Musculoskeletal magnetic resonance imaging findings support a common spectrum of giant cell arteritis and polymyalgia rheumatica.

OBJECTIVES: To investigate the proportion and distribution of contrast enhancement (CE) of musculoskeletal structures with MRI of the thorax/abdomen/pelvis in giant cell arteritis (GCA). METHODS: CE at 34 musculoskeletal sites was rated with a 4-point ordinal scale. Patients were divided into groups with/without glucocorticoid (GC) treatment and with/without symptoms of polymyalgia rheumatica (PMR). Two composite scores were created: an MRI-score, including seven sites and a Limited-MRI-score, including four sites. RESULTS: Retrospectively, 90 consecutive patients with GCA were included. The population included 54 and 36 patients with and without PMR symptoms, respectively, and 45 (50%) patients were receiving GCs at the time of MRI. CE was found in 90.7% of lumbar spines, 87.5% of the pelvis, 82.2% of shoulder girdles and in 95.6% at any site in patients without GCs. The proportion of patients without and with GCs with at least moderate enhancement was 91.1%/75.6% at ≥ 1-3, 75.6%/51.1% at ≥ 4-6 and 64.4%/28.9% at ≥ 7-9 sites. The mean difference between the proportion of pathological CE in patients with and without GCs was 27.4% for synovial sites and 18.3% for periarticular/musculotendinous sites. Both composite scores captured substantial differences between groups, correlation was very strong between scores. CONCLUSIONS: MRI shows CE of musculoskeletal structures typical of PMR in most patients with GCA, supporting the concept of "GCA-PMR Spectrum Disease". Changes are more frequent at periarticular/musculotendinous sites and in the presence of PMR symptoms. A clear response to GCs is evident, less so for periarticular/musculotendinous sites.

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.

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.

Diffusion-weighted magnetic resonance imaging for the diagnosis of giant cell arteritis - a comparison with T1-weighted black-blood imaging.

OBJECTIVES: To investigate the diagnostic performance of diffusion-weighted imaging (DWI) of the superficial cranial arteries in the diagnosis of giant cell arteritis (GCA). METHODS: Retrospectively, 156 patients with clinically suspected GCA were included. A new 4-point ordinal DWI rating scale was developed. A post-contrast, fat-suppressed, T1-weighted "black-blood" sequence (T1-BB) was rated for comparison. Ten arterial segments were assessed: common superficial temporal arteries, temporal and parietal branches, occipital and posterior auricular arteries bilaterally. The expert clinical diagnosis after ≥ 6 months of follow-up was the diagnostic reference standard. Diagnostic accuracy was evaluated for different rating methods. RESULTS: The study cohort consisted of 87 patients with and 69 without GCA. For DWI, the area under the curve was 0.90. For a cut-off of ≥ 2 consecutive pathological slices, DWI showed a sensitivity of 75.9%, a specificity of 94.2% and a positive likelihood ratio of 13.09. With a cut-off of ≥ 3 consecutive pathological slices, sensitivity was 70.1%, specificity was 98.6%, and the positive likelihood ratio was 48.38. For the T1-BB, values were 88.5%, 88.4% and 7.63, respectively. The inter-rater analysis for DWI with a cut-off of ≥ 2 pathological slices showed a kappa of 1.00 on the patient level and 0.85 on the arterial segment level. For the T1-BB the kappa was 0.78 and 0.79, respectively. CONCLUSION: DWI of the superficial cranial arteries demonstrates a good diagnostic accuracy and reliability for the diagnosis of GCA. DWI is widely available and can be used immediately in clinical practice for patients with suspected GCA.

[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.

[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.

Spectrum of Large and Medium Vessel Vasculitis in Adults: Primary Vasculitides, Arthritides, Connective Tissue, and Fibroinflammatory Diseases.

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. 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.

Spectrum of Large- and Medium-Vessel Vasculitis in Adults: Neoplastic, Infectious, Drug-Induced, Autoinflammatory, and Primary Immunodeficiency Diseases.

PURPOSE OF REVIEW: To provide a comprehensive review of drugs and neoplastic, infectious, autoinflammatory, and immunodeficiency diseases causing medium- to large-vessel vasculitis in adults with emphasis on information essential for the initial diagnostic process. RECENT FINDINGS: Entities with medium- to large-vessel vasculitis as clinical manifestations have been described recently (e.g., adenosine deaminase-2 deficiency, VEXAS-Syndrome), and vasculitis in established autoinflammatory or immunodeficiency diseases is increasingly being identified. In the diagnostic process of medium- to large-vessel vasculitis in adults, a large variety of rare diseases should be included in the differential diagnosis, especially if diagnosis is made without histologic confirmation and in younger patients. Although these disorders should be considered, they will undoubtedly remain rare in daily practice.

[How to deal with alcohol: a qualitative evaluation of 30 interviews with alcohol-dependent patients]. / Über den Umgang mit Alkohol ­ eine qualitative Auswertung von 30 Interviews mit alkoholabhängigen Patienten.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Quantitative ultrasound to monitor the vascular response to tocilizumab in giant cell arteritis.

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.

Cocaine-induced ANCA-associated renal disease: a case-based review.

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.

DWI scrolling artery sign for the diagnosis of giant cell arteritis: a pattern recognition approach.

