Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory autoimmune disease in childhood, significantly contributing to both short- and long-term disability. While certain human leukocyte antigen (HLA) class II alleles are known to be associated with specific subgroups of JIA, emerging evidence suggests a strong correlation between these alleles and treatment response. This study involved 143 JIA patients diagnosed according to International League of Associations for Rheumatology criteria. Each patient underwent HLA class II typing, including HLA-B27, as well as tests for rheumatoid factor (RF) and antinuclear antibodies (ANA). Comprehensive rheumatological assessments were conducted at diagnosis, with follow-ups at three and six months post-onset. After six months of methotrexate (MTX) treatment, patients were categorized as responders or non-responders. Responders achieved clinically inactive disease based on the American College of Rheumatology Provisional Criteria for Defining Clinical Inactive Disease and Clinical Remission. Non-responders, who did not reach clinically inactive disease after six months of treatment, required the addition of another non-biological disease-modifying antirheumatic drug (DMARD) or a biological DMARD. Our analysis revealed that the HLA-DRB1*01 allele is a significant prognostic marker for therapeutic response, predicting therapeutic resistance (P=0.01). The most prevalent HLA-DRB1 alleles in the treatment-resistant group were HLA-DRB1*08:11 (11.3%), HLA-DRB1*01:01 (8.5%), HLA-DRB1*01:13, HLA-DRB1*04:11 (7%), HLA-DRB1*08:13, and HLA-DRB1*08:15 (4.2%). These findings highlight the critical role of HLA class II alleles in pediatric rheumatology, particularly in relation to treatment response and disease prognosis. In the era of personalized medicine, understanding the genetic contributions to treatment response and outcomes in JIA patients is essential. A key limitation of this study was the lack of comparison of treatment responses across different JIA subtypes. Future studies should prioritize evaluating MTX efficacy within specific JIA subgroups to enable a more tailored understanding of its effectiveness.

PAPA syndrome (Pyogenic Arthritis, Pyoderma gangrenosum and Acne) is an autosomal dominant, hereditary autoinflammatory disease resulting from mutations in the PstPiP1/Cd2BP1 gene on chromosome 15q. The disease begins in childhood, most often from the age of 2 to 11, and it is characterised by a triad of symptoms: pyogenic (sterile) arthritis, pyoderma gangrenosum and acne. The disease usually begins with arthritis and is rarely recognised in the initial stage. The appearance of skin symptoms of the disease, either acne or pyoderma gangrenosum, along with the previously existing arthritis, should arouse suspicion of the existence of PAPA syndrome and direct doctors to perform further genetic testing. The triad of symptoms does not always have to be present, but the presence of two of the three symptoms with a confirmed gene mutation is a sufficient criterion for the diagnosis of the disease. Biological drugs have shown the greatest effectiveness in treatment, and il1 inhibitors or tnF alpha inhibitors are most often used medications. in later life, the joint manifestations gradually calm down, but the skin manifestations can last for many years with frequent relapses and remissions even with applied therapy, which makes this syndrome a great challenge for the treatment of this disease. Considering the small number of cases with PAPA syndrome described in the literature, we present to you an interesting case of a twenty-five-year-old patient with this disease and his challenging diagnostic and therapeutic path from childhood to adulthood.

Aim To analyse the association of human leukocyte antigen B27 with clinical and laboratory parameters in patients with juvenile idiopathic arthritis (JIA) at the disease onset. Methods A retrospective review of medical records of 25 HLAB27 positive and 25 HLA-B27 negative JIA patients was performed. The diagnosis of JIA was based on the 1997-2001 International League Against Rheumatism (ILAR) criteria. Collected data: age, sex, HLA- B27 antigen presence, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid-factor (RF), antinuclear antibody (ANA), fever, rash, uveitis, enthesitis, inflamed joints and subtype of JIA. Results HLA- B27 positive study group had more boys (p=0.01), higher erythrocyte sedimentation rate (p=0.038), higher presence of fever (p= 0.025) and enthesitis (p=0.024). Any significant difference in age of the disease onset, CRP, ANA, RF, rash, uveitis, inflamed joint and dactylitis was not noticed. The most common subtype of JIA in the HLA-B27 positive patients was ERA (60%). Conclusion This study showed that the presence of HLA- B27 antigen plays a significant role in determining the presenting clinical and laboratory characteristics in JIA patients.

