Annular plaques on the back.

Annular lichen planus is a rare clinical variant of the lichen planus presenting with round-oval, red to brown macules and plaques with no central atrophy and slightly raised, nonscaly borders. Histopathological features are indistinguishable from typical lichen planus. Given that the accurate diagnosis relies on both the clinical presentation and typical histological features, it is important to be aware of the clinical spectrum of lichen planus. Click https://wileyhealthlearning.com/#/online-courses/6be3b20c-e9c3-40e9-8f36-bfcda6718a73 for the corresponding questions to this CME article.

Serum autoantibody reactivity in bullous pemphigoid is associated with neuropsychiatric disorders and the use of antidiabetics and antipsychotics: a large, prospective cohort study.

BACKGROUND: Bullous pemphigoid (BP), the by far most frequent autoimmune blistering skin disease (AIBD), is immunopathologically characterized by autoantibodies against the two hemidesmosomal proteins BP180 (collagen type XVII) and BP230 (BPAG1 or dystonin). Several comorbidities and potentially disease-inducing medication have been described in BP, yet a systematic analysis of these clinically relevant findings and autoantibody reactivities has not been performed. OBJECTIVE: To determine associations of autoantibody reactivities with comorbidities and concomitant medication. METHODS: In this prospective multicenter study, 499 patients diagnosed with BP in 16 European referral centers were included. The relation between anti-BP180 NC16A and anti-BP230 IgG ELISA values at the time of diagnosis as well as comorbidities and concomitant medication collected by a standardized form were analysed. RESULTS: An association between higher serum anti-BP180 reactivity and neuropsychiatric but not atopic and metabolic disorders was observed as well as with the use of insulin or antipsychotics but not with dipeptidyl peptidase-4 (DPP4) inhibitors, inhibitors of platelet aggregation and L-thyroxine. The use of DPP4 inhibitors was associated with less anti-BP180 and anti-BP230 reactivity compared with BP patients without these drugs. This finding was even more pronounced when compared with diabetic BP patients without DPP4 inhibitors. Associations between anti-BP180 and anti-BP230 reactivities were also found in patients using insulin and antipsychotics, respectively, compared with patients without this medication, but not for the use of inhibitors of platelet aggregation, and L-thyroxine. CONCLUSION: Taken together, these data imply a relation between autoantibody reactivities at the time of diagnosis and both neuropsychiatric comorbidities as well as distinct concomitant medication suggesting a link between the pathological immune mechanisms and clinical conditions that precede the clinically overt AIBD.

Patients with bullous pemphigoid and comorbid psoriasis present with less blisters and lower serum levels of anti-BP180 autoantibodies.

BACKGROUND: Although the association of bullous pemphigoid (BP) and psoriasis is well-established, the clinical and immunological features of patients with coexisting BP and psoriasis are yet to be investigated. OBJECTIVE: We aimed to estimate the prevalence of psoriasis amongst patients with BP and to elucidate the clinical and immunological characteristics of BP patients with comorbid psoriasis. METHODS: A retrospective cohort study including all consecutive patients diagnosed with BP throughout the years 2009-2019 in a tertiary referral centre. RESULTS: The study encompassed 273 patients with BP, of whom 11 (4.0%; 95% CI, 2.3-7.1%) had comorbid psoriasis. The onset of psoriasis preceded that of BP in 81.8% of patients by a median (range) latency of 26.5 (5.0-34.0) years. Compared to BP patients without psoriasis, those with BP and comorbid psoriasis were significantly younger at the onset of BP [71.8 (9.3) vs. 79.4 (9.8) years; P = 0.023], had a milder erosive phenotype [erosion/blister BPDAI mean (SD)score; 5 (4.1) vs. 22.3 (15.2); P = 0.025], lower levels of anti-BP180 NC16A serum autoantibodies [236.6 (266.3) vs. 556.2 (1323.6) U/mL; P = 0.008] and a higher prevalence of isolated linear C3 deposits (36.4% vs. 14.1%; P = 0.043) and a lower prevalence of linear immunoglobulin G deposits (36.4% vs. 68.7%; P = 0.025) along the dermal-epidermal junction by direct immunofluorescence microscopy. CONCLUSIONS: Patients with BP and comorbid psoriasis present at a younger age with milder erosive phenotype and lower levels of pathogenic autoantibodies.

