Biomedical subjects
Publications and source records attributed to Amita Aggarwal.
We report a rare case of disseminated histoplasmosis in a immunocompetent young adult person involving bone marrow, liver, spleen and oral cavity. He presented with oral ulcers, weight loss and pancytopenia. His bone marrow aspiration examination revealed Histoplasma capsulatum.
There is a paucity of data regarding the outcome of pregnancy from the Indian subcontinent. Therefore, we decided to analyse the outcome of pregnancy in our cohort of mothers with systemic lupus erythematosus (SLE). Data regarding pregnancies after onset of disease in patients with SLE was analysed in terms of number of pregnancies, effect of pregnancy on disease activity and effect of disease such as organ involvement, presence of anticardiolipin and anti-Ro antibodies, on the outcome of pregnancy. Fifty-two pregnancies occurred in 31 patients. Thirty-one and 21 pregnancies occurred when the disease was inactive and active, respectively. Excluding the 11 induced abortions, the live birth rate was 82.6% in the inactive group and 27.7% in the active group. Foetal loss was mainly due to 12 spontaneous abortions. There were three stillbirths and two neonatal deaths. Disease flare occurred only in the active group, one during pregnancy and two post-partum, one of which resulted in the death of the patient. The presence of antibodies to cardiolipin and to Ro/La was not associated with adverse outcome. Thus, the live birth rate in developing countries in SLE mothers is worse compared with developed countries. Active disease during pregnancy is significantly associated with increased foetal loss.
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.
Eosinophilic fasciitis presents with skin thickening involving the extremities, and sparing the hands. Raynaud's phenomenon is usually absent. It can be precipitated by undue exertion and is characterized by eosinophilia and infiltration of skin and subcutaneous tissue by mixed inflammatory infiltrate including eosinophils. We present a young man who developed eosinophilic fasciitis following severe gymnastic activity.
Methotrexate induced accelerated nodulosis (MIAN) is a rare but unique side effect of methotrexate therapy. There is paucity of data from our country about this entity. We analyzed 14 cases of MIAN and studied its association with gender, rheumatoid factor positivity and dose and duration of methotrexate. Fourteen patients (8 females), 12 with rheumatoid arthritis (8 seropositive), one each with juvenile idiopathic (JIA) and psoriatic arthritis (PsA) were detected to have MIAN during study period. All the patients presented with acute onset of multiple nodules. Radial border of fingers was the most commonly involved site. Disease was inactive in all but two patients at the time of appearance of MIAN. There was no association of MIAN with gender, rheumatoid factor positivity, disease duration, cumulative dose and duration of methotrexate therapy. Two patients each were treated with colchicine, D-penicillamine or hydroxy-chloroquine for 3-6 months without any response. We conclude that MIAN is a benign side effect of methotrexate treatment.
OBJECTIVES: Juvenile and adult forms of ankylosing spondylitis (AS) have been shown to have different clinical presentation and outcome in Caucasians. We did this retrospective analysis to see if similar differences exist in the Indian population. PATIENTS AND METHODS: Case records of 210 Indian patients diagnosed with AS according to modified New York criteria were reviewed. Data were collected regarding age of onset, clinical features, drug treatment, and outcome at last follow-up. Patients with onset before 17 years of age were classified as having juvenile AS (JAS) and the rest with adult AS (AAS). RESULTS: There were 150 patients with AAS and 60 with JAS. The latter had higher male preponderance, more frequent onset with peripheral arthritis, and greater involvement of hip and knee joints. Valvular dysfunction was seen only in patients with JAS. CONCLUSION: In this group of subjects, juvenile AS had onset more often with oligoarthritis and enthesitis than with spinal disease. Hip and knee joint involvement was more common in JAS than AAS.
