P075 Contribution of biothérapy in pediatric rheumatology: tolérance and efficacy

Background Biotherapy result of spectacular advances in genetics and research in molecular and cellular biology, has considerably improved the management of rheumatic and autoinflammatory diseases in children. The Objective is to assess the efficacy and tolerance of biotherapy in pediatrics Methods A retro-prospective study was carried out in the Pediatric Department B at the pediatric rheumatology consultation, university hospital center. An operating sheet was drawn up including epidemiological, clinical, paraclinical and therapeutic data of the cases diagnosed as well as their evolution on biotherapy. Results 26 children received treatment with biotherapy. 73% presented with JIA (54% systemic, 19% polyarticular with positive RF, 19% severe uveitis, and 4% familial Mediterranean fever. 4% behçet disease The mean time to start biotherapy was 12 months [2–48]. There is a clear clinical and biological improvement for 93% of patients. Etanercept was effective in polyarticular-progressive JIA, Adalimumab in oligoarthritis with severe uveitis, Tocilizumab in systemic forms of JIA and Anakinra in familial Mediterranean fever resistant to colchicine and systemic arthritis. The adverse reactions noted were: one case of tuberculosis, hepatic cytolysis in 4 cases, and one case of psoriasis. Conclusion The introduction of biotherapy in pediatric has considerably improved the management of inflammatory rheumatic diseases and transformed the prognosis of these chronic diseases. The maintenance of the good response to treatment and the good tolerance of biotherapy must be evaluated prospectively over the long term.

P024 Efficacy and tolerance of methotrexate in patients with Juvenile Idiopathic Arthritis

Background Juvenile idiopathic arthritis (JIA) is the most common inflammatory rheumatic disease for children. The therapeutic management depends on several factors and is based on different treatments including methotrexate (MTX). The aim of our study was to determine the efficacy and safety of MTX in JIA. Methods This is a monocentric retrospective study of 37 patients followed for JIA according to the 2001 International League of Association of Rheumatology (ILAR) criteria and treated with MTX. Socio-demographic, clinical, paraclinical and therapeutic data were collected. Disease activity was assessed by the JADAS score. Highly active JIA was defined as JADAS superior to 25. Results There were 25 boys (67.5%) and 12 girls (32.4%) with a median age of 6.3 years [4–13]. The average duration of the rheumatic disease was 2.7 years [2.5–5.3]. The type of JIA was: oligoarticular in 22 cases (59.4%), polyarticular in 10 cases (27%), arthritis related to enthesitis in 3 cases (8.1%) and systemic in 2 cases (5.4%). Twenty patients (54%) received oral corticosteroid therapy for a mean period of 1.7 years [0.6–3] with a mean daily dose of 10 mg/day of prednisone or equivalent. Oral MTX was prescribed to all patients with a mean weekly dose of 10 mg/m2 body surface [10–15]. MTX was initiated after a mean period of 6.2 months [3.1–11.4] from diagnosis. The mean treatment duration was 50 months [34–66]. Observance of MTX was 80.5%. Remission with MTX was achieved in 28 patients (75.6%) after a mean treatment duration of 7.5 months [5–11], with a mean JADAS of 5.1 [3.5–10]. Despite good observance of MTX, eight patients (21.6%) continued to have high disease activity with a mean JADAS score of 32 [25–40]. Tolerance to oral MTX was good, with side effects occurring only with 5 patients (13.5%), such as epigastralgia in 2 cases (which disappeared after switching to the intramuscular administration), a skin reaction in one case, and hepatic cytolysis reversible when stopping the treatment in 2 other cases. Conclusion MTX still has a place in the therapeutic management of JIA and appears to be a well-tolerated and effective treatment.

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.

