Trial of Intravenous Immune Globulin in Dermatomyositis.

BACKGROUND: Intravenous immune globulin (IVIG) for the treatment of dermatomyositis has not been extensively evaluated. METHODS: We conducted a randomized, placebo-controlled trial involving patients with active dermatomyositis. The patients were assigned in a 1:1 ratio to receive IVIG at a dose of 2.0 g per kilogram of body weight or placebo every 4 weeks for 16 weeks. The patients who received placebo and those without confirmed clinical deterioration while receiving IVIG could enter an open-label extension phase for another 24 weeks. The primary end point was a response, defined as a Total Improvement Score (TIS) of at least 20 (indicating at least minimal improvement) at week 16 and no confirmed deterioration up to week 16. The TIS is a weighted composite score reflecting the change in a core set of six measures of myositis activity over time; scores range from 0 to 100, with higher scores indicating greater improvement. Key secondary end points included at least moderate improvement (TIS ≥40) and major improvement (TIS ≥60), and change in score on the Cutaneous Dermatomyositis Disease Area and Severity Index. RESULTS: A total of 95 patients underwent randomization: 47 patients were assigned to the IVIG group, and 48 to the placebo group. At 16 weeks, 79% of the patients in the IVIG group (37 of 47) and 44% of those in the placebo group (21 of 48) had a TIS of at least 20 (difference, 35 percentage points; 95% confidence interval, 17 to 53; P<0.001). The results with respect to the secondary end points, including at least moderate improvement and major improvement, were generally in the same direction as the results of the primary end-point analysis, except for the change in creatine kinase level (an individual core measure of the TIS), which did not differ meaningfully between the two groups. Over 40 weeks, 282 treatment-related adverse events occurred in the IVIG group, including headache (in 42% of patients), pyrexia (in 19%), and nausea (in 16%). A total of 9 serious adverse events that were considered to be related to IVIG occurred, including 6 thromboembolic events. CONCLUSIONS: In this 16-week trial involving adults with dermatomyositis, the percentage of patients with a response of at least minimal improvement based on a composite score of disease activity was significantly greater among those who received IVIG than among those who received placebo. IVIG was associated with adverse events, including thromboembolism. (Funded by Octapharma Pharmazeutika; ProDERM ClinicalTrials.gov number, NCT02728752.).

Efficacy and safety of adjuvant immunoadsorption in pemphigus vulgaris and pemphigus foliaceus (IA-Pem Study): a multicentre randomized controlled trial.

BACKGROUND: Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are potentially life-threatening autoimmune blistering diseases. Treatment is based on long-term immunosuppression with high doses of glucocorticosteroids in combination with potentially corticosteroid-sparing agents and/or rituximab. Immunoadsorption (IA) has emerged as a fast-acting adjuvant treatment option. OBJECTIVES: To assess the clinical efficacy of IA in addition to best medical treatment (BMT). METHODS: We conducted a multicentre (26 centres from Germany and Austria) randomized controlled trial in 72 patients with newly diagnosed, relapsed or chronic active PV or PF (34 female patients and 38 male patients, aged 42-72 years) comparing BMT (prednisolone 1.0 mg kg-1 per day plus azathioprine or mycophenolate) with adjuvant IA (BMT + IA). Central 1 : 1 randomization was done at the coordinating centre for clinical trials (KKS Marburg). The primary endpoint was analysed using Kaplan-Meier and Cox regression methods. RESULTS: The study was ended prematurely owing to safety concerns after random allocation of 72 patients to BMT + IA (n = 34) or BMT (n = 38). The primary endpoint, time to complete remission on therapy, was not significantly different for the two groups [hazard ratio (HR) 1.35, 95% confidence interval (CI) 0.68-2.69; P = 0.39]. The cumulative dose of prednisolone was significantly lower in the BMT + IA group compared with BMT alone (difference -1214, 95% CI -2225 to -70; P = 0.03). In a post hoc analysis, patients with more extensive PV/PF showed a tendency towards a shorter time to remission in the BMT + IA group compared with the BMT group (HR 1.87, P = 0.17 in patients with baseline Pemphigus Disease Area Index ≥ 15). While more adverse events were observed in patients in the BMT group (29 vs. 25), severe adverse events were more frequent in patients in the BMT + IA group (17 events in 10 patients vs. 11 events in 8 patients). CONCLUSIONS: In this study, adjuvant IA did not demonstrate a shorter time to clinical remission, but a corticosteroid-sparing effect was observed. In patients with extensive PV/PF, post hoc analysis suggests that adjuvant IA may lead to earlier remission, but potential adverse events must be carefully weighed against the expected benefits.

