Poor obstetric outcomes in Indian women with Takayasu arteritis

Abstract Introduction: Takayasu's arteritis (TA) affects young women in the childbearing age group. We studied obstetric outcomes in these patients before and after disease onset. Methods: Women aged more than 18 years with Takayasu's arteritis (ACR 1990 criteria) were included. Demographic data, clinical features, disease activity using Indian Takayasu Arteritis clinical score (ITAS), Disease Extent Index for TA (DEI. TaK) and damage assessment using TA Damage score (TA), history of conception and maternal and fetal outcomes were recorded from hospital records and telephonic interview. Results are in median and IQR. Results: Of the 64 women interviewed, aged 29 (24-38) years and disease duration 5 (4-10) years, 74 and 38 pregnancies had occurred before and after disease diagnosis in 29 and 20 women respectively. In eight, the diagnosis was made during pregnancy. Age at disease onset was 22 (18-30) years. Type 5 disease was the most common ( n = 32, 59.3%), and an equal number of patients had Ishikawa's class I and II disease ( n = 26, 40.6%). Median ITAS ( n = 44) was 13 (7-16), DEI. Tak 12.5 (9-16.75) and TADS 8 (6.5-10). Twenty-five patients wanted to get pregnant, of which 8 (32%) did not do so because of their disease. Fifteen were unmarried of whom 6 did not marry due to disease. Obstetric outcomes were poorer in pregnancies that occurred after the onset of disease as compared with those before it (RR = 1.5, p = 0.01). Pregnancies after the onset of TA carried a very high risk of maternal [RR3.9 (1.8-8.5), P < 0.001] as well as fetal complications [RR = 2.0 (1.2-3.4), p = 0.001]. Hypertension was the most common maternal complication and occurred most often in the last trimester. The baby weight at birth was lower in pregnancies after disease (2.3 vs. 3.0, p = 0.01). Wong's score greater than or equal to 4 predicted lower birth weight ( p = 0.04). ITAS, ITAS-A, DEI. Tak and TADS could not predict obstetric outcomes, and ITAS score exhibited moderate correlation with DEI. Tak ( r = 0.78) and TADS ( r = 0.58). Conclusion: Women with TA suffer from extremely high risk of poor maternal and foetal outcomes. Wong's scoring can be useful to predict birth weight.(AU)

Renal cell carcinoma and systemic onset juvenile idiopathic arthritis.

Renal cell carcinoma (RCC) accounts for majority of malignancies arising out of the kidney. Paraneoplastic rheumatologic manifestations; myositis, vasculitis, and arthritis have been described in a few cases with RCC. Systemic onset juvenile idiopathic arthritis (JIA) is characterized by intermittent fever, arthritis, reticulo-endothelial cell hyperplasia and absence of rheumatoid factor and antinuclear antibodies. Herein, we report a 16-year-old boy with systemic onset JIA for 5 years who developed RCC and his systemic and articular symptoms paralleled the course of RCC. The common pathophysiologic influence of the cytokine Interleukin-6 possibly played a role in the exacerbation of symptoms of systemic onset JIA during the relapse of the RCC. The case is presented to highlight the rare co-occurrence of these two diseases and their influence on each other.

Induction of metalloproteinases expression by TLR ligands in human fibroblast like synoviocytes from juvenile idiopathic arthritis patients.

