Skin persistence of SARS-CoV-2 may depend on timing of skin lesions, viral load and immune response.

Background: Previously, a new dichotomous outcome was developed, calculated as 55% reduction in the International Hidradenitis Suppurativa 4 score (IHS4-55). It was validated in datasets of adalimumab and placebo treated HS patients. External validation is an important aspect of clinical outcomes. Objectives: We aimed to externally validate the novel dichotomous IHS4-55 in a non-biologic treated dataset of HS patients. Methods: Data from a previously published European-wide prospective clinical study of antibiotic treatment of HS patients was used to assess the association of IHS4-55 achievement with individual reduction in inflammatory nodules, abscesses and draining tunnels. Moreover, the associations between IHS4-55 positivity and achievement of the minimal clinically important differences (MCID) for Dermatology Life Quality Index (DLQI), numerical rating scale (NRS) Pain, and NRS Pruritus were analyzed. Results: Data was obtained from 283 individual patients, of which 36.4% (103/283) were treated with clindamycin and rifampicin and 63.6% (180/283) with tetracyclines for 12 weeks. Achievers of the IHS4-55 demonstrated a significant reduction the counts of inflammatory nodules, abscesses, and draining tunnels (all p

During the COVID-19 pandemic, rapid, real-world evidence is essential for the development of knowledge and subsequent public health response. In dermatology, provider-facing and patient-facing registries focused on COVID-19 have been important sources of research and new information aimed at guiding optimal patient care. The 7 dermatology registries included in this update now include more than 8000 case reports sourced from physicians and patients from countries all over the world.

BACKGROUND Erythropoietic protoporphyria (EPP) is a rare disorder of heme biosynthesis hallmarked by early-onset photosensitivity and mainly due to defective ferrochelatase activity leading to increased erythrocyte protoporphyrin IX (PPIX) levels. Evidence regarding the relationship between erythrocyte PPIX concentration and photosensitivity is limited. METHODS To investigate the relationship between free erythrocyte PPIX (FEP) concentration; routine laboratory tests, particularly iron metabolism biomarkers; and ultraviolet (UV) A/visible light phototesting findings, 20 genetically confirmed EPP and one XLPP treatment-naive patients were included in our study. They underwent UVA and visible light phototesting. On the same day, blood samples were collected for measurement of FEP, serum iron, transferrin, transferrin saturation, and ferritin, 25-hydroxyvitamin D, and liver enzyme levels. RESULTS Median FEP concentration at the time of phototesting was 57.50 (IQR: 34.58-102.70) μg/g of Hb. UVA and visible light phototesting were positive in 9 (42.9%) and 8 (38.1%) patients, respectively. Median FEP concentration was significantly higher in UVA phototest-positive patients than in those negative (64.37 [IQR: 57.45-121.82] vs 45.35 [IQR: 24.53-74.61] μg/g of Hb, respectively; P = .04486). Similarly, UVA photosensitive individuals had significantly lower median serum iron levels (61.5 [IQR: 33.5-84] μg/dL vs 109 [IQR: 63.25-154] μg/dL, respectively; P = .01862) and transferrin saturation values (15.005 [IQR: 7.0775-18.41] % vs 29.645 [IQR: 17.8225-34.3575] %; P = .0109) than those negative. CONCLUSIONS Our study demonstrates that UVA phototest positivity is associated with higher FEP concentration and lower transferrin saturation and serum iron concentration in EPP.

This guideline has been initiated by the task force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology, including physicians from all relevant disciplines and patient organizations. It is a S3 consensus‐based guideline that systematically reviewed the literature on mucous membrane pemphigoid (MMP) in the MEDLINE and EMBASE databases until June 2019, with no limitations on language. While the first part of this guideline addressed methodology, as well as epidemiology, terminology, aetiology, clinical presentation and outcome measures in MMP, the second part presents the diagnostics and management of MMP. MMP should be suspected in cases with predominant mucosal lesions. Direct immunofluorescence microscopy to detect tissue‐bound IgG, IgA and/or complement C3, combined with serological testing for circulating autoantibodies are recommended. In most patients, serum autoantibodies are present only in low levels and in variable proportions, depending on the clinical sites involved. Circulating autoantibodies are determined by indirect IF assays using tissue substrates, or ELISA using different recombinant forms of the target antigens or immunoblotting using different substrates. The major target antigen in MMP is type XVII collagen (BP180), although in 10–25% of patients laminin 332 is recognized. In 25–30% of MMP patients with anti‐laminin 332 reactivity, malignancies have been associated. As first‐line treatment of mild/moderate MMP, dapsone, methotrexate or tetracyclines and/or topical corticosteroids are recommended. For severe MMP, dapsone and oral or intravenous cyclophosphamide and/or oral corticosteroids are recommended as first‐line regimens. Additional recommendations are given, tailored to treatment of single‐site MMP such as oral, ocular, laryngeal, oesophageal and genital MMP, as well as the diagnosis of ocular MMP. Treatment recommendations are limited by the complete lack of high‐quality randomized controlled trials.