Pemphigus vulgaris and pemphigus foliaceus are potentially life-threatening autoantibody-driven blistering diseases, which present with erosions or blisters on skin and/or mucous membranes. Treatment is based on long-term immunosuppressive agents. Immunoadsorption (IA) is a procedure that removes autoantibodies from the blood and has emerged as a fast-acting treatment option for pemphigus.We conducted a trial comparing best medical treatment (BMT) (prednisolone 1.0 mg kg per day plus azathioprine or mycophenolate) with best medical treatment plus IA (BMT + IA). A total of 26 centres from Germany and Austria recruited 72 patients with active pemphigus (34 women and 38 men, aged 42­72 years) who were randomly allocated in a ratio of 1 : 1 to the treatment groups.Following inclusion of 72 patients in the BMT + IA (n = 34) or BMT (n = 38) groups, the study ended prematurely owing to safety concerns. The main outcome, time to complete remission (relief of all symptoms) while still receiving therapy, was not significantly different for the two groups. In contrast, the cumulative dose of prednisolone was significantly lower in the BMT + IA compared with BMT alone. In an additional analysis, patients with more extensive pemphigus showed a tendency towards a shorter time to remission in the BMT + IA group compared with the BMT group. While more adverse events were observed in the BMT group (29 vs. 25), severe adverse events were more frequent in the BMT + IA group (17 vs. 11). In this study, IA did not show a shorter time to clinical remission, but a prednisolone-sparing effect was observed. In patients with extensive pemphigus, adjuvant IA may possibly lead to earlier remission, but potential adverse events must be carefully weighed against the expected benefits.

S2k guidelines on diagnosis and treatment of linear IgA dermatosis initiated by the European Academy of Dermatology and Venereology.

INTRODUCTION: Linear IgA dermatosis (LAD) is a rare subepidermal autoimmune bullous disease (AIBD) defined by predominant or exclusive immune deposits of immunoglobulin A at the basement membrane zone of skin or mucous membranes. This disorder is a rare, clinically and immunologically heterogeneous disease occurring both in children and in adults. The aim of this project is to present the main clinical features of LAD, to propose a diagnostic algorithm and provide management guidelines based primarily on experts' opinion because of the lack of large methodologically sound clinical studies. METHODS: These guidelines were initiated by the European Academy of Dermatology and Venereology (EADV) Task Force Autoimmune Bullous Diseases (AIBD). To achieve a broad consensus for these S2k consensus-based guidelines, a total of 29 experts from different countries, both European and non-European, including dermatologists, paediatric dermatologists and paediatricians were invited. All members of the guidelines committee agreed to develop consensus-based (S2k) guidelines. Prior to a first virtual consensus meeting, each of the invited authors elaborated a section of the present guidelines focusing on a selected topic, based on the relevant literature. All drafts were circulated among members of the writing group, and recommendations were discussed and voted during two hybrid consensus meetings. RESULTS: The guidelines summarizes evidence-based and expert opinion-based recommendations (S2 level) on the diagnosis and treatment of LAD. CONCLUSION: These guidelines will support dermatologists to improve their knowledge on the diagnosis and management of LAD.

Divergent in situ expression of IL-31 and IL-31RA between bullous pemphigoid and pemphigus vulgaris.

Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are two major autoimmune blistering skin diseases. Unlike PV, BP is accompanied by intense pruritus, suggesting possible involvement of the pruritogenic cytokine IL-31. However, the underlying mechanisms of the clinical difference between BP and PV in terms of pruritus are not fully understood. To compare the expression levels of IL-31 and its receptor IL-31RA in the lesional skin, including peripheral nerves in BP and PV patients, immunohistochemical staining for IL-31 and IL-31RA was performed in skin samples of BP and PV patients and healthy controls (HC). The IL-31RA-expressing area in epidermis and peripheral nerves was analysed using ImageJ and the percentage of positive cells for IL-31/IL-31RA in dermal infiltrating cells was manually quantified. Quantitative analyses revealed that IL-31/IL-31RA expressions in the epidermis and dermal infiltrate were significantly increased in BP compared to PV and HC. The difference between BP and PV became more obvious when advanced bullous lesions were compared. Peripheral nerves in BP lesions presented significantly higher IL-31RA expression compared to PV lesions. In conclusion, we found significantly augmented expressions of IL-31/IL-31RA in BP lesions, including peripheral nerves, in comparison to PV. These results suggest a possible contribution of IL-31/IL-31RA signalling to the difference between BP and PV in the facilitation of pruritus and local skin inflammation, raising the possibility of therapeutic targeting of the IL-31/IL-31RA pathway in BP patients.

Societal costs and health related quality of life in adult atopic dermatitis.

BACKGROUND: Cost-of-illness studies are widely used for healthcare decision-making in chronic conditions. Our aim was to assess the cost-of-illness of adult atopic dermatitis (AD) from the societal perspective in Hungary. METHODS: We conducted a multicentre, cross-sectional questionnaire survey between February 2018 and January 2021. Data was collected from consecutive AD patients aged ≥ 18 years and their physicians at dermatology departments in Hungary. We calculated direct and indirect costs, including costs for treatments, outpatient visits, hospital admissions, informal care, travel costs and productivity loss. To assess indirect costs, the Work Productivity and Activity Impairment (WPAI) questionnaire was used to collect data, and costs were estimated with the human capital approach. Generalized linear model was used to analyse predictors of total, direct and indirect costs. RESULTS: Altogether 218 patients completed the survey (57.8% female) with an average age of 31.3 (SD = 11.7). Patients' average Dermatology Life Quality Index (DLQI) score was 13.5 (SD = 8.5). According to Eczema Area and Severity Index (EASI) score, 2.3% (n = 5), 21.2% (n = 46), 54.4% (n = 118) and 22.1% (n = 48) had clear, mild, moderate, and severe AD, respectively. We found that the average total, direct medical, direct non-medical and indirect annual costs per patients were €4,331, €1,136, €747, and €2450, respectively, with absenteeism and presenteeism being the main cost drivers, accounting for 24% and 29% of the total cost of AD. A one-year longer disease duration led to, on average, 1.6%, and 4.2% increase in total and direct non-medical costs, respectively. Patients with worse health-related quality of life (higher DLQI score) had significantly higher total, direct medical, direct non-medical costs, and indirect costs. CONCLUSIONS: Our results indicate a substantial economic burden of AD from a societal perspective, mainly driven by productivity losses.

[Geriatric dermatology]. / Geriatrische Dermatologie.

BACKGROUND: With an ageing society the incidences of skin diseases increase. OBJECTIVE: The most important skin diseases in geriatric patients are discussed. MATERIAL AND METHODS: A literature search was conducted using the PubMed database and standard dermatological textbooks. RESULTS: Skin diseases in geriatric patients are often more susceptible to external influences and can be affected by visceral diseases. Due to a delayed diagnosis, malignant skin diseases in geriatric patients are first diagnosed at a higher stage. CONCLUSION: Physiological skin changes are to be treated with appropriate care. In the case of unclear skin changes, a timely dermatological check-up is to be done.

Genetic association and differential expression of HLAComplexGroup lncRNAs in pemphigus.

