Anti-Ku + myositis: an acquired inflammatory protein-aggregate myopathy.

Myositis with anti-Ku-autoantibodies is a rare inflammatory myopathy associated with various connective tissue diseases. Histopathological studies have identified inflammatory and necrotizing aspects, but a precise morphological analysis and pathomechanistic disease model are lacking. We therefore aimed to carry out an in-depth morpho-molecular analysis to uncover possible pathomechanisms. Muscle biopsy specimens from 26 patients with anti-Ku-antibodies and unequivocal myositis were analyzed by immunohistochemistry, immunofluorescence, transcriptomics, and proteomics and compared to biopsy specimens of non-disease controls, immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM). Clinical findings and laboratory parameters were evaluated retrospectively and correlated with morphological and molecular features. Patients were mainly female (92%) with a median age of 56.5 years. Isolated myositis and overlap with systemic sclerosis were reported in 31%, respectively. Isolated myositis presented with higher creatine kinase levels and cardiac involvement (83%), whereas systemic sclerosis-overlap patients often had interstitial lung disease (57%). Histopathology showed a wide spectrum from mild to pronounced myositis with diffuse sarcolemmal MHC-class I (100%) and -II (69%) immunoreactivity, myofiber necrosis (88%), endomysial inflammation (85%), thickened capillaries (84%), and vacuoles (60%). Conspicuous sarcoplasmic protein aggregates were p62, BAG3, myotilin, or immunoproteasomal beta5i-positive. Proteomic and transcriptomic analysis identified prominent up-regulation of autophagy, proteasome, and hnRNP-related cell stress. To conclude, Ku + myositis is morphologically characterized by myofiber necrosis, MHC-class I and II positivity, variable endomysial inflammation, and distinct protein aggregation varying from IBM and IMNM, and it can be placed in the spectrum of scleromyositis and overlap myositis. It features characteristic sarcoplasmic protein aggregation on an acquired basis being functionally associated with altered chaperone, proteasome, and autophagy function indicating that Ku + myositis exhibit aspects of an acquired inflammatory protein-aggregate myopathy.

The Joint Vasculitis Registry in German-speaking countries (GeVas): subgroup analysis of 266 AAV patients.

OBJECTIVES: Prospective long-term observational data on the disease course of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) were missing in Germany to date. Therefore, the Joint Vasculitis Registry in German-speaking countries (GeVas) has been established to follow the course of patients with AAV. The aim of this study is to present baseline data of patients with newly diagnosed and relapsing AAV enrolled in the GeVas registry. METHODS: GeVas is a prospective, web-based, multicentre, clinician-driven registry for the documentation of organ manifestations, damage, long-term outcomes, and therapy regimens in various types of vasculitis. Recruitment started in June 2019. RESULTS: Between June 2019 and October 2022, 266 patients with AAV were included in the GeVas registry: 173 (65%) with new-onset and 93 (35%) with relapsing AAV. One hundred and sixty-two (61%) patients were classified as granulomatosis with polyangiitis (GPA), 66 (25%) as microscopic polyangiitis (MPA), 36 (13%) as eosinophilic granulomatosis with polyangiitis (EGPA), and 2 (1%) as renal limited AAV. The median age was 59 years (51-70 years, IQR), 130 (51%) patients were female. Most patients were ANCA positive (177; 67%) and affected by general symptoms, pulmonary, ear nose throat (ENT), renal and neurological involvement. For induction of remission, the majority of patients received glucocorticoids (247, 93%) in combination with either rituximab (118, 45%) or cyclophosphamide (112, 42%). CONCLUSIONS: Demographic characteristics are comparable to those in other European countries. Differences were found regarding ANCA status, frequencies of organ manifestations, and therapeutic regimens. The GeVas registry will allow longitudinal observations and prospective outcome measures in AAV.

The Joint Vasculitis Registry in German-speaking countries (GeVas): subgroup analysis of 195 GCA patients.

