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BACKGROUND Apremilast is an oral phosphodiesterase-4 inhibitor indicated for patients with moderate-to-severe chronic plaque psoriasis and active psoriatic arthritis. OBJECTIVES To examine the effectiveness of apremilast on Dermatology Life Quality Index (DLQI), Psoriasis Area and Severity Index (PASI) and nail, scalp and palmoplantar involvement, when administered prior to biologics. METHODS This 52-week real-world study included biologic-naive adults with moderate psoriasis (psoriasis-involved body surface area 10% to

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: Bruton tyrosine kinase (BTK) inhibition targets B-cell and other non-T-cell immune cells implicated in the pathophysiology of pemphigus, an autoimmune disease driven by anti-desmoglein autoantibodies. Rilzabrutinib is a new reversible, covalent BTK inhibitor demonstrating preclinical efficacy as monotherapy in canine pemphigus foliaceus. OBJECTIVES: To evaluate the efficacy and safety of oral rilzabrutinib in patients with pemphigus vulgaris in a multicentre, proof-of-concept, phase II trial. METHODS: Patients with Pemphigus Disease Area Index severity scores 8-45 received 12 weeks of oral rilzabrutinib 400-600 mg twice daily and 12 weeks of follow-up. Patients initially received between 0 and ≤ 0·5 mg kg-1 prednisone-equivalent corticosteroid (CS; i.e. 'low dose'), tapered after control of disease activity (CDA; no new lesions, existing lesions healing). The primary endpoints were CDA within 4 weeks on zero-to-low-dose CS and safety. RESULTS: In total, 27 patients with pemphigus vulgaris were included: nine newly diagnosed (33%) and 18 relapsing (67%); 11 had moderate disease (41%) and 16 moderate to severe (59%). The primary endpoint, CDA, was achieved in 14 patients (52%, 95% confidence interval 32-71): 11 using low-dose CS and three using no CS. Over 12 weeks of treatment, mean CS doses reduced from 20·0 to 11·8 mg per day for newly diagnosed patients and from 10·3 to 7·8 mg per day for relapsing patients. Six patients (22%) achieved complete response by week 24, including four (15%) by week 12. Treatment-related adverse events were mostly mild (grade 1 or 2); one patient experienced grade 3 cellulitis. CONCLUSIONS: Rilzabrutinib alone, or with much lower CS doses than usual, was safe, with rapid clinical activity in pemphigus vulgaris. These data suggest that BTK inhibition may be a promising treatment strategy and support further investigation of rilzabrutinib for the treatment of pemphigus.

BACKGROUND The Bullous Pemphigoid Disease Area Index (BPDAI) score has been proposed to provide an objective measure of bullous pemphigoid (BP) activity. OBJECTIVES The objective of this study was to calculate BPDAI cut-off values defining mild, moderate and severe BP. We also aimed to assess the interrater reliability and correlation with the number of daily new blisters, and anti-BP180 and anti-BP230 antibodies. METHODS Severity scores were recorded by two blinded investigators. Anti-BP180 and anti-BP230 antibodies were measured using an enzyme-linked immunosorbent assay (ELISA). Cut-off values defining mild, moderate and severe subgroups were calculated based on the 25th and 75th percentiles of the BPDAI score. RESULTS In total, 285 patients with BP were enrolled from 50 dermatology departments in Europe. Median BPDAI activity was 37·5 points (range 0-164). Cut-off values corresponding to the first and third quartiles of the BPDAI score were 20 and 57, respectively; thus, these values were used to define mild (≤ 19), moderate (≥ 20 and ≤ 56) and severe (≥ 57) BP. The median BPDAI score for patients with ≤ 10 daily new blisters was 26 [interquartile range (IQR) 17-45], and for patients with > 10 daily new blisters the median score was 55 (IQR 39-82). The BPDAI intraclass correlation coefficient measured at baseline was 0·97 and remained higher than 0·90 up to month 6. The improvement in the BPDAI score was correlated with the absolute decrease in anti-BP180 ELISA value (Spearman's rank r = 0·34, P

Background The current standard in the serologic diagnosis of autoimmune bullous diseases (AIBD) is a multistep procedure sequentially applying different assays. In contrast, the BIOCHIP Mosaic technology combines multiple substrates for parallel analysis by indirect immunofluorescence. Methods Sera from 749 consecutive, prospectively recruited patients with direct immunofluorescence–positive AIBD from 13 international study centers were analyzed independently and blinded by using (1) a BIOCHIP Mosaic including primate esophagus, salt-split skin, rat bladder, monkey liver, monkey liver with serosa, recombinant BP180 NC16A, and gliadin GAF3X, as well as HEK293 cells expressing recombinant desmoglein 1, desmoglein 3, type VII collagen, and BP230 C-terminus and (2) the conventional multistep approach of the Department of Dermatology, University of Lubeck. Results In 731 of 749 sera (97.6%), specific autoantibodies could be detected with the BIOCHIP Mosaic, similar to the conventional procedure (725 cases, 96.8%). The Cohen κ for both serologic approaches ranged from 0.84 to 1.00. In 6.5% of sera, differences between the 2 approaches occurred and were mainly attributed to autoantigen fragments not present on the BIOCHIP Mosaic. Limitations Laminin 332 and laminin γ1 are not represented on the BIOCHIP Mosaic. Conclusions The BIOCHIP Mosaic is a standardized time- and serum-saving approach that further facilitates the serologic diagnosis of AIBD.