BACKGROUND: Pemphigus is a group of bullous diseases characterized by acantholysis and skin blisters. As for other autoimmune diseases, the strongest genetic associations found so far for pemphigus foliaceus (PF) and vulgaris (PV) are with alleles of HLA genes. However, apart from protein-coding genes, the MHC region includes a set of poorly explored long non-coding RNA (lncRNA) genes, the HLA complex group (HCG). OBJECTIVES: To investigate if HCG lncRNA alleles are associated with pemphigus susceptibility. METHODS AND RESULTS: We analyzed SNPs in 13 HCG lncRNA genes, both in PV (Germany: 241 patients; 1,188 controls) and endemic PF (Brazil: 227 patients; 194 controls), applying multivariate logistic regression. We found 55 associations with PV (pcorr < 0.01) and nine with endemic PF (pcorr < 0.05), the majority located in TSBP1-AS1 (which includes HCG23) and HCG27 lncRNA genes, independently of HLA alleles previously associated with pemphigus. The association of TSBP1-AS1 rs3129949*A allele was further replicated in sporadic PF (p = 0.027, OR = 0.054; 75 patients and 150 controls, all from Germany). Next, we evaluated the expression levels of TSBP1-AS1, TSBP1, HCG23, and HCG27 in blood mononuclear cells of Brazilian patients and controls. HCG27 was upregulated in endemic PF (p = 0.035, log2 FC = 1.3), while TSBP1-AS1 was downregulated in PV (p = 0.029, log2 FC = -1.29). The same expression patterns were also seen in cultured keratinocytes stimulated with IgG antibodies from patients and controls from Germany. TSBP1 mRNA levels were also decreased in endemic PF blood cells (p = 0.042, log2 FC = -2.14). TSBP1-AS1 and HCG27 were also observed downregulated in CD19+ cells of endemic PF (p < 0.01, log2 FC = -0.226 and -0.46 respectively). CONCLUSIONS: HCG lncRNAs are associated with susceptibility to pemphigus, being TSBP1-AS1 and HCG27 also differentially expressed in distinct cell populations. These results suggest a role for HCG lncRNAs in pemphigus autoimmunity.

New-generation diagnostics in inflammatory skin diseases: Immunofluorescence and histopathological assessment using ex vivo confocal laser scanning microscopy in cutaneous lupus erythematosus.

Ex vivo confocal laser scanning microscopy (CLSM) offers real-time examination of excised tissue in reflectance, fluorescence and digital haematoxylin-eosin (H&E)-like staining modes enabling application of fluorescent-labelled antibodies. We aimed to assess the diagnostic performance of ex vivo CLSM in identifying histopathological features and lupus band test in cutaneous lupus erythematosus (CLE) with comparison to conventional histopathology and direct immunofluorescence (DIF). A total of 72 sections of 18 CLE patients were stained with acridine orange (AO), anti-IgG, anti-IgM and anti-IgA; 21 control samples were stained with AO. Subsequently, ex vivo CLSM examination of all samples was performed in reflectance, fluorescence and digital H&E-like staining modes. Superficial and deep perivascular inflammatory infiltration (94.4%), interface dermatitis (88.9%), spongiosis (83.3%) and vacuolar degeneration (77.7%) were the most common features detected with ex vivo CLSM. Kappa test revealed a level of agreement ranging within "perfect" to "good" between ex vivo CLSM and conventional histopathology. ROC analysis showed that the combination of perivascular infiltration, interface dermatitis and spongiosis detected by ex vivo CLSM has the potential to distinguish between CLE and controls. Basement membrane immunoreactivity with IgG, IgM and IgA was identified in 88.8% (n = 15), 55.5% (n = 10) and 55.5% (n = 10) of the CLE samples using ex vivo CLSM, respectively, whereas DIF showed IgG, IgM and IgA positivity in 94.4% (n = 17), 100% (n = 18) and 88.9% (n = 16) of patients, respectively. In conclusion, ex vivo CLSM enables simultaneous histopathological and immunofluorescence examination in CLE showing a high agreement with conventional histopathology, albeit with a lower performance than conventional DIF.