OBJECTIVES: Giant cell arteritis (GCA) is one of the most common forms of vasculitis. There is an abundance of studies which are conducted in a randomised controlled trial setting but limited with respect to cohort size and follow-up time. GeVas is the first large-scale registry for vasculitides in German-speaking countries that enables to evaluate this rare disease. Herein we focus on the subgroup of GCA patients including follow-up data up to one year. METHODS: GeVas is a prospective, web-based, multicentre registry for the documentation of organ manifestations, outcomes, and therapy regimens in vasculitides. Recruitment started in June 2019. By April 2023, 15 centres were initiated and have started to enrol patients. RESULTS: After 4 years, 195 GCA-patients were included in the registry, of which 64% were female and 36% were male. The average age was 76 years at the time of recruitment (IQR=69-82). Seventy-nine percent were included in the registry because of a newly diagnosed GCA and 21% because of a relapse. At the first assessment most of the patients (89%) described general symptoms. Thirty-one percent stated ocular symptoms. Cranial symptoms were documented in 78% of the cases. All patients were documented with immunosuppressive treatment at start, of whom 95% received prednisolone, 16% cyclophosphamide, 20% methotrexate, and 48% tocilizumab. After three months 62% and after one year 91% of the patients achieved remission. CONCLUSIONS: Regarding demographics, clinical manifestations and diagnostics, our study showed a similar composition compared to other studies. However, our data differed in terms of treatment regimens.

Clinical presentation and genetic variants in patients with autoinflammatory diseases: results from the German GARROD registry.

To investigate clinical symptoms and genetic variants in patients from the German anti-IL-1 registry for autoinflammatory orphan diseases (GARROD) between 2013 and 2022. Multicentre, retrospective analysis of demographic, clinical and genetic data of patients with autoinflammatory diseases (AID) who received anti-IL-1 targeted therapy. The cohort comprised 152 patients with familial Mediterranean fever (FMF; n = 71), cryopyrin-associated periodic syndromes (CAPS; n = 43), TNF-receptor associated periodic syndrome (TRAPS; n = 19), mevalonate kinase deficiency (MKD; n = 3) and unclassified AID (uAID; n = 16). Inflammatory attacks started in 61.2% of the patients before the age of 18 years. The delay between the first AID attack and anti-IL-1 therapy was 17.8 years. Monogenetic AIDs were diagnosed by clinical symptoms. Genetic analyses confirmed the diagnosis in 87.3% of patients with FMF, 65.2% with CAPS and 94.8% with TRAPS. Among this group, heterozygous MEFV variants and variants of unknown significance (VUS) were detected in 22.5% of patients with FMF, 51.2% with CAPS and 47.4% with TRAPS. Patients with VUS were older at disease onset which is consistent with a milder phenotype. Twenty-four patients had secondary AA amyloidosis (AA) at initiation of anti-IL-1 therapy. The mean age of these patients was 16.4 years at their first attack and 44.9 years at the time of AA diagnosis. Turkish-Armenian ancestry correlated with MEFV variants and higher FMF disease activity compared to German ancestry. Molecular genetic analyses should substantiate the clinical diagnosis of a monogenetic AID. Our data support the concept of variable penetrance of VUS which can be associated with late-onset AID.

[Hemophagocytic lymphohistiocytosis and macrophage activation syndrome : A multidisciplinary challenge]. / Hämophagozytische Lymphohistiozytose und Makrophagenaktivierungssyndrom : Eine multidisziplinäre Herausforderung.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome that is characterized by hyperferritinemia, cytopenia, disseminated intravascular coagulopathy and functional disorders of the liver and the central nervous system. The term macrophage activation syndrome is predominantly used for secondary HLH in the context of autoimmune diseases (e.g., systemic juvenile idiopathic arthritis). In addition, malignancies and genetic inborn errors of immunity can predispose to the development of HLH. Infections (e.g., Epstein-Barr virus) in turn represent possible triggers of an acute episode. Due to the unspecific manifestation of the disease, a systematic evaluation of the organ systems is recommended in the clinical and laboratory analytical clarification of hyperinflammatory syndromes. In general, the treatment should be carried out by a multidisciplinary team with expertise in rheumatology, hematological oncology, infectious diseases and intensive care medicine. The primary treatment of HLH usually consists of glucocorticoids and in cases of a rapid deterioration of the condition anakinra (interleukin 1 block) and intravenous immunoglobulins can be employed. Treatment of the underlying disease should be consequently carried out in parallel, together with antimicrobial treatment.

