Variability in phenotype and response to treatment in chronic nonbacterial osteomyelitis; the Irish experience of a national cohort.

BACKGROUND: Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory disease affecting bone with considerable phenotypic heterogeneity and variable association with other autoinflammatory conditions. Disease pathogenesis is incompletely understood, and treatment protocols vary between physicians with no clinical treatment guidelines available prior to 2017. Although CNO was previously considered benign, it is now clear that long-term sequelae do occur. The aim of this study is to provide a detailed phenotypic description of children and adolescents with CNO who attended tertiary paediatric rheumatology services in Ireland between September 2017 and September 2019, their disease course, treatment and outcomes. METHODS: This study involved retrospective review of clinical notes, laboratory, radiology and histology results of Irish children and adolescents with CNO who are currently attending tertiary paediatric rheumatology services. The Bristol diagnostic criteria were applied retrospectively; only patients who met these criteria were included. Criteria for remission and partial response were based on the Childhood Arthritis and Rheumatology Research Alliance (CARRA) criteria for treatment failure. RESULTS: Forty-four children and adolescents were recruited. Demographics in terms of age of onset, gender and number of sites were similar to those previously reported. Overall, 18/44 (40.9%) had extraosseous manifestations associated with CNO; 12/44 (27.2%) had cutaneous involvement. All patients received a regular nonsteroidal anti-inflammatory drug (NSAID) after diagnosis with 27/44 (61.4%) requiring at least 1 second-line medication. Second-line agents used in this cohort were bisphosphonates, methotrexate and TNF-blockers. No patients received systemic corticosteroids. CONCLUSION: This national cohort showed a high prevalence of extraosseous involvement and a low response rate to NSAID treatment. This may reflect a more inflammatory phenotype and highlights the need to define different subtypes of CNO.

Arthropathy of Down syndrome: an under-diagnosed inflammatory joint disease that warrants a name change.

There is an increased incidence and prevalence of arthropathy in children with Down syndrome. However, it is rarely reported or recognised at onset, and remains under-diagnosed. Children with arthropathy of Down syndrome (A-DS) are presenting with significant joint damage and disability at diagnosis. Objective: To identify undiagnosed cases of A-DS and document time to diagnosis. Also to describe clinical, laboratory and radiological features of A-DS at diagnosis. Methodology: Children with Down syndrome (DS) (0-21 years) were invited to attend a musculoskeletal screening clinic. A second physician at a further clinic confirmed suspected cases of A-DS. Investigations and treatment were instigated as per normal clinical practice for Juvenile idiopathic arthritis (JIA). Data on a convenience sample of 21 newly diagnosed children with JIA was collected to create a comparison group. Results: Over an 18-month period, 503 children with DS were screened for arthritis and 18 new cases diagnosed. In total, 33 children were identified with A-DS (combining cases attending pre-dating commencement of the study and those referred to our centre during the study period). This suggests prevalence of A-DS is 20/1000. A significant delay in diagnosis of A-DS was observed. The majority of children presented with polyarticular-rheumatoid factor-negative arthritis, with predominance in the small joints of the hands and wrists. Erosive changes were reported on X-ray in a significantly greater proportion (42%) of children with A-DS than JIA (14%). MRI was used to confirm diagnosis in four cases. Conclusion: Children with DS are at increased risk of arthritis. Future research to accurately define disease pathogenesis and identify a biomarker of disease would be of benefit.

Isolated ocular lichen planus in a child.

Lichen planus (LP) is an autoimmune inflammatory condition of the skin and mucous membranes, of unknown aetiology, that infrequently involves the eye. Ocular LP has not been described in children. We present the case of an 8-year-old girl with severe, filamentous dry eyes and persistent conjunctival hyperemia with bilateral progressive conjunctival symblepharon. Her conjunctival biopsy showed heavy linear fibrinogen deposits along the basement membrane without IgG, IgA, IgM, or C3 deposition, consistent with LP. No skin or other mucosal lesions were present, suggesting a diagnosis of isolated conjunctival LP. Oral and topical cyclosporine combined with methotrexate and low-dose oral steroids led to sustained disease remission. To our knowledge, this is the first case of isolated ocular LP in a child.

Takayasu arteritis presenting in the context of active tuberculosis: a pediatric case.

Takayasu arteritis (TA) is a large-vessel vasculitis, most commonly presenting in young adults and more rarely in pediatric patients. An apparent association between TA and Mycobacterium tuberculosis has been noted previously, although this potential relationship is not yet understood. We present the case of a 16-year-old Haitian girl diagnosed with TA, originally presenting in the context of active tuberculosis. Our patient has been treated with antituberculosis therapy, corticosteroids, methotrexate, and rituximab to control her continued active vasculitis. With this case report, we seek to promote further exploration of the apparent association between TA and tuberculosis, as further clarification of the nature of this relationship may lead to the development of more targeted therapies and better outcomes for TA patients.

Pharmacotherapy of lupus nephritis in children: a recommended treatment approach.

Systemic lupus erythematosus (SLE) is a multisystem inflammatory disease of unknown aetiology, which is characterised by recurrent disease flares that may affect any organ system. Renal involvement remains one of the chief causes of morbidity and mortality in children with lupus. Nephritis occurs in approximately two-thirds of patients, ranging from mild glomerulitis to life-threatening occurrences of diffuse proliferative glomerulonephritis. As lupus nephritis is a condition of no single aetiology, there is no single cure. Corticosteroids, although still the first line of treatment, are increasingly being superseded by cytotoxic drugs, in particular cyclophosphamide and corticosteroid-sparing agents. Newer agents such as mycophenolate mofetil, although effective in the treatment of lupus in adults, are less effective in children. Standard of care for highly active lupus nephritis in children remains intravenous cyclophosphamide, although preliminary experience suggests that the addition of rituximab may allow for remission induction with a reduction in cumulative cyclophosphamide dose. Combination therapies and newer agents appear promising for the future as our understanding of the immune system and its dysregulation in SLE improves. In this review, we discuss the current standards of care, newer therapies currently in use, and emerging treatments still undergoing development and investigation. We conclude by discussing our guidelines for treatment at the present time and suggestions for the comprehensive care of children with lupus nephritis.