Gallbladder diaphragm: about a case

Diaphragm gallbladder is a very rare anomaly of gallbladder embryogenesis. This malformation is very rare in adults and represents 0.1% of gallbladder anomalies. It can remain asymptomatic for a long time and be discovered fortuitously during a radiological examination for another pathology or be revealed by chronic abdominal pain or by a complication such as cholecystitis or biliary peritonitis. We report the observation of a 34 years old woman with chronic hepatic colic. The biological work-up including a blood count, a hepatic cytolysis and cholestas and CRP determination did not reveal any abnormality, whose morphological examinations concluded to an uncomplicated diaphragm gallbladder. A laparoscopic cholecystectomy was performed. The post-operative course was unremarkable. The intraoperative finding by opening the cholecystectomy specimen confirmed the diagnosis of a diaphragm gallbladder. Histological study confirms the diagnosis of diaphragm vesicle cholecystitis. In this document, we described the clinical and radiological characteristics of this rare anomaly.

AB0190 LIVER INVOLVEMENT IN RHEUMATOID ARTHRITIS

Background:Rheumatoid arthritis (RA) can be associated to extra-articular manifestations and comorbidities, including hepatic disturbances. It can be related to an underlying viral, metabolic or immune disease, or to a medical treatment toxicity [1].Objectives:We aim to study liver involvement in a group of RA patients.Methods:We performed a cross sectional study in 249 RA patients responding to the ACR/EULAR 2010 criteria for RA diagnosis. Hepatic enzymes, B and C hepatitis viruses screening tests, abdominal ultrasonography, biliary tract MRIs, fibrotests and fibroscans if available were collected and analysed.Results:Two hundred and forty-nine patients were included with 83.8% of women. The mean age was 59±11.67 years. The mean age at diagnosis was 47±14.9 years with a mean disease evolution of 11±8.83 years.The mean disease activity (DAS28) was 4,66 with levels ranging from 0.12 to 7.78.Liver abnormalities were found in 68 patients (27.3%).Viral disease represented 32.3% of liver abnormalities and was found in 8.8% of the total number of patients. Positive anti-HBc antibodies with negative HBs antigen were found in 8.4% of the patients, no viral reactivation with conventional or biological disease-modifying anti-rheumatic drugs was noted.Besides, 4 of the 249 patients had positive HCV antibodies tests; one of them had a reactivation of a hepatitis C infection after treatment with leflunomide, one had a chronic C hepatitis with chronic liver disease, one had an old B and C hepatitis infection and the last one had an associated liver nodule for which an exploration was triggered. One patient had post hepatitis C cirrhosis associated with a hepatocellular carcinoma treated with surgery and an association of ledipasvir and sofosbuvir with a negative serology.Medical treatment toxicity was responsible for 25% of liver abnormalities. Paracetamol caused both hepatic cholestasis and cytolysis in 5 patients, and isolated cholestasis in 2 patients. NSAIDs caused both hepatic cholestasis and cytolysis in 2 patients, and isolated cholestasis in one patient. Methotrexate was responsible for isolated cholestasis in 2 patients, isolated hepatic cytolysis in one patient and both cholestasis and cytolysis in one patient. An interaction between methotrexate and fluconazole caused one case of hepatic cholestasis and cytolysis. Treatment of a latent tuberculosis with isoniazid and rifampicin was responsible for cholestasis in one patient.Immune hepatic disease was present in 3 patients: 2 patients had a primary biliary cholangitis that manifested with a cholestasis and one patient had an auto-immune hepatitis that manifested with cytolysis and cholestasis.The prevalence of hepatic steatosis was of 4.8%, assessed with ultrasonography or microscopic examination of a liver biopsy. Hepatic enzymes test was normal in 2%, showed isolated cholestasis in 2% and both cholestasis and hepatic cytolysis in 0.8% of the patients.One patient had a secondary hemochromatosis to multiple transfusions for sickle cell anaemia, causing cholestasis and cytolysis.No aetiology was found for hepatic cholestasis and/or cytolysis in 7.2% of patients.Conclusion:Liver involvement in RA is common and has different aspects. A careful monitoring of liver enzymes tests is crucial to detect hepatic disease and prevent its evolution to a chronic liver disease and cirrhosis. On the other hand, screening for viral hepatitis B and C is necessary to prevent an aggravation of a chronic infection and a reactivation of a latent one [2].References:[1]Sellami M, Saidane O, Mahmoud I, Tekaya AB, Tekaya R, Abdelmoula L. Etiological Features of Liver Involvement in Rheumatoid Arthritis. Curr Rheumatol Rev. 2020;16(4):332-6.[2]Karadağ Ö, Kaşifoğlu T, Özer B, Kaymakoğlu S, Kuş Y, İnanç M, et al. Viral hepatitis screening guideline before biological drug use in rheumatic patients. Eur J Rheumatol. mars 2016;3(1):25-8.Disclosure of Interests:None declared

