Lipopolysaccharide (LPS)-responsive and beige like anchor (LRBA) deficiency is categorized as a subtype of common variable immune deficiency (CVID). A growing number of case reports and cohorts ...reveal a broad spectrum of clinical manifestations and variable phenotype expression, including immune dysregulation, enteropathy and recurrent infections. The association between rheumatic disease and CVID generally has been well established, arthritis has been less frequently reported and minimal data regarding its clinical features and characteristic in LRBA deficiency has been published. This case report and literature review evaluates the characteristics and features of arthritis in LRBA deficiency patients.
Herein, we describe a unique case of LRBA deficiency first presented with poly articular arthritis. Alongside the report, a literature review focusing on LRBA deficiency, rheumatic disease and arthritis has been conducted. We reviewed 43 publications. Among these, 7 patients were identified with arthritis. Age of first presentation was six weeks to 3 years. Male to female ratio was 4/3. Two patients were diagnosed with polyarticular Juvenile idiopathic arthritis (JIA) and three with oligoarticular JIA. Each patient was found to have different genomic mutation. The treatment was diverse and included corticosteroids, cyclosporine, methotrexate, adalidumab and abatacept.
Joint involvement is variable in LRBA deficiency, hence it should always be kept in mind as a differential diagnosis for a patient with combination of juvenile arthritis and clinically atypical immune dysregulation and / or immunodeficiency.
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome characterized by a dysregulated hyperinflammatory response associated with aberrant activation of lymphocytes and macrophages ...that results in hypercytokinemia. It is classically divided into two types: (1) primary or familial HLH and (2) secondary HLH. Familial HLH is generally an autosomal recessive condition, whereas secondary HLH is usually associated with infectious diseases, autoinflammatory and autoimmune diseases (where it is more commonly known as macrophage activation syndrome), malignancy, immunosuppression, hematopoietic stem cell transplantation, organ transplantation, HIV infection, and metabolic diseases. Although its clinical presentation is often similar to bacterial sepsis or systemic inflammatory response syndrome, HLH can be life-threatening. As such, it is imperative to recognize and diagnose HLH in a timely manner to optimize care. Pediatr Ann. 2017;46(8):e309-e313..
Objective
To evaluate the proportion of children with juvenile idiopathic arthritis (JIA) who met criteria for comorbid juvenile fibromyalgia (FM) using the Pain and Symptom Assessment Tool (PSAT), ...and to identify clinical and demographic differences among JIA patients with and without juvenile FM.
Methods
Patients ages 11–17 years with JIA were recruited from 4 North American pediatric rheumatology centers. Each patient completed the PSAT. Additional clinical and disease activity measures included pain visual analog scale, patient global assessment of disease activity (PtGA) and physician global assessment of disease activity (PhGA), the Functional Disability Inventory (FDI), and the Pain Catastrophizing Scale in children.
Results
Of 129 patients, 11 met criteria for juvenile FM. FDI scores were markedly higher in patients who tested positive for juvenile FM, with a mean of 24.8 compared to 6.9 in patients without juvenile FM (P < 0.001). Pain catastrophizing scores were also significantly higher, by ~14 points, in patients with juvenile FM. There was a significant tendency for patients to give higher disease activity scores than physicians, which was more marked among patients with juvenile FM. In patients with juvenile FM, PtGA scores exceeded PhGA scores by a mean of 3.7, compared to a mean of 0.7 among patients without juvenile FM (P < 0.001).
Conclusion
A minority of JIA patients (8.5%) met criteria for juvenile FM. This group demonstrated markedly more functional impairment. PtGA scores were strikingly higher than PhGA scores among patients with JIA who met juvenile FM criteria, suggesting that providers might consider a more expansive approach to chronic pain and non‐musculoskeletal symptom assessment and treatment in JIA patients.
The interleukin (IL) -1 family of cytokines are involved in different aspects of inflammation with IL-1 beta being the best known and most powerful proinflammatory cytokine. Dysregulation of IL-1 ...beta and other family members results in autoinflammatory conditions such as systemic juvenile idiopathic arthritis and familial Mediterranean fever. The growing understanding and knowledge of the pathophysiology of many autoinflammatory diseases have led to the development and use of IL-1 blocking medications for many chronic and disabling diseases. In this article, we present the anti-IL-1 agents and their major indications in pediatric rheumatology.
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Mucosal-associated lymphoid tissue (MALT) lymphoma is rare in the pediatric population, but primary Sjogren syndrome is a well-established risk factor for this malignancy. This report describes 2 ...cases of MALT lymphoma in children with Sjogren syndrome. A 15-year-old girl developed MALT lymphoma of the parotid gland as the presenting symptom of Sjogren syndrome. In the second case, a 15-year-old boy with known Sjogren syndrome presenting mainly with arthritis was diagnosed with MALT lymphoma, also of the parotid gland. With early diagnosis and treatment, outcomes in pediatric MALT lymphoma are generally encouraging. Pediatric oncology specialists should be aware of the association of MALT lymphoma with Sjogren syndrome and have a high index of suspicion for this malignant complication.