Background Early-stage mycosis fungoides (MF) includes involvement of dermatopathic lymph nodes (LNs) or early lymphomatous LNs. There is a lack of unanimity among current guidelines regarding the indications for initial staging imaging in early-stage presentation of MF in the absence of enlarged palpable LNs. Objectives To investigate how often imaging is performed in patients with early-stage presentation of MF, to assess the yield of LN imaging, and to determine what disease characteristics promoted imaging. Methods A review of clinicopathologically confirmed newly diagnosed patients with cutaneous patch/plaque (T1/T2) MF from PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) data. Results PROCLIPI enrolled 375 patients with stage T1/T2 MF: 304 with classical MF and 71 with folliculotropic MF. Imaging was performed in 169 patients (45%): 83 with computed tomography, 18 with positron emission tomography-computed tomography and 68 with ultrasound. Only nine of these (5%) had palpable enlarged (>= 15 mm) LNs, with an over-representation of plaques, irrespectively of the 10% body surface area cutoff that distinguishes T1 from T2. Folliculotropic MF was not more frequently imaged than classical MF. Radiologically enlarged LNs (>= 15 mm) were detected in 30 patients (18%); only seven had clinical lymphadenopathy. On multivariate analysis, plaque presentation was the sole parameter significantly associated with radiologically enlarged LNs. Imaging of only clinically enlarged LNs upstaged 4% of patients (seven of 169) to at least IIA, whereas nonselective imaging upstaged another 14% (24 of 169). LN biopsy, performed in eight of 30 patients, identified N3 (extensive lymphomatous involvement) in two and N1 (dermatopathic changes) in six. Conclusions Physical examination was a poor determinant of LN enlargement or involvement. Presence of plaques was associated with a significant increase in identification of enlarged or involved LNs in patients with early-stage presentation of MF, which may be important when deciding who to image. Imaging increases the detection rate of stage IIA MF, and identifies rare cases of extensive lymphomatous nodes, upstaging them to advanced-stage IVA2.

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.

Objective The human microbiome refers to the entire habitat, including microorganisms, their genomes and the surrounding environmental conditions of the microbial ecosystem. When the equilibrium between microbial habitats and host is disturbed, dysbiosis is caused. The oral microbiome (OMB) has been implicated in the manifestation of many intra- and extraoral diseases. Lately, there has been an intense effort to investigate and specify the relationship between microbial complexes, especially that of the oral cavity and intestine and autoimmunity. This study aimed to review the current literature about the possible role of the OMB in the pathogenesis of autoimmune diseases. Methods We searched for published articles in English indexed in PubMed, Medline, Research Gate and Google Scholar using a search strategy that included terms for oral microbiome, autoimmune diseases, dysbiosis and next-generation sequencing. Results An important number of articles were gathered and used for the description of the possible impact of dysbiosis of OMB in the pathogenesis of Sjogren’s syndrome, systemic lupus erythematosus, rheumatoid arthritis, Behcet’s disease, Crohn’s disease and psoriasis. Conclusion This review article draws attention to the relationship between OMB and the triggering of a number of autoimmune diseases. Although this specific topic has been previously reviewed, herein, the authors review recent literature regarding the full list of nosological entities related to the OMB, point out the interaction between the microbiome and sex hormones with regard to their role in autoimmunity and discuss novel and promising therapeutic approaches for systemic autoimmune diseases. Furthermore, the question arises of whether the OMB is associated with oral bullous autoimmune diseases.

Background Milia are superficial keratinous cysts seen as pearly white, dome-shaped lesions 1–2 mm in diameter. Milia are associated with diseases that cause subepidermal blistering, such as hereditary forms of epidermolysis bullosa, epidermolysis bullosa acquisita, bullous pemphigoid, bullous lichen planus, and porphyria cutanea tarda. Multiple eruptive milia are rare and more extensive in number than primary milia. Objective The aim of this study was to search the literature for cases of blistering diseases with multiple milia formation, especially in areas of the skin where there was no evidence of blistering or trauma, and review the interpretations of their pathogenesis. Methods We performed a literature search with the terms multiple milia and bullous diseases, pemphigoid, and pemphigus. Results Very few studies have investigated the origin of milia. Primary milia are thought to originate from the sebaceous collar of vellus hairs, and secondary milia are believed to derive from eccrine ducts more commonly than from overlying epidermis, hair follicles, or sebaceous ducts. Milia secondary to blisters or trauma are speculated to be produced through the regeneration process of disrupted sweat glands or hair follicles. Immunological predisposition, aberrant interaction between the hemidesmosomes, and the extracellular matrix components beneath the hemidesmosomes have been described with regard to the formation of numerous milia during recovery. Multiple milia could be a primary manifestation of dystrophic epidermolysis bullosa in skin areas without evidence of blistering. Conclusion The exact etiology of multiple milia remains unknown. Immunological predisposition and improper interaction between hemidesmosomes and extracellular matrix components are speculated to play a role in the formation of milia during recovery of bullous lesions in blistering diseases. Still, further studies on the triggering mechanisms of keratinocyte dysfunction in cases of multiple milia formation without evidence of prior blistering are needed.

Non-melanoma skin cancer (NMSC) is the commonest malignancy worldwide (>80% located in the head and neck area). The aim of this study was to assess risk factors predisposing to local recurrence of NMSC of the middle third of the face (MTF). This was a single-centre retrospective analysis of patients with NMSC of the MTF treated during 1995-2010. Data on epidemiological and tumour characteristics were collected. Survival analysis was performed and log-rank tests were used to compare differences in survival for each variable. A total of 531 patients with basal cell carcinoma (BCC) of the MTF were identified. Most tumours were nodular type (28.4%), located on the nose (34.3%), and confined to the dermis (75.5%). Negative margins were achieved in 91% of cases. Median follow-up time was 35 months and 15.2% of patients developed local recurrence. Incomplete excision was the only variable predisposing to local recurrence. The cohort also included 114 patients with squamous cell carcinoma (SCC). Most tumours were well differentiated (43.9%), located at the zygomatic area (49.1%), excised with negative margins (93%), and confined to the dermis (67.8%). At a median follow-up time of 42 months, local recurrence occurred in 15.7% of patients. Tumour size, depth of invasion, and prior history of head and neck SCC were risk factors for local recurrence. The variables predictive of recurrence of BCC were incomplete excision and for SCC tumour size, depth of invasion, and a prior history of head and neck SCC.