Background & objective: Juvenile idiopathic arthritis (JIA) is characterized by chronic synovitis, cartilage damage and bone erosion. Both genetic and environmental factors and microbes probably play a role in pathogenesis. Microbes are recognized by Toll like receptors (TLRs) and activate innate immune response. We studied the ability of bacterial and viral products to produce matrix metalloproteinases (MMPs) and cytokines by fibroblast like synoviocytes (FLS) from patients with JIA. Methods: FLS were cultured from synovial fluid (SF) of patients with JIA and subsequently stimulated for 48 h by different TLR ligands [peptidoglycan (PG) for TLR2, poly(I-C) for TLR3, lipopolysaccharide (LPS) for TLR4, flagellin for TLR5, imiquimod for TLR7 and CpG DNA for TLR9]. Later the production of IL6, IL8, MMP-1, MMP-3, tissue inhibitors of metalloproteinase (TIMP1) was measured in the culture supernatants by ELISA. Expression of TLR2, TLR4, TLR7 and TLR9 was studied in FLS derived from JIA patients by RT-PCR. Results: IL6, IL8, MMP3 and MMP1 production was induced on stimulation of FLS with TLR2 ligand, TLR3 ligand, TLR4 ligand, TLR5 ligand but not with TLR7 ligand and TLR9 ligand. There was no effect of these ligands on the production of TIMP thus the balance was tilted in favour of MMPs after TLR ligation. TLR2, TLR4 and low expression of TLR9 was found but, no expression of TLR7 was found in FLS from JIA patients. Interpretation & conclusion: TLR pathway stimulation by microbial products or endogenous ligands could be involved in the production of MMPs in JIA and may contribute to disease pathology. Thus it may be beneficial to inhibit TLR pathway to reduce cartilage destruction.

Antinuclear antibodies by indirect immunofluorescence : optimum screening dilution for diagnosis of systemic lupus erythematosus.

BACKGROUND & OBJECTIVES: Antinuclear antibodies (ANA) are serological hallmark of systemic lupus erythematosus (SLE). Conventionally, the test is carried out on human epithelial cells (HEp2) by indirect immunofluorescence (IIF) technique. Since culturing and maintaining HEp2 cells in the laboratory are labour intensive, in-house assays have given way to kits manufactured by commercial companies. The reference screening dilutions provided by the manufacturers are based on different ethnic population than ours. Therefore, it becomes mandatory for every laboratory to have its own screening dilutions for the local population that distinguishes best between healthy and diseased state. As, there is paucity of such data, we aimed to define the optimum screening dilution that distinguishes the patient with SLE from healthy individuals. METHODS: Sera of patients fulfilling ACR criteria for diagnosis of SLE, idiopathic inflammatory polymyositis/dermatomyositis (PM/DM) and rheumatoid arthritis (RA), and age and sex matched healthy individuals were tested for ANA by IIF using a commercial kit (Euroimmun, Germany) at 5 dilutions, namely 1:40, 1:80, 1:160, 1:320 and 1:640. Receiver operator characteristics (ROC) curve were constructed to define the optimum dilution that distinguished healthy sera from the diseased ones. RESULTS: Test was performed on 213 sera from 94 healthy individuals, and 43 SLE, 37 RA and 39 DM/PM patients. In healthy individuals, ANA at dilutions 1:40, 1:80, 1:160, 1:320 and 1:640 was positive in 13.8, 4.3, 2.1, 2.1 and 0 per cent respectively, whereas in SLE it was positive in 95.3, 95.3, 65.1, 53.5 and 23.3 per cent respectively. INTERPRETATION & CONCLUSION: ROC curves analysis showed that at 1:40 dilution, sera of 95.3 per cent of SLE and 13.8 per cent of normal individuals were (ANA) positive, whereas at 1:80 dilution it was 95.3 per cent for SLE and 4.3 per cent for healthy individuals. A fluorescent intensity of > or =2 was more specific for SLE. The best discrimination between healthy individuals and the SLE patients was found at screening dilution of 1:80 and fluorescent intensity of > or =2 in our laboratory.

Correlation between methotrexate efficacy & toxicity with C677T polymorphism of the methylenetetrahydrofolate gene in rheumatoid arthritis patients on folate supplementation.