OBJECTIVES: Methotrexate (MTX) is one of the most widely used disease-modifying antirheumatoid drugs in the treatment of juvenile rheumatoid arthritis (JRA). We studied its effect on the production of two proinflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFalpha), by peripheral blood cells in patients with JRA. METHODS: Interleukin-6 and TNFalpha levels were measured at 0 and 4 weeks in whole blood cultures with and without lipopolysaccharide (LPS) stimulation in 19 children treated with MTX (10 mg/m(2 )per week) or placebo. Ten healthy individuals were included as healthy controls. RESULTS: Spontaneous production of IL-6 and TNFalpha by peripheral blood cells of patients with JRA was higher than in healthy controls ( P<0.01). However, IL-6 and TNFalpha production after LPS stimulation was similar in healthy controls and patients. The two groups of patients, i.e., those treated with placebo and those treated with MTX, had similar spontaneous and induced IL-6 and TNFalpha production. At 4 weeks, the drop in spontaneous IL-6 and TNFalpha production was no different in the two groups, but LPS-stimulated IL-6 production was significantly lower in the MTX-treated group than the placebo group ( P<0.05). CONCLUSION: Methotrexate reduces the production of IL-6 by activated cells, and this may be responsible for its anti-inflammatory property.
OBJECTIVE: To define the candidate bacterial trigger and cytokine profile of synovial fluid mononuclear cells (SFMC) in patients with sporadic enteric reactive arthritis (ReA) and undifferentiated spondyloarthropathy (uSpA). METHODS: The study group comprised 10 patients with ReA and 23 with uSpA who fulfilled European Spondylarthropathy Study Group criteria. Ten patients with rheumatoid arthritis (RA) served as disease controls. IgG, IgA, and IgM antibodies to Shigella flexneri, Salmonella typhimurium, and Yersinia enterocolitica were measured in sera and SF by ELISA. Peripheral blood mononuclear cell (PBMC) and SFMC proliferation assays were done in the presence or absence of crude bacterial lysates. Bacterial antigens and DNA in synovial cells were detected by indirect immunofluorescence and polymerase chain reaction, respectively. Interferon-g (IFN-g), interleukin 10 (IL-10), and IL-4 were measured in 18 h SFMC culture supernatants in presence of bacterial lysate. RESULTS: Antibodies to S. typhimurium were significantly elevated in the sera of 8 of 25 patients compared to controls (0/22; p < 0.05). The ratio of SF:serum anti-salmonella IgA was significantly higher in patients compared to controls (p < 0.0002). The ratio of SF:serum IgA antibodies to S. typhimurium was higher than that for S. flexneri (p < 0.007) and Y. enterocolitica (p < 0.05). Out of 25 patients, 8, 2, and none had elevated antigen-specific SFMC proliferation response to S. typhimurium, S. flexneri, and Y. enterocolitica, respectively, whereas no control had elevated response. Salmonella antigens were detected in the synovial cells of 4 out of 14 patients. There was significantly higher IFN-g production from SFMC of patients who had increased proliferative response to Salmonella (LTT+) in the presence of Salmonella antigens compared to antigen control. The mean +/- SD of the ratio of IFN-g:IL-10 in the LTT+ patients was significantly lower compared to controls. Conclusion. S. typhimurium is probably one of the triggers for enteric ReA and uSpA in our cohort of patients, and the immune response is characterized by increased production of both IL-10 and IFN-g.
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OBJECTIVE: To study the prevalence of secondary amyloidosis in Asian North Indian patients with rheumatoid arthritis (RA) and to determine its clinical significance. METHODS: RA patients with disease duration > 5 years were included in this prospective study over a 2 year period. Abdominal subcutaneous fat pad aspiration (ASFA) was performed, and smears were stained with Congo red and observed for apple-green birefringence under polarized light microscopy. The amyloid deposits were graded from 1+ to 3+. Clinical, radiological, and laboratory variables of the patients were correlated with the presence or absence of amyloidosis. RESULTS: Thirty out of 113 patients were positive for amyloid by ASFA (26.5%). Out of these, 8 patients had features suggestive of clinical amyloidosis in the form of proteinuria, organomegaly, or symptomatic gastrointestinal involvement. In another 22 patients amyloidosis was subclinical. The majority of patients with clinical amyloidosis had either 2+ or 3+ deposits. CONCLUSION: Abdominal fat amyloid deposits are not uncommon in adult Asian North Indian patients with RA. However, only one-fourth of patients had evidence of clinical amyloidosis. A longer followup and a larger multicentric collaborative study is needed to determine the significance of subclinical amyloid deposits.