Bruton Tyrosine Kinase (BTK) has a key role in multiple pathways involved in inflammation and autoimmunity. Therefore, BTK has become a new therapeutic target for a group of hematologic and autoimmune disorders. The pharmaceutical industry has invested in the clinical development of BTK inhibitors during the last decade. Ibrutinib, for example, which was the first BTK inhibitor to be used in clinical trials, has two approved indications, mantle cell lymphoma and chronic lymphocytic leukemia, and remains under evaluation for additional indications. Rillzabrutinib (PRN1008) is a new, highly potent and selective inhibitor of BTK. Early studies performed in canine pemphigus demonstrated effectiveness. A proof-of-concept, multicenter, phase 2 trial has recently showed the efficacy and safety of oral rilzabrutinib in pemphigus vulgaris. In this mini review, we present evidence regarding the mechanisms affected by BTK inhibition and the concept of BTK inhibition as an emerging new treatment in pemphigus.

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, medical professionals have been overwhelmed by questions beyond the infection itself. In dermatology practice, clinicians have been facing difficulties about the management of chronic immune-mediated skin diseases. Issues arose, such as the grade of immunosuppression or immunomodulation, discontinuation or modification of treatment, and initiation of new treatments. In this comprehensive review, we present the current evidence about the course and management of chronic inflammatory dermatoses during the COVID-19 pandemic, focusing on psoriasis, atopic dermatitis, and hidradenitis suppurativa.

The presence of sebaceous neoplasm should alert physicians to thoroughly investigate for underlying malignancies. Awareness on MTS should be raised within physicians, since this may be just the thin end of the wedge.

It is common for multiple autoimmune diseases to occur in the same patient. However, autoimmune blistering diseases (AIBD) do not commonly associate with dermatomyositis (DM). We performed a literature review and found 12 previous reports that may be attributed to misdiagnosis, underreporting, or true rarity of association. Herein, we present a case of pemphigus vulgaris and a case of mucous membrane pemphigoid associated with DM and review the related literature. AIBD-associated interstitial lung disease, genetic predisposition, potential environmental triggers of both AIBD and DM, drug-related triggers, and paraneoplastic processes are discussed. Dermatologists must be vigilant for a second autoimmune disease in patients with AIBD that may have therapeutic implications. Keywords: Dermatomyositis, interstitial lung disease, pemphigus, pemphigoid, autoimmune, blistering

Autoimmune bullous diseases during pregnancy pose a therapeutic challenge for medical dermatologists. There are main concerns with regard to the regimen, dose, route of administration, and potential harm to the fetus. Many therapeutic options may be safe during pregnancy despite official classifications. Furthermore, there are always questions regarding management during the lactation period. Additionally, issues exist about male and female fertility and the time of discontinuation of certain medications before conception. In this article, we present an overview of the literature based on answers to these issues to solve common and uncommon management problems that arise about a spectrum of autoimmune bullous diseases before conception, as well as during pregnancy and the lactation period. Keywords: Pemphigus, pemphigoid, bullous, pregnancy, lactation fertility

Pemphigus vulgaris is a rare chronic blistering skin disease resulting from IgG autoantibodies directed against transmembrane desmosomal glycoprotein desmoglein 3 and is the most common form of pemphigus. Since interleukin-1 receptor-associated kinase (IRAK-1)/nuclear factor-kappa B (NF-kappa B) pathway plays an essential role in the pathogenesis of autoimmune diseases, the aim of the present study was to explore the role of polymorphisms in three genes, named IRAK1 (rs3027898), NFKBIA (rs696) and NFKB1 (-94ATTG insertion/deletion variant, - rs28362491), in PV susceptibility. Forty-four unrelated patients with PV (23 males) were enrolled in the study. Additionally, 77 ethnic matching healthy volunteers (45 males) with no personal or family history of chronic autoimmune or infectious diseases were studied. Strong statistical significant difference was observed between PV patients and controls for polymorphism -94 insertion/deletion ATTG in the promoter region of NFKB1 gene (P = 0.00005). Additional dedicated studies in larger groups of patients of various ethnicities are needed to replicate and confirm the preliminary findings.

BACKGROUND Despite the wide therapeutic options available for the treatment of melasma, including many active topical medications, technologies with lights and peelings, clinical control of this disorder is extremely challenging. OBJECTIVES To evaluate the effect of microneedling with topical vitamin C in the treatment of melasma. METHODS Thirty female patients with melasma received six sessions of microneedling with addition of topical vitamin C every two weeks. At each session, photos were taken and Melasma Area and Severity Index (MASI) score was calculated to assess the clinical improvement. RESULTS Mean age of the eligible patients was 33.2 ± 5.77 years. About 50% of cases were of Fitzpatrick skin type III. All patients showed improvement at the end of the sessions. Mean MASI score in the first session was 8.61 ± 4.45 and there was a gradual decline in its value till it reached a mean of 5.75 ± 4.16 in the last session (P

Background The PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study is a prospective analysis of an international database. Here we examine front-line treatments and quality of life (QoL) in patients with newly diagnosed mycosis fungoides (MF).Objectives To identify (i) differences in first-line approaches according to tumour-nodes-metastasis-blood (TNMB) staging; (ii) parameters related to a first-line systemic approach and (iii) response rates and QoL measures.Methods In total, 395 newly diagnosed patients with early-stage MF (stage IA-IIA) were recruited from 41 centres in 17 countries between 1 January 2015 and 31 December 2018 following central clinicopathological review.Results The most common first-line therapy was skin-directed therapy (SDT) (322 cases, 81 center dot 5%), while a smaller percentage (44 cases, 11 center dot 1%) received systemic therapy. Expectant observation was used in 7 center dot 3%. In univariate analysis, the use of systemic therapy was significantly associated with higher clinical stage (IA, 6%; IB, 14%; IIA, 20%; IA-IB vs. IIA, P < 0 center dot 001), presence of plaques (T1a/T2a, 5%; T1b/T2b, 17%; P < 0 center dot 001), higher modified Severity Weighted Assessment Tool (> 10, 15%

