Rubella vaccine-induced granulomas are a novel phenotype with incomplete penetrance of genetic defects in cytotoxicity.

BACKGROUND: Rubella virus-induced granulomas have been described in patients with various inborn errors of immunity. Most defects impair T-cell immunity, suggesting a critical role of T cells in rubella elimination. However, the molecular mechanism of virus control remains elusive. OBJECTIVE: This study sought to understand the defective effector mechanism allowing rubella vaccine virus persistence in granulomas. METHODS: Starting from an index case with Griscelli syndrome type 2 and rubella skin granulomas, this study combined an international survey with a literature search to identify patients with cytotoxicity defects and granuloma. The investigators performed rubella virus immunohistochemistry and PCR and T-cell migration assays. RESULTS: This study identified 21 patients with various genetically confirmed cytotoxicity defects, who presented with skin and visceral granulomas. Rubella virus was demonstrated in all 12 accessible biopsies. Granuloma onset was typically before 2 years of age and lesions persisted from months to years. Granulomas were particularly frequent in MUNC13-4 and RAB27A deficiency, where 50% of patients at risk were affected. Although these proteins have also been implicated in lymphocyte migration, 3-dimensional migration assays revealed no evidence of impaired migration of patient T cells. Notably, patients showed no evidence of reduced control of concomitantly given measles, mumps, or varicella live-attenuated vaccine or severe infections with other viruses. CONCLUSIONS: This study identified lymphocyte cytotoxicity as a key effector mechanism for control of rubella vaccine virus, without evidence for its need in control of live measles, mumps, or varicella vaccines. Rubella vaccine-induced granulomas are a novel phenotype with incomplete penetrance of genetic disorders of cytotoxicity.

Effects of multimodal rheumatologic complex treatment in patients with rheumatoid arthritis: a monocentric prospective study.

OBJECTIVES: To prospectively evaluate the effects of multimodal rheumatologic complex treatment (MRCT), a special concept of in-patient physical treatment (PT), in patients with rheumatoid arthritis (RA). METHODS: RA patients receiving a 16-day MRCT were eligible. MRCT was delivered to participants in 64 PT sessions of various modalities with a minimum of 1.400 Minutes of treatment. The primary outcome was the change in pain levels measured on a numeric rating scale (0-10) between baseline and discharge. Secondary outcomes were assessments of i) disease activity, ii) functional disabilities, iii) serum cytokine levels, iv) analgesic usage, v) patient global health and vi) patient's satisfaction with their therapeutic response to MRCT from baseline to discharge and over a 12-week follow-up. RESULTS: 53 RA patients completed the study and were analysed. Pain levels were reduced significantly and clinically meaningfully (mean ± standard error: -2.1 ± 0.3, p<0.001). Effects of MRCT lasted up to 12 weeks after discharge. After MRCT and during the 12-week follow-up use of analgesics was reduced compared to baseline. Regression analyses revealed no influencing factors on change in pain levels. Patient global health assessment remained improved throughout the entire follow-up period. No MRCT-related side effects were recorded. CONCLUSIONS: MRCT as a multimodal treatment concept with a strong emphasis on PT reduces pain significantly and in a clinically meaningful manner allowing for reduced analgesic usage.

Multimodal rheumatologic complex treatment in patients with spondyloarthritis - a prospective study.

INTRODUCTION: Aim of this study was to prospectively assess the effects of multimodal rheumatologic complex treatment (MRCT), a special concept of in-patient physical treatment (PT) for treating spondyloarthritis (SpA), namely radiographic (r-) and non-radiographic (nr-) axial (ax-) SpA and psoriatic arthritis (PsA). METHODS: r-, nr-axSpA and PsA patients receiving a 16-day MRCT were eligible. MRCT was delivered to participants over 64 PT sessions of various modalities with a minimum of 1,400 min of treatment. Primary outcome was a change in pain levels measured on a numeric rating scale (NRS, 0 - 10) between baseline and discharge. Secondary outcomes were assessments of i) disease activity ii) functional disabilities iii) serum cytokine levels iv) analgesic usage v) patient global health assessment and patients' satisfaction with their therapeutic response to MRCT from baseline to discharge and over a 12-week follow-up. RESULTS: 50 patients completed the study and were analysed. Pain levels were improved significantly (p < 0.001, 95% confidence interval -2.25 to -0.8,). Further analyses revealed no influencing factors or relevant inter-group differences. Positive effects of MRCT lasted up to 12 weeks after discharge. Analgesic usage was reduced compared to baseline. Patient global health assessment continued to be improved throughout the whole follow-up. No MRCT-related harms were recorded. CONCLUSION: MRCT as a multimodal treatment concept with a strong emphasis on PT reduces pain in SpA meaningfully and facilitates reduced analgesic usage.

Serial locally applied water-filtered infrared a radiation in axial spondyloarthritis - a randomized controlled trial.