The measurement performance of the EQ-5D-5L versus EQ-5D-3L in patients with hidradenitis suppurativa.

PURPOSE: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that affects up to 1% of the population in Europe. The EQ-5D is the most commonly used generic instrument for measuring health-related quality of life among HS patients. This study aims to compare the measurement properties of the two adult versions of EQ-5D (EQ-5D-3L and EQ-5D-5L) in patients with HS. METHODS: We recruited 200 consecutive patients with HS (mean age 37 years, 38% severe or very severe HS) to participate in a multicentre cross-sectional survey. Patients completed the EQ-5D-3L, EQ-5D-5L, Dermatology Life Quality Index (DLQI) and Skindex-16 questionnaires. RESULTS: More than twice as many different health state profiles occurred in the EQ-5D-5L compared to the EQ-5D-3L (101 vs. 43). A significant reduction in ceiling effect was found for the mobility, self-care and usual activities dimensions. A good agreement was established between the EQ-5D-3L and EQ-5D-5L with an intraclass correlation coefficient of 0.872 (95% CI 0.830-0.903; p < 0.001) that was confirmed by a Bland-Altman plot. EQ-5D-5L improved both the absolute and relative informativity in all dimensions except for anxiety/depression. EQ-5D-3L and EQ-5D-5L demonstrated similar convergent validity with DLQI and Skindex-16. EQ-5D-5L was able to better discriminate between known groups of patients based on the number of comorbidities and disease severity (HS-Physician's Global Assessment). CONCLUSION: In patients with HS, the EQ-5D-5L outperformed the EQ-5D-3L in feasibility, ceiling effects, informativity and known-groups validity for many important clinical characteristics. We recommend using the EQ-5D-5L in HS patients across various settings, including clinical care, research and economic evaluations.

A Rasch model analysis of two interpretations of 'not relevant' responses on the Dermatology Life Quality Index (DLQI).

PURPOSE: Eight of the ten items of the Dermatology Life Quality Index (DLQI) have a 'not relevant' response (NRR) option. There are two possible ways to interpret NRRs: they may be considered 'not at all' or missing responses. We aim to compare the measurement performance of the DLQI in psoriasis patients when NRRs are scored as '0' (hereafter zero-scoring) and 'missing' (hereafter missing-scoring) using Rasch model analysis. METHODS: Data of 425 patients with psoriasis from two earlier cross-sectional surveys were re-analysed. All patients completed the paper-based Hungarian version of the DLQI. A partial credit model was applied. The following model assumptions and measurement properties were tested: dimensionality, item fit, person reliability, order of response options and differential item functioning (DIF). RESULTS: Principal component analysis of the residuals of the Rasch model confirmed the unidimensional structure of the DLQI. Person separation reliability indices were similar with zero-scoring (0.910) and missing-scoring (0.914) NRRs. With zero-scoring, items 6 (sport), 7 (working/studying) and 9 (sexual difficulties) suffered from item misfit and item-level disordering. With missing-scoring, no misfit was observed and only item 7 was illogically ordered. Six and three items showed DIF for gender and age, respectively, that were reduced to four and three by missing-scoring. CONCLUSIONS: Missing-scoring NRRs resulted in an improved measurement performance of the scale. DLQI scores of patients with at least one vs. no NRRs cannot be directly compared. Our findings provide further empirical support to the DLQI-R scoring modification that treats NRRs as missing and replaces them with the average score of the relevant items.

Interactions between immune system and the microbiome of skin, blood and gut in pathogenesis of rosacea.