Background: COronaVIrus Disease 2019 (COVID-19) affects children with less severe symptoms than adults. However, severe COVID-19 paediatric cases are increasingly reported, including patients with Kawasaki disease (KD) or a multisystem inflammatory syndrome (MIS-C) that can present with features resembling KD. Summary: MIS-C is an emerging severe paediatric syndrome associated with COVID-19 that can show overlapping features of KD, KD shock syndrome, and toxic shock syndrome. MIS-C might be an inflammatory disease distinct from KD resulting from an exaggerated immune response. A high prevalence of mucocutaneous manifestations – in addition to gastrointestinal and cardiovascular involvements – was found in MIS-C. The most frequent mucocutaneous findings were conjunctivitis and rash, often described as macular and/or papular or polymorphous. In this article, we present a brief overview of MIS-C with an emphasis on mucocutaneous findings and the relationship with KD.

The registration of the tumour necrosis factor-α inhibitor adalimumab in 2015 was a major step forward in the treatment of hidradenitis suppurativa/acne inversa (HS). However, it soon became evident that the effectiveness of adalimumab in daily practice was highly variable. A significant unmet medical need of HS patients remained, and the search for novel therapeutic targets was intensified. During the 10th European Hidradenitis Suppurativa Foundation (EHSF) e.V. Conference, reknown international HS investigators virtually presented and discussed the published data on these potential target molecules for future HS treatment. This article addresses the most promising molecules currently under investigation from a pathophysiological and clinical point of view. With phase III trials ongoing, the anti- interleukin (IL)-17 biologics bimekizumab and secukinumab are in the most advanced stage of clinical development showing promising results. In addition, targeting IL-1α with bermekimab has shown encouraging results in two clinical trials. Directing treatment at neutrophil recruitment and activation by targeting IL-36 with spesolimab fits well in the pathogenic concept of HS and clinical phase II trial results are pending. In contrast to in situ evidence, Complement 5a (C5a) and C5a receptor blockade have only shown greater clinical benefit in patients with severe HS. Inhibition of Janus kinase (JAK) 1 signalling in HS showed clinical efficacy only in the highest dosage, highlighting that careful surveillance of the balance between safety and efficacy of JAK inhibition is warranted. Overall, clinical efficacies of all novel treatments reported so far are modest. To guide drug development, more and better-defined translational data on the pathogenesis of this severe and enigmatic inflammatory skin disease are required.

The reported incidence of COVID‐19 among cohorts of patients with inflammatory bowel and skin diseases under treatment with biologicals is low. Treatment may further modify disease severity as some biological modifiers, such as anakinra, are also proposed for the management of COVID‐19 patients potentially providing HS patients with an advantage. The above preliminary evidence suggests that hidradenitis suppurativa (HS) does probably not provide an increased susceptibility for COVID‐19 and that any susceptibility is unlikely to be modified negatively by treatment with biologicals. On the occasion of its 10th International Conference, experts of the European Hidradenitis Suppurativa Foundation e.V. have prepared a consensus statement regarding anti‐COVID‐19 measurements for HS patients. Based on the available knowledge, patients with HS may be vaccinated against SARS‐CoV2 and patients affected by metabolic syndrome constitute a high‐risk group for COVID‐19 and should be vaccinated at the earliest convenient point in time. HS patients on treatment with adalimumab can be vaccinated with non‐living virus anti‐SARS‐CoV2 vaccines. A possible suboptimal effect of the vaccine may be suspected but might not be expected universally. The management of the biological treatment in HS patients is at the discretion of the dermatologist / responsible physician.

Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer in the world after basal cell carcinoma. Treatment of choice for cSCC is surgery, but radiotherapy (RT) is a valid alternative and has been recommended in selected cases. The aim was to evaluate the cure rate of RT for cSCC and to compare the results in the two settings of RT as exclusive or second line treatment.The outcome of 92 cSCC treated with RT in the period from 2002 to 2019 in our department was retrospectively reviewed.In 56 cases RT was first-line treatment while in 36 it was administered as second-line treatment after incomplete excision or failure of previous treatments. The five-year cure-rate was 74% (71.34% in patients treated with primary RT and 77.37% in patients treated with RT as second-line treatment), while the ten-year cure-rate was 67% (57.07% and 77.37% respectively in patients treated with primary RT or with second line RT). Log rank test showed statistical significance between the cure-rate of the two groups with better therapeutic results after second-line RT (P0.05).Our data confirm RT as an effective therapy for cSCC when surgery excision is contraindicated or in case of tumors localized in certain regions where the cosmetic-functional outcome is better than surgery. Better therapeutic results are achieved with second-line RT.