[Behçet's and Cogan's syndromes - The Variable Vessel Vasculitides]. / Behçet- und Cogan-Syndrom.

Behçet's syndrome and Cogan's syndrome constitute the group of variable vessel vasculitides in the Chapel-Hill Nomenclature. They involve arteries and veins of all sizes. As reflected in the name "syndrome", both diseases can manifest with different individual symptoms. Both formally are rare diseases, but the Cogan syndrome is much rarer than Behçet`s. For the latter, there are diagnosis and classification criteria as well as European (EULAR, European Alliance of Associations for Rheumatology) treatment recommendations. The symptomatology, diagnostic measures and treatment as well as some considerations about pathogenesis will be discussed in this article.

EULAR study group on 'MHC-I-opathy': identifying disease-overarching mechanisms across disciplines and borders.

The 'MHC-I (major histocompatibility complex class I)-opathy' concept describes a family of inflammatory conditions with overlapping clinical manifestations and a strong genetic link to the MHC-I antigen presentation pathway. Classical MHC-I-opathies such as spondyloarthritis, Behçet's disease, psoriasis and birdshot uveitis are widely recognised for their strong association with certain MHC-I alleles and gene variants of the antigen processing aminopeptidases ERAP1 and ERAP2 that implicates altered MHC-I peptide presentation to CD8+T cells in the pathogenesis. Progress in understanding the cause and treatment of these disorders is hampered by patient phenotypic heterogeneity and lack of systematic investigation of the MHC-I pathway.Here, we discuss new insights into the biology of MHC-I-opathies that strongly advocate for disease-overarching and integrated molecular and clinical investigation to decipher underlying disease mechanisms. Because this requires transformative multidisciplinary collaboration, we introduce the EULAR study group on MHC-I-opathies to unite clinical expertise in rheumatology, dermatology and ophthalmology, with fundamental and translational researchers from multiple disciplines such as immunology, genomics and proteomics, alongside patient partners. We prioritise standardisation of disease phenotypes and scientific nomenclature and propose interdisciplinary genetic and translational studies to exploit emerging therapeutic strategies to understand MHC-I-mediated disease mechanisms. These collaborative efforts are required to address outstanding questions in the etiopathogenesis of MHC-I-opathies towards improving patient treatment and prognostication.

How to treat VEXAS syndrome: a systematic review on effectiveness and safety of current treatment strategies.

OBJECTIVES: To evaluate the effectiveness and safety of current treatment strategies for the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. METHODS: A protocolized systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed. Three databases were searched for reports on treatment strategies for VEXAS. Data from the included publications was extracted and a narrative synthesis was performed. Treatment response was recorded as complete (CR), partial (PR) or none (NR) depending on changes in clinical symptoms and laboratory parameters. Patient characteristics, safety data and previous treatments were analysed. RESULTS: We identified 36 publications with a total of 116 patients; 113 (98.3%) were male. The identified reports included azacytidine (CR 9/36, 25%; PR 14/36, 38.9%), Janus kinase inhibitors (JAKi) (CR 11/33, 33%; PR 9/33, 27.3%), tocilizumab (CR 3/15, 20%; PR 6/15, 40%), allogeneic stem cell transplantation (CR 6/7, 85.7%; one patient died), anakinra (CR 4/5, 80%; NR 1/5, 20%), canakinumab (CR 1/2, 50%; PR 1/2, 50%) and glucocorticoid monotherapy (CR 1/6, 16.7%; PR 4/6, 66.7%). Individual reports were available for TNF inhibitors, rituximab and MTX. Data on adverse events were available for 67 patients (67/116, 57.8%) and included: pneumonia (12/67, 17.9%), other infections (9/67, 13.4%), venous thromboembolisms (6/67, 8.9%), cytopenias (4/67, 5.9%), and acute (4/67, 5.9%) and chronic graft-vs-host-disease (2/67, 2.9%). CONCLUSION: Current data on VEXAS treatment are limited and inhomogeneous. Treatment decisions should be individualized. For the devolvement of treatment algorithms clinical trials are needed. Adverse events remain a challenge, especially an elevated risk for venous thromboembolism associated to JAKi treatment should be carefully considered.