Introduction Dermatitis herpetiformis (DH) is a chronic, pruritic, gluten-induced skin disorder characterized by subepidermal granular IgA deposition and a variable degree of enteropathy identical to that seen in coeliac disease. So far, there has been no European consensus about the management of DH. Methods The guidelines were created by small subgroups of a guideline committee consisting of 26 specialists from various medical fields and one patients' representative. The members of the committee then discussed the guidelines and voted for the final version at two consensus meetings. The guidelines were developed under the support of the European Academy of Dermatology and Venereology (EADV) and in collaboration with the European Dermatology Forum (EDF). Results The guidelines summarize evidence-based and expert-based recommendations (S2 level) for the management of DH (see Appendix). Conclusion These guidelines will improve the quality of management of DH and support dermatologists in their diagnostic and therapeutic decisions.

Primary cutaneous lymphomas are defined as a heterogenic group of T- and B-cell non-Hodgkin lymphomas that present initially in the skin. Patients with primary cutaneous lymphomas are at a higher risk for developing complications in case of infection with the novel coronavirus severe acute respiratory syndrome coronavirus 2. The coronavirus disease 2019 (COVID-19) pandemic has affected the established diagnostic approach, staging, and therapeutic guidelines in patients with primary cutaneous lymphomas. In the light of the current global health crisis, management of primary cutaneous lymphomas needs to be adjusted. The key to achieving this is to balance the optimal control of the lymphoma, with a minimal increase of the personal risk for COVID-19 exposure and complications.

Background Survival in mycosis fungoides (MF) is varied and may be poor. The PROCLIPI (PROspective Cutaneous Lymphoma International Prognostic Index) study is a web‐based data collection system for early‐stage MF with legal data‐sharing agreements permitting international collaboration in a rare cancer with complex pathology. Clinicopathological data must be 100% complete and in‐built intelligence in the database system ensures accurate staging. Objectives To develop a prognostic index for MF. Methods Predefined datasets for clinical, haematological, radiological, immunohistochemical, genotypic, treatment and quality of life are collected at first diagnosis of MF and annually to test against survival. Biobanked tissue samples are recorded within a Federated Biobank for translational studies. Results In total, 430 patients were enrolled from 29 centres in 15 countries spanning five continents. Altogether, 348 were confirmed as having early‐stage MF at central review. The majority had classical MF (81·6%) with a CD4 phenotype (88·2%). Folliculotropic MF was diagnosed in 17·8%. Most presented with stage I (IA: 49·4%; IB: 42·8%), but 7·8% presented with enlarged lymph nodes (stage IIA). A diagnostic delay between first symptom development and initial diagnosis was frequent [85·6%; median delay 36 months (interquartile range 1290)]. This highlights the difficulties in accurate diagnosis, which includes lack of a singular diagnostic test for MF. Conclusions This confirmed early‐stage MF cohort is being followed‐up to identify prognostic factors, which may allow better management and improve survival by identifying patients at risk of disease progression. This study design is a useful model for collaboration in other rare diseases, especially where pathological diagnosis can be complex.

International audience; Background-Several European countries recently developed international diagnostic and management guidelines for pemphigus, which have been instrumental in the standardization of pemphigus management. Objective-We now present results from a subsequent Delphi consensus to broaden the generalizability of the recommendations. Methods-A preliminary survey, based on the European Dermatology Forum and the European Academy of Dermatology and Venereology guidelines, was sent to a panel of international experts to determine the level of consensus. The results were discussed at the International Bullous Diseases Consensus Group in March 2016 during the annual American Academy of Dermatology conference. Following the meeting, a second survey was sent to more experts to achieve greater international consensus. Results-The 39 experts participated in the first round of the Delphi survey, and 54 experts from 21 countries completed the second round. The number of statements in the survey was reduced from 175 topics in Delphi I to 24 topics in Delphi II on the basis of Delphi results and meeting discussion. Limitations-Each recommendation represents the majority opinion and therefore may not reflect all possible treatment options available. Conclusions-We present here the recommendations resulting from this Delphi process. This international consensus includes intravenous CD20 inhibitors as a first-line therapy option for moderate-to-severe pemphigus. Keywords CD20 inhibitor; consensus; guidelines; pemphigus foliaceus; pemphigus vulgaris; treatment Pemphigus encompasses a spectrum of rare mucocutaneous bullous diseases that are autoimmune in origin. Because of the rarity of these diseases, it can take patients months before their pemphigus is diagnosed, during which time many are treated for other blistering diseases. 1,2 Even once the diagnosis has been made, treatment regimens can vary greatly, as