A 14-year-old boy presented with months of severe widespread musculoskeletal pain. He was profoundly fatigued and unable to attend school. Laboratory evaluation, including complete blood count, ...comprehensive metabolic panel, inflammatory markers, and thyroid function, was unrevealing. Physical examination was also normal except for multiple tender points. The patient was diagnosed with juvenile primary fibromyalgia syndrome and referred for multidisciplinary treatment including physical therapy, exercise, and counseling, and his daily functioning gradually improves. Juvenile fibromyalgia is a complex syndrome that often severely limits patients' activities and can impede normal adolescent development. Effective treatment requires an understanding of the biologic, psychologic, and social factors contributing to the perpetuation of chronic pain. The author reviews the diagnostic criteria, pathophysiology, and treatment of juvenile fibromyalgia. Medications, particularly antidepressants and anticonvulsants, can be useful adjuncts to therapy. However, multimodal pain management including intensive physical therapy, exercise, counseling, and sleep hygiene is most effective in treating fibromyalgia.
Objective
To determine the relationship between serum levels of S100A8/A9 and S100A12 and the maintenance of clinically inactive disease during anti–tumor necrosis factor (anti‐TNF) therapy and the ...occurrence of disease flare following withdrawal of anti‐TNF therapy in patients with polyarticular forms of juvenile idiopathic arthritis (JIA).
Methods
In this prospective, multicenter study, 137 patients with polyarticular‐course JIA whose disease was clinically inactive while receiving anti‐TNF therapy were enrolled. Patients were observed for an initial 6‐month phase during which anti‐TNF treatment was continued. For those patients who maintained clinically inactive disease over the 6 months, anti‐TNF was withdrawn and they were followed up for 8 months to assess for the occurrence of flare. Serum S100 levels were measured at baseline and at the time of anti‐TNF withdrawal. Spearman's rank correlation test, Mann‐Whitney U test, Kruskal‐Wallis test, receiver operating characteristic (ROC) curve, and Kaplan‐Meier survival analyses were used to assess the relationship between serum S100 levels and maintenance of clinically inactive disease and occurrence of disease flare after anti‐TNF withdrawal.
Results
Over the 6‐month initial phase with anti‐TNF therapy, the disease state reverted from clinically inactive to clinically active in 24 (18%) of the 130 evaluable patients with polyarticular‐course JIA; following anti‐TNF withdrawal, 39 (37%) of the 106 evaluable patients experienced a flare. Serum levels of S100A8/A9 and S100A12 were elevated in up to 45% of patients. Results of the ROC analysis revealed that serum S100 levels did not predict maintenance of clinically inactive disease during anti‐TNF therapy nor did they predict disease flare after treatment withdrawal. Elevated levels of S100A8/A9 were not predictive of the occurrence of a disease flare within 30 days, 60 days, 90 days, or 8 months following anti‐TNF withdrawal, and elevated S100A12 levels had a modest predictive ability for determining the risk of flare within 30, 60, and 90 days after treatment withdrawal. Serum S100A12 levels at the time of anti‐TNF withdrawal were inversely correlated with the time to disease flare (r = −0.36).
Conclusion
Serum S100 levels did not predict maintenance of clinically inactive disease or occurrence of disease flare in patients with polyarticular‐course JIA, and S100A12 levels were only moderately, and inversely, correlated with the time to disease flare.
Objective
To determine the frequency, time to flare, and predictors of disease flare upon withdrawal of anti–tumor necrosis factor (anti‐TNF) therapy in children with polyarticular forms of juvenile ...idiopathic arthritis (JIA) who demonstrated ≥6 months of continuous clinically inactive disease.
Methods
In 16 centers 137 patients with clinically inactive JIA who were receiving anti‐TNF therapy (42% of whom were also receiving methotrexate MTX) were prospectively followed up. If the disease remained clinically inactive for the initial 6 months of the study, anti‐TNF was stopped and patients were assessed for flare at 1, 2, 3, 4, 6, and 8 months. Life‐table analysis, t‐tests, chi‐square test, and Cox regression analysis were used to identify independent variables that could significantly predict flare by 8 months or time to flare.
Results
Of 137 patients, 106 (77%) maintained clinically inactive disease while receiving anti‐TNF therapy for the initial 6 months and were included in the phase of the study in which anti‐TNF therapy was stopped. Stopping anti‐TNF resulted in disease flare in 39 (37%) of 106 patients by 8 months. The mean/median ± SEM time to flare was 212/250 ± 9.77 days. Patients with shorter disease duration at enrollment, older age at onset and diagnosis, shorter disease duration prior to experiencing clinically inactive disease, and shorter time from onset of clinically inactive disease to enrollment were found to have significantly lower hazard ratios for likelihood of flare by 8 months (P < 0.05).
Conclusion
Over one‐third of patients with polyarticular JIA with sustained clinically inactive disease will experience a flare by 8 months after discontinuation of anti‐TNF therapy. Several predictors of lower likelihood of flare were identified.
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