Progressive pseudorheumatoid dysplasia misdiagnosed as juvenile idiopathic arthritis: a case report

Background Progressive pseudorheumatoid dysplasia is a rare, autosomal recessively inherited, noninflammatory musculoskeletal disorder caused by mutations occurring in the WNT1-inducible signaling pathway protein 3 gene. Joint cartilage is the primary site of involvement, leading to arthralgia, joint stiffness, contractures, enlargement of the epiphyses and metaphysis of the hand joints, spinal abnormalities, short stature, early osteoarthritis, and osteoporosis. Juvenile idiopathic arthritis is the most common chronic rheumatic disease in childhood and has unknown etiology. Clinical features of progressive pseudorheumatoid dysplasia resemble those of juvenile idiopathic arthritis. Patients with progressive pseudorheumatoid dysplasia are usually misdiagnosed as having juvenile idiopathic arthritis. Case presentation A 13-year-old Yemeni female presented to the rheumatology clinic with a history of joint pains, bone pains, and bone deformity for 7 years. Weight and height were below the third percentiles. There was no tender swelling of metacarpophalangeal and interphalangeal joints, and she presented with scoliosis. Radiographs of the hands revealed the widening of the epiphyses. Progressive pseudorheumatoid dysplasia was suspected, and genetic testing for WNT1-inducible signaling pathway protein 1, 2, and 3 was requested with these findings. A homozygous, likely pathogenic variant was identified in the WNT1-inducible signaling pathway protein 3 gene, which confirmed our diagnosis. Conclusion Progressive pseudorheumatoid dysplasia is a rare form of spondyloepimetaphyseal dysplasia and is clinically misdiagnosed as juvenile idiopathic arthritis. It is crucial to consider progressive pseudorheumatoid dysplasia, especially in patients with standard inflammatory markers who are being followed up for juvenile idiopathic arthritis and not improving with antirheumatic intervention.

Fifteen-minute guide to managing oligoarticular juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease affecting children and young people today. However, it is not a single disease entity, but an umbrella term that gathers together a heterogeneous collection of complex, chronic inflammatory conditions with oligoarticular JIA the most common form in both Europe and North America. Due to its relative rarity in daily practice and potential to mimic other conditions, oligoarticular JIA can present a diagnostic and management challenge to healthcare professionals in both primary care and general paediatrics. The aim of this article is to provide a summary of the key aspects of diagnosis, investigation and management of this condition, with the hopes of building clinicians’ confidence when facing a possible case of oligoarticular JIA.

Mini Review: Pulmonary Toxicity Secondary to Immunosuppressive Agents in the Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic rheumatic disease, characterized by erosive and destructive arthritis, representing an important cause of disability. Interstitial lung disease is not a rare event and can be aggravated by several immunosuppressive medications. Methotrexate, once seen as a drug associated with interstitial pneumonitis, is now seen as an agent capable of slowing or preventing the progression of lung disease related to rheumatoid arthritis. Anti-TNFs currently represent the class with the greatest impact on the course of pulmonary disease in RA, with a significant increase in mortality. Among the immunobiological agents, abatacept and Rituximab stand out in relation to the pulmonary safety profile.

LACC1 deficiency links juvenile arthritis with autophagy and metabolism in macrophages

Juvenile idiopathic arthritis is the most common chronic rheumatic disease in children, and its etiology remains poorly understood. Here, we explored four families with early-onset arthritis carrying homozygous loss-of-expression mutations in LACC1. To understand the link between LACC1 and inflammation, we performed a functional study of LACC1 in human immune cells. We showed that LACC1 was primarily expressed in macrophages upon mTOR signaling. We found that LACC1 deficiency had no obvious impact on inflammasome activation, type I interferon response, or NF-κB regulation. Using bimolecular fluorescence complementation and biochemical assays, we showed that autophagy-inducing proteins, RACK1 and AMPK, interacted with LACC1. Autophagy blockade in macrophages was associated with LACC1 cleavage and degradation. Moreover, LACC1 deficiency reduced autophagy flux in primary macrophages. This was associated with a defect in the accumulation of lipid droplets and mitochondrial respiration, suggesting that LACC1-dependent autophagy fuels macrophage bioenergetics metabolism. Altogether, LACC1 deficiency defines a novel form of genetically inherited juvenile arthritis associated with impaired autophagy in macrophages.