Background Retinoids have long been used in the treatment of cutaneous T-cell lymphomas. However, data on acitretin use for mycosis fungoides (MF) are very limited. Objectives To evaluate treatment outcomes of acitretin in patients with MF attending three academic referral centres in different regions of Greece. Methods Data on effectiveness, safety and drug survival of acitretin as monotherapy or as adjuvant regimen were collected in a multicentre, register-based, retrospective study. Results Overall, 128 patients (64.8% male; mean age at MF diagnosis 59.7 years) were included. Folliculotropic MF was present in 24 (18.8%) cases. Most patients (n = 118; 92.2%) had early-stage disease (≤IIA) at acitretin initiation. In all, 28 (21.9%) patients received acitretin monotherapy, while 100 (78.1%) subjects on acitretin concomitantly received phototherapy (n = 65; 50.8%) or topical steroids (n = 27; 21.1%). Acitretin was given as a first-line agent in 73 (57%) cases. A 77.3% overall response rate was noted: 44.5% and 32.8% for complete and partial responses, respectively. Acitretin was more effective as first-line than as a subsequent agent (P = 0.008). A trend towards better response was observed in the combination arm compared to patients receiving acitretin alone (P = 0.056). Median time to best response was 6.9 months (IQR 4.4-9.4); median duration of response was 23.7 months (IQR 11.9-35.4). Overall, the mean length of all treatment patterns was 569 days (SD 718.8). Therapy was discontinued in 5 (3.9%) cases due to drug intolerance. Adverse effects were recorded in 62 (48.4%) cases with dyslipidaemia (n = 31; 24.2%), xerosis (n = 24; 18.6%) and hair loss (n = 10; 7.8%) being the most commonly recorded. Conclusions Acitretin, either alone or as adjuvant, showed a stable long-term effectiveness in this cohort, especially when used in the first-line setting. This RAR-selective agonist may serve as an attractive option for treatment of MF and should be further evaluated.

Objective Merkel cell carcinoma (MCC) is a rare cutaneous malignancy with a high recurrence and mortality rates. More than half of MCCs occur in the head and neck region. This paper aims to present a retrospective case series study of primary MCCs of the head and neck treated in our department over 12 years. Study Design Six patients were identified, and their characteristics, treatment modalities, and outcomes are reported. A critical review of the current literature is also included to provide up-to-date information on MCCs with special emphasis on treatment modalities and disease prognosis. Results Management of head and neck MCCs requires early and accurate diagnosis and includes surgery, radiotherapy, and/or combination chemotherapy. Accurate cervical nodal staging is of paramount importance before establishing the definite treatment plan. Conclusions The results of both our case series and literature data review indicate that elective management of regional lymph nodes is recommended instead of an observation approach for patients with no identifiable disease in the lymph nodes (cN0). Because the majority of MCCs arise in the head and neck region, oral and maxillofacial surgeons are likely be the first professionals who will encounter this disease and should therefore be aware of the current diagnostic and treatment modalities.

Introduction: Mycosis fungoides (MF), the most common form of cutaneous T-cell lymphomas presents with a broad spectrum of clinical and histopathologic manifestations. Diagnosis is often delayed, especially at the early stages. Clinicopathologic correlation and integration of molecular data is essential for a timely diagnosis and treatment. The use of microRNAs as biomarkers in biopsies and/or biological fluids has gained great interest over the last years. The aim of the present study was to analyze the expression levels of microRNAs (mir)-146a and -155 in the plasma of MF patients and healthy volunteers and to detect the presence of single nucleotide polymorphisms (SNPs) in their genes. Patients and methods: The appropriate sample size for statistical power equal to 0.94 (1–β=94%) and significance level at 0.05 (α=5%) was determined by a pilot study, using G.Power 3.1.9.2. The optimal sample size was calculated at n=82, with a ratio of MF patients/healthy individuals equal to 1:1. All samples were derived from consenting individuals. The mirs’ plasma expression was evaluated with real-time quantitative reverse transcription PCR, and the relative quantity was calculated by the 2–ΔCt method using cel-mir-39 as reference gene. In a subset of patients, the promoter region and/or the pre-microRNA genomic region of these mirs were scanned for the presence of SNPs in DNA extracted from white blood cells, by Sanger sequencing. Statistical analysis was performed with the statistical package IBM SPSS 25. Results: Plasma levels of mir-146a and mir-155 were significantly higher in patients with MF as compared to healthy volunteers (p=0.001 and p=0.028 respectively). Moreover, plasma levels were higher in patients with early MF vs healthy individuals (p=0.001 and p Discussion: The presence of SNPs regulating mirs’ function may need to be evaluated in larger cohorts, while the detection of increased mir-146a and mir-155 plasma levels in MF patients is an important finding in the attempt to establish putative non-invasive biomarkers for prompt diagnosis, prognosis, and adequate therapy of these patients.

Background: Chlormethine gel is a skin-directed therapy used for patients with mycosis fungoides (MF) that has shown promising results in a randomized clinical trial. Currently, data on chlormethine gel use in real-world settings is limited. Objectives: To assess safety and efficacy of chlormethine gel treatment in patients treated during daily clinical practice, and investigate associations between response and disease stage, lesion type, mono- or combination therapy, and occurrence of dermatitis. Methods: A retrospective chart review of patients using chlormethine gel from 3 sites in Greece was performed. Efficacy was assessed through modified Severity-Weighted Assessment Tool (mSWAT) scores. Safety assessments included analysis of the occurrence and severity of dermatitis. The Skindex-29 questionnaire was used to evaluate quality of life. Results: A total of 58 patients were included. The overall response rate (ORR) increased from 37.9% at month 1 to 80.8% at month 9. For 64.2% of patients, response was maintained for at least 4 months (ORR4). At month 3, a higher ORR was seen for patients with patches (69.7%) than patients with plaques/tumors (both 15.2%). A higher ORR4 was observed for patients with early-stage vs late-stage disease (71.4% vs 36.4%) and patients on mono- vs combination therapy (75% vs 47.6%). Dermatitis was observed in the majority of patients (72.4%), but the presence or severity of dermatitis was not directly correlated with treatment response. Both mSWAT and Skindex-29 scores decreased significantly during treatment, and changes in these scores from baseline to month 6 showed a positive correlation (r=0.55, p=0.026). Conclusions: Chlormethine gel treatment was effective for patients with all stages of MF in clinical practice, although patients with patch-stage or early-stage disease may have higher response rates or more durable responses compared with patients with more-advanced disease. Response rates increased over time, indicating that continued treatment with the gel is important. Dermatitis may be managed by reducing the treatment frequency, and the occurrence of dermatitis did not affect the response to CL gel treatment.