INTRODUCTION: Aim of this randomized controlled trial was to evaluate the effects of serial locally applied water-filtered infrared A radiation (sl-wIRAR) in patients with axial spondyloarthritis (axSpA). METHODS: axSpA patients with active disease undergoing a 7-day multimodal rheumatologic complex treatment under non-steroidal anti-inflammatory drug (NSAID) therapy were eligible. Patients were randomly assigned in a 1:1 ratio. The intervention group (IG) received additional sl-wIRAR treatment of the back (2 treatments for 30 min per day for 6 days) to assess whether locally applied hyperthermia can i) reduce pain levels, ii) reduce disease activity and improve functionality and iii) whether an effect on tumor necrosis factor α (TNFα) levels is detectable. Additionally, it was examined whether a reduction in NSAID therapy could be achieved after trial completion. RESULTS: 71 patients completed the trial (IG: 36 patients, control group (CG) 35 patients). sl-wIRAR led to a significant pain reduction measured by a numeric rating scale (p < .0005) and in comparison, to the CG (p = .006). sl-wIRAR treatment resulted in a significant reduction in the Bath Anyklosing Spondylitis Disease Activity Index (BASDAI) (p = .004) and Bath Ankylosing Spondylitis Functional Index (p = .004) with no significant difference to the CG. TNF-α levels were significantly decreased (p = .001) only in the IG with a significant difference to the CG (p = .01). 26 (76%) of patients in the IC reduced their NSAID therapy after trial completion. CONCLUSION: sl-wIRAR treatment in axSpA leads to a rapid reduction in pain allowing NSAID dosage reduction. A reason for these desirable effects could be a change in TNFα levels.

Evaluation of a special concept of physical therapy in spondyloarthritis: German multimodal rheumatologic complex treatment for spondyloarthritis.

OBJECTIVES: Multimodal rheumatologic complex treatment (MRCT) is a specific concept of German inpatient care focusing on physical therapy for patients with rheumatic diseases suffering from exacerbated pain and functional impairment. As physical therapy is a key concept in the treatment of spondyloarthritis (SpA), we conducted a monocentric retrospective analysis of the effects of MRCT on pain and functional status in patients with SpA including patients with axial spondyloarthritis (axSpA), non-radiographic axial spondyloarthritis (nr-axSpA) and psoriatic arthritis with axial involvement (axPsA). METHODS: 134 treatment episodes provided to 100 patients with SpA between 2014 and 2017 were analysed. We evaluated changes in pain intensity, in functional status and in disease activity before and after a treatment episode. In addition, we assessed potential influences of various patient characteristics, the course of the disease and comorbidities. RESULTS: Overall, MRCT resulted in significant amelioration of pain (NRS: p < 0.001), significant improvement of functional capacity (FFbH: p = 0.03; HAQ: p = 0.02; BASFI: p < 0.001) and significant reduction of disease activity (BASDAI p < 0.001; DAS28: p = 0.009). In general, treatment effects on axSpA, nr-axSpA and axPsA were comparable. Different aspects of the disease and its previous course did not have a significant effect on the outcome parameters. Comorbidities (e.g. fibromyalgia) did not significantly influence treatment response. CONCLUSION: MRCT not only decreases pain and improves function but also reduces disease activity in patients with axSpA, nr-axSpA and axPsA irrespective of the course of disease and comorbidities (e.g. fibromyalgia), thus underlining the importance of non-pharmacological and physical treatment in the treatment of SpA.Key Points• Physical treatment is a key component in treating SpA.• Multimodal rheumatologic complex treatment (MRCT) is a specific concept of German inpatient care focusing on physical therapy for patients with rheumatic diseases suffering from exacerbated pain and functional impairment.• MRCT not only decreases pain and improves function but also reduces disease activity in patients with axSpA, nr-axSpA and axPsA irrespective of the course of disease and comorbidities (e.g. fibromyalgia).• MRCT could be a role model of treating SpA by means of physical therapy as its effects are not influenced by therapy, disease duration or comorbidities and as it has no side effects.

Case report of severe PCR-confirmed COVID-19 myocarditis in a European patient manifesting in mid January 2020.

BACKGROUND: Viral genesis is the most common cause of myocarditis. COVID-19-associated myocarditis seems to be a notable extrapulmonary manifestation, which may result in the need for a different treatment. There has been no positive polymerase chain reaction (PCR) testing of SARS-CoV-2 in heart specimens, thus far. CASE SUMMARY: A 48-year-old male patient presented with fever, dyspnoea, and haemoptysis. Laboratory findings showed highly elevated inflammatory and cardiac damage markers. Thoracic computed tomography (CT) revealed bilateral, patchy peripheral ground-glass opacities with a crazy-paving pattern, focal consolidations, and mild pleural effusions. Cardiac imaging with echocardiography and magnetic resonance imaging (MRI) detected a reduced biventricular function. MRI additionally showed myocardial oedema and late gadolinium enhancement. Lung and heart biopsies were performed, revealing alveolitis with necrosis and acute lymphocytic myocarditis. Testing for usual cardiotropic viruses was negative, and no aspects of vasculitis or granuloma could be found. Due to fulfilling the criteria, the patient was diagnosed with rheumatic vasculitis. Treatment with cyclophosphamide and steroids was initiated. Later, the patient reported a history of travel to Tyrol in mid January. Consequently, PCR testing for SARS-CoV-2 was performed, which was positive in the heart specimen. Immunosuppressive treatment was discontinued. During a follow-up visit at the end of April, the patient's recovery was stable. DISCUSSION: In COVID-19 infections, myocardial inflammation can be present as an extrapulmonary manifestation. Positive PCR testing confirms myocardial invasion of the virus. Imaging and laboratory studies correlate with the histopathological findings, and thus should be performed in COVID-19 patients who are suspicious for myocarditis. Supportive treatment with steroids may be useful in these patients.

[A rare manifestation of an inflammatory rheumatic systemic disease]. / Eine seltene Manifestation einer entzündlich rheumatischen Systemerkrankung.

Granulomatosis with polyangiitis (GPA) is an ANCA(anti-neutrophil cytoplasmatic antibody)-associated small vessel vasculitis usually affecting the respiratory tract and the kidneys. This article reports on a 46-year-old male patient with a rare organ manifestation pattern of GPA: besides a fulminantly progressive tetraparesis the patient suffered from severe ulcerative colitis. The early diagnosis of GPA with unusual findings and its delineation from a septic event is essential.