P032 Methotrexate and hepatic tolerance in Juvenile Idiopathic Arthritis

Background Methotrexate (MTX) is considered as the main treatment for some juvenile idiopathic arthritis (JIA) subtypes. The hepatic toxicity of MTX has been reported in numerous studies in rheumatoid arthritis which have shown that prolonged treatment can induce hepatic fibrosis and a disturbance of the liver biologic tests. In patients with JIA, the potential hepatic toxicity of MTX needs to be confirmed. Methods A retrospective study of patients followed for JIA and treated with MTX was conducted. The results of the hepatic assessment looking for cytolysis or cholestasis performed during the pre-treatment assessment and then during regular checks were noted. Results Thirty-nine JIA patients were included. The mean age of disease onset was 8 years [1.5–17 years]. The JIA subtype was systemic in 11 cases, enthesitis related arthritis in 5 cases, rheumatoid factor seronegative polyarthritis in 15 cases and rheumatoid factor seropositive polyarthritis in 2 cases, and oligoarthritis in 2 cases. Patients were treated with low doses of corticosteroids (0.2–0.4 mg/kg) in majority of cases (82%). Non steroid anti-inflammatory drugs were used in 51% of cases. MTX was prescribed as monotherapy in 20 cases, in combination with Sulfasalazine in 6 cases and Anti TNF alpha in 12 cases. MTX has been used on average for 11 years [2 months-26 years]. This drug was stopped for ineffectiveness in 7 cases, for digestive intolerance in 2 cases and in one case for severe hepatic cytolysis after 2 years of treatment with a progressive normalization of hepatic laboratory tests after 6 months. During regular monitoring, no further disturbances of liver function were observed. Conclusion MTX hepatotoxicity appears to be very mild and rare in JIA. These results are reassuring given that MTX is a highly effective treatment in JIA.

Successful Use of Adalimumab in Children with Uveitis-Associated Juvenile Idiopathic Arthritis

Objective of the Paper: To describe clinical cases of successful use of adalimumab in children with uveitis-associated juvenile idiopathic arthritis (JIA). Key Points. One of the extraarticular manifestations of JIA is uveitis, i. e. inflammation of the vascular tract of the eye. JIA-associated uveitis is diagnosed primarily in small girls with oligoarthritis, early seronegative polyarthritis; in patients with arthritis associated with enthesitis and psoriatic arthritis. The article describes clinical cases of the use of adalimumab in JIA and uveitis where the therapy with methotrexate and topical glucocorticosteroids fails. Conclusion. Uveitis-associated JIA is one of the most disabling forms of JIA, since, despite timely and adequate management, very often it results in severe ocular complications: cataract, glaucoma and even blindness. Adalimumab, a human anti-TNFα monoclonal antibody, is available and it helps in achieving uveitis remission where methotrexate and topical glucocorticosteroids fail, as well as in delaying ocular complications. Keywords: juvenile idiopathic arthritis, uveitis, adalimumab, children.

Recurrent Polychondritis as a Paraneoplastic Phenomenon in a Patient With Myelodysplastic Syndrome

Myelodysplastic syndromes are a heterogeneous group of hematological diseases, characterized by ineffective hematopoiesis with risk of progression to acute myeloid leukemia. They can be associated to autoimmune manifestations in 10-30% of patients, appearing before, during or after the diagnosis of the hematological disorder. The prevalence of relapsing polychondritis as a paraneoplastic phenomenon is 0.7-5.4%, occurring simultaneously in the majority of cases. Other associated autoimmune processes include: systemic vasculitis, seronegative polyarthritis, neutrophilic dermatosis, immunomediated cytopenias, presence of autoantibodies and cryoglobulinemia. We report the case of a 60-year-old woman, with no previous medical history, who presented with recurrent polychondritis and systemic vasculitis associated with myelodysplasia.

A 27-year-old man with recurrent sinopulmonary and cutaneous infections

The increasing availability of genetic testing for modern immunologists in the evaluation of immune diseases could provide a definite diagnosis in elusive cases. A 27-year-old white male patient presented to the clinic with recurrent sinopulmonary and cutaneous infections since childhood. The patient’s mother had seronegative polyarthritis, and one of two sisters of the patient had chronic sinopulmonary infections. Serum immunoglobulins, immunoglobulin G (IgG) subclasses, lymphocyte subset markers, mannose-binding lectin, mitogen and antigen stimulation, bacteriophage study, and Streptococcus pneumoniae titers to 23 serotypes were all normal. B-cell phenotyping revealed a decrease in both nonswitched memory B cells (CD19+CD27+IgD+) and switched memory B-cells (CD19+CD27+IgD−). Genetic testing and the improvement of clinical symptoms after IgG replacement led to the final diagnosis.

Seronegative Arthritis and Whipple Disease: Risk of Misdiagnosis in the Era of Biologic Agents

We report 2 cases of Whipple disease (WD), previously diagnosed as seronegative polyarthritis and treated for several years with immunosuppressive agents, accordingly. Both cases had been treated over years with cDMARDs and bDMARDs. The first patient was a 48-year-old male, who developed a life-threatening disease characterized by fever, significant weight loss, and bloody diarrhoea, supported with RBC transfusions. The second patient was a 55-year-old man, presenting with arthritis, fever, serositis, lymphadenopathy, thoracic rash, and systemic inflammation; at the beginning he was diagnosed as adult onset Still’s disease. He was treated with steroids and antitumour necrosis factor agents, but showed no improvement. Both patients were eventually treated with antimicrobial therapy for WD with dramatic improvement and no clinical relapse in 6 months. This paper reviews the literature on WD mimicking chronic inflammatory arthritis. WD may lead to chronic seronegative arthritis that might often be misrecognized. Importantly, patients treated with bDMARDs and glucocorticoids might develop a life-threatening disease. Therefore, WD should be suspected and excluded in patients showing resistance or frequent recurrence of chronic arthritis, if seronegative, under treatment with bDMARDs, especially in the presence of new, unexpected sign and/or symptoms.

Influence of -174G/C IL-6 gene polymorphism on the susceptibility to rheumatoid arthritis in children and adults in the Republic Of Belarus

The usage of clinical and instrumental methods only may be not sufficient for early diagnosis of autoimmune rheumatic diseases, as well as for their course prediction. The progress of modern rheumatology is largely conditioned by the investigation of molecular-genetic nature of diseases and the identification of biomarkers that can significantly improve diagnostics and therapeutic approach. The present study aimed to evaluate the effect of -174G/C IL-6 gene polymorphism on the risk of developing rheumatoid arthritis (RA) in children and adults in Republic of Belarus. It was established that the CC genotype frequency (p = 0.01, OR = 2.19; 95 % CI [1.31-3.67]) as well as the С allele frequency (p = 0.03; OR = 1.44; 95 % CI [1.04-2.00]) was significantly higher among patients with juvenile idiopathic arthritis (JIA) in the entire group and especially in girls (p = 0.04, OR = 2.55; 95 % CI [1.22-5.36]) in comparison with the controls. In addition, there is a tendency to higher frequency of the С allele in adult patients with RA (p = 0.07), reaching statistical significance in the case of RF-negative arthritis (p = 0.03, OR = 3.04; 95 % CI [1.15-8.06]). The minor С allele (p = 0.03, OR = 2.04; 95 % CI [1.09-3.82]) and homozygous CC genotype (p = 0.02, OR = 3.34; 95 % CI [1.38-8.07]) are also associated with seronegative polyarthritis in children. Thus, the presence of this allele in the tested locus increases the likelihood of developing certain rheumatoid arthritis subtypes in adults and children and can be used to reveal individuals with genetic predisposition.