Pemphigus is a rare autoimmune disease during pregnancy. Among the different pemphigus types, pemphigus foliaceus (PF) is even rarer than pemphigus vulgaris. We present a case of PF in a 36-year-old female patient who presented with PF onset during pregnancy in the form of a disseminated, erythematosquamous rash. A diagnosis was made on the basis of histologic, immunofluorescence, and enzyme-linked immunosorbent assay results. A complete remission was recorded a month after steroid treatment initiation. The patient delivered a premature (33 weeks) but otherwise healthy baby girl. Only three cases of PF have been reported in two retrospective studies found in the English-language bibliography. Although pemphigus during pregnancy is a rare disease and treatment guidelines have not yet been elucidated, the management of these cases is individually evaluated. In all cases, the primary goal should be the control of the maternal disease along with the safety of the fetus.

Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous adverse reaction mainly attributed to antibiotics. It is characterized by numerous, nonfollicular, sterile pustules, arising on an exanthematous and edematous base. It is a serious adverse reaction accompanied by fever and leukocytosis. Piperacillin/tazobactam is indicated for the treatment of patients with moderate to severe infections. Herein is reported a case of AGEP caused by piperacillin/tazobactam. A 78-year-old woman with metastatic breast cancer was presented to the emergency department reporting fever and groin pain. The laboratory analysis and more specifically urine cultivation showed a urinary tract infection by E. coli with sensitivity to piperacillin/tazobactam. She had no known allergies. She was started on intravenous piperacillin/tazobactam; she improved clinically on the second day, but on the fourth day of intravenous therapy, she developed extensive pustular rash on the folds and anterior proximal thighs, accompanied by fever and neutrophilia. Piperacillin/tazobactam administration was interrupted and she was given prednisolone for ten days. The patient improved clinically and her laboratory tests returned to normal after two weeks. AGEP is an uncommon side effect of piperacillin/tazobactam treatment and there are few cases reported.

BACKGROUND The BIOCHIP (Dermatology Mosaic 7; EUROIMMUN, Lubeck, Germany) is a novel multiplex indirect immunofluorescence (IIF) technique used in the serological diagnosis of bullous pemphigoid (BP) and pemphigus. OBJECTIVE To validate the accuracy and inter-rater reliability (IRR) of the BIOCHIP in the diagnosis of BP, pemphigus foliaceus (PF) and pemphigus vulgaris (PV). METHODS Sera from patients with BP (n = 38), PF (n = 8), PV (n = 23), control patients (n = 64) and healthy control volunteers (n = 39) were tested. Sera were collected and analysed during the course of the disease at 1-5 different time points. The BIOCHIP was performed for all patients, digital images were captured of each incubated field, and the images were shared with 10 dermatologists experienced in reading IF from around the world to report. There were 312 BIOCHIP slides consisting of 1872 photos in total. All patients were de-identified. Fleiss Kappa was used to estimate the IRR. RESULTS Fleiss Kappa was computed for each category (Oesophagus, Oesophagus immunofluorescence pattern, Salt-Split Skin (SSS), SSS immunofluorescence location, BP180, BP230, Dsg 1 and Ds3). The inter-rater agreement between the 10 raters varied between fair and moderate for all categories. Those that demonstrated fair concordance included monkey oesophagus (k = 0.257, P

Bullous pemphigoid (BP) is the most common autoimmune blistering disease affecting the elderly but is quite rare in childhood. The majority of pediatric cases have been reported during early childhood. Adolescence is divided into three phases: early (10-13 years), middle (14-17), and late (18-21). This review aimed to identify BP cases in adolescence and demonstrate their clinical features and course. Our literature search was performed in Medline with the terms "bullous pemphigoid in childhood and adolescence," "childhood bullous pemphigoid," "juvenile bullous pemphigoid," and "autoimmune blistering and autoimmune bullous diseases in childhood." The data extraction for late adolescence was limited by the fact that this age group is included in adult BP registries. We identified nine cases in early adolescence. Mucosa were affected in 5 of 9 cases. Treatment consisted of systemic prednisone (8/9), in combination with dapsone (2/9), azathioprine (2/9), or erythromycin/nicotinamide (1/9). Relapses were reported in 3 of 9 cases. We identified five cases occuring in middle adolescence. Mucosa were not affected. Treatment consisted of systemic prednisone (5/5), in combination with dapsone (3/5), azathioprine (2/5), doxycycline/nicotinamide (1/5), or mycophenolate mofetil (1/5). Relapses were reported in two of five cases. No case of BP in the late adolescence was included in the results, as only one case met the search criteria, and overlapped with pemphigus vulgaris. With only 14 cases found in our review, BP in adolescence appears even rarer than in earlier childhood. Despite its low prevalence, BP should be included in the differential diagnosis of autoimmune blistering diseases in adolescents.

Hidradenitis suppurativa (HS) is a relapsing, inflammatory disease characterized by painful nodules, abscesses, sinuses track formation and scarring. HS has a great impact on patients’ quality of life and its treatment may be really challenging. Adalimumab provides a new therapeutic option for HS. Our aim was to assess the therapeutic potential of adalimumab on patients with HS based on the data from the daily clinical practice of an HS Outpatient Clinic. 19 patients with clinically evident moderate to severe HS, under adalimumab treatment for at least 24 week, participated in this observational, retrospective study. The Hidradenitis Suppurativa Physician’s Global Assessment scale, Modified Santorius scale and Dermatology Life Quality Index (DLQI) at baseline, week 4, week 12 and week 24 were retrieved from the records. Both Modified Santorius score and DLQI were significantly decreased during the weeks of evaluation (Friedman’s test; P < 0.001). The proportion of patients who achieved clinical response was 10.5% (n = 2) at week 4, 42.1% (n = 8) at week 12 and 63.2% (n = 12) at week 24. Treatment with adalimumab was linked with both clinical remission of HS and improvement of patients’ quality of life.