Deoxyribonuclease 1 like 3 (DNASE1L3) is a secreted enzyme that has been shown to digest the extracellular chromatin derived from apoptotic bodies, and DNASE1L3 pathogenic variants have been associated to a lupus phenotype. It is unclear whether interferon signaling is sustained in DNASE1L3 deficiency in humans. Here we report four new patients carrying biallelic DNASE1L3 pathogenic variations, including two previously unreported mutations. Disease in one patient was characterized by lupus nephritis and skin lesions, while two others exhibited hypocomplementemic urticarial vasculitis syndrome. The fourth patient presented with early-onset inflammatory bowel disease. To explore whether or not the interferon cascade was strongly and sustainably induced, Interferon stimulated genes (ISGs) expression was assessed for each patient. Contrary to canonical type-I interferonopathies, we noticed a transient increase of ISGs in blood, which reverted to normal with disease remission. Reviewing previous reports, DNASE1L3-related disease appears to carry a significant risk of lupus nephritis and a poor outcome together with the presence of anti-neutrophil cytoplasmic antibodies (ANCA). DNASE1L3 deficiency may share the pathogenesis with C1q deficiency by affecting efferocytosis, and this report suggests that interferon production is not directly driven by DNASE1L3 pathogenic variants.

Background Juvenile-onset systemic lupus erythematosus (JSLE) is multisystemic, autoimmune disease that is characterised by widespread immune dysregulation, formation of autoantibodies and immune complexis, resulting in inflammation of blood vessels and connective tissue with potential damage to variety of organs. Antinuclear antibodies (ANA) are present in the sera of 95-98% children with JSLE. Anti-double stranded DNA antibodies (Anti-dsDNA) are highly specific for JSLE and are present in about 61-93% children with active disease, especially active nephritis. Anti-Smith antibodies are also highly specific for JSLE, but they are detected in only about 50% of patients. As a part of disease presentation, many children diagnosed with JSLE have skin and oral lesions. Mucocutaneous lesions, as defined by the American College of Rheumatology (ACR) in 1997, include malar rash, discoid rash, photosensitivity and oral ulcers. In order to avoid delay in diagnosis it is very important to understand mucocutaneous signs and symptoms of lupus in children. Objectives To characterize mucocutaneous manifestations in juvenile-onset systemic lupus erythematosus and to study it's associations with autoantibodies. Methods A single-center cohort study of all patients with newly diagnosed JSLE seen over an 10-year period was performed. All patients fulfilled the clinical and laboratory criteria of the American College of Rheumatology (ACR). Serum autoantibody profiles and extensive list of mucocutaneous manifestation were evaluated. Results A total of twelve patients during period of January 2005 to January 2015 were identified. All had positive ANA, Direct Coombs test, significantly reduced C3 and C4 and high titres of Anticardiolipin antibodies IgG. Eleven patients (91%) had high titers of ANTIdsDNA. Two patients (16.6%) was identified as having discoid lupus and it was corelated with negative sera ENA- 6 profile. Two children (16,6%) had positive Anti SSA/Anti SSB and it was correlated with clinical findings of livedo reticularis. Nine patients (74%) had malar rash and eight (66%) had oral ulcers, but we were not able to demonstrate specific correlation with autoantibody profiles in this subset of patients. Conclusions Patients with JSLE commonly present with mucocutaneous manifestations, and it is therefore important to recognize the lesions to make an accurate diagnosis. In the consecutive cohort of patients with JSLE we have identified association of specific autoantibody to mucucotaneous lesions that may have clinical, therapeutic and prognostic implications. References Chiewchengchol D, Murphy R, Morgan T, Edwards SW, Leone V, Friswell M, et al. Mucocutaneous manifestations in a UK national cohort of juvenile-onset systemic lupus erythematosus patients. Rheumatology (Oxford) 2014;53:1504. Chiewchengchol et al. Mucocutaneous manifestations in juvenile-onset systemic lupus erythematosus: a review of literature. Pediatric Rheumatology 2015, 13:1 Disclosure of Interest None declared

Objective: Although the incidence of acute rheumatic fever (ARF) has significantly decreased, individually reported outbreaks of the disease still occur in developed countries. The aim of this report is to present three patients with an initial attack of ARF, treated in the Department for Allergology, Rheumatology and Clinical Immunology during 2012 and 2013. Methods: The medical records of these three patients with ATF – who were treated in our department during the abovementioned period, and whose diagnoses were established according to the revised Jones criteria from 1992 – were reviewed. Results: Of the three patients, two were female (13 and 17 years old) and one was male (9 years old). Clinical and laboratory data were: migrating arthritis (3); carditis (1); fever (3); raised inflammatory markers – erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) (3) – and a prolonged PR interval on electrocardiogram; and first-degree heart block (3). All patients had elevated antistreprolysin titres and all were evaluated by echocardiography. One patient had mitral regurgitation. We introduced streptococcus eradication therapy with penicillin, therapeutic doses of aspirin, corticosteroids (for the patient with carditis) and secondary prevention of streptococcal infections with 4-weekly doses of benzathine penicillin G. Patients have been monitored as outpatients, and as yet there is no evidence of recurrence of the disease or its complications. Conclusion: ARF still occurs occasionally in developed countries. It is a disease that has not been eradicated, and this should not be forgotten in our efforts to reduce long-term morbidity and mortality.