The increasingly wide use of next-generation sequencing technologies has revolutionised our knowledge of microbial environments associated with human skin, gastrointestinal tract and blood. The collective set of microorganisms influences metabolic processes, affects immune responses, and so directly or indirectly modulates disease. Rosacea is a skin condition of abnormal inflammation and vascular dysfunction, and its progression is affected by Demodex mites on the skin surface. When looking into the effects influencing development of rosacea, it is not only the skin microbiome change that needs to be considered. Changes in the intestinal microbiome and their circulating metabolites, as well as changes in the blood microbiome also affect the progression of rosacea. Recent research has confirmed the increased presence of bacterial genera like Acidaminococcus and Megasphera in the intestinal microbiome and Rheinheimera and Sphingobium in the blood microbiome of rosacea patients. In this review we discuss our current knowledge of the interactions between the immune system and the skin, gut and blood microbiome, with particular attention to rosacea diagnostic opportunities.

Rosacea and perioral dermatitis: a single-center retrospective analysis of the clinical presentation of 1032 patients.

BACKGROUND: Rosacea is a common chronic inflammatory cutaneous disorder affecting nearly 5.5 % of the adult population. Our aim was to evaluate the prevalence and epidemiology of rosacea and perioral dermatitis (POD) in an ambulatory care setting. METHODS: We retrospectively analyzed medical data of patients with a confirmed diagnosis of rosacea or perioral dermatitis (POD) presenting at our university hospital outpatient clinic during a 3-year period. RESULTS: Out of 1032 patients, 81.5 % were diagnosed with rosacea and 18.5 % with POD. Overall prevalence was 1.4 % for rosacea and 0.3 % for POD. 69.3 % of the analyzed patients were female. Overall mean age was 49.3 ± 7.7 (1-92) years; the women's average age was less than the men's. Patients with POD were younger and predominantly female, whereas patients with phymatous rosacea were older and predominantly male. The most common phenotypes were papulopustular rosacea (68.4 %), erythematotelangiectatic rosacea (22.5 %), and phymatous rosacea (8.0 %). Special forms of rosacea were diagnosed in 15.8 % of the patients; the most frequent were ocular rosacea (6.9 %) and steroid-induced rosacea (5.4 %). CONCLUSIONS: The large patient cohort analyzed in our study provides a good estimate of the frequency of the rosacea subtypes, special forms and of perioral dermatitis in a hospital-based outpatient care setting.

Transglutaminases in autoimmune and inherited skin diseases: The phenomena of epitope spreading and functional compensation.

Transglutaminases (TGs) are structurally and functionally related enzymes that modify the post-translational structure and activity of proteins or peptides, and thus are able to turn on or switch off their function. Depending on location and activities, TGs are able to modify the signalling, the function and the fate of cells and extracellular connective tissues. Besides mouse models, human diseases enable us to appreciate the function of various TGs. In this study, skin diseases induced by genetic damages or autoimmune targeting of these enzymes will be discussed. TG1, TG3 and TG5 contribute to the cutaneous barrier and thus to the integrity and function of epidermis. TGM1 mutations related to autosomal recessive ichthyosis subtypes, TGM5 mutations to a mild epidermolysis bullosa phenotype and as novelty TGM3 mutation to uncombable hair syndrome will be discussed. Autoimmunity to TG2, TG3 and TG6 may develop in a few of those genetically determined individuals who lost tolerance to gluten, and manifest as coeliac disease, dermatitis herpetiformis or gluten-dependent neurological symptoms, respectively. These gluten responder diseases commonly occur in combination. In autoimmune diseases, the epitope spreading is remarkable, while in some inherited pathologies, a unique compensation of the lost enzyme function is noted.

Contact hypersensitivity in adolescents.