Scleredema diabeticorum is an uncommon skin disorder which is characterized by stiffness and hardening of the subcutaneous tissues located on the upper back and posterior neck. Patients with this skin disease typically experience pain and stiffness on the neck. Scleredema associated with diabetes mellitus may often go unrecognized. We report a case of a 55-year-old female patient with diabetes mellitus type 1, who presented with skin tightness on her upper back and decreased range of motion. Scleredema diabeticorum is rare and its treatment is difficult and tricky, as no specific regimen has been instituted to treat this skin disease.

Summary Background Applicability of dermoscopy in evaluation of outcome and monitoring of superficial basal cell carcinoma (sBCC) after nonablative therapies has not been sufficiently assessed. Objectives Certain dermoscopic criteria, namely pigmented structures, ulceration and arborizing vessels, have been suggested to predict the presence of residual disease [residual disease-associated dermoscopic criteria (RDADC)]. We aimed to assess this hypothesis. Patients and methods Lesions exhibiting RDADC 3 months after treatment were biopsied and in the case of histopathological confirmation were excised. Lesions characterized by white/red structureless areas, superficial fine telangiectasias, or lacking any dermoscopic criterion, were monitored for 12 months. Results At the 3-month evaluation, one or more of the RDADC were detected in 25/98 (25·5%) sBCCs, in which histology confirmed tumour persistence. In 45 (61·6%) of the 73 remaining lesions, dermoscopy showed white/red structureless areas and/or superficial fine telangiectasias. Twenty-eight lacked any dermoscopic criterion of sBCC. The two latter groups entered follow-up. In total, disease recurred in 13 (17·8%) of the 73 lesions. Conclusions RDADC accurately predict residual disease. Absence of dermoscopic criteria of sBCC safely predicts complete histopathological clearance. Detection of white/red structureless areas and/or superficial fine telangiectasias warrants close monitoring to recognize early recurrence.

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This study investigated the expression of interleukin (IL)-17A, -17F and -22 in mycosis fungoides. Blood samples were collected from 50 patients with mycosis fungoides and 50 healthy controls. Skin samples were obtained from 26 patients with mycosis fungoides and 5 healthy controls. Protein levels of IL-17A, -17F and -22 were measured in serum by multiplex enzyme-linked immunosorbent assay, and mRNA expression levels were measured in blood and skin samples by real-time quantitative reverse transcription PCR. Both IL-17A and IL-17F mRNA expression levels were significantly lower in blood of patients with mycosis fungoides in comparison with healthy controls. IL-22 serum levels and expression levels of IL-22 mRNA in skin tissue, were significantly increased in patients with mycosis fungoides in comparison with healthy controls. These results suggest that low levels of IL-17A and IL-17F in mycosis fungoides may be connected to impaired immune surveillance contributing to tumourigenesis. Upregulation of IL-22 may play a role in the establishment of the tumour microenvironment in mycosis fungoides.

Background Metabolic syndrome, a risk factor of cardiovascular disease, is more common in patients with psoriasis than in the general population. Circulating adipokine concentrations are altered in patients with psoriasis and are suggested to represent the pathophysiological link between psoriatic lesions and metabolic alterations. Objectives To perform a systematic review of the literature for studies that investigated possible differences in circulating levels of leptin, adiponectin or resistin in patients with psoriasis before and after any treatment intervention, and to meta-analyse the best evidence available. Methods A search was conducted in three databases (PubMed, Central and Embase). Eligible for the review were studies that assessed leptin, adiponectin or resistin concentrations in patients with psoriasis before and after any topical or systemic treatment. Results After treatment, blood concentrations of leptin were similar to those before treatment [standardized mean difference (SMD) 0·06, 95% confidence interval (CI) -0·09 to 0·20], with no heterogeneity among studies (I2 = 0%, P = 0·88). After treatment, blood concentrations of adiponectin were similar to those before treatment (SMD -0·14, 95% CI -0·34 to 0·05), with significant heterogeneity among studies (I2 = 36·8%, P = 0·032). After treatment, blood concentrations of resistin were significantly lower than those before treatment (SMD 0·50, 95% CI 0·20-0·79), with significant heterogeneity among studies (I2 = 61·4%, P Conclusions There is no evidence that treatment for psoriasis modifies leptin and adiponectin concentrations. However, treatment intervention reduces resistin concentrations, a finding that is expected to be of clinical importance.

BACKGROUND: Epidermolysis bullosa acquisita (EBA) is a complex autoimmune bullous disease disease with variable clinical presentations and multiple possible diagnostic tests, making an international consensus on the diagnosis of EBA essential. ----- OBJECTIVES: To obtain an international consensus on the clinical and diagnostic criteria for EBA. ----- METHODS: The International Bullous Diseases Group (IBDG) met three times to discuss the clinical and diagnostic criteria for EBA. For the final voting exercise, 22 experts from 14 different countries voted on 50 different items. When > 30% disagreed with a proposal, a discussion was held and re-voting carried out. ----- RESULTS: In total, 48 of 50 proposals achieved consensus after discussion. This included nine diagnostic criteria, which are summarized in a flow chart. The IBDG was unable to determine one procedure that would be applicable worldwide. A limitation of the study is that differential diagnosis of bullous systemic lupus erythematosus has not been addressed. ----- CONCLUSIONS: This first international consensus conference established generally agreed-upon clinical and laboratory criteria defining the clinical classification of and diagnostic testing for EBA. Holding these voting exercises in person with the possibility of discussion prior to voting has advantages in reaching consensus over Delphi exercises with remote voting.

