Despoina Maritsi

Clinical Features, Treatment, and Outcome of Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: A Multinational, Multicenter Study of 362 Patients

To describe the clinical, laboratory, and histopathologic features, current treatment, and outcome of patients with macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (JIA).

Bartonella henselae Infection: An Uncommon Mimicker of Autoimmune Disease

We present a case of a seven-year-old immunocompetent female patient who developed systemic symptoms mimicking an autoimmune rather than an infectious disease. The patient presented with rash, biquotidian fever, night sweats, and arthralgias. There was no antecedent history of cat contact. Investigations showed increased inflammatory markers, leukocytosis, thrombocytosis, hypercalcemia, and raised angiotensin-converting enzyme. Interferon-gamma releasing assay for tuberculosis infection was negative. Abdominal imaging demonstrated multifocal lesions of the liver and spleen (later proved to be granulomata), chest X-ray showed enlarged hilar lymph nodes, and ophthalmology review revealed uveitis. Clinical, laboratory, and imaging features pointed towards sarcoidosis. Subsequently, raised titers (IgM 1 : 32, IgG 1 : 256) against Bartonella confirmed the diagnosis of B. henselae infection. She was treated with gentamycin followed by ciprofloxacin; repeat investigations showed complete resolution of findings. The presence of hepatic and splenic lesions in children with bartonellosis is well documented. Our case, however, exhibited certain unusual findings such as the coexistence of acute ocular and systemic involvement in an immunocompetent host. Serological testing is an inexpensive and effective way to diagnose bartonellosis in immunocompetent patients; we suggest that bartonella serology is included in the baseline tests performed on children with prolonged fever even in the absence of contact with cats in countries where bartonellosis is prevalent.

Effect of Biologic Therapy on Clinical and Laboratory Features of Macrophage Activation Syndrome Associated With Systemic Juvenile Idiopathic Arthritis

To assess performance of the 2016 macrophage activation syndrome (MAS) classification criteria for patients with systemic juvenile idiopathic arthritis (JIA) who develop MAS while treated with biologic medications.

The Performance of Quantiferon TB Gold In-Tube as a Screening Tool in Paediatric Rheumatology prior to Initiation of Infliximab: A Single Centre's Experience

Background. Patients with autoimmune diseases and latent tuberculosis infection (LTBI) are at risk of developing catastrophic tuberculosis disease following infliximab treatment. Quantiferon-TB gold in-Tube (QTB) has proven a more accurate screening tool than tuberculin skin test (TST) in adult populations. Objectives. To assess the utility and validity of QTB in children, prior to treatment with infliximab. Methods. Retrospective cohort of patients started on infliximab following endorsement of QTB as a screening tool by the NICE guidelines in 2006. Results. Twenty three patients (12 females and 11 males) were included in the study. A chest radiograph (CXR) and QTB was performed prior to starting infliximab. Fourteen patients had a recorded negative TST result. One patient had a positive QTB while two had indeterminate results. Their CXRs were not suggestive of TB and TSTs were negative. The patients with indeterminate results were started on infliximab and had regular clinical assessment for TB disease. Repeat QTB was negative in one while remained indeterminate in the other. None of our 23 patients developed TB. Conclusion. QTB is a useful screen tool for LTBI. Indeterminate results warrant careful assessment and re-evaluation, but should not preclude from initiation of anti TNF treatment.

An unusual case of epidermolysis bullosa complicated by persistent oligoarticular juvenile idiopathic arthritis; lessons to be learned

Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a rare and severe hereditary skin disease. Oligoarticular Juvenile Idiopathic Arthritis (JIA) although infrequent in the general paediatric population, is the most frequent type of autoimmune joint disease in children. While different in aetiology, both diseases are characterized by gradual deterioration in mobility and function. We report a female patient, diagnosed with RDEB at birth, who presented with inflammatory bowel disease (IBD) at the age of four years, and subsequently developed oligoarticular JIA at seven years of age, and discuss the diagnostic and treatment challenges of this unusual case. This report, besides presenting a unique case, also highlights the important issues that need to be taken into account when assessing and managing patients with such complex conditions.

Complete clinical remission with tocilizumab in two infants with systemic juvenile idiopathic arthritis: a case series

Systemic juvenile idiopathic arthritis (sJIA) is a multisystem inflammatory disorder affecting 1–20 per 300 000 children annually and accounts for 10–20% of patients with JIA (1). sJIA is rarely diagnosed in children under 2 years of age. Cardinal features include biquotidian fever, rash, serositis, and hepatosplenomegaly. Arthritis may be absent at disease onset (2). Macrophage and neutrophil activation occurs, while interleukin (IL)-1 and IL-6 are the pivotal players in this systemic inflammatory reaction (3, 4). Over the past decade, blockage of these cytokines has led to effective and sustained control of the disease, as established by open-label studies and randomized controlled trials (RCTs) performed in children (5, 6). Tocilizumab, an anti-IL-6 blocking agent found to be highly effective in multiple autoimmune diseases, is now considered the mainstay treatment for difficult-to-treat sJIA in patients over 4 years of age (7, 8). We present the cases of two infants with sJIA who failed to respond to conventional treatment and were successfully treated with tocilizumab. To our knowledge, there are no previous data on the efficacy and safety of this drug in such a young age. An 8-month-old male infant presented with a 1-week history of persistent fever and raised inflammatory markers; no source of infection was identified. He had splenomegaly and lymphadenopathy. The patient underwent major work-up for infection and malignancy and received broad-spectrum antibiotics. Ultrasonography revealed free peritoneal and pericardiac fluid. His symptoms persisted despite the use of antibiotics. He subsequently developed a maculopapular rash on his trunk and the following day he developed arthritis of the wrists, knees, ankles, and third and fourth proximal interphalangeal (PIP) joints. The patient was diagnosed with sJIA and received pulses of methylprednisolone; methotrexate was initiated. Genetic testing for autoinflammatory diseases (FMF, TRAPS, HIDS, CAPS) was negative; genetic and functional screening assays such as intracellular perforin staining and degranulation of T cells and natural killer (NK) cell assays for primary haemophagocytic lymphohistiocytosis (HLH) were normal (9). Serositis, arthritis, and lymphadenopathy improved after initiation of treatment. At 12 weeks, fever spikes and rash persisted despite continuous significant doses of prednisolone (Table 1). In addition, the infant became cushingoid, hypertensive, and extremely irritable. Inflammatory markers were high with persistent thrombocytosis (Table 2). We initiated tocilizumab. One month later, the patient’s condition had markedly improved, although he occasionally presented with a rash. Twelve months later, the patient remained asymptomatic, leading a fully normal life.