When it looks like Behçet's syndrome but is something else: differential diagnosis of Behçet's syndrome: a two-centre retrospective analysis.

OBJECTIVE: To investigate the differential diagnostic spectrum in patients with suspected Behçet's syndrome (BS) in low prevalence regions. In addition, the number of patients fulfilling the ICBD criteria despite not having BS was evaluated. METHODS: This retrospective analysis was performed in two referral centres for BS. Patients with confirmed BS (clinical diagnosis with fulfilment of ISG criteria or a score of ≥5 points in the ICBD criteria) were excluded. The remaining patients were divided into 11 differential diagnosis categories. If no definitive alternative diagnosis could be established, patients were termed 'probable BS' in case of (i) relapsing orogenital aphthosis in the absence of other causes and either HLA-B51 positivity, or origin from an endemic area or presence of an additional typical BS symptom that is not part of the classification criteria, or (ii) with 3-4 points scored in the ICBD criteria. RESULTS: In total 202 patients were included and categorized as follows: 58 patients (28.7%) as 'probable BS', 57 (28.2%) skin disease, 26 (12.9%) chronic pain syndrome, 14 (6.9%) eye disease, 11 (5.4%) spondyloarthropathy, 9 (4.5%) gastrointestinal disease, 7 (3.5%) neurological disease, 4 (2%) arthritis, 3 (1.5%) auto-inflammation, 3 (1.5%) connective tissue disease and 10 (5.0%) miscellaneous disease. HLA-B51 was positive in 55/132 (41.7%); 75/202 (37.1%) of the patients fulfilled the ICBD criteria. CONCLUSION: In a low disease prevalence setting, the straightforward application of the ICBD criteria may lead to overdiagnosis of BS. The differential diagnosis of BS is enormously broad. Clinicians should be aware that HLA-B51 positivity is still not considered as a diagnostic feature in BS.

Anti-acid therapy in SSc-associated interstitial lung disease: long-term outcomes from the German Network for Systemic Sclerosis.

OBJECTIVES: Gastroesophageal reflux disease (GERD) occurs frequently in patients with SSc. We investigated whether the presence of GERD and/or the use of anti-acid therapy, specifically proton-pump inhibitors (PPIs), are associated with long-term outcomes, especially in SSc-associated interstitial lung disease (SSc-ILD). METHODS: We retrospectively analysed patients with SSc and SSc-ILD from the German Network for Systemic Sclerosis (DNSS) database (2003 onwards). Kaplan-Meier analysis compared overall survival (OS) and progression-free survival (PFS) in patients with GERD vs without GERD (SSc and SSc-ILD), and PPI vs no PPI use (SSc-ILD only). Progression was defined as a decrease in either percentage predicted forced vital capacity of ≥10% or single-breath diffusing capacity for carbon monoxide of ≥15%, or death. RESULTS: It was found that 2693/4306 (63%) registered patients with SSc and 1204/1931 (62%) with SSc-ILD had GERD. GERD was not associated with decreased OS or decreased PFS in patients in either cohort. In SSc-ILD, PPI use was associated with improved OS vs no PPI use after 1 year [98.4% (95% CI: 97.6, 99.3); n = 760 vs 90.8% (87.9-93.8); n = 290] and after 5 years [91.4% (89.2-93.8); n = 357 vs 70.9% (65.2-77.1); n = 106; P < 0.0001]. PPI use was also associated with improved PFS vs no PPI use after 1 year [95.9% (94.6-97.3); n = 745 vs 86.4% (82.9-90.1); n = 278] and after 5 years [66.8% (63.0-70.8); n = 286 vs 45.9% (39.6-53.2); n = 69; P < 0.0001]. CONCLUSION: GERD had no effect on survival in SSc or SSc-ILD. PPIs improved survival in patients with SSc-ILD. Controlled, prospective trials are needed to confirm this finding.