Tetracyclines and clindamycin plus rifampicin combination therapy are both considered first-line therapy in current Hidradenitis Suppurativa (HS) guidelines. However, evidence for their efficacy is drawn from small studies, often without validated outcomes., info:eu-repo/semantics/published

Background: Coronavirus disease-19 (COVID-19) is an ongoing global pandemic caused by the “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2), which was isolated for the first time in Wuhan (China) in December 2019. Common symptoms include fever, cough, fatigue, dyspnea and hypogeusia/hyposmia. Among extrapulmonary signs associated with COVID-19, dermatological manifestations have been increasingly reported in the last few months. Summary: The polymorphic nature of COVID-19-associated cutaneous manifestations led our group to propose a classification, which distinguishes the following six main clinical patterns: (i) urticarial rash, (ii) confluent erythematous/maculopapular/morbilliform rash, (iii) papulovesicular exanthem, (iv) chilblain-like acral pattern, (v) livedo reticularis/racemosa-like pattern, (vi) purpuric “vasculitic” pattern. This review summarizes the current knowledge on COVID-19-associated cutaneous manifestations, focusing on clinical features and therapeutic management of each category and attempting to give an overview of the hypothesized pathophysiological mechanisms of these conditions.

Panniculitis, or inflammation of the fatty tissue, is an ongoing diagnostic challenge to both dermatologists and pathologists. The basis of the current panniculitis classification is histology, whether the inflammation is mainly located in the fibrovascular septa or in the adipose lobules thereafter with or without vasculitis. However, overall, the difficulty rises due to various terminologies and lack of clinical relevance with this classification. In addition to that, the majority of panniculitides have mixed infiltration of both lobular and septal and not a clear-cut distinction. The aim of this article is to provide a novel clinical algorithm to the diagnosis of panniculitis and thus to provide guidelines for all clinicians who may encounter this challenging condition in their clinical practice.

Background:Acne is a common condition. Sometimes acne or acne-like features are a part of autoinflammatory diseases such as PAPA spectrum disorders. Our objective wasto determine whether acne in PAPA spectrum disorders has specific phenotypic traits. Summary: This is aliterature review on reported cases of patients with PAPA, PAMI, PASH, PAPASH, PsAPASH, PAC or PASS syndrome. Acne was classified into four categories: moderate, severe, nodulocystic, acne fulminans.One hundred patients were included. Age of onset of acne and topography were the same as in acne vulgaris. Acne’s phenotype was at least severe (including acne fulminans, nodulocystic and severe) in 83% of cases. Genetic mutations or variants with potential pathological significance were reported in 49 patients. The addition of isotretinoin to biotherapies was required to control acne in several patients.

Background: Pemphigus encompasses a group of life-threatening autoimmune bullous diseases characterized by blisters and erosions of the mucous membranes and skin. Before the era of immunosuppressive treatment, the prognosis of pemphigus was almost always fatal. Due to its rarity, only few randomized controlled therapeutic trials are available. Recently, rituximab has been approved as first-line treatment for moderate and severe pemphigus vulgaris in Europe and the USA.Objectives: The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology (EADV) has initiated a throughout update of the guideline for the management of patients with pemphigus. Results: The guidelines for the management of pemphigus were updated and the degree of consent among all task force members was included. The final version of the guideline was consented by the European Dermatology Forum (EDF) and several patient organisations.

SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by moderate to severe plaque psoriasis. The content of the guideline includes general information on the scope and purpose, health questions covered, target users and strength/limitations of the guideline, suggestions for disease severity grading and treatment goals. It presents the general treatment recommendations as well as detailed management and monitoring recommendations for the individual drugs including acitretin, cyclosporine, fumarates, methotrexate, adalimumab, apremilast, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, ixekizumab, risankizumab, secukinumab, tildrakizumab and ustekinumab. Moreover, the guideline provides guidance for specific clinical situations such as patient with concomitant psoriatic arthritis, inflammatory bowel disease, a history of malignancies, a history of depression, diabetes, viral hepatitis, disease affecting the heart or the kidneys as well as concomitant neurological disease. Advice on how to screen for tuberculosis and recommendations on how to manage patients with a positive tuberculosis test result are given. It further covers treatment for pregnant women or those with childbearing potential. Information on vaccination, immunogenicity and systemic treatment during the COVID-19 pandemic is also provided.