MO426HANTA HEMORRHAGIC FEVER WITH RENAL SYNDROME CAUSED BY HANTAAN SEROTIPE IN BALKAN PENINSULA - AN UNESPECTED FINDING

Background and Aims Hantavirus infection is a zoonosis rare in the Balkan Peninsula but with increasing frequency and geographic spread, causing two major syndromes, depending on the viral serotype: hemorrhagic fever with renal syndrome (HFRS) and cardiopulmonary syndrome (CPS). Because there is no specific treatment or vaccine for this condition, the key for minimizing the progression to chronic kidney disease, secondary hypertension or death is early diagnosis and prompt therapy. This paper presents a case of HFSR in which needle kidney biopsy played a major role in diagnosis and draws attention on this zoonosis that might be highly underdiagnosed in Balkan Peninsula. Method A 26-year-old female with no medical history was admitted in our department with acute kidney injury (AKI), nephritic syndrome with nephrotic range proteinuria, high blood pressure, hepatic cytolysis, severe thrombocytopenia, anemia and leukocytosis, elevated LDH, normal haptoglobin, positive Coombs test (Table 1). Immunological testing (C3, C4, ANA, ANCA, antiGBM), viral infection markers (hepatitis B/C, HIV, Epstein-Barr, Cytomegalovirus), IgA/M/G were all negative and ADAMTS13 activity was normal. Abdominal sonography showed both kidneys of normal size and shape. A kidney biopsy was performed. The biopsy specimen showed macroscopic features of hemorrhage in the renal medulla. In immunofluorescence the staining was negative for IgA, IgG, IgM, C1q, C3c, k and λ chains, albumin and fibrinogen. Light microscopy (LM) revealed normal glomeruli and arterioles, dilated proximal tubules with resorption droplets at the apical pole and erythrocytes in the lumen, important interstitial hemorrhage in the medulla, with no inflammation or interstitial fibrosis. The electron microscopy (EM) showed segmental foot process effacement, endotheliosis of the peritubular capillaries, rare plasmocytes and macrophages in the interstitium (Figure 1). The aspect of hemorrhagic interstitial nephritis suggested Hantavirus infection. Serological testing revealed both IgM and IgG antibodies for the Hantaan serotype (HTNV). The final diagnosis was HTNV hemorrhagic interstitial nephritis with intrinsic AKI and secondary hypertension. MO426 Figure 1: A, B LM, Toluidine Blue staining. Normal glomerulus. Resorption droplets in the proximal tubular cells. C, D LM, Toluidine Blue staining. Extensive interstitial hemorrhage in medulla, tubulitis. E EM. Interstitial extravasation of erythrocytes. F EM. Endothelial swelling, foot process effacement. Results The patient was treated with oral methylprednisolone 16mg/d for 2 weeks, with progressive tampering of the dose and removal after 2 months. She received antihypertensive and antiproteinuric treatment with ramipril. The evolution was good, with creatinine and liver enzymes returning to normal. Conclusion HFRS belongs to a group of rare zoonoses in Balkan Peninsula, the most involved serotypes being Dobrava and Puumala. This case had positive serology for HTNV usually being found in China and Russia, but our patient didn’t travel abroad before she got ill, so we can’t consider the case as being an imported infection. That highlights a possible underdiagnosis of the disease in this region and also the need to re-evaluate geographic distribution of different strains and changes in ecological aspects given that they may pose a major risk to public health. The disease begins with flu-like symptoms and progresses to AKI with severe thrombocytopenia, anemia and coagulation disorders, being easily mistaken for haemolytic uremic syndrome. In a region with sporadic cases, we face diagnosis difficulties related especially to the absence of initial diagnosis suspicion, so we emphasize the need to include this pathology in the differential diagnosis algorithm of diseases evolving with thrombocytopenia, anemia, hepatic cytolysis and renal injury.

