A new strategy of drug treatment in NSAID-unresponsive ankylosing spondylitis: combination of pamidronate and methylprednisolone monthly intravenous infusions on the background of a combination of disease modifying drugs sulfasalazine and methotrexate.

OBJECTIVES: To assess short term efficacy and tolerability of a therapeutic strategy in patients with ankylosing spondylitis (AS) unresponsive to nonsteroidal anti-inflammatory drugs (NSAIDs) or coxibs and unable to take anti-tumour necrosis factor-alpha (anti-TNFalpha) biological treatment. METHODS: Established AS patients were given a background treatment consisting of subcutaneous injections of methotrexate weekly (MTX, dose stepped up to a maximum of 20 to 25 mg), weekly 12-16 mg of methylprednisolone orally 30 mts before methotrexate dose (for nausea prevention), sulfasalazine (SSZ, 1 gm orally twice per day) with folic acid supplementation (5 mg daily except on the day of MTX). Additionally, they were given monthly cycles of intravenous (IV) methylprednisolone 'pulse' (MPP) and pamidronate infusions (MPP 500 mg 3 consecutive days + pamidronate 60 mg in a slow IV infusion on day 2 of the MPP infusion). A minimum of six treatment cycles at monthly intervals were given. Adjunct treatment consisted of 1 gm elemental calcium supplementation, paracetamol 650 mg 'as-and-when-required' for symptomatic pain relief, amitriptyline 10 mg 2 hours before bed time daily. RESULTS: Of a total of 46 intent-to-treat patients, 39 patients achieved ASAS-20 and BASDAI-50 response (85%, 95% CI, range 71% to 94%); 7 (15 %) patients failed to improve. The expense involved in 6 months of treatment was approximately 10-fold less than anti-TNFalpha treatment over the same period of time. CONCLUSION: For AS patients unresponsive to standard NSAIDs/coxibs and unable to take anti-TNF biological agents a combination therapeutic strategy showed efficacy and good tolerability in a majority of patients evaluated over a short-term.

Refractory thrombocytopenia in antiphospholipid syndrome.

Thrombocytopenia is the second most common manifestation of antiphospholipid syndrome (APS). It is found in approximately 22% of the patients with this disease. Often it is not severe, platelet counts usually range between 50 x 10(9)/L and 150 x 10(9)/L without bleeding problems. Yet, it does not protect patients against thrombotic events. It rarely requires treatment and, due to similarities to idiopathic thrombocytopenic purpura (ITP), similar treatment rules usually apply. In this report two patients with APS are described who presented with severe thrombocytopenia that did not respond to standard treatment regimen namely glucocorticoids (GC) followed by intravenous immunoglobulin therapy (IVIG). Splenectomy had to be resorted to relieve the condition.

Deferiprone, efficacy and safety.

OBJECTIVE: Deferiprone (L1), the new oral iron chelator has been studied in several countries for its efficacy and toxicity with some conflicting observations. Toxicity involving joints has been reported more frequently in Indian patients. The authors planned to include larger number of Indian thalassemics in studying safety and efficacy of Deferiprone. METHODS: Seventy five thalassemic children (4-14 yr) were studied for one year with various investigations done periodically. Thirty patients (group A) received 50 mg/kg dose and 21 others (group B) received 75 mg/kg dose of Deferiprone. Rest of the patients were followed up without any chelator. RESULTS: The serum ferritin levels reduced significantly in both groups (P < 0.01 each); more in 75 mg/kg than the 50 mg/kg group. Arthropathy appeared in 15 (50%) patients in Group A and 6 (28.6%) of Group B after 1-12 (mean 6) months of L1 treatment; however, only one patient needed withdrawal of L1. Eleven patients needed indomethacin for pain relief. Seropositivity for antinuclear factor and rheumatoid factor had no relation to dose or duration of L1 therapy, arthropathy or the serum ferritin level. Twelve patients developed leucopenia (< 3.0 x 10(9)/L) and neutropenia (0-1.8 x 10(9)/L) after 2-11 months of L1 therapy and was not related to the dose or duration of therapy. The drug was restarted in 10 patients and only one of them developed a second episode of neutropenia. CONCLUSION: Deferiprone is an effective iron chelator, but arthropathy and neutropenia are very frequent side effects and need strict monitoring during therapy. Most of the neutropenia are neither very severe nor recur with re-challenge with the drug. Similarly, arthropathy does not need withdrawal of drug in majority of patients.

