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ObjectiveTo 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.MethodsThis 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.ResultsIn 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.ConclusionIn 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.

© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/., 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.

ZusammenfassungKokain ist ein psychoaktives Tropanalkaloid, das typischerweise in Form von Pulver nasal konsumiert wird. Das in Deutschland im Umlauf befindliche Kokain ist häufig mit Levamisol, einem Anthelminthikum mit immunmodulatorischer Wirkung, versetzt. Sowohl Kokain als auch Levamisol werden mit der Entwicklung von klinisch bedeutsamen Autoimmunphänomenen in Verbindung gebracht. Bei den sog. „cocaine-induced midline destructive lesions“ handelt es sich um Gewebedestruktionen des HNO-Traktes, die eine lokalisierte Granulomatose mit Polyangiitis imitieren können. Zusätzlich wurde auch die Entwicklung einer systemischen Vaskulitis durch Kokain und Levamisol beschrieben. Die Unterscheidung dieser Syndrome von einer primären Vaskulitis stellt häufig eine klinische Herausforderung dar, da immunserologisch in den meisten Fällen antineutrophile zytoplasmatische Antikörper (ANCA) nachweisbar sind. Die klinische Besserung ist eng mit der Beendigung des Substanzkonsums verknüpft, deshalb kommt der frühzeitigen Diagnosestellung eine besondere Bedeutung zu.

Zusammenfassung Einleitung Die Alkoholabhängigkeit ist eine chronisch-rezidivierende Abhängigkeitserkrankung. Für verschiedene Behandlungsformen konnte eine positive Wirksamkeit auf den Verlauf der Erkrankung nachgewiesen werden. Die subjektive Sicht der Patienten auf ihre Erkrankung und die angebotenen Behandlungen ist bislang noch wenig untersucht. Methoden 30 Patienten mit einer Alkoholabhängigkeitserkrankung (n = 20 Psychiatrische Klinik, n = 10 Suchtberatung) wurden gefragt, wie sie in der Vergangenheit mit dem Alkoholproblem umgegangen sind. Die Interviews wurden aufgezeichnet, transkribiert und anhand aktueller qualitativer Auswertungsmethoden analysiert. Ergebnisse Die Aussagen der Patienten konnten drei Kategorien zugeordnet werden. Die Alkoholabstinenz, die Suchtbehandlungen und das soziale Umfeld wurden mehrheitlich positiv beschrieben. Allerdings zeigten die meisten Patienten sowohl positive als auch negative Aussagen in diesen Bereichen. Diskussion Die gegensätzlichen Aussagen zeigen ein Spannungsfeld auf, das die Ambivalenz der alkoholabhängigen Patienten in relevanten Bereichen demonstriert. Diese Ambivalenz kann wichtig für die Therapie und den Verlauf der Erkrankung sein.

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.Kokain ist ein psychoaktives Tropanalkaloid, das typischerweise in Form von Pulver nasal konsumiert wird. Das in Deutschland im Umlauf befindliche Kokain ist häufig mit Levamisol, einem Anthelminthikum mit immunmodulatorischer Wirkung, versetzt. Sowohl Kokain als auch Levamisol werden mit der Entwicklung von klinisch bedeutsamen Autoimmunphänomenen in Verbindung gebracht. Bei den sog. „cocaine-induced midline destructive lesions“ handelt es sich um Gewebedestruktionen des HNO-Traktes, die eine lokalisierte Granulomatose mit Polyangiitis imitieren können. Zusätzlich wurde auch die Entwicklung einer systemischen Vaskulitis durch Kokain und Levamisol beschrieben. Die Unterscheidung dieser Syndrome von einer primären Vaskulitis stellt häufig eine klinische Herausforderung dar, da immunserologisch in den meisten Fällen antineutrophile zytoplasmatische Antikörper (ANCA) nachweisbar sind. Die klinische Besserung ist eng mit der Beendigung des Substanzkonsums verknüpft, deshalb kommt der frühzeitigen Diagnosestellung eine besondere Bedeutung zu.

Purpose of Review To provide a comprehensive overview of the spectrum of large and medium vessel vasculitis in adults with primary vasculitides, arthritides, connective tissue, and fibroinflammatory diseases as well as vasculitis mimics, for an efficient differential diagnosis and initial diagnostic approach. Recent Findings Imaging has had a tremendous impact on the diagnosis of medium to large vessel vasculitis, now often replacing histopathologic confirmation and identifying new disease manifestations (e.g., intracranial disease in giant cell arteritis; vascular manifestations of IgG4-related disease). Novel diseases or syndromes involving blood vessels have been described (e.g., VEXAS-Syndrome with polychondritis). The use of the terms “medium” or “large” vessel varies considerably between medical specialties. Summary The differential diagnosis of large and medium vessel vasculitis is becoming increasingly complex as new entities or disease manifestations of known inflammatory rheumatic diseases are regularly identified. A more precise and widely recognized definition of the vessel sizes would make future research more comparable.