The impact of lesional inflammatory cellular infiltrate on the phenotype of bullous pemphigoid.

BACKGROUND: The influence of cutaneous cellular infiltration on the phenotype of bullous pemphigoid (BP) remains to be established. OBJECTIVES: To evaluate the main histopathological characteristics of patients with BP and to assess the association between the composition of lesional inflammatory infiltrate and the various clinical, immunological and immunopathological aspects of the disease. METHODS: Retrospective study encompassing patients diagnosed with BP throughout the years 2009-2020 in a specialized tertiary referral centre. RESULTS: The study encompassed 136 patients with BP, of whom 27 (19.9%) demonstrated a cell-poor inflammatory infiltrate in lesional skin specimens. Overall, 78 (57.4%), 71 (52.2%) and 5 (3.7%) specimens were found to include eosinophil-predominant, lymphocyte-predominant and neutrophil-predominant inflammatory infiltrates, respectively. Relative to the remaining patients with BP, those with an eosinophil-predominant inflammatory infiltrate had higher (90.8% vs. 77.2%; P = 0.030) whilst those with a cell-poor inflammatory infiltrate lower (70.3% vs. 88.7%; P = 0.017) seropositivity of anti-BP180 NC16A IgG. The latter subgroup presented with higher prevalence of mucosal involvement (25.9% vs. 8.3%; P = 0.011) and a non-inflammatory clinical phenotype (50.0% vs. 17.1%; P = 0.041). Patients with lymphocyte-predominant inflammatory infiltrate manifested with higher severity BPDAI scores and a lower frequency of the non-inflammatory subtype (11.1% vs. 36.4%; P = 0.035), whilst those with a neutrophilic infiltrate presented with lower mean (SD) levels of anti-BP180 NC16A IgG [269.3 (227.6) vs. 722.7 (1499.6) U/mL; P = 0.003]. CONCLUSIONS: Eosinophil-predominance and high cellularity in the lesional inflammatory infiltrate of BP skin are associated with increased seropositivity of anti-BP180 NC16A IgG. Lymphocyte-predominant infiltrates predict a more severe phenotype, pointing towards a pathogenic role of autoreactive lymphocytes.

Expression of PD-1 and Tim-3 is increased in skin of patients with bullous pemphigoid and pemphigus vulgaris.

BACKGROUND: Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are common autoimmune bullous dermatoses (AIBD) characterized by blisters and erosions. Treatment options are limited and often insufficient. Immune checkpoint receptors play critical roles in immune homoeostasis and self- tolerance. Targeting checkpoint receptors is highly efficient in treatment of various cancers, but often also associated with autoimmune side effects. OBJECTIVES: We therefore aimed to investigate the expression of immune checkpoint receptors in patients with BP and PV. METHODS: We analysed expression of the checkpoint receptors programmed cell death protein 1 (PD-1), T-cell immunoglobulin and mucin domain 3 (Tim-3) and lymphocyte activation gene 3 (Lag-3) in lesional skin of patients with BP and PV compared to healthy control skin as well as the expression patterns of PD-1 and Tim-3 on various infiltrating immune cells in skin sections of AIBD by immunohistochemistry and immunofluorescence. We also measured serum levels of soluble PD-1, Tim-3 and Lag-3 in AIBD patients by ELISA. RESULTS: We report on increased expression of PD-1 and Tim-3, but not Lag-3, in lesional skin of patients with BP and PV. Investigating the expression pattern of PD-1 and Tim-3 on different cutaneous immune cells, we observed significant upregulation of PD-1 predominantly on infiltrating CD8 T cells and upregulation of Tim-3 on CD8 T cells as well as macrophages. CONCLUSIONS: Our results suggest exploring immune checkpoint receptors as novel therapeutic targets using an agonistic approach in autoimmune bullous diseases.