Wegener's granulomatosis in India: clinical features, treatment and outcome of twenty-five patients.

OBJECTIVE: To report our clinical experience on Wegener's granulomatosis (WG). METHODS: A retrospective review of case records of all patients with WG in our Rheumatology Clinic during the period July 1988 to June 2000 was carried out and the details of demography, clinical and laboratory data, treatment and outcome were obtained and analysed. RESULTS: Twenty-five patients (16 females and 9 males) were found eligible for inclusion in the study. The mean age and duration of symptoms at presentation were 33.5 years and 5.5 months, respectively. Two patients had limited WG. Twenty-two patients with generalized WG were treated with standard regimen comprising oral prednisolone (1 mg/kg/day) and oral cyclophosphamide (2 mg/kg/day). Cyclophosphamide was continued for at least one year after the patient attained remission. One patient was treated with intravenous cyclophosphamide regimen. The two patients with limited WG were treated with oral prednisolone and methotrexate (10-12.5 mg as a single dose per week). Remission was achieved in 24 patients after a median time of six months. The median follow-up of patients was five years (range 4 months-11 years). Five patients were lost to follow-up. Eight patients suffered a relapse. The mean time for relapse was 34 months after the initial remission. Seven out of eight patients remitted again after reinstitution of the initial induction regimen. One patient died of diffuse pulmonary haemorrhage despite early institution of therapy. CONCLUSION: WG is being increasingly diagnosed in India now because of greater awareness and diagnostic aids. Although remissions are easy to achieve, relapses continue to pose a challenge to the treating physician.

Juvenile rheumatoid arthritis--clinical manifestations.

Chronic inflammatory arthritis in childhood could be due to an obvious cause (e.g. sepsis, rheumatic fever, systemic lupus erythematosus etc.), or it could be idiopathic. After excluding those with obvious cause there still remains a large group of chronic inflammatory arthritis in childhood. This category has been variously called 'juvenile rheumatoid arthritis', 'juvenile arthritis', 'juvenile chronic arthritis', and more recently, 'idiopathic arthritis of childhood', The present article reviews the various classification criteria used for defining this group of disorders with emphasis on the common features as well as the major differences between these criteria. The major classes within this group with their characteristic clinical and laboratory features are also discussed.

Common variable immunodeficiency (CVID) in northern India.

Fourteen patients with common variable immunodeficiency (CVID) were studied. The common clinical manifestations were recurrent sore throat, sinusitis, respiratory infections, diarrhea, and malnutrition. All had low IgG, with normal cell-mediated immunity. Treatment with immunoglobulin and/or plasma was effective in most of them. There were no severe adverse events with the therapy.

Methotrexate in psoriatic arthritis.

Thirty three patients with psoriatic arthritis were treated with starting dose of 7.5 mg of methotrexate orally, every week for a period of 6 months to 7 years (mean 2.2 years) along with non-steroidal anti-inflammatory agents. The dose of methotrexate during the course of therapy ranged 5 to 15 mg/week (mean 7.8 mg). There was complete to partial remission in arthritis and psoriatic skin lesions in 94% (31) patients. No response was noticed in 2 patients. Regular monitoring of haematological, renal and liver function tests was done. No significant side effects of the drug, requiring discontinuation of the therapy, were seen during the treatment. Methotrexate can be used early in the course of psoriatic arthritis with good results.

Lupus anticoagulant and anticardiolipin antibodies in systemic lupus erythematosus.