Objectives To characterize the effect of ultra-short glucocorticoids followed by Tocilizumab monotherapy on the intima-media thickness (IMT) in GCA. Methods Eighteen GCA patients received 500 mg for 3 consecutive days (total of 1500mg) i.v. methylprednisolone on days 0–2, followed by i.v. Tocilizumab (8 mg/kg) on day 3 and thereafter weekly s.c. Tocilizumab injections (162 mg) over 52 weeks. US of temporal (TAs), axillary (AAs) and subclavian (SAs) arteries was performed at baseline, on days 2–3, and at weeks 4, 8, 12, 24 and 52. The largest IMT of all segments and IMT at landmarks of AA/SA were recorded. IMT was scaled by mean normal values and averaged. Each segment was classified according to diagnostic cut-offs. Results Of the 18 GCA patients, 16 patients had TA and 6 had extracranial large artery involvement. The IMT showed a sharp decline on day 2/3 in the TAs and AAs/SAs. In TAs, this was followed by an increase to baseline levels at week 4 and a subsequent slow decrease, which was paralleled by decreasing symptoms and achievement of clinical remission. The AAs/SAs showed a new signal of vasculitis at week 4 in three patients, with an IMT increase up to week 8. Conclusion Glucocorticoid pulse therapy induced a transient decrease of the IMT in TAs and AAs/SAs. Tocilizumab monotherapy resulted in a slow and steady decrease in IMT of the TAs and a smaller and delayed effect on the AAs/SAs. The data strongly support a remission-inducing effect of Tocilizumab and argue the case for US having an important role in monitoring disease activity in GCA. Trial registration ClinicalTrials.gov, www.clinicaltrials.gov, NCT03745586.

Idiopathic antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of diseases that are often difficult to diagnose due to the wide range of clinical manifestations. Notably, renal involvement is a serious organ complication, which usually requires intensive immunosuppressive therapy and is prone to recurrence. In recent years, there has been some progress regarding the understanding of the pathogenesis of the diseases. It has been shown that both cocaine and levamisole, which is a common adulterant of cocaine, can trigger the formation of ANCAs and lead to the corresponding symptoms. We report two cases of AAV with different renal manifestations associated with cocaine consumption. Furthermore, we performed a review of the literature to identify, characterize and describe histologically documented cases of renal involvement in AAV, related to cocaine abuse. Cocaine/levamisole-induced vasculitis may, therefore, mimic idiopathic AAV. Although the detection of ANCA and anti-PR3 (proteinase 3, PR3) as well as anti-MPO antibodies (myeloperoxidase, MPO) are the serological hallmark of idiopathic AAV, certain clinical- and antibody constellations should lead to consideration of illicit drugs as inductors of the disease. Especially in young patients, certain serologic constellations (e.g., PR3 and MPO double positivity, positive antinuclear antibodies, low complement level, and positive testing for antiphospholipid antibodies), skin involvement, musculoskeletal symptoms and hematologic (anemia, leukopenia) affections should prompt testing for cocaine and levamisole consumption via urine drug testing. Treatment includes both immunosuppressive approaches and drug cessation but is difficult since many patients continue cocaine consumption.

Behçet‘s Syndrome (BS) is a variable vessel vasculitis according to the Chapel Hill Consensus Nomenclature (1) and may thus affect any organ, including major and minor arterial and venous vessels to a varying degree and with varying frequency. Although the main features of BS are recurrent oral and genital aphthous ulcers, cutaneous lesions, ocular inflammation and arthritis—major vessel and life—or organ threatening involvement of internal organs and the central and peripheral nervous system occur. In general, BS in Europe appears to form six phenotypes of clinical manifestations (2), which are (1) mucocutaneous only, (2) predominant arthritis/articular involvement, (3) vascular phenotype, (4) ocular manifestations, which are most likely associated with CNS manifestations and HLA-B51, (5) dominant parenchymal CNS manifestations (being associated with the ocular ones), and (6) gastrointestinal involvement. Mucocutaneous manifestations are present in almost all patients/all phenotypes. In the following review, we summarize the current knowledge concerning vascular, neurologic, gastrointestinal and musculoskeletal manifestations of the disease.