Sjögren-Larsson syndrome is a rare neurocutaneous disorder characterized by ichthyosis, spastic diplegia or tetraplegia, and intellectual disability. Herein, we describe a case of a Greek patient with ichthyosis and spasticity of the legs but with normal intelligence (IQ 95). This syndrome should be suspected when a child presents with ichthyosis and spastic diplegia or tetraplegia, even if intelligence is normal.

Leukemic infiltrates may be seen in the skin in the absence of detectable bone marrow involvement. Leukemia cutis may exceptionally occupy the eyelids. An unusual case of a 58-year-old man presenting bilateral erythematous eyelid lesions, proven to be aleukemic leukemia cutis, is reported. Biopsy was conducted and hematoxylin/eosin stained sections were histologically evaluated. Immunohistochemistry was also performed.Light microscopy revealed cutaneous infiltration by a neoplastic population consisting of medium-sized cells. These cells infiltrated the overlying epidermis leading to focal microulcerations. The morphological and immunohistochemical characteristics of the neoplastic population were compatible with myeloid leukemia cutis. The bone marrow biopsy was normocellular for the patient's age. Although chemotherapy was advised, the patient refused any treatment. He remains free of leukemia or evolution of eyelid lesions approximately 1 year after diagnosis. Leukemia cutis of the eyelids is a rare manifestation of acute leukemia and may remain aleukemic in adults for an indefinite period of time.

Summary Nail psoriasis and onychomycosis can often be hard to differentiate clinically and may coexist, complicating each other's course. The aim of this study was to determine the prevalence of onychomycosis among patients with nail psoriasis not being treated with immunosuppressive agents, which constitute an independent risk factor for fungal infections. A cross-sectional study was performed. All adult patients with nail psoriasis who were not receiving antifungal and/or immunosuppressive treatment were recruited at the 2nd University Dermatology Department of Aristotle University of Thessaloniki from 10/2016 till 02/2017. If onychomycosis was clinically suspected, nail samples were collected and direct microscopy with 15% KOH solution and culture were performed. Target-NAPSI and DLQI score were also calculated. Of the 23 patients recruited, 20 were men and 3 were women, with a mean age of 53.43 years (48.25, 58.62), a mean target-NAPSI score of 10.72 (9.62, 11.77) and a mean DLQI score of 10.17 (7.46, 12.89). A total of 34.78% of patients tested positive for onychomycosis. Yeast were isolated in 37.50% of cases, non-dermatophyte filamentous fungi in 37.50% and T. rubrum in 12.50%. The prevalence of onychomycosis among nail psoriasis patients is higher than that among the general population of Greece (15%-20%). Yeast and moulds predominate in infection cases of nail psoriasis patients.

Background: Psoriasis is an immune-mediated, inflammatory disease. Adipokines contribute to the regulation of immune-mediated processes and inflammation. Objective: The aim of our study was to systematically review the literature for studies that have evaluated the circulating concentrations of adipokines in patients with psoriasis and controls and to meta-analyze the best evidence available. Methods: Eligible were studies that have assessed leptin, resistin, or adiponectin concentrations in psoriatic patients and a reference group. The study was conducted in adherence with the PRISMA standards. Results: Psoriatic patients had higher leptin concentrations compared to controls (random effects model, mean difference, MD = 5.64 ng/mL, 95% CI: 3.00-8.29, p < 0.0001). Heterogeneity among studies was high (I2 = 95.9%). Psoriatic patients had higher resistin concentrations compared to controls (MD = 4.66 ng/mL, 95% CI: 2.62-6.69, p < 0.0001). Heterogeneity was high (I2 = 99.2%). Finally, psoriatic patients had lower adiponectin concentrations compared to controls (MD = -1.87 μg/mL, 95% CI: -2.76 to -0.98, p < 0.0001). Heterogeneity was high (I2 = 95.9%). Conclusion: The study supported the hypothesis that leptin and resistin concentrations are higher and adiponectin concentrations are lower in patients with psoriasis compared to controls. Hereby, the suggested pathogenic link between psoriasis and metabolic syndrome/obesity is reinforced and the role of comorbidities in psoriasis is highlighted.

Background A validated tool for the dynamic severity assessment of hidradenitis suppurativa (HS) is lacking. The aim of this study was to develop and validate such a novel scoring system. Methods A Delphi voting procedure was conducted among the members of the European Hidradenitis Suppurativa Foundation (EHSF) to achieve consensus towards an initial HS Severity Score System (HS4). Strengths and weaknesses of HS4 were examined by a multicenter prospective study. Multivariate logistic regression, discriminant analysis and receiver operating characteristic curves and examination for correlation (Spearman's rho) and agreement (Cohen's kappa) with existing scores were engaged to recognize the variables for a new International HS Severity Scoring System (IHS4) that was established by a 2nd Delphi round. Results Consensus HS4 was based on the number of skin lesions, the number of skin areas involved and the Dermatology Life Quality Index and was evaluated by a sample of 236 patients from 11 centers. Subsequently, a multivariate regression model calculated adjusted odds ratios for several clinical signs. Nodules, abscesses and draining tunnels resulted as the scoring variables. Three candidate scores were presented to the 2nd Delphi round. The resulting IHS4 score is calculated by the number of nodules (multiplied by 1) + the number of abscesses (multiplied by 2) + the number of draining tunnels (multiplied by 4). A total score of 3 or less signifies mild, 4-10 signifies moderate and 11 or higher signifies severe disease. Cohen's kappa was fair (κ=0.317) compared with Hurley classification and moderate (κ=0.493) compared with Expert Opinion. Correlation was good (rho>0.6) with Hurley classification, Expert Opinion, Physician's Global Assessment and Modified Sartorius score and moderate for Dermatology Life Quality Index (rho=0.356). Conclusion The novel IHS4 is a validated tool to dynamically assess HS severity and can be used both in real-life and the clinical trials setting.