GALLBLADDER CONDITION IN PATIENTS WITH RHEUMATIC FEVER AND ACQUIRED VALVE DEFECTS OF RHEUMATIC ORIGIN

Gallbladder (GB) and heart are linked by viscero-visceral reflexes, but little is known about the connections between GB and heart in patients with acute and chronic rheumatic heart disease. Purpose of the study. To assess the GB condition in patients with acute and chronic rheumatic disease and the difference in structural and functional sonographic parameters of heart in dependence of GB condition. Materials and methods. We examined 136 patients including 58 patients with active rheumatism (mean age 36,72 ± 3,00 years), 44 patients with chronic rheumatic heart disease (CRHD), who underwent surgical correction of the valvular defect (mean age 54,00 ± 3,69 years), and 34 patients with CHD, who were treated as inpatients withour surgery (mean age 61,48 ± 4,50 years). Results. Among 136 patients with acute and chronic forms of rheumatic heart disease, GB changes were significantly more common than intact GB (62,5 ± 4,1% vs. 37,5 ± 4,1%, p < 0,05). The incidence of GB disorders was the highest in patients with CRHD, who underwent drug treatment (76,5 ± 7,3% vs. 58,7 ± 6,5% and 50,0 ± 7,5%, both p < 0,05), which were characterized by older age. No significant differences in the incidence of various pathological conditions of GB were revealed between acute and chronic rheumatic heart disease groups. The most common pathological GB changes included signs of cholecystitis, biliary sludge and cholesterosis, cholelithiasis, the least common – GB removal due to cholelithiasis. Patients with biliary autonomic viscero-visceral cardioneuropathy differed from those with intact GB by the thickening of the interventricular septum and posterior wall of the left ventricle, which correlated with the increased duration of inpatient treatment, diastolic hypertension and lower alanine aminotransferase. Conclusions. In patients with acute and chronic forms of rheumatic heart disease, the GB condition is often changed. These changes affect heart condition, blood pressure and carbohydrate metabolism. Keywords: gallbladder, chronic rheumatic heart disease, valvular defects, rheumatic fever, echocardiography.

13 year old Female with Progressive Pseudorheumatoid Dysplasia misdiagnosed as Juvenile idiopathic arthritis

Background: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood and is of unknown aetiology. Progressive pseudorheumotoid dysplasia is a rare, autosomal recessively inherited, non-inflammatory musculoskeletal disorder caused by mutations occurring in the WISP3 gene. Joint cartilage is the primary site of involvement, leading to arthralgia, joint stiffness, contractures, enlargement of the epiphyses and metaphysis of the hand joints, spinal abnormalities, short stature, early osteoarthritis, and osteoporosis. The clinical features resemble juvenile idiopathic arthritis (JIA), and patients with PPD are usually misdiagnosed as JIA.Case Presentation: A 13 year old female presented to the rheumatology clinic with history of joint pains, bone pains and bone deformity for 5 years. Weight and Height were below the 3rd centiles. There was none tender swelling of metacarpophalangeal and interphalangeal joints and with scoliosis. Radiographs of the hands revealed widening of the epiphyses. With these findings Progressive Pseudorhematoid Dysplasia was suspected and genetic testing for WISP1, WISP2 and WISP3 was requested. A homozygous, likely pathogenic, variant was identified in WISP3 gene which confirmed our diagnosis.Conclusion: Progressive Pseudorhematoid Dysplasia is a rare form of spondylo-epi-metaphyseal dysplasia and clinically misdiagnosed as Juvenile Idiopathic arthritis. It’s important to consider PPD especially in patients with normal inflammatory markers who are being followed up for arthritis and not improving on anti-rheumatic intervention.

Psychometric assessment of chronic pain syndrome in juvenile idiopathic arthritis

Background. Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood. Chronic pain is one of the most frequent and difficult to objectively assess symptom of JIA. The influence of psychosocial factors on the severity of pain complicates the objective assessment of pain syndrome in JIA, necessary to assess the control of the disease and raises the question of the possible use of psychological questionnaires to objectify pain in patients with JIA. Aim: to assess the intensity of pain syndrome, the level of social disadaptations, description of sensory and affective components of pain in patients with JIA, depending on the activity of the disease and the presence or absence of chronic pain syndrome. Materials and methods. 147 school-age patients with verified diagnosis of JIA were examined. All patients included in the study underwent a traditional rheumatological examination with the assessment of disease activity according to the criteria of the American College of rheumatologists for pediatric patients. The severity of pain syndrome on a visual analog scale (VAS) from 0 to 10 was determined separately by patients and their parents, patients independently filled in the Von Korff Questionnaire and the McGill pain questionnaire. Results. There were no differences in the severity of pain syndrome between patients with signs of arthritis activity and without signs of arthritis activity according to VAS, Van Korff and McGill questionnaires. Conclusion. On the example of the studied patients, it is not possible to link chronic pain syndrome in JIA with the activity of arthritis. It is necessary to further study the possible causes of chronic pain syndrome in children with JIA, including anxiety and depressive disorders for a better understanding of the nature of chronic pain and search for additional methods of its treatment.

Chronic rheumatic disease

Chronic rheumatic heart disease (RHD) is thought to occur following multiple recurrent episodes of acute carditis and may occur in approximately 60% of patients following an episode of rheumatic carditis. It is estimated that approximately 30 million people have RHD and that the disease accounts for approximately 345,000 deaths per year. Several studies have demonstrated that the prevalence of RHD is underestimated when based solely on clinical examination compared to using echocardiographic screening. The contemporary burden of RHD is seen in the developing world, among native populations of the pacific, in certain countries in Eastern Europe, and among immigrant populations in the developed world. Most patients present late with severe valvular heart disease complicated by heart failure, pulmonary hypertension, arrhythmias such as atrial fibrillation, and occasionally cardioembolic stroke.