Coexistence of bullous pemphigoid with neuropsychiatric comorbidities is associated with anti-BP230 seropositivity.

BACKGROUND: While clustering of bullous pemphigoid (BP) with neuropsychiatric diseases is well-established, the clinical and immunological profile of BP patients with this comorbidity remains to be decisively determined. OBJECTIVES: To evaluate the burden of neurological and psychiatric comorbidities among patients with BP and to elucidate the clinical, immunological and immunopathological features of patients with BP and comorbid neuropsychiatric conditions. METHODS: We performed a retrospective study encompassing patients diagnosed with BP throughout the years 2009-2020 in a specialized tertiary referral centre. Multivariate logistic regression model was used to identify predictors of neuropsychiatric conditions among patients with BP. RESULTS: The study included 273 patients with BP, of whom 123 (45.1%) presented with comorbid neuropsychiatric disease. Compared to the remaining patients with BP (n = 150), those with pre-existing neuropsychiatric diseases demonstrated older mean [standard deviation (SD)] age [81.7 (9.1) vs. 76.9 (10.1); P < 0.001], female preponderance (65.0% vs. 49.3%; P = 0.009), higher seropositivity rate of anti-BP230 (67.7% vs. 36.5%; P = 0.006) and higher levels of anti-BP180 NC16A IgG [651.3 (1279.6) vs. 370.4 (818.6) U/mL; P = 0.039]. In multivariate analysis, anti-BP230 seropositivity was independently associated with coexistence of BP with neuropsychiatric conditions [adjusted odds ratio (OR), 3.43; 95% CI, 1.24-9.52; P = 0.018]. In a sensitivity analysis confined to patients with neurological diseases (n = 103), older age [82.1 (8.4) vs. 77.2 (10.3); P < 0.001] and increased anti-BP230 seropositivity (68.0% vs. 39.7%; P = 0.018) were identified. CONCLUSIONS: The coexistence of BP with neuropsychiatric diseases is independently associated with the generation of anti-BP230 antibodies.

Incidence of pemphigoid diseases in Northern Germany in 2016 - first data from the Schleswig-Holstein Registry of Autoimmune Bullous Diseases.

BACKGROUND: Autoimmune bullous diseases (AIBD) are rare disorders characterized by autoantibody formation against components of adhesion molecules; in pemphigoid diseases (PD), these are proteins of hemidesmosomes and basement membrane, important for cell-matrix adhesion in skin and/or mucous membranes. Incidences of these diseases vary considerably between different populations. OBJECTIVES: To establish a registry prospectively recruiting all AIBD patients in a geographically well-defined region in Northern Germany (Schleswig-Holstein). METHODS: Only patients with verified disease (by clinical presentation, histology, direct and/or indirect immunofluorescence and /or ELISA) living in Schleswig-Holstein were included. Incidences of PD were estimated based on the total number of inhabitants in Schleswig-Holstein, stratified by birth year and sex. RESULTS: Of 67 patients with PD [35 male, 32 female, mean age 75 (standard deviation 14.3 years)], 83% were patients with bullous pemphigoid [n = 56, 28 male, 28 female, mean age 78 (SD 9.9)]. The resulting crude incidences were 23.4 patients/million/year for all pemphigoid patients, 19.6 patients/million/year for bullous pemphigoid (age-standardized 16.9 patients/million/year) with a strong increase in bullous pemphigoid patients in the age group of 85-90 years with 262 patients/million/year. Incidences for bullous pemphigoid were higher in urban compared to rural areas. Other PD (mucous membrane pemphigoid, linear IgA disease, anti-p200 pemphigoid) were less frequent with crude incidences of 2.1, 1.0 and 0.7 patients/million/year, respectively. CONCLUSIONS: This study prospectively analyses the incidence of PD in a carefully defined geographical area. The highest incidence among PD patients was found for bullous pemphigoid. The incidence of bullous pemphigoid is considerably increased compared to previous reports and reveals regional differences. Further studies are needed in order to clarify these findings.

European guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology - Part I.

This guideline on mucous membrane pemphigoid (MMP) has been elaborated by the Task Force for Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology (EADV) with a contribution of physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline encompassing a systematic review of the literature until June 2019 in the MEDLINE and EMBASE databases. This first part covers methodology, the clinical definition of MMP, epidemiology, MMP subtypes, immunopathological characteristics, disease assessment and outcome scores. MMP describes a group of autoimmune skin and mucous membrane blistering diseases, characterized by a chronic course and by predominant involvement of the mucous membranes, such as the oral, ocular, nasal, nasopharyngeal, anogenital, laryngeal and oesophageal mucosa. MMP patients may present with mono- or multisite involvement. Patients' autoantibodies have been shown to be predominantly directed against BP180 (also called BPAG2, type XVII collagen), BP230, laminin 332 and type VII collagen, components of junctional adhesion complexes promoting epithelial stromal attachment in stratified epithelia. Various disease assessment scores are available, including the Mucous Membrane Pemphigoid Disease Area Index (MMPDAI), the Autoimmune Bullous Skin disorder Intensity Score (ABSIS), the 'Cicatrising Conjunctivitis Assessment Tool' and the Oral Disease Severity Score (ODSS). Patient-reported outcome measurements (PROMs), including DLQI, ABQOL and TABQOL, can be used for assessment of quality of life to evaluate the effectiveness of therapeutic interventions and monitor disease course.

European Guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology - Part II.

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.

Long-term outcomes of rituximab therapy in pemphigus.

BACKGROUND: Rituximab induces a rapid remission in most patients with pemphigus. OBJECTIVE: Our aim was to assess the long-term efficacy of rituximab in this disease. METHOD: We conducted a retrospective study of 59 patients with pemphigus treated with rituximab and observed over a median period of 104 months. RESULTS: The rate of complete remission off therapy (CRoff) after the first rituximab cycle was 39%, increasing to 61% with additional rituximab courses. Long-term CRoff was achieved in 27% of patients. The recurrence rate after the first rituximab cycle was 63%, decreasing to approximately 40% with subsequent rituximab cycles. Median time to relapse after the first and subsequent rituximab cycles was 25 months. Renewed rituximab therapy reinduced complete remission in 94% of cases. Baseline anti-desmoglein antibody levels of ≤250 U/mL were significantly associated with the outcome of CRoff. In paired serum samples obtained before the first and six months after the last rituximab therapy, significant reductions of desmoglein-specific autoantibodies were observed. Patients relapsing after a complete remission induced by the first rituximab cycle were more likely to achieve CRoff than patients relapsing after a less favourable outcome and non-responders. There was no significant difference in age, sex, pemphigus subtype, rituximab dosing and disease duration between patients achieving CRoff and those not meeting this end point. CONCLUSIONS: Lower desmoglein-specific antibody levels at baseline were predictive of CRoff. In patients receiving multiple rituximab cycles, complete remission after the first cycle was associated with a favourable long-term outcome. Repeated rituximab courses were highly effective for relapsed disease and improved the overall outcome.

Prevalence and age distribution of pemphigus and pemphigoid diseases among paediatric patients in Germany.

BACKGROUND: Autoimmune bullous diseases are rare and mostly occur in adults. Several cases and small case series have been described in children, but no systematic study about the prevalence of autoimmune bullous diseases (AIBD) in children is available. PATIENTS AND METHODS: We analysed data of 1.7 million children insured in the largest German health insurance company based on the ICD-10-GM classification for the year 2015. Data were adjusted to the general German population based on the data of the Federal Statistical Office for the year 2015. RESULTS: The prevalence of AIBD was calculated to 101.1/million children in 2015, resulting in about 1351 patients below the age of 18 years in Germany. The highest prevalence of all AIBD was seen for pemphigus vulgaris (30.5/million children) followed by linear IgA disease (24.5/million children) and bullous pemphigoid (4.9/million children). CONCLUSION: Autoimmune bullous diseases in minors are scarce but should be taken into consideration in patients with pruritus and/or blisters and erosions on the skin and/or mucous membranes. Treatment is challenging, and due to the rarity of AIBD in minors, the management of these disorders in this patient population is best performed in specialized centres in a multidisciplinary approach, including paediatric dermatologists or dermatologists and paediatricians.