Secondary immune-mediated thrombotic thrombocytopenic purpura in idiopathic inflammatory myopathy: a case-based review.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a potentially fatal acquired thrombotic microangiopathy syndrome that frequently develops in the context of infectious diseases or systemic autoimmune conditions including connective tissue diseases. We report the case of a 42-year-old female suffering from severe iTTP associated with anti-Jo-1 positive antisynthetase syndrome, which was successfully treated with combination therapy of intravenous immune globulin, rituximab and plasma exchange. Based on a systematic review of the literature, two additional cases of idiopathic inflammatory myopathy-associated iTTP (secondary iTTP) were identified. In conclusion, iTTP may be a rare complication of IIM that clinicians should consider in cases of marked thrombocytopenia. Further work-up of this finding should include a peripheral blood smear (schistocyte count) and ADAMTS13 activity. The concomitant manifestation of these autoimmune conditions may require intensive immunosuppressive therapy.

[Cocaine-induced vasculitis and mimics of vasculitis]. / Kokain-induzierte Vaskulitiden und Vaskulitis-Mimics.

Cocaine is a psychotropic tropane alkaloid and stimulant drug. Nasal insufflation of cocaine powder is a common route of administration. In Germany, cocaine is frequently adulterated with levamisole, an anthelminthic drug with immunomodulatory effects. Both substances are linked to various autoimmune conditions. Cocaine-induced midline destructive lesions cause a progressive destruction of osteocartilaginous structures within the upper respiratory tract and can mimic localized granulomatosis with polyangiitis. In addition, systemic vasculitis due to cocaine and levamisole has been reported. Differentiation of these conditions from primary vasculitis can be challenging because antineutrophil cytoplasmic antibodies (ANCA) are commonly detected. Early diagnosis of these conditions is crucial as clinical improvement is closely related to drug cessation.

[Hughes-Stovin syndrome: a life-threatening manifestation of Behçet's syndrome]. / Hughes-Stovin-Syndrom: eine lebensbedrohliche Manifestation des Behçet-Syndroms.

Hughes-Stovin syndrome (HSS) is a systemic inflammatory condition of unknown origin that is considered to be part of the Behçet's syndrome (BS) spectrum. Recurrent venous thrombosis and superficial thrombophlebitis in combination with bilateral pulmonary artery aneurysms (PAA) represent the hallmark of HSS. The diagnostic evaluation includes computed tomography pulmonary angiography to detect signs of pulmonary vasculitis. The management of HSS is based on the European Alliance of Associations for Rheumatology (EULAR) recommendations for BS and mainly comprises immunosuppressive therapy with glucocorticoids and cyclophosphamide. In addition to drug therapy, PAA should be evaluated for interventional treatment. Spontaneous PAA rupture due to fragile vessel architecture can occur even in cases of remission and/or PAA regression.

[Chronic Tropheryma whipplei infection: an important differential diagnosis of refractory polyarthritis]. / Chronische Tropheryma-whipplei-Infektion: Eine wichtige Differentialdiagnose der therapierefraktären Polyarthritis.

BACKGROUND: Refractory arthritis is a common problem in routine rheumatology practice, and can be a diagnostic challenge. In these cases, chronic Tropheryma whipplei (T. whipplei) infection is an important differential diagnosis that should be considered. OBJECTIVE: Based on five clinical cases, this case-based review describes the diagnostic and therapeutic principles in the management of chronic T. whipplei infection. RESULTS: Whipple's disease is a multisystemic infectious disease caused by the bacterium T. whipplei. The disease typically manifests with arthralgia, weight loss and diarrhoea. Joint involvement often develops years before gastrointestinal symptoms occur. In addition to systemic manifestations ("classic Whipple's disease"), T. whipplei can also lead to localized joint infections without gastrointestinal involvement. Articular manifestations of systemic and localized T. whipplei infections are commonly misdiagnosed as a sign of various forms of autoimmmune arthritis. DISCUSSION: Whipple's disease and localized T. whipplei joint infection should be considered in the diagnostic work-up of refractory arthritis. Synovial fluid analysis by means of specific polymerase chain reaction-based testing for T. whipplei is diagnostically ground-breaking.