OBJECTIVE: To study the prevalence and antigenic specificity of antineutrophil cytoplasmic autoantibodies (ANCA) in patients with systemic sclerosis (SSc). METHODS: Sera from 68 patients with SSc were screened for ANCA by indirect immunofluorescence (IIF) assay and for antibodies to myeloperoxidase (MPO) by ELISA. All sera positive for ANCA on IIF were analyzed for reactivity against antigenic targets other than MPO [bactericidal/permeability-increasing protein (BPI), cathepsin G, lysozyme, elastase, PR3, and lactoferrin]. Twenty-three sera negative for ANCA were also tested for antibodies to BPI and cathepsin G using ELISA. RESULTS: The study included 33 patients with diffuse and 35 with limited SSc. ANCA was detected in 24 of the 68 sera (35.3%). In these 24 sera the antigenic targets were BPI in 14, cathepsin G in 13, and MPO in 8. Sera of 11 patients had reactivity against both BPI and cathepsin G. In sera, that were negative for ANCA, antibodies to BPI (4/23), cathepsin G (3/23), and MPO (1/44) were found in a small proportion of patients. Patients with antibodies to BPI had lower skin score, whereas no patient with antibodies to MPO had renal disease. CONCLUSION: BPI and cathepsin G are the major antigenic targets of ANCA seen in patients with SSc. Patients with antibodies to BPI had lower skin scores.
The relationship of the neurological manifestations to the lupus disease process is not always clear. We present a case of systemic lupus erythematosus (SLE) with subacute onset muscle weakness, which was due to polyradiculopathy, a rarely described neurological manifestation of SLE.
OBJECTIVE: Primary Sjogren's syndrome (SS) is rarely reported from India. We have studied the clinical spectrum and immunological profile of patients with primary SS. METHODS: A prospective analysis of patients with primary Sjogren's syndrome fulfilling San Francisco criteria, seen at our clinic in the last 10 years was carried out. RESULTS: The study included 26 patients, 21 being women. The presenting symptoms included dry eyes, dry mouth, and arthritis/arthralgia. Extra-glandular manifestations were glomerulonephritis, vasculitis, renal tubular acidosis and peripheral neuropathy. The important laboratory abnormalities were hypergammaglobulinaemia (16/20), antinuclear antibodies (18/26), anti-La (11/19) and anti-Ro (10/19). Minor salivary gland provided a definitive diagnosis in 16/26 (60%). CONCLUSION: The prevalence of primary Sjogren's syndrome is rare even in tertiary care rheumatology clinics. The clinical and immunological profile as seen here is similar to that reported in Western countries.
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BACKGROUND & OBJECTIVES: Early onset pauciarticular disease with uveitis is distinctly uncommon in Indian children with juvenile rheumatoid arthritis (JRA). The occurrence of anti-histone antibodies (AHA) in serum is strongly associated with presence of uveitis. There is a paucity of information from India on the levels of AHA in patients of JRA. In this study, an attempt was made to evaluate the levels of IgG and IgM antibodies to histones in children with JRA in north India. METHODS: Serum samples of 148 children with JRA (84 boys, 64 girls) were collected. Clinical details including onset, symptoms and course of the disease in each patient were recorded. Detailed eye examination including slit lamp examination was done in all patients at presentation and yearly thereafter to rule out uveitis. The presence of antihistone IgG and IgM antibodies was studied by ELISA. Antinuclear antibodies (ANA) were measured by indirect immunofluorescence using HEP-2 cells as substrate at a screening dilution of 1:40. RESULTS: Of the 148 children, 54 had pauciarticular (12 early onset and 42 late onset), 64 polyarticular and 30 systemic onset disease respectively. ANA were present in two children. AHA were raised in 15 (10%) children, of whom 10 had IgM antibodies, 3 had IgG and 2 had both isotypes. None of the children with early onset pauciarticular disease had uveitis, ANA or AHA. INTERPRETATION & CONCLUSION: The low occurrence of AHA and uveitis in our subset of patients with JRA is in contrast to that reported from Western countries. The low occurrence is unlikely due to technical reasons as the antigen that has been used consistently showed significant binding to serum from patients with systemic lupus erythematosus (SLE). This is in accordance with the rarity of early onset pauciarticular disease and chronic uveitis in these patients. More studies from other parts of the country are required to validate this observation.