BACKGROUND: Contact hypersensitivity is common in adolescents, but data in the literature are limited. Adolescents often use cosmetics, wear jewelry, and obtain tattoos, which can be sources of allergens. METHODS: This was a retrospective, noninterventional cohort study of 100 adolescents (aged 13-18; 74 girls, 26 boys) who were consecutively patch tested. RESULTS: We detected contact hypersensitivity in 51 of the 100 patch-tested patients (51%): 52.7% of the girls and 46.2% of the boys were sensitized. The most common allergens were nickel (17%), thimerosal (12%), para-phenylenediamine (8%), cobalt (7%), and fragrance mix I (6%). Thirteen percent of the reactions did not appear until the seventh day. The majority of clinical lesions affected the hands and face. The most common contact allergens were mercury derivatives, lanolin, and para-phenylenediamine in boys and nickel, thimerosal, para-phenylenediamine, cobalt, and fragrance mix I in girls. Of the 47 adolescents with atopic dermatitis 51.1% had contact hypersensitivity. In this group, skin care product ingredients were the typical allergens (25.5%). The most common contact allergens of those with atopic dermatitis were nickel (12.8%), lanolin (10.6%), and thimerosal (8.5%). CONCLUSION: Contact hypersensitivity is common in adolescents. For patients with therapy-resistant skin lesions affecting the face and hands, patch testing with an evaluation for 7 days is recommended. Our results provide the first data on frequency of contact hypersensitivity in this age group in Hungary. Metals, fragrances, mercuric derivatives, dyeing materials, and skin care products were the most common allergens.

Comorbidity of localized scleroderma and primary biliary cholangitis.

BACKGROUND AND OBJECTIVES: Morphea is frequently associated with other autoimmune disorders. Little is known about the association of morphea and primary biliary cholangitis (PBC). The objective of this case series was to study the possible association of morphea with PBC and to identify risk factors. PATIENTS AND METHODS: Patients with morphea were screened for anti-mitochondrial antibodies (AMA) by indirect immunofluorescence and/or immunoblot. Human leucocyte antigen (HLA) genotyping and deep sequencing for the HLA DRB1 subgroup were confirmed in AMA-positive patients. RESULTS: 6 of 91 patients (6.6 %) showed positivity for AMA, and 4 (4.39 %) had PBC. The mean age of AMA-positive patients was 69.0 years. Of 6 AMA-positive patients, common predisposing alleles (HLA DRB1*15: 01 and HLA DRB1*08) were detectable in two patients. One patient had predisposing alleles for both diseases (HLA DRB1*03: 01 and HLA DRB1*14). One patient had a PBC-conferring allele. Female gender, menopause and tendency for remission of morphea were common in all patients. CONCLUSION: The coexistence of morphea, AMA positivity and PBC is a rare but possible association. Common predisposing HLA alleles might interact in such a simultaneous manifestation. We suggest AMA screening for female patients with generalized morphea before the initiation of methotrexate.

[Cutaneous manifestations in primary immunodeficiency diseases]. / Az elsodleges immunhiány-betegségek bormanifesztációi.

Primary immunodeficiency diseases (PIDs) are inherited, genetic disorders. The majority of PIDs are diagnosed in infancy or early childhood, but manifestation in adulthood may also occur. Frequent, recurrent and prolonged infections, which respond poorly to treatment may be heralding signs. PID patients may have increased suspectibility to infections, that mostly affect the sino-pulmonary and intestinal tracts and the skin. PIDs are also frequently associated with autoimmune and inflammatory disorders. Cutaneous manifestations affect 40% to 70% of patients with diagnosed PID. Bacterial and fungal infections of the skin, recurrent pyogen abscesses are common complications. Severe atopy, eczema and erythroderma occurring early in childhood should raise awareness of PID. Cutaneous granulomas, pigment changes and dysplasia of skin, hair, and nails can also be seen frequently in some of these conditions. Here we overview the most frequent dermatological diseases occuring in patients with PID. Orv Hetil. 2018; 159(23): 937-947.

[Assessment of health-related quality of life in psoriasis patients in Hungary]. / Psoriasisban szenvedo betegek életminoségének vizsgálata Magyarországon.