Updated S2K guidelines on the management of pemphigus vulgaris and foliaceus initiated by the european academy of dermatology and venereology (EADV).

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, 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 United States. 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 organizations.

Combined culture and metagenomic analyses reveal significant shifts in the composition of the cutaneous microbiome in psoriasis.

BACKGROUND: The treatment of psoriasis has been revolutionized by the development of biologic therapies. However, the pathogenesis of psoriasis, in particular the role of the cutaneous microbiome, remains incompletely understood. Moreover, skin microbiome studies have relied heavily on 16S rRNA sequencing data in the absence of bacterial culture. OBJECTIVES: To characterize and compare the cutaneous microbiome in 20 healthy controls and 23 patients with psoriasis using metagenomic analyses and to determine changes in the microbiome during treatment. METHODS: Swabs from lesional and nonlesional skin from patients with psoriasis, and from controls matched for site and skin microenvironment, were analysed using both 16S rRNA sequencing and traditional culture combined with mass spectrometry (MALDI-TOF) in a prospective study. RESULTS: Psoriasis was associated with an increased abundance of Firmicutes and a corresponding reduction in Actinobacteria, most marked in lesional skin, and at least partially reversed during systemic treatment. Shifts in bacterial community composition in lesional sites were reflected in similar changes in culturable bacteria, although changes in the microbiota over repeated swabbing were detectable only with sequencing. The composition of the microbial communities varied by skin site and microenvironment. Prevotella and Staphylococcus were significantly associated with lesional skin, and Anaerococcus and Propionibacterium with nonlesional skin. There were no significant differences in the amount of bacteria cultured from the skin of healthy controls and patients with psoriasis. CONCLUSIONS: Shifts in the cutaneous microbiome in psoriasis, particularly during treatment, may shed new light on the pathogenesis of the disease and may be clinically exploited to predict treatment response. What's already known about this topic? Alterations in the composition of the cutaneous microbiome have been described in psoriasis, although methodological differences in study design prevent direct comparison of results. To date, most cutaneous microbiome studies have focused on 16S rRNA sequencing data, including both living and dead bacteria. What does this study add? This prospective observational study confirms that changes in the composition of the cutaneous microbiome, detected by 16S rRNA sequencing, are consistent with those identified by bacterial culture and mass spectrometry. The changes in the microbiome during antipsoriasis therapy should be further investigated to determine whether these represent potential novel biomarkers of treatment response. What is the translational message? Characterization of cutaneous microbiota may ultimately move into the clinic to help facilitate treatment selection, not only by optimizing currently available treatments, but also by identifying new therapeutic targets.

A sensitive and specific assay for the serological diagnosis of antilaminin 332 mucous membrane pemphigoid.

BACKGROUND: Antilaminin 332 mucous membrane pemphigoid (MMP) is an autoimmune subepidermal blistering disease with predominant mucosal involvement and autoantibodies against laminin 332. Malignancies have been associated with this disease; however, no standardized detection system for antilaminin 332 serum antibodies is widely available. OBJECTIVES: Development of a sensitive and specific assay for the detection of antilaminin 332 antibodies. METHODS: An indirect immunofluorescence (IF) assay using recombinant laminin 332 was developed and probed with a large number of antilaminin 332 MMP patient sera (n = 93), as well as sera from patients with antilaminin 332-negative MMP (n = 153), bullous pemphigoid (n = 20), pemphigus vulgaris (n = 20) and noninflammatory dermatoses (n = 22), and healthy blood donors (n = 100). RESULTS: In the novel IF assay, sensitivities with the laminin 332 heterotrimer and the individual α3, ß3 and γ2 chains were 77%, 43%, 41% and 13%, respectively, with specificities of 100% for each substrate. The sensitivity for the heterotrimer increased when an anti-IgG4 enriched antitotal IgG conjugate was applied. Antilaminin 332 reactivity paralleled disease activity and was associated with malignancies in 25% of patients with antilaminin 332 MMP. CONCLUSIONS: The novel IF-based assay will facilitate the serological diagnosis of antilaminin 332 MMP and may help to identify patients at risk of a malignancy.

