Treatment of giant cell arteritis - current approach and new possibilities.

Giant Cell Arteritis (GCA) is an autoimmune mediated systemic vasculitis affecting large arteries - the aorta and its branches. It has the highest incidence of all systemic vasculitides and manifests nearly exclusively in patients aged 50 or older. Amongst its non-specific and specific symptoms are headaches, mastication claudication or signs of rheumatic polymyalgia, a relatively common and immediate treatment requiring condition being acute vision loss due to optic ischemia. A GCA diagnosis is based on clinical and paraclinical findings and imaging techniques including PET/CT; with an important role still being played by histological verification from temporal artery biopsy. Treatment is based on immunosuppressive agents - systemic glucocorticoids, with adjunct therapy options being methotrexate and tocilizumab. Currently, there are also several clinical trials examining the efficacy of other modern biological agents in GCA.

Diffuse alveolar hemorrhage as a life threatening manifestation of newly diagnosed granulomatosis with polyangiitis following COVID-19 infection - a case report.

A case report of a patient with newly diagnosed granulomatosis with polyangiitis (GPA) after undergoing COVID-19 (Coronavirus Disease 2019) is discussed. GPA is one of the ANCA-associated vasculitis, which is characterized by the presence of autoantibodies against cytoplasmic enzymes neutrophils (Anti Neutrophil Cytoplasmatic Antibodies). It is a vasculitis that mainly affects small blood vessels, leading to damage to the kidneys, lungs, and upper respiratory tract, including the paranasal sinuses and orbits. This disease can result in an acute life-threatening condition. Such complications include diffuse alveolar hemorrhage (DAH), a condition characterized by blood leakage from the pulmonary vessels into the alveoli, often leading to acute vital signs and even respiratory failure. DAH can have many causes - autoimmune diseases including vasculitides as well as non-immunological causes. Early and adequate comprehensive therapy including immunosuppressive treatment (cyclophosphamide/rituximab and glucocorticoids) can be life-saving.

The beneficial effect of csDMARDs co-medication on drug persistence of first-line TNF inhibitor in rheumatoid arthritis patients: data from Czech ATTRA registry.

The study aimed to compare treatment retention for first-line TNF inhibitor (TNFi) in the ATTRA registry patients receiving either combination with conventional synthetic DMARDs or TNFi as monotherapy. A retrospective multicenter study analyzed data of all adult patients with rheumatoid arthritis (n = 3032) starting TNF inhibitor as the first-line biological therapy in combination with csDMARDs or in monotherapy from January 1st 2012 to December 31st 2020. Kaplan-Meier method was employed to calculate drug retentions. Survival curves of treatment retentions were compared through Log-rank test between the studied subgroups. The hazard ratio for drug discontinuation was assessed through univariate cox regression models. In patients who started the first line TNFi therapy, the median treatment retention was 47.7 (42.2; 53.1) months for combination therapy and 22.7 (14.9; 30.6) months for TNFi monotherapy (p < 0.001). Estimated one-year survival was higher in patients on TNFi combined with csDMARDs as compared with TNFi monotherapy (75.3% vs 65.7%); two-year survival rate was 63.2% vs 49.2%, three-year survival rate was 55.4% vs 42.4% and five-year survival 44.9% vs 26.4% of patients. The estimated survival on the first TNFi was higher in patients taking combination therapy with methotrexate than with other csDMARDs (p = 0.003). Use of csDMARDs co-medication was associated with significantly better first TNFi drug survival compared to monotherapy. The combination of TNFi with MTX is more effective than the combination with leflunomide, which did not demonstrate a significant effect.

[Life threatening manifestations of lupus and antiphospholipid syndrome in internal medicine]. / Zivot ohrozující projevy systémového lupusu a antifosfolipidového syndromu ve vnitrním lékarství.

The clinical picture of systemic lupus and antiphospholipid syndrome is remarkably varied and disease manifestations are commonly very heterogeneous. Relatively often both diseases are associated with severe, acute and life threatening manifestations, which places demands on the knowledge of differential diagnostics and experience of the physicians. This article deals with the serious and mostly acute impairment of cardiovascular, respiratory, renal, gastrointestinal, hematopoietic or nervous systems, briefly discusses the acute pregnancy complication and summarizes the basic therapeutic option. It emphasizes the role of both, sometimes inseparable, diseases in differential diagnosis of acute symptoms in internal medicine.Key words: clinical symptoms - diagnostics - live threatening manifestations - lupus erythematosus - systemic antiphospholipid syndrome - therapy.

Serum protein pattern associated with organ damage and lupus nephritis in systemic lupus erythematosus revealed by PEA immunoassay.