P653 Rheumatic extraintestinal manifestations in ulcerative colitis : Prevalence and predictive factors

Background Ulcerative colitis (UC) are an inflammatory condition affecting the gastrointestinal tract. They are considered as chronic disease with complex genetic, immune and environmental components. UC are not exclusive to the gastrointestinal system as they have been identified to be associated with extraintestinal manifestations (EIM) that encompass every other organ in the human body including musculoskeletal system. The aim of this study was to evaluate the prevalence and predictive factors of rheumatic EIM among patients with UC. Methods We carried out a retrospective study from January 2000 to December 2018 including all patients with UC. A complete rheumatologic examination, osteodensitometry,lumbosacral and sacroiliac X-rays were performed.The variables retrospectively analyzed were: gender, age,habits, location and extension of the disease, biochemical markers, other EIM, and previous immunosuppressive therapy. We investigated associations between rheumatic manifestations and clinical and biological criteria. Results Seventy eight patients were included in our study with an average age of 47,56 years [24–85 years]. Sex ratio M/F 0,85. Rheumatic manifestations of any type were present in 42,3%(33 of 78). Peripheral arthritis were observed in 3,8%. Axial involvement including sacroiliitis (SI), with or without spondylitis was noticed in 8,97%. Bone mineral loss was present in 25,6% with 13 cases of osteopenia and 7 cases of osteoporosis. Three patients (3,8%) had an association of SI and osteoporosis. No cases of enthesopathy have been reported. Otherwise, univariate and multivariate logistic regression methods testing for each predictor and their possible association with rheumatic manifestations among UC had shown a decreased risk for rheumatic manifestations with an age over 40 years (p=0,018), an hepatobiliary disorders such as the presence of hepatic cytolysis (p=0,034) and cholestasis (p=0,017) , the coexistence of dermatologic EIM (p=0,048). Forms complicated with an acute severe ulcerative colitis are likely to be correlated with rheumatologic manifestations (p=0,039) but location and extension of the disease had not shown any significant association. And finally, patients who underwent systemic corticosteroid treatment were highly associated with a decreased risk for rheumatic manifestations (p=0,044). Conclusion Predictive factors involved in the occurrence of rheumatic manifestations are: an advanced age, presence of other EIM, severe forms and the use of steroid. Regular screening for EIM and early use of biological therapies may prevent the development of musculoskeletal involvement . Medical care for patients with UC should be multidisciplinary involving the coordination between rheumatologists and gastroenterologists .

Hepatocellular carcinoma associated with pregnancy about 2 cases at the gynecological and obstetrical clinic of the Aristide Le Dantec hospital, Dakar, Senegal

The objective of our study was to report 2 cases of hepatocellular carcinomas associated with pregnancy followed in our structure and to review the literature. Our patients were 30 and 37-year-old multi-gesture females with chronic unattended viral hepatitis B in whom the diagnosis of hepatocellular carcinoma was made in the third trimester of pregnancy at 31 weeks of amenorrhea and 4 days and at 32 weeks of amenorrhea after the incidental finding of tumor hepatomegaly on abdominal-pelvic ultrasound. The main clinical signs were jaundice and hepatomegaly and paraclinical signs were dominated by hepatic cytolysis and anemia in addition to ultrasound images. Follow-up of pregnancies revealed no particularities. A caesarean section was scheduled at 32 weeks of amenorrhea and 32 weeks of amenorrhea and 3 days allowing the birth of two preterm newborns weighing 1210 and 1500 gm with Apgar scores of 8-10/10 and 7-9/10 respectively at the fifth minute. The immediate post-operative follow-up was simple. However, the maternal-fetal prognosis was poor with the death of both patients in a multi-visceral failure table occurring respectively at 6 weeks and 3 weeks after caesarean section. The newborns had died 8 days after birth. Although rare, these two cases challenge any obstetrician to think about liver cancer in pregnant women, especially those with chronic hepatitis B. Ultrasound examination of the liver, or even better, the MRI, which is more efficient, in order to suspect early on a possible liver cancer. Indeed, early diagnosis and a thorough medical approach are essential for the treatment of HCC in pregnant patients.