Sex-specific analysis in Behçet's disease reveals higher genetic risk in male patients.

OBJECTIVES: Behçet's disease tends to be more severe in men than women. This study was undertaken to investigate sex-specific genetic effects in Behçet's disease. METHODS: A total of 1762 male and 1216 female patients with Behçet's disease from six diverse populations were studied, with the majority of patients of Turkish origin. Genotyping was performed using an Infinium ImmunoArray-24 BeadChip, or extracted from available genotyping data. Following imputation and extensive quality control measures, genome-wide association analysis was performed comparing male to female patients in the Turkish cohort, followed by a meta-analysis of significant results in all six populations. In addition, a weighted genetic risk score for Behçet's disease was calculated and compared between male and female patients. RESULTS: Genetic association analysis comparing male to female patients with Behçet's disease from Turkey revealed an association with male sex in HLA-B/MICA within the HLA region with a GWAS level of significance (rs2848712, OR = 1.46, P = 1.22 × 10-8). Meta-analysis of the effect in rs2848712 across six populations confirmed these results. Genetic risk score for Behçet's disease was significantly higher in male compared to female patients from Turkey. Higher genetic risk for Behçet's disease was observed in male patients in HLA-B/MICA (rs116799036, OR = 1.45, P = 1.95 × 10-8), HLA-C (rs12525170, OR = 1.46, P = 5.66 × 10-7), and KLRC4 (rs2617170, OR = 1.20, P = 0.019). In contrast, IFNGR1 (rs4896243, OR = 0.86, P = 0.011) was shown to confer higher genetic risk in female patients. CONCLUSIONS: Male patients with Behçet's disease are characterized by higher genetic risk compared to female patients. This genetic difference, primarily derived from our Turkish cohort, is largely explained by risk within the HLA region. These data suggest that genetic factors might contribute to differences in disease presentation between men and women with Behçet's disease.

New-onset dermatomyositis following SARS-CoV-2 infection and vaccination: a case-based review.

Dermatomyositis is a rare, type I interferon-driven autoimmune disease, which can affect muscle, skin and internal organs (especially the pulmonary system). In 2021, we have noted an increase in new-onset dermatomyositis compared to the years before the SARS-CoV-2 pandemic in our center. We present four cases of new-onset NXP2 and/or MDA5 positive dermatomyositis shortly after SARS-CoV-2 infection or vaccination. Three cases occurred within days after vaccination with Comirnaty and one case after SARS-CoV-2 infection. All patients required intensive immunosuppressive treatment. MDA5 antibodies could be detected in three patients and NXP2 antibodies were found in two patients (one patient was positive for both antibodies). In this case-based systematic review, we further analyze and discuss the literature on SARS-CoV-2 and associated dermatomyositis. In the literature, sixteen reports (with a total of seventeen patients) of new-onset dermatomyositis in association with a SARS-CoV-2 infection or vaccination were identified. Ten cases occurred after infection and seven after vaccination. All vaccination-associated cases were seen in mRNA vaccines. The reported antibodies included for instance MDA5, NXP2, Mi-2 and TIF1γ. The reviewed literature and our cases suggest that SARS-CoV-2 infection and vaccination may be considered as a potential trigger of interferon-pathway. Consequently, this might serve as a stimulus for the production of dermatomyositis-specific autoantibodies like MDA5 and NXP2 which are closely related to viral defense or viral RNA interaction supporting the concept of infection and vaccination associated dermatomyositis.

[Differential diagnosis of a vasculitic syndrome of the lower limb]. / Differenzialdiagnose eines vaskulitischen Syndroms der unteren Extremität.