BACKGROUND: Systemic lupus erythematosus (SLE) is a remarkably heterogeneous autoimmune disease. Despite tremendous efforts, our knowledge of serum protein patterns in severe SLE phenotypes is still limited. We investigated the serum protein pattern of SLE, with special emphasis on irreversible organ damage and active lupus nephritis (LN) as assessed by renal Systemic Lupus Erythematosus Disease Activity Index. METHODS: We used proximity extension immunoassay (PEA, Proseek Multiplex, Olink) to assess the serum levels of ninety-two inflammation-related proteins in Czech patients with SLE (n = 75) and age-matched healthy control subjects (n = 23). Subgroup analysis was carried out on the basis of organ damage (with/without, 42/33) and biopsy-proven LN (with/without, 27/48; active LN, n = 13; inactive LN, n = 14). RESULTS: Of thirty deregulated proteins between SLE and the healthy controls (Pcorr  < 0.05), the top upregulated proteins in SLE were sirtuin 2, interleukin 18 (IL18), and caspase 8 (Pcorr  < 0.0006). Of these, sirtuin 2 and caspase 8 had not yet been reported with SLE. Elevated levels of IL8, CCL2/MCP1, CCL11, and MMP10 (Pcorr  < 0.05) were detected in patients with organ damage for which the serum levels of CCL11 and MMP10 were particularly informative in organ damage prediction. Comparing patients based on LN, elevated levels of CSF1, sIL15RA, sCD40, sCX3CL1, caspase 8, sIL18R1, bNGF, and GDNF (Pcorr  < 0.05) were detected in active LN. Except GDNF, all LN-associated markers showed usefulness in prediction of active renal disease. CONCLUSIONS: This highly sensitive PEA analysis identified the serum pattern of SLE, organ damage, and active LN, with many novel candidate proteins detected. Their exact role and suitability as biomarkers in SLE deserve further investigation.

Higher levels of matrix metalloproteinase-3 in patients with RA reflect disease activity and structural damage.

AIMS: To evaluate the serum levels of matrix metalloproteinase-3 (MMP-3) as a potential marker of disease activity and joint damage in 92 patients with rheumatoid arthritis (RA), compared to 24 osteoarthritis (OA) patients and 26 healthy controls. METHODS: The concentrations of MMP-3 were measured by ELISA using the commercial kit AESKULISA DF MMP-3 (AESKU.Diagnostics, Germany) and compared with other laboratory parameters routinely used to assess the disease status, clinical score (DAS28) and radiographic stage in the group of RA patients. RESULTS: The mean serum concentrations of MMP-3 were 199.1 ± 160 ng/mL in RA patients, 113.9 ± 96.9 ng/mL in OA patients and 48.3 ± 19.2 in healthy controls. The differences were highly significant: RA patients and healthy controls (P<0.0001), RA and OA patients (P=0.008) as well as between OA patients and controls (P=0.009). MMP-3 concentrations were further compared with other laboratory parameters and clinical and structural damage data. There were correlations between MMP-3 and CRP (r=0.304, P<0.01), DAS28 (r=0.301, P<0.05), levels of anti-cyclic citrullinated peptide antibodies (r=0.241, P<0.05), erythrocyte sedimentation rate (r=0.200, P=0.059) and radiographic disease stage (r=0.197, P=0.063). CONCLUSION: These results demonstrated that measurement of MMP-3 could become a marker of disease activity in RA patients.

Renal manifestations of rheumatic diseases. A review.

BACKGROUND: Renal manifestations of rheumatic diaseases are sometimes very discrete and mild. At others, they can present the leading symptomatology of a given disease. Systemic lupus erythematosus, systemic scleroderma, renal vasculitis, rheumatoid arthritis, mixed connective tissue disease, Sjögren's syndrome and gout can all manifest in or be accompanied by renal impairment. METHODS AND RESULTS: The authors reviewed the literature on renal manifestation of rheumatic diseases using the key words, lupus erythematosus, systemic autoimmune diseases, rheumatoid arthritis, vasculitis and gout. The review below is accompanied by their own histological findings. CONCLUSION: Diagnosis requires proper interpretation of the clinical situation, laboratory results and image analysis methods plus close interdisciplinary collaboration between nephrologist and clinical pathologist/nephropathologist.

The antioxidant acetylcysteine reduces oxidative stress by decreasing level of AOPPs.

Oxidative stress and especially its connection with many diseases has been discussed much recently. Among markers of oxidative stress there appear new and quite specific ones called advanced oxidation protein products (AOPPs). We tried to influence the level of AOPPs by an antioxidant therapy with N-acetylcysteine. Fourteen individuals with many cardiovascular risk factors were examined. All these patients were administered acetylcysteine (NAC) 600 mg/day orally during 20 days. Before starting the therapy we determined AOPP, albumin cobalt binding (ACB), glucose, creatinine, urea, ALT, AST, cholesterol, LDL, HDL and triglycerides values in peripheral venous blood in all individuals. After finishing our intervention we determined AOPP, ACB and glucose level again. Our results show a statistically significant decrease in AOPP levels after 20-day N-acetylcysteine therapy (medians, initially 82.2, at study end 74.3 umol/l, p = 0.039). We demonstrate a significant decrease in AOPP levels after 20-day N-acetylcysteine therapy in dose 600 mg/day.