SAT0500 The Immune Response to Hepatitis a Vaccine in Children with Pfapa Syndrome

Background Hepatitis A is an indolent disease with a varying clinical spectrum and consequences. Little is known about the immune response to hepatitis A virus (HAV) vaccination in children with Periodic Fever, Aphtous Stomatitis, Pharyngitis, Adenitis Syndrome (PFAPA). Objectives To assess the sero-protective efficacy and safety of immunization against hepatitis A in PFAPA patients, not previously exposed to HAV, and compare these to healthy controls. Methods Matched case control study including patients with PFAPA and controls. All subjects received two doses of the inactivated anti-HAV vaccine at zero and six months. Seroconversion and seroprotection rates and anti-HAV-IgG antibodies were assessed at enrollment,1 month after the first dose and 1 and 12 months after the last dose. Exclusion criteria were infection or disease flare concomitant or up to ten days prior to immunization, known liver disease or immunodeficiency, and serum testing positive for HAV-infection. Clinical,demographic data and medications used were collected for each patient. Onset of PFAPA symptoms within a week from vaccination was defined as a flare. Results 28 patients with a mean age of 4.4 years completed the study. Thirteen (46%) patients received NSAIDS, 9 (32%) received NSAIDS+steroids, 3 (10%) patients received steroids and 3 did not receive any treatment at the time of PFAPA flares. The control group consisted of 76 healthy individuals (mean age 4.75 years). A month after primary vaccination 92.9% of patients and 77.6% of the controls attained seroprotection (p=0.07), while rates further increased to 100% and and 96.1% a month after the second dose respectively (p=0.2). In both groups, seroprotection rates remained elevated 12 months following completion of the study (100% vs 95%).Seroconversion rates measured at timely intervals were satisfactory for both groups. No statistically significant difference was detected amongst the two groups. Mean anti-HAV IgG concentration at 4 weeks was 110mIU/ml in the patient and 96mIU/ml in the control group while it reached 223mIU/ml and 218mIU/ml after the second dose respectively, and at 18 months it was 278 mIU/ml in the patient group and 245 mIU/ml in the control group. Mean IgG concentration was not statistically different between patient and control groups at 1 month after the first dose (p=0.3), 1 month after the second dose (p=0.8) and at 18 months after initial vaccination (p=0.2). Subgroup analysis of the PFAPA group showed that the use of steroids or NSAIDS did not affect sero-conversion and seroprotection rates or mean antibody titers. Overall four (14.2%) patients in the PFAPA group developed a flare (one after the first dose, three after the second dose). The use of steroids did not seem to affect the development of flare. Mild adverse events were noticed in 6 (17%) patients and 15 (21%) controls. Conclusions Two doses of HAV vaccine are safe and effective in the vast majority of children with PFAPA. In fact, patients with PFAPA boosted a better immune response at all time points compared to their healthy counterparts. Nevertheless, a proportion of these patients developed a flare. Systemic illness should not preclude from completion of the vaccination schedule in cases where anti-HAV vaccine is mandatory, provided the parents are aware of the possibility of a flare. Larger prospective studies are required to verify the aforementioned results. Disclosure of Interest None declared

The response to hepatitis a vaccine in children with JIA on immunosuppresive treatment

methotrexate and 27 received both. The control group consisted of 76 healthy individuals (mean age 5.2 years). At four weeks after primary vaccination 48% of patients and 65% (P<0.01) of the controls attained seroprotection. Ninety-four percent of the patients and 99% (P=0.07) of the controls seroconverted four weeks after the second dose. Seroconversion rate was 91.5% for the patient group and 97% for the controls at 52 weeks post the second dose. Mean IgG concentration at 4 weeks was 45mIU/ml in the patient an d8 9mIU/ml in the control group (P=0.04) while it reached 118mIU/ml and 213 mIU/ml after the second dose respectively (P=0.03). Subgroup analysis showed patients on biologics had better seroconversion rates compared to children on MTX or children on biologics+MTX. Vaccines were well tolerated. Mild adverse events were noticed in 7 patients and 8 controls. None of the patients developed a flare. Conclusion Two doses of HAV vaccine are safe and effective in the majority of children with JIA, whereas a single dose seems inefficient. Systemic illness should not preclude from completion of the vaccination schedule. Seroconversion rates are lower in children whose treatment regime includes MTX. Disclosure of interest None declared.

Clinical features, treatment, and outcome of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis

To describe the clinical, laboratory, and histopathologic features, current treatment, and outcome of patients with macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (JIA).

Clinical Features, Treatment, and Outcome of Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: A Multinational, Multicenter Study of 362 Patients: Macrophage Activation Syndrome in Systemic JIA

To describe the clinical, laboratory, and histopathologic features, current treatment, and outcome of patients with macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (JIA).