Laboratory investigations are an integral part of evaluation of a child with rheumatic disease. In rheumatic diseases markers of inflammation like CRP and erythrocyte sedimentation are usually raised. In addition, various autoantibodies like anti-nuclear antibody, rheumatoid factor, anti-neutrophil cytoplasmic antibody help in diagnosis of systemic autoimmune rheumatic diseases. Synovial fluid analysis is useful in evaluating a patient with monoarthritis. The lab tests should not be done indiscriminately and choice of test should be based on provisional clinical diagnosis. A high pre-test probability increases the utility of test. Tests with high sensitivity should be used for screening whereas tests with high specificity should be used for confirmation of diagnosis. Finally, mere presence of an abnormal test does not mean disease.
Methotrexate (MTX) is the most commonly used disease-modifying antirheumatoid drug used in patients with rheumatoid arthritis. It is usually given on a weekly schedule, but as the half-life of its active compound, the polyglutamate MTX, is 3 days, we did a pilot study to see if MTX twice weekly is superior to MTX once weekly. Eighty patients with rheumatoid arthritis (RA) fulfilling the American College of Rheumatology (ACR) criteria were enrolled into a double-blind, controlled trial of 16-week duration. Patients achieving ACR scores of 20 and 50 were determined at 8 and 16 weeks. In addition, the incidence of hepatotoxicity was also studied. Of the 80 patients, 66 completed 8 weeks of study, whereas 53 completed 16 weeks of study. Most withdrawals were because of inefficacy. At 8 weeks, ACR 20 response (24/34 in once weekly and 22/32 in twice weekly) and ACR 50 response (16/34 in once weekly and 16/32 in twice weekly) in both groups were similar. Even at 16 weeks, there was no significant difference in ACR 20 and ACR 50 responses. Intent-to-treat analysis also yielded similar results. Five patients in each group had a mild reversible rise in transaminases. Our study suggests that MTX twice weekly has no advantage over once weekly regarding efficacy, and thus the currently used once weekly regimen is good enough till alternate dosing schedules are evaluated in a large multicentric trial.
TNF-alpha has emerged as the major pro-inflammatory cytokine involved in the pathogenesis of rheumatoid arthritis (RA). LPS is a potent stimulator of TNF-alpha production by human monocytes. Ceramide, a structural homolog of LPS and a second messenger in the sphingomyelin signal transduction pathway has been shown to stimulate TNF-alpha production from murine macrophages. We have previously shown that GSTM, an anti-rheumatic drug inhibits LPS stimulated TNF-alpha production by normal PBMCs. We studied the ability of ceramide to stimulate TNF-alpha production by human PBMCs and the mechanism of action of GSTM on ceramide and LPS induced TNF-alpha production. LPS induced significant TNF-alpha production in PBMCs and THP-1. However, C(2) ceramide stimulated TNF-alpha production in 5 of 10 PBMCs (ceramide responder); it did not do so in the other 5 PBMCs (ceramide non-responder) or the THP-1 cell line. GSTM inhibited LPS stimulated TNF-alpha productions in PBMCs of all 5 ceramide responders both at protein and mRNA expression level. We also found that GSTM inhibited LPS induced NF-kappaB level only in ceramide responder. Thus, we for the first time report that GSTM inhibits LPS stimulated TNF-alpha production through ceramide pathway and anti-inflammatory activity of GSTM in treatment of RA may depend on its ability to inhibit NF-kappaB activation and TNF-alpha production.