Alcohol dependence syndrome is a chronic-recurrent substance use disorder. Various treatments have been shown to be effective with a positive impact on the course of the disease. The patients' subjective perception of their disease and the offered treatments remain unclear.30 alcohol-dependent patients (n = 20 psychiatric clinic, n = 10 addiction counseling) were asked how they had dealt with their alcohol problem in the past. The interviews were recorded, transcribed and analyzed using current qualitative research methods.While most patients positively rated many aspects in the three areas of alcohol abstinence, treatment and the social environment, they also described negative aspects in these areas.The contradicting statements show an area of conflict that demonstrates the ambivalence of alcohol-dependent patients in relevant fields. This ambivalence can be considered as important for the therapy and the course of the disease.Die Alkoholabhängigkeit ist eine chronisch-rezidivierende Abhängigkeitserkrankung. Für verschiedene Behandlungsformen konnte eine positive Wirksamkeit auf den Verlauf der Erkrankung nachgewiesen werden. Die subjektive Sicht der Patienten auf ihre Erkrankung und die angebotenen Behandlungen ist bislang noch wenig untersucht.30 Patienten mit einer Alkoholabhängigkeitserkrankung (n = 20 Psychiatrische Klinik, n = 10 Suchtberatung) wurden gefragt, wie sie in der Vergangenheit mit dem Alkoholproblem umgegangen sind. Die Interviews wurden aufgezeichnet, transkribiert und anhand aktueller qualitativer Auswertungsmethoden analysiert.Die Aussagen der Patienten konnten drei Kategorien zugeordnet werden. Die Alkoholabstinenz, die Suchtbehandlungen und das soziale Umfeld wurden mehrheitlich positiv beschrieben. Allerdings zeigten die meisten Patienten sowohl positive als auch negative Aussagen in diesen Bereichen.Die gegensätzlichen Aussagen zeigen ein Spannungsfeld auf, das die Ambivalenz der alkoholabhängigen Patienten in relevanten Bereichen demonstriert. Diese Ambivalenz kann wichtig für die Therapie und den Verlauf der Erkrankung sein.

Thymic hyperplasia (TH) with lymphoepithelial sialadenitis (LESA)-like features (LESA-like TH) has been described as a tumor-like, benign proliferation of thymic epithelial cells and lymphoid follicles. We aimed to determine the frequency of lymphoma and autoimmunity in LESA-like TH and performed retrospective analysis of cases with LESA-like TH and/or thymic MALT-lymphoma. Among 36 patients (21 males) with LESA-like TH (age 52 years, 32&ndash, 80, lesion diameter 7.0 cm, 1&ndash, 14.5, median, range), five (14%) showed associated lymphomas, including four (11%) thymic MALT lymphomas and one (3%) diffuse large B-cell lymphoma. One additional case showed a clonal B-cell-receptor rearrangement without evidence of lymphoma. Twelve (33%) patients (7 women) suffered from partially overlapping autoimmune diseases: systemic lupus erythematosus (n = 4, 11%), rheumatoid arthritis (n = 3, 8%), myasthenia gravis (n = 2, 6%), asthma (n = 2, 6%), scleroderma, Sj&ouml, gren syndrome, pure red cell aplasia, Grave&rsquo, s disease and anti-IgLON5 syndrome (each n = 1, 3%). Among 11 primary thymic MALT lymphomas, remnants of LESA-like TH were found in two cases (18%). In summary, LESA-like TH shows a striking association with autoimmunity and predisposes to lymphomas. Thus, a hematologic and rheumatologic workup should become standard in patients diagnosed with LESA-like TH. Radiologists and clinicians should be aware of LESA-like TH as a differential diagnosis for mediastinal mass lesions in patients with autoimmune diseases.

The number of elderly people is growing in western populations, but only few maximal performance data exist for people >75 years, in particular for European octogenarians. This study was performed to characterize maximal performance of 55 independently living subjects (32 women, 81.1 +/- 3.4 years; 23 men, 81.7 +/- 2.9 years) with a focus on sex differences. Maximal performance was determined in a ramp test to exhaustion on a bicycle ergometer with ergospirometry, electrocardiogram and blood lactate measurements. Maximal isometric extension strength of the legs (MEL) was measured on a force platform in a seated position. Body composition was quantified by X-ray absorptiometry. In >25% of the subjects, serious cardiac abnormalities were detected during the ramp test with men more frequently being affected than women. Maximal oxygen consumption and power output were 18.2 +/- 3.2 versus 25.9 +/- 5.9 ml min(-1) kg(-1) and 66 +/- 12 versus 138 +/- 40 W for women versus men, with a significant sex difference for both parameters. Men outperformed women for MEL with 19.0 +/- 3.8 versus 13.6 +/- 3.3 N kg(-1). Concomitantly, we found a higher proportion of whole body fat in women (32.1 +/- 6.2%) compared to men (20.5 +/- 4.4%). Our study extends previously available maximal performance data for endurance and strength to independently living European octogenarians. As all sex-related differences were still apparent after normalization to lean body mass, it is concluded that it is essential to differentiate between female and male subjects when considering maximal performance parameters in the oldest segment of our population.