BACKGROUND & OBJECTIVES: C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene has been proposed as a pharmacogenomic marker for toxicity of methotrexate (MTX). We studied the relationship between the C677T gene polymorphism and toxicity and efficacy of MTX in patients with rheumatoid arthritis (RA) on folate supplementation. METHODS: A total of 150 RA patients fulfilling American College of Rheumatology (ACR) criteria and on MTX treatment were evaluated. The mean age of the patients was 42.9 +/- 11.1 yr, mean disease duration was 7.65 +/- 5.2 yr and the mean duration of MTX treatment was 26.1 +/- 20.6 months. Genotype analysis of MTHFR gene was done by PCR and restriction enzyme method. Primary endpoint for treatment efficacy was change in disease activity score 28 (DAS28) from baseline. Drug toxicity was evaluated by blood count, renal and liver function tests and a standardized questionnaire. RESULTS: The mean DAS at baseline was 5.02 +/- 0.8. All patients received 10 mg/wk folic acid supplementation. Forty two per cent (63/150) of the patients had C677T polymorphism of which 4 were homozygous (T/T) and 59 were heterozygous (C/T). The baseline characteristics of the patients with or without polymorphism were comparable. The frequency of adverse events was not increased in patients with C677T polymorphism with 11 patients experiencing adverse events as compared to 19 in the group without polymorphism (of whom 4 and 7 patients respectively discontinued treatment). The C677T polymorphism was not associated with any difference in response to treatment. INTERPRETATION & CONCLUSION: Our findings suggest that C677T polymorphism in the MTHFR gene is not predictive of toxicity or efficacy of MTX treatment in RA patients receiving folate supplementation. Further studies need to be done to look at polymorphisms in other enzymes that may have association with MTX clinical efficacy and toxicity.

Physical, psychosocial and economic impact of rheumatoid arthritis: a pilot study of patients seen at a tertiary care referral centre.

BACKGROUND: Rheumatoid arthritis is associated with marked physical disability. In addition, it has an impact on patients' psyche and social well-being, and entails a major financial burden. The impact of the disease in different cultural and social backgrounds is varied. Limited data are available from India on this aspect. METHODS: Patients with rheumatoid arthritis satisfying the 1987 modified American College of Rheumatology criteria were included. Besides demographic data, functional impact was assessed using the Health Assessment Questionnaire (HAQ). The psychosocial impact was measured using the medical outcomes study short form 36 (SF-36) with minor modifications. Data on direct and indirect health costs were collected by direct interview. RESULTS: The mean age of 101 patients (90 women) was 43.2 years and mean duration of disease was 8 years. Their mean (SD) HAQ score was 0.97 (0.69) with 8 patients having scores > 2. On the SF-36 scale (0-100) the mean (SD) score for various domains were: physical functioning 49.90 (28.55), social functioning 55.51 (20.59), role limitation due to physical problems 32.67 (41.34), role limitation due to emotional problems 47.54 (40.08), mental health 47.36 (7.99), general health perception 52.38 (8.30), energy and vitality 58.56 (6.09), and bodily pain 49.26 (18.87). The summary score for the physical component was 37.95 (9.03) and for the mental component it was 47.71 (4.81). While the physical component summary score had excellent negative correlation with the HAQ score (r = -0.84), correlation with the mental component summary score was poor (r = 0.32). The annual average total cost burden per patient was Rs 16 758, of which Rs 11 617 (67%) was spent on health services and the rest on non-health services (travel, home help and loss of wages). CONCLUSION: Rheumatoid arthritis causes significant physical and social disability besides being an economic burden. Indian patients had good scores for mental and social health suggesting good family support systems or reluctance to express their feelings despite physical disability.

Low prevalence of IgA deficiency in north Indian population.

BACKGROUND AND OBJECTIVES: IgA deficient patients are at risk of severe anaphylactic reaction on being transfused blood and blood products, and its prevalence varies in different parts of the world. No data are available from India.We did a blood donor survey to look for prevalence of IgA deficiency in north India. METHODS: A sensitive enzyme linked immunosorbent assay developed in-house was used to detect IgA deficiency in a total of 3818 blood donors. Complete IgA deficiency was defined as value less than 5 mg/dl whereas partial IgA deficiency was defined as value between 5-30 mg/dl. RESULTS: Of the 3818 blood donors screened, 3640 (95.3%) were males with a mean age of 31.2 yr. No donor was found to have complete IgA deficiency; however, 257 (6.7%) had partial IgA deficiency. INTERPRETATION AND CONCLUSION: Our study shows that IgA deficiency is rare in north India.

