[Diffuse alveolar hemorrhage - acute, life-threatening situation in rheumatology]. / Difuzní alveolární hemoragie - akutní, zivot ohrozující stav v revmatologii.

Diffuse alveolar hemorrhage (DAH) is a life-threatening acute manifestation of systemic diseases, the most commonly of systemic vasculitis. Clinically DAH manifests by a rapidly progressive respiratory and renal failure. The decisive for diagnose is immediate bronchoscopic examination with the bronchoalveolar lavage examination. CT mostly show bilateral pulmonary infiltrates, in blood picture rapidly come to anemia. In the majority of patients it can be found positive ANCA antibodies. DAH should be suspected in the case of acute respiratory failure also in patients without history of systemic disease. On the set of 33 patients with acute DAH episode, we demonstrate the importance of rapid diagnosis and aggressive therapy. In a third of our patients was DAH the first manifestation of systemic disease. Immunomodulatory treatment must be initiated immediately after diagnose. Hospital mortality in our group was 27 %, although 42 % of the patients were required ventilation support and one-third of patients had acute renal failure. After handling of acute episode of DAH is the prognosis quoad vitam promising.Key words: bronchoalveolar fluid - diffuse alveolar haemorrhage - granulomatosis with polyangiitis - intensive care in rheumatology - vasculitis.

Methotrexate impact on radiographic progression in biologic-treated rheumatoid arthritis under clinical remission: A case report on monozygotic Caucasian twins.

We describe Caucasian monozygotic twin brothers with rheumatoid arthritis (RA) and discuss influence of predictors to methotrexate (MTX) outcome treatment. Single nucleotide polymorphisms (SNPs) of the MTX metabolic pathways were genotyped. Twins have multiple mutations: a CC mutation of SNP 1298A>C in methylenetetrahydrofolate reductase (MTHFR) gene, CC mutations of three SNPs in the adenosine receptor gene ADORA2A (rs3761422_4217241T>C, rs2267076_4221164T>C, rs2236624_4226593T>C), and a heterozygous genotype in SNPs ATIC_rs2372536_347C>G, MTHFD1_rs2236225_1958G>A. These mutations are known to predict a worse outcome of MTX treatment. The twins had different lifestyles (alcohol drinking and smoking in Twin 1, regular coffee consumption in Twin 2), but a very similar clinical presentation of the outset of RA, radiographic scoring according to the Sharp/van der Heijde method with an almost identical antibodies presentation. The period of the patients before anti-TNFα treatment was characterized by unsuccessful per oral MTX pharmacotherapy in both cases (a low effect of MTX in Twin 1; an early discontinuation of MTX due to an adverse event in Twin 2). In both twins, the outcome of well-controlled anti-TNFα treatment (co-medication with MTX in Twin 1) for 10 years was expressed as low disease activity measured using composite index DAS28. It is interesting that Twin 2 had an unfavorable radiographic scoring after a 10-year follow-up than Twin 1 in spite of the comparable DAS28 in Twin 2 and smoking in Twin 1. In conclusion, co-medication of MTX with biologics may impact on RA radiographic progression despite predicted bad MTX outcome based on pharmacogenetic analysis.

Risk Factors of Acute Pancreatitis in Oral Double Balloon Enteroscopy.

Double balloon enteroscopy (DBE) was introduced 15 years ago. The complications of diagnostic DBE are rare, acute pancreatitis is most redoubtable one (incidence about 0.3%). Hyperamylasemia after DBE seems to be a rather common condition respectively. The most probable cause seems to be a mechanical straining of the pancreas. We tried to identify patients in a higher risk of acute pancreatitis after DBE. We investigated several laboratory markers before and after DBE (serum cathepsin B, lactoferrin, E-selectin, SPINK 1, procalcitonin, S100 proteins, alfa-1-antitrypsin, hs-CRP, malondialdehyde, serum and urine amylase and serum lipase). Serum amylase and lipase rose significantly with the maximum 4 hours after DBE. Serum cathepsin and procalcitonin decreased significantly 4 hours after DBE compared to healthy controls and patients values before DBE. Either serum amylase or lipase 4 hours after DBE did not correlate with any markers before DBE. There was a trend for an association between the number of push-and-pull cycles and procalcitonin and urine amylase 4 hours after DBE; between procalcitonin and alfa-1-antitrypsin, cathepsin and hs-CRP; and between E-selectin and malondialdehyde 4 hours after DBE. We found no laboratory markers determinative in advance those patients in a higher risk of acute pancreatitis after DBE.