OBJECTIVES: To investigate the diagnostic accuracy of a pattern recognition approach for the evaluation of MRI scans of the head with diffusion-weighted imaging (DWI) in suspected giant cell arteritis (GCA). METHODS: Retrospectively, 156 patients with suspected GCA were included. The 'DWI-Scrolling-Artery-Sign' (DSAS) was defined as hyperintense DWI signals in the cranial subcutaneous tissue that gives the impression of a blood vessel when scrolling through a stack of images. The DSAS was rated by experts and a novice in four regions (frontotemporal and occipital, bilaterally). The temporal, occipital and posterior auricular arteries were assessed in the T1-weighted black-blood sequence (T1-BB). The diagnostic reference was the clinical diagnosis after ≥6 months of follow-up. RESULTS: The population consisted of 87 patients with and 69 without GCA; median age was 71 years and 59% were women. The DSAS showed a sensitivity of 73.6% and specificity of 94.2% (experts) and 59.8% and 95.7% (novice), respectively. Agreement between DSAS and T1-BB was 80% for the region level (499/624; kappa(κ)=0.59) and 86.5% for the patient level (135/156; κ=0.73). Inter-reader agreement was 95% (19/20; κ=0.90) for DSAS on the patient level and 91.3% (73/80; κ=0.81) on the region level for experts. For expert versus novice, inter-reader agreement for DSAS was 87.8% on the patient level (137/156; κ=0.75) and 91.2% on the region level (569/624; κ=0.77). CONCLUSIONS: The DSAS can be assessed in less than 1 min and has a good diagnostic accuracy and reliability for the diagnosis of GCA. The DSAS can be used immediately in clinical practice.

Ultrasound intima-media thickness cut-off values for the diagnosis of giant cell arteritis using a dual clinical and MRI reference standard and cardiovascular risk stratification.

Objectives: To derive segmental cut-off values and measures of diagnostic accuracy for the intima-media thickness of compressed temporal artery segments for the diagnosis of giant cell arteritis (GCA) on the patient level. To examine the influence of cardiovascular risk. Methods: Retrospectively, patients evaluated for GCA with an ultrasound of the temporal arteries and an MRI of the head, including a T1-fatsat-black blood (T1-BB) sequence, were identified and classified based on cardiovascular risk and a dual reference standard of T1-BB on the segmental level and the clinical diagnosis on the patient level. Intima-media thickness of the common superficial temporal artery (CSTA), frontal and parietal branches (FB, PB) were measured by compression technique. Statistically and clinically optimal (specificity of approx. 90% for the patient level) cut-offs were derived. Diagnostic accuracy was evaluated on the patient level. Results: The population consisted of 144 patients, 74 (51.4%) with and 70 (48.6%) without GCA. The statistically optimal cut-offs were 0.86 mm, 0.68 mm and 0.67 mm for the CSTA, the FB and PB, respectively. On the patient level sensitivity and specificity were 86.5 and 81.4%. Clinically optimal cut-offs were 1.01 mm, 0.82 mm and 0.69 mm and showed a sensitivity of 79.7% and a specificity of 90.0%. For patients without high cardiovascular risk, statistically optimal cut-offs showed a sensitivity of 89.6% and a specificity of 90.5%. Conclusion: Newly derived ultrasound intima-media thickness cut-offs with a dual reference standard show high diagnostic accuracy on the patient level for the diagnosis of GCA, particularly in patients without high cardiovascular risk.

Behçet's Syndrome Apart From the Triple Symptom Complex: Vascular, Neurologic, Gastrointestinal, and Musculoskeletal Manifestations. A Mini Review.

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.

Case Report: Genetic Double Strike: VEXAS and TET2-Positive Myelodysplastic Syndrome in a Patient With Long-Standing Refractory Autoinflammatory Disease.

Somatic genetic mutations involving the innate and inflammasome signaling are key drivers of the pathogenesis of myelodysplastic syndromes (MDS). Herein, we present a patient, who suffered from a long-standing refractory adult-onset autoinflammatory syndrome (AIS), previously interpreted as various distinct rheumatic disorders. Developing pancytopenia and particularly macrocytic anemia prompted the screening for a hematological malignancy, which led to the diagnosis of a TET-2-positive MDS. The impressive and continuously changing range of organ involvement, with remarkable refractoriness to anti-inflammatory treatment, exceeded the common autoinflammatory phenotype of MDS patients. This prompted us to suspect a recently discovered disease, characterized by somatic mutations of the UBA1 gene: the VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome, which was ultimately confirmed by genetic testing. Reevaluation of previous bone marrow biopsies showed the presence of characteristic vacuoles in myeloid- and erythroid progenitor cells. Our case illustrates that the triad of an unresponsive multisystemic autoinflammatory disease, hematological abnormalities and vacuoles in myeloid- and erythroid progenitors in the bone marrow biopsy should prompt screening for the VEXAS syndrome.

Thymic Hyperplasia with Lymphoepithelial Sialadenitis (LESA)-Like Features: Strong Association with Lymphomas and Non-Myasthenic Autoimmune Diseases.

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, 32-80; lesion diameter 7.0 cm, 1-14.5; 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, Sjögren syndrome, pure red cell aplasia, Grave'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.

Biologically relevant sex differences for fitness-related parameters in active octogenarians.

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.