Angiomatous malformation: a rare cause of recurrent swelling of the knee joint.

Angiomatous malformation of the muscle around the knee joint is an extremely uncommon cause of recurrent swelling of the joint. We report a case of a 13-year-old boy who presented with recurrent episodes of knee joint swelling. Though the history and physical examination was typical, magnetic resonance imaging clinched the diagnosis.

Outcome in juvenile rheumatoid arthritis in India.

Juvenile rheumatoid arthritis (JRA) leads to significant morbidity due to continued disease activity and drug toxicity. Retrospective analysis of patients with JRA seen at a tertiary care hospital between 1990-2000 was done. Data regarding the type of onset, course of disease, joints involved, treatment received, drug toxicity and outcome at last visit were retrieved from case records. There were 214 children (76 oligoarticular, 93 polyarticular and 45 systemic onset) with 135 of them being boys. At last followup, with median disease duration of 6 years; 128 had active disease, 58 had stable disease and 28 had inactive disease. Polyarticular group had the worst outcome with only 3 of the 93 having inactive disease (13/76 in oligoarticular group and 12/45 in systemic onset disease). Intramuscular gold and D-Penicillamine were associated with significant drug toxicity. Outcome of children with JRA in our country is poorer as compared to developed countries.

Arthritis in lymphomatoid granulomatosis: report of a case and review of literature.

Lymphomatoid granulomatosis (LG) is a rare systemic vasculitis caused by Epstein Barr virus induced transformation of the B-cells in a T-cell rich environment. The predominant clinical presentations are confined to the pulmonary system however; extra-pulmonary manifestations can sometimes be the main feature of the disease. Here in we describe a 52-year-old female who presented with symmetric polyarthritis and generalized stiffness for 7 months and papular lesions over extremities for 3 months duration. She in addition had generalized lymphadenopathy. Histopathological examination of the cutaneous lesions confirmed LG. Patient died despite therapy with cyclophosphamide and prednisolone. This is the first report of LG mimicking rheumatoid arthritis from India.

Isolated necrotizing vasculitis of gallbladder: a report of two cases and review of literature.

We report two cases of isolated necrotizing vasculitis of gallbladder without evidence of systemic involvement which was histologically indistinguishable from classic polyarteritis nodosa (PAN), displaying vascular lesions in different stages of progression like those of PAN. The literature has been reviewed in order to evaluate the significance and possible aetio-pathogenesis of gallbladder (GB) vasculitis. Localized PAN of gallbladder is a rare incidental postoperative finding, the serological work-up for autoantibodies may be negative and the disease is likely to remain self-limited.

Outcome in juvenile dermatomyositis.

The clinical features, outcome and complications of juvenile dermatomyositis were studied in a tertiary care hospital by retrospective analysis of case records. Nineteen patients were treated over an 11-year period. Median age at diagnosis was 12 years (2.5-16 years). Median duration of disease prior to diagnosis was 12 months (2-96 months). Proximal muscle weakness was seen in all 19 cases, neck muscle weakness in 14, pharyngeal muscle involvement in 5 and respiratory muscle involvement in 3 cases. Heliotrope rash was seen in 9 and Gottrons rash in 8 patients. Myocarditis and GI bleed were seen in 1 each while interstitial lung disease was seen in 2 patients. All except one patient received prednisolone. Methotrexate was used in 13 and azathioprine in 3 patients. Eight patients are in complete remission (CR), 8 partial remission and 2 patients had no response. Complications were calcinosis in 5, contractures in 2, TB in 4 and pyogenic infections in 4 patients. Juvenile dermatomyositis needs to be recognised early and treated aggressively to improve outcome.