Grover disease and bullous pemphigoid: a clinicopathological study of six cases.

Grover disease (GD) is an idiopathic dermatosis that typically manifests as itchy papules over the trunk in middle-aged men. Bullous pemphigoid (BP) is an autoimmune bullous disease that affects older people. Not only are the two diseases easily distinguishable on clinical grounds, they are also characterized by differences in histopathology, pathogenesis and response to treatment Thus, the co-occurrence of these two conditions in the same patient is usually considered coincidental. In this report, we present a multicentre retrospective analysis of six patients who developed both GD and BP over a short period of time, and in all cases but one, GD preceded BP. We discuss the clinical and histopathological features of these patients, and the suggested mechanisms of the diseases. We conclude that GD might predispose to the development of BP.

[Anti-p200 pemphigoid]. / Anti-p200-Pemphigoid.

Anti-p200 pemphigoid is a rare autoimmune blistering disease. It belongs to the group of pemphigoid diseases and was first described in 1996. The diagnostic gold standard is the combination of (1) linear deposits of immunoreactants at the dermal epidermal junction by direct immunofluorescence microscopy of a perilesional skin biopsy, (2) detection of circulating autoantibodies binding to the dermal side (blister floor) of human salt split skin by indirect immunofluorescence microscopy, and reactivity with a 200 kDa protein (p200) in extract of human dermis by immunoblotting. In 2009, laminin γ1 was described as an additional target antigen in 90% of anti-p200 pemphigoid patients. Since ex vivo and in vivo studies have shown no direct pathogenic relevance for laminin γ1 antibodies and the preadsorption of patient sera against laminin γ1 does not reduce their reactivity with p200, the molecular identity of p200 still remains to be elucidated. The clinical phenotype of the disease is heterogeneous; in most cases, however, it resembles bullous pemphigoid. Anti-p200 patients are younger and skin lesions more often appear on palms of the hands and soles of the feet than in bullous pemphigoid. Therapy consists of topical and systemic corticosteroids. In addition, the use of daspone and immunosuppressants has been reported.

[Therapy of pemphigus]. / Aktuelle Therapie des Pemphigus.

BACKGROUND: Pemphigus diseases are a heterogeneous group of potentially life-threatening autoimmune bullous disorders. Therefore, rapidly acting and effective therapeutic approaches are essential. OBJECTIVES: In this review, current therapeutic options in line with available guidelines are presented and new therapeutic approaches are discussed. METHODS: A literature search was performed using PubMed. RESULTS: Treatment of pemphigus is based on systemic glucocorticosteroids, frequently combined with potentially corticosteroid-sparing immunosuppressants such as azathioprine and mycophenolate mofetil/mycophenolic acid. Recently, the impressive efficacy of the anti-CD20 antibody rituximab has been shown in a prospective randomized trial. In severe or treatment-refractory cases, immunoadsorption or high-dose intravenous immunoglobulins (IVIG) are recommended. Adjuvant immunoadsorption also seems to be useful within the first 8-12 weeks of therapy in patients with very high autoantibody levels. A variety of new therapeutic approaches is currently evaluated in phase IIa studies. CONCLUSION: Therapy of pemphigus has been greatly improved by the employment of rituximab. The use of glucocorticosteroids, associated with a high number of adverse events and elevated mortality, could be reduced by the additional use of rituximab. After approval of rituximab for the treatment of pemphigus by the US Food and Drug Administration in 2018, licensing in Europe is expected in 2019.