INTRODUCTION: The health status and health-related quality of life (HRQoL) of patients with psoriasis in Hungary are understudied. AIM: To assess HRQoL in psoriasis patients, to compare HRQoL of psoriasis patients to that of the general public in Hungary and to identify predictors of HRQoL. METHOD: Between 2012 and 2016, two cross-sectional surveys were carried out among psoriasis patients at two academic dermatology departments. HRQoL was assessed by EQ-5D-3L, EQ Visual Analogue Scale (EQ VAS) and Dermatology Life Quality Index (DLQI). Predictors of HRQoL were analysed by multivariate linear regression. RESULTS: 434 patients were enrolled (mean age 49 years, 65% male, 81% moderate-to-severe psoriasis, 43% treated with biologics). Mean EQ-5D-3L, EQ VAS and DLQI scores were 0.74 ± 0.28, 69.06 ± 20.98 and 6.78 ± 7.38, respectively. Overall, 54%, 43%, 40%, 32% and 15% of patients indicated at least some problems in pain/discomfort, anxiety/depression, mobility, usual activities and self-care. EQ-5D-3L index scores in patients were lower compared to the age- and gender-matched general population in Hungary. The difference was statistically significant for the age groups 25-34 and 45-64 in males, and 18-64 in females (p<0.05). Female gender (p = 0.042), psoriatic arthritis (p<0.001) and palmoplantar psoriasis (p = 0.031) were associated with lower EQ-5D-3L index scores. On the contrary, employed and highly educated patients reported higher EQ-5D-3L index scores (p<0.001). CONCLUSIONS: We were the first to assess HRQoL in psoriasis patients by using EQ-5D questionnaire in Hungary, and more broadly in Central and Eastern Europe. Our findings are useful for cost-effectiveness modelling of psoriasis treatments and decision-making in healthcare. Orv Hetil. 2018; 159(21): 837-846.

Routine detection of serum antidesmocollin autoantibodies is only useful in patients with atypical pemphigus.

Autoantibodies against the 3 desmocollin (Dsc; Dsc1-Dsc3) isoforms have been described in different pemphigus variants. Here, we developed state-of-the-art detection systems for serum anti-Dsc1, Dsc2 and Dsc1 IgG and IgA. These assays were applied in 5 different cohorts including pemphigus vulgaris (PV) patients with compatible direct immunofluorescence (IF) microscopy but no reactivity against desmogleins 1 and 3 (n = 24) and sera from patients with autoimmune blistering diseases with positive direct IF microscopy taken at the time of diagnosis (n = 749). We found that detection of anti-Dsc serum reactivity is not helpful in the routine diagnosis of PV, pemphigus foliaceus and paraneoplastic pemphigus but may be valuable in pemphigus vegetans.

Genomewide association study identifies GALC as susceptibility gene for mucous membrane pemphigoid.

Mucous membrane pemphigoid (MMP) is a rare, chronic and often aggressive subepidermal autoimmune blistering disease potentially affecting several mucous membranes with blisters and secondary erosions and scars. The pathogenesis of MMP is poorly understood, and the contribution of genetic predispositions, other than HLA class II allele variants to MMP, is unknown. The objective of this study is to identify susceptibility genes for MMP in a British cohort of MMP patients. A GWAS was conducted in a British cohort of 106 MMP patients. Publicly available genotypes of 2900 blood donors of the UK Blood Service and of 6740 individuals of the 1958 British Birth Cohort served as control. Subsequently, putative susceptibility genes were independently replicated in a German cohort of 42 MMP patients. The GWAS found 38 SNPs in 28 haploblocks with an odds ratio >2 reaching genomewide significance (P < 5.7 × 10-7 ). Replication confirmed an association of MMP with SNPs in rs17203398 (OR: 3.9), located intronically in the ß-galactocerebrosidase gene (GALC) on chromosome 14 and with recessive polymorphisms in rs9936045 (OR: 3.1) in the intergenic region between CASC16 and CHD9 on chromosome 16. The risk of developing MMP is partially genetically determined. SNPs in GALC enhance the risk for MMP, indicating that ß-galactocerebrosidase may be involved in the pathogenesis of MMP. Likewise, impacts of polymorphisms in the intergenic region between CASC16 and CHD9 on the activity of neighbouring genes may facilitate the emergence of MMP. The putative role of both polymorphisms requires functional studies in the future.

Pemphigus Vulgaris Persistently Localized to the Nose with Local and Systemic Response to Topical Steroids.

is missing (Short communication).