Vasculitides can present with various clinical signs and symptoms. Besides disease-specific organ manifestations, the skin, peripheral nerves and musculature are frequently involved. The combination of elevated serological inflammatory markers, vasculitic skin lesions, active polyneuropathy and immobilizing myalgia of the lower limb musculature is highly suspicious for muscular polyarteritis nodosa (mPAN). Based on the case of a 63-year-old female patient with a vasculitic syndrome confined to the lower limb due to mPAN, important differential diagnoses of the these disease manifestations are discussed. Magnetic resonance imaging of the affected muscles and subsequent muscle biopsy (including skin and fascia) provide the relevant diagnostic data.

[Visceral leishmaniasis mimicking Felty's syndrome in rheumatoid arthritis treated with methotrexate and etanercept]. / Imitation eines Felty-Syndroms durch eine viszerale Leishmaniasis bei rheumatoider Arthritis unter Therapie mit Methotrexat und Etanercept.

Visceral leishmaniasis (VL) is a chronic parasitic disease caused by pathogens of the genus Leishmania, which can mimic numerous diseases. The leading symptoms of VL (splenomegaly, pancytopenia, fever) can be misinterpreted, especially if autoantibodies are detected, and lead to the misdiagnosis of an underlying rheumatic disease (e.g. systemic lupus erythematosus, Felty's syndrome). Proinflammatory cytokines such as tumour necrosis factor alpha (TNF-α) play an important role in infection control. In this context, there are increasing reports of VL as an opportunistic infection during treatment with anti-TNF­α agents. A case of VL mimicking Felty's syndrome in a patient with rheumatoid arthritis treated with methotrexate and etanercept is presented.

[Renal manifestations in connective tissue diseases]. / Nierenbeteiligung bei Kollagenosen.

Connective tissue diseases (CTD) comprise a group of inflammatory systemic diseases that can affect various organs. Kidney involvement is frequently associated with significant irreversible damage and often before patients become symptomatic. Screening tests of blood and urine as well as clinical vigilance are therefore essential for all CTDs with possible renal involvement. A kidney biopsy is the gold standard for the diagnosis, prognosis and treatment decisions. A common and severe organ involvement in systemic lupus erythematosus (SLE) is glomerulonephritis (GN), also collectively referred to as lupus nephritis (LN). If left untreated LN often leads to end-stage renal failure. The treatment depends on the clinical parameters and histopathology of the renal involvement. Mycophenolate mofetil and cyclophosphamide are potent but nonspecific immunosuppressants which have been available for many years. Recently, new substances specific for LN have also been approved for the first time. Kidney involvement in Sjogren's syndrome has been far less studied. In studies the frequency of renal involvement is still unclear and ranges from 5% to 33%. Tubulointerstitial nephritis (IN) is the typical form of renal involvement which clearly differs from GN in its clinical presentation. Recommendations for treatment are based exclusively on retrospective studies. A renal crisis in systemic scleroderma (SSc) is a rare but feared complication with a high mortality. An antiphospholipid syndrome (APS) nephropathy (APSN) can occur during CTD. These entities are vasculopathies and often thrombotic microangiopathies, which clearly differ from GN and IN in terms of pathophysiology, clinical features and treatment. This article provides an overview of the diversity of the most important renal manifestations of CTDs.

[Clinical aspects, diagnostics and differential diagnostics of uveitis for rheumatologists]. / Klinik, Diagnostik und Differenzialdiagnostik der Uveitis für Rheumatologen.

This review article presents the different forms of uveitis and their clinical manifestations. The exact type and localization of the ocular inflammation is crucial for the probability of the underlying rheumatological disease and thus for a correct differential diagnosis. In this first part, in addition to the anatomy of the eye, the different forms of uveitis including the associated nomenclature, typical symptoms, diagnostics and possible complications are presented. In a following second part ("Association of the different forms of uveitis with inflammatory rheumatic diseases and their treatment"), the associations with rheumatological and other systemic diseases are explained and highlighted from an ophthalmological and rheumatological perspective.