[Anti-laminin 332 mucous membrane pemphigoid with irreversible ocular and tracheobronchial involvement : Delayed diagnosis of a severe autoimmune bullous disease]. / Anti-Laminin-332-Schleimhautpemphigoid mit irreversiblem okulärem und tracheobronchialem Befall : Verspätete Diagnosestellung einer schweren bullösen Autoimmunerkrankung.

A 53-year-old man presented with a 37-year history of erosive and scarring mucosal lesions of several organs. An initial diagnosis of Stevens-Johnson syndrome was maintained for many years. Due to late correct diagnosis of an anti-laminin 332 mucous membrane pemphigoid and the fact that early, targeted, intensified immunosuppressive therapy was not initiated, the disease led to almost complete loss of vision and obstruction of airways.

Accelerated barrier recovery and enhancement of the barrier integrity and properties by topical application of a pH 4 vs. a pH 5·8 water-in-oil emulsion in aged skin.

BACKGROUND: Increased skin-surface pH is an important host-related factor for deteriorated barrier function in aged skin. OBJECTIVES: We investigated whether restoration of skin pH through topical application of a water-in-oil emulsion with pH 4 improved the barrier homeostasis in aged skin, and compared the effects with an identical galenic formulation with pH 5·8. METHODS: The effects of the test formulations on barrier recovery were investigated by repeated measurements of transepidermal water loss (TEWL) and skin pH 3 h, 6 h and 24 h after acetone-induced impairment of barrier function in aged skin. The long-term effects of the pH 4 and pH 5·8 emulsions were analysed by investigation of the barrier integrity and cohesion, the skin-surface pH and the skin roughness and scaliness before and after a 4-week, controlled application of the formulations. RESULTS: The application of the pH 4 emulsion accelerated barrier recovery in aged skin: 3 h and 6 h after acetone-induced barrier disruption the differences in the TEWL recovery between the pH 4 treated and acetone control fields were significant. Furthermore, long-term application of the pH 4 formulation resulted in significantly decreased skin pH, enhanced barrier integrity and reduced skin-surface roughness and scaliness. At the same time points, the pH 5·8 formulation exerted only minor effects on the barrier function parameters. CONCLUSIONS: Exogenous acidification through topical application of a water-in-oil emulsion with pH 4 leads to improvement of the skin barrier function and maintenance of the barrier homeostasis in aged skin.

The role of the microbiome in psoriasis: moving from disease description to treatment selection?

BACKGROUND: With several million microbes per square centimetre of skin, the task of mapping the physiological cutaneous microbiome is enormous. Indeed, the reliance on bacterial culture to identify cutaneous bacterial communities has led to a systematic underappreciation of cutaneous microbial diversity, potentially limiting our understanding of common inflammatory skin diseases, including psoriasis. However, based heavily on developments in molecular biology and bioinformatics, including next-generation sequencing, the last decade has witnessed a marked increase in our understanding of the extent and composition of the cutaneous microbiome. It is already clear that skin-specific (skin site and skin microenvironment), individual-specific (hygiene, sex, age and hormonal status), disease-specific (atopic eczema, acne) and genetic factors can all influence the cutaneous microbiome, albeit to varying and, as yet, ill-defined extents. OBJECTIVES: To investigate the role of the microbiome in psoriasis and to outline how microbiome studies can be harnessed to provide new insights into disease pathogenesis and treatment selection. METHODS: This review briefly describes the process of 16S ribosomal RNA sequencing and then charts our current understanding of the cutaneous microbiome in health and the alterations (dysbiosis) associated with chronic inflammatory diseases, with particular reference to psoriasis. RESULTS: The possibility and clinical relevance of intraindividual cross-talk between the various microbiomes is discussed and potential mechanisms underpinning the interactions between resident skin flora and the immune system are highlighted. CONCLUSIONS: Ultimately, in the age of personalized medicine, the integration of cutaneous microbiome signatures and comprehensive disease and drug response endotypes will herald a novel approach in the clinical management of chronic multisystem inflammatory diseases.