BACKGROUND. Lupus anticoagulant and anticardiolipin antibodies are antiphospholipid antibodies which have been independently associated with a high incidence of thrombotic diseases. However, the importance of their combined occurrence has not yet been examined. METHODS. We investigated 70 patients with systemic lupus erythematosus for the presence of anticardiolipin antibodies paying particular attention to a history of thrombosis and abortion. Lupus anticoagulant was detected using the kaolin clotting time, its mixing tests with normal plasma and the inosithin neutralization test. Anticardiolipin antibodies were detected using the ELISA technique. RESULTS. Lupus anticoagulant was detected in 11 patients (16%) and anticardiolipin antibodies in 13 (19%). Six patients were positive for both lupus anticoagulant and anticardiolipin antibodies. These patients had a higher incidence of thrombosis or recurrent abortion (5 of 6) compared to those with lupus anticoagulant (2 of 5) or anticardiolipin antibodies alone (1 of 7). The amount of inosithin required to neutralize lupus anticoagulant was greater [mean (SD) 27.5 (20.5) micrograms] in patients with both lupus anticoagulant and anticardiolipin antibodies than in patients with lupus anticoagulant alone [mean (SD) 4.0 (5.4) micrograms]. CONCLUSION. The presence of lupus anticoagulant is associated with thrombosis and recurrent abortion which are more frequent when both lupus anticoagulant and anticardiolipin antibodies are present and these patients probably have more severe disease as the amount of inosithin required to neutralize the lupus anticoagulant was greater.

Restriction fragment length polymorphisms in HLA-DR4-DQ3 haplotypes associated with rheumatoid arthritis.

Restriction fragment length polymorphism (RFLP) patterns were studied in serologically confirmed DR4-DQ3 positive patients with rheumatoid arthritis by Southern blot analysis using full length cDNA probes specific for DRB, DQA and DQB hybridized with genomic DNA digested with informative restriction endonucleases. The RFLP patterns correlated with serology confirming all patients to be DR4+ve. The DQB1*0302 (DQ8) allele identified by 12.0kb BamHI, 3.3kb Hind III and 1.8kb Taql fragments was present in all patients suggesting them to be DR4-DQB1*0302. Hybridization of Taq 1 and PVU II digested genomic DNA with DQA cDNA probe revealed four informative RFLP patterns. While three of them correlated with known DR4 subtypes, one was a new polymorphism observed specifically in Indian patients with rheumatoid arthritis. The study further indicated that two of the several known subtypes of DR4, viz., DRB1*0401-DW4-DQB1*0302 and DRB1*0404-DW14-DQB1*0302 may be implicated in susceptibility to rheumatoid arthritis in the Indian population.

Effect of D-penicillamine on lymphocyte subsets: correlation with clinical response in rheumatoid arthritis.

We studied the effects of D-penicillamine (DP) on the clinical response, immunoinflammatory parameters and the lymphocyte subsets in 46 patients with rheumatoid arthritis (RA). Patients were evaluated before the start of the drug and then at 3 and 9 months during the follow up. 38 of 46 (82.6%) patients could continue DP treatment for over 9 months, while in 8 the drug was withdrawn due to adverse effects. Improvement in the various disease activity indices of more than 50% (responders) was seen in 25 of 38 (65.8%) patients. Responders showed a significant decrease in the serum IgA and IgM at 9 months, and in IgM only at 3 months. The serum levels of C3 and C4 did not show any significant change. Serum levels of C-reactive protein and rheumatoid factor (RF) showed a significant decrease at 3 and 9 months. A significant decrease in CD3+ and CD4+ lymphocytes along with a fall in CD4+/CD8+ lymphocyte ratio was also seen in responders at 3 and 9 months, compared to the baseline. Our results suggest that DP may have immunomodulatory action in RA.

Acquired immunodeficiency syndrome (AIDS) in multitransfused children with thalassemia.

Two hundred and three multi-transfused children with thalassemia attending the Thalassemia Clinic of the Charak Palika Hospital, New Delhi were screened for human immunodeficiency virus (HIV) antibodies by ELISA and all positive cases were confirmed by Western Blot. Of the 203 children screened, 18 (8.9%) were HIV positive, and in these children a detailed immunological work up was done and compared to 18 age-matched HIV negative thalassemics as controls. The tests included absolute lymphocyte counts (ALC), absolute and percentages of CD4+ and CD8+ cells and their ratios (CD4/CD8), immunoglobulin levels (IgG, IgM and IgA) and delayed cutaneous hypersensitivity (DCH) test by Multitest CMI in all the cases and the controls. Of the 18 HIV positive children, 6 were diagnosed to have clinical AIDS as per the WHO criteria. After immunological testing, the children were further classified according to the CDC criteria. By these criteria, 11 children were classified as P1 A (asymptomatic infection, normal immune function), 1 child as P1 B (asymptomatic infection, abnormal immune function), 2 children as P2 A (symptomatic infection with non-specific findings), 1 child as P2 C (lymphocytic interstitial pneumonitis), 1 child as P2 D1 (Pneumocystis carinii pneumonia) and 2 children as P2 D2 (symptomatic infection with infections). In this paper, the clinical features of the children with AIDS is described, and the immunologic functions of these children are compared with the HIV positive asymptomatic children and with controls. These are the first cases of AIDS in the pediatric age group from India.