Genetic polymorphisms in metabolic pathways of leflunomide in the treatment of rheumatoid arthritis.

Leflunomide (LEF) is a disease-modifying anti-rheumatic drug used for treating rheumatoid arthritis (RA). More than 50% of patients are withdrawn from LEF treatment within one year, mainly due to AEs. Importantly, it is not possible to predict which patients will respond to LEF therapy nor if adverse outcome occurs. Pharmacogenetic studies indicate an impact of single nucleotid polymorphisms (SNPs) on the variability in LEF serum levels with potential relevance to effectiveness and tolerability in individual RA patients. In vitro studies have demonstrated that cytochromes P450 (CYPs), mainly CYP1A2, CYP2C19, and CYP3A4, are involved in LEF metabolite activation. It was shown that CYP1A2*1F allele may be associated with LEF toxicity in patients with RA. In case of dihydroorotate dehydrogenase (DHODH) gene SNP (rs3213422, 19C>A), it was shown that C allele may be associated with LEF toxicity and therapeutic effect. Finally, oestrogen receptor genes SNPs in females may be associated with LEF therapy efficacy. In summary, the results of the current studies suggest a possible diagnostic value of genotyping for patients with RA as biomarkers of LEF therapy efficacy or conversely as indicators of serious side effects. In the future, it will be necessary to corroborate these results in studies with larger numbers of patients and longer follow-up. Moreover, it would be appropriate to focus on CYP2C19, ATP5A1 and PKD1L3 genes.

Whipple's Disease: Our Own Experience and Review of the Literature.

Whipple's disease is a chronic infectious systemic disease caused by the bacterium Tropheryma whipplei. Nondeforming arthritis is frequently an initial complaint. Gastrointestinal and general symptoms include marked diarrhoea (with serious malabsorption), abdominal pain, prominent weight loss, and low-grade fever. Possible neurologic symptoms (up to 20%) might be associated with worse prognosis. Diagnosis is based on the clinical picture and small intestinal histology revealing foamy macrophages containing periodic-acid-Schiff- (PAS-) positive material. Long-term (up to one year) antibiotic therapy provides a favourable outcome in the vast majority of cases. This paper provides review of the literature and an analysis of our 5 patients recorded within a 20-year period at a tertiary gastroenterology centre. Patients were treated using i.v. penicillin G or amoxicillin-clavulanic acid + i.v. gentamicin for two weeks, followed by p.o. doxycycline (100 mg per day) plus p.o. salazopyrine (3 g per day) for 1 year. Full remission was achieved in all our patients.

[Updated view of fibromyalgia]. / Aktuální pohled na fibromyalgii.

Fibromyalgia is a chronic syndrome characterized by dysfunction of pain processing and regulation. Although the definite etiology has not been recognized yet, the key role in the pathogenesis of this syndrome probably plays the central sensitization process with the development of chronic (central) pain and other associated symptoms (fatigue, stiffness, sleep disorders, cognitive and vegetative disturbance). The absence of objective diagnostic tests often results in delayed diagnosis and patient fluctuation among a number of specialists with uncertainty and fear of a serious disease. The treatment is based on the individually adjusted and multidisciplinary approach to the patient, combining pharmacological and non-pharmacological therapy. New drugs introduced to the therapy in the recent years can have positive effect on symptom reduction and improvement of patients quality of life. Key words: fibromyalgia, chronic pain, fatigue, central sensitization.

The manifestation of systemic vasculitis in the central nervous system--a case report.

We present a case of a patient with systemic vasculitis suffering--besides heart, skin and gastrointestinal lesions--from the rarely reported involvement of the central nervous system. Even though the diagnosis could not be ascertained precisely, immunosuppressive therapy led to prompt regression of symptoms including initially present neurologic manifestations.