Juvenile idiopathic arthritis in Southeast Asia: the Singapore experience over two decades

Clinical Rheumatology - To examine the clinical characteristics, treatment and outcomes of juvenile idiopathic arthritis (JIA) patients evaluated in Singapore and compare those with reports...     

Identification of IgG subclasses and C-reactive protein in lupus nephritis: the relationship between the composition of immune deposits and FCgamma receptor type IIA alleles

OBJECTIVE: To characterize the subclass composition of IgG deposited in lupus glomeruli, to examine its relationship to allelic polymorphisms of IgG receptors (Fcgamma receptors [FcgammaR]), and to determine whether C-reactive protein (CRP), a ligand for FcgammaRIIa, is present in these immune deposits. METHODS: Renal biopsy samples from 80 patients with lupus nephritis were examined by light microscopy and indirect immunofluorescence with IgG-subclass-specific monoclonal antibodies. FcgammaRIIA genotypes were determined using allele-specific polymerase chain reaction. Immunostaining for CRP was performed on lupus and nonlupus glomerulonephritis specimens. RESULTS: IgG2 and IgG3 were the predominant subclasses in immune deposits in all World Health Organization classes of nephritis. The frequency of genotypes containing the low-binding IgG2 allele, FcgammaRIIa-R131, was significantly greater than expected in patients with class III or class IV nephritis and in patients with intense IgG2 deposition. CRP, a ligand with particular affinity for FcgammaRIIa-R131, was consistently present in the renal immune deposits of lupus nephritis specimens. CONCLUSION: FcgammaRIIA genes are associated with proliferative renal disease and may contribute to disease pathogenesis. FcgammaRIIa-R131, the variant with low affinity for IgG2, has high affinity for CRP. Thus, FcgammaRIIa-R131 may contribute to impaired removal of circulating immune complexes, as well as efficiently triggering phagocyte activation and the release of inflammatory mediators within glomeruli.     

Neonatal lupus erythematosus complicated by mucocutaneous and visceral hemangiomas

Neonatal lupus erythematosus (NLE) is a passively acquired autoimmune syndrome resulting from transplacental passage of maternal anti-Ro/SSA and/or anti-La/SSB antibodies to the fetus. Characteristic manifestations of NLE include transient dermatitis, hepatic and hematologic abnormalities and congenital heart block. Skin lesions in NLE resemble subacute cutaneous lupus erythematosus and typically consist of annular, erythematous, scaly plaques. Telangiectasias, vascular abnormalities resulting from dilation of superficial dermal vessels, may also affect the skin in a minority of patients. The etiology of telangiectasias in NLE is unknown, but disordered angiogenesis likely plays a role. Hemangiomas are a common disorder of angiogenesis frequently encountered in infancy. There have been no reported cases of neonatal lupus associated with the development of hemangiomas. We present a case of an infant diagnosed with NLE after manifesting classic dermatitis, hepatic and hematologic abnormalities who later developed mucocutaneous and visceral hemangiomas. We further postulate that disordered angiogenesis, possibly dysregulated production of vascular endothelial growth factor, may play a primary role in the development of these cutaneous vascular lesions in NLE.     

Sacroiliitis at diagnosis as a protective predictor against disease flare after stopping medication: outcomes of a Southeast Asian enthesitis-related arthritis (ERA) longitudinal cohort

Clinical Rheumatology - To assess short- and long-term outcomes of ERA in a large monocentric cohort in Singapore. Children diagnosed with ERA according to ILAR criteria from 2002 to 2021 were...     

Use of biologics in the treatment of childhood rheumatic diseases

Over the last two decades, progression in the knowledge of molecular biologic techniques has led to a better understanding of immunopathogenesis and identification of several cytokines, which propagate chronic arthritis in both adult and pediatric patients. A number of biologic agents have been developed in targeting different immune markers or mediators with the hope that they may help in controlling the inflammation in the group of patients who are resistant to disease-modifying antirheumatic drugs (DMARDs) and may alter the natural history of the diseases. Tumor necrosis factor (TNF)-a is the first to be targeted and its antagonists have been approved. Other biologic agents targeting different markers/mediators have followed and have been tested in clinical trials especially in adult rheumatoid arthritis (RA). Experiences in pediatric use are limited and agents proved to be effective in adult RA are not always transferred the same efficacy in different subtypes of juvenile idiopathic arthritis (JIA). It is reasonable to see the efficacy, and more importantly the safety profiles of each agent before the decision is made to use them in children. This article reviews the published and anecdotal reports of biologic agents that have been used in children with JIA and also focuses on the potential use of other biologic agents in JIA that have been used in trials to combat adult RA.     

Orbital pseudotumour as a presentation of paediatric ulcerative colitis

A 2-year-old girl presented with a one-day history of acute-onset bilateral painful, swollen eyes and a two-month history of loose stools. Physical examination revealed a right eyelid swelling with proptosis. Magnetic resonance imaging revealed a right orbital pseudotumour. The patient responded well to treatment with intravenous antibiotics and nonsteroidal anti-inflammatory drugs. However, three weeks later, she was readmitted with a vasculitic lesion over her left upper chest, with mucous-bloody diarrhoea. Histopathology confirmed the diagnosis of ulcerative colitis. The patient was treated with intravenous pulse methylprednisolone and sulphasalazine. Two weeks after discharge, she was readmitted for cutaneous vasculitis and worsening diarrhoea. The patient’s bowel and extraintestinal diseases resolved upon addition of infliximab to her treatment regimen. Her inflammatory markers also normalised. Azathioprine was subsequently added. Infliximab was discontinued after four doses and prednisolone was tapered off. The patient remained well without any flare-up after 24 months of follow-up.