Pneumocystis carinii infection in patients of AIDS in India.

This is the first report of Pneumocystis carinii infection seen in patients with AIDS in India. Two of the three patients were of Indian origin while the third was an American tourist. This report indicates that the technical problem of demonstrating P carinii may be an important factor underlying the diagnosis of PCP.

Dapsone in cutaneous lesions of SLE: an open study.

This short report describes a possible beneficial effect of dapsone in the treatment of chronic unresponsive muco-cutaneous lesions of systemic lupus erythematosus (SLE) without any serious side effects.

Changing spectrum of clinical and laboratory profile of infective endocarditis.

The clinical profile of 28 consecutive patients admitted with infective endocarditis (IE) between 1987 and 1988 was studied. There were 21 males and seven females with a mean age of 24 +/- 11 years. Rheumatic heart disease (RHD) was the commonest underlying disease (68%) followed by congenital heart disease (CHD). Mitral regurgitation with aortic regurgitation were the commonest valvular lesions (47%) in those with RHD while ventricular septal defect was the commonest (43%) in those with CHD. A younger age of onset, complicated course and high mortality were seen in these six patients with acute IE. Persistently positive blood cultures during life or at autopsy were obtained in 21%. Strep viridans was the commonest isolate and was often resistant to streptomycin. 2D echocardicgram revealed vegetations in 96% of patients, the aortic valve (39%) being more commonly affected than the mitral valve (11%). ESR of more than 20 mm drop 1st hour (Wintrobe) was seen in 96%. Thrombophlebitis was a common complication of therapy and cloxacillin the commonest drug implicated. A mortality of 21% as a result of refractory congestive heart failure (CHF) (50%), uncontrolled sepsis (33%) and embolic events (17%) was seen. A rising incidence of culture negative IE, combined aortic and mitral valve disease and CHF is noted.

Methotrexate: clinical and immunological effects in refractory rheumatoid arthritis.

Thirty five patients with refractory rheumatoid arthritis were given 7.5 mg of methotrexate (Mtx) every week. Eleven patients had to discontinue treatment either because of adverse effects or unresponsiveness. Twenty four patients showed clinical response and significant improvement in ESR and they continued Mtx for a mean of 25.24 months. Seven patients achieved clinical remission as defined by ARA criteria. Immunological parameeters including IgG, IgM, IgA, lymphocyte subsets (CD3+, CD4+, CD8+ and B), C3 and C4 however, did not show any change during this treatment in any of the groups upto 6 months. There was a significant fall in the erythrocyte sedimentation rate (ESR), c-reactive protein (CRP) and rheumatoid factor (RF) levels in responders only.

Wegener's granulomatosis in northern India.

Till recently, Wegener's granulomatosis (WG) was considered a rare disease in India. Over the last 5 years we studied 13 proven cases of WG. This paper describes the details of the disease as seen in these patients, and response to corticosteroid and cyclophosphamide therapy, and compares these observations with a Western and an Indian study.

Intermittent intravenous pulse cyclophosphamide treatment in systemic lupus erythematosus.

To determine the efficacy and safety of intermittent intravenous pulse cyclophosphamide in patients of severe systemic lupus erythematosus (SLE), 50 patients having severe/refractory lupus nephritis, vasculitis or neuropsychiatric manifestations were treated with 3 weekly pulses of cyclophosphamide for 6 such pulses. This treatment was found to be associated with significant and sustained improvement during a 2 yr follow up with respect to the mean renal activity score, individual renal parameters (proteinuria, erythrocyturia, and serum creatinine levels), focal neurological manifestations, vasculitic lesions, antinuclear antibody titers, complement component C3, anti-dsDNA antibodies levels and ESR. There was a sustained decrease in the overall mean disease activity score, and the mean daily dose of prednisolone (pretreatment 32.62 mg daily to 3.75 mg daily after 24 months). There was a significant decline in the percentage and absolute B cell count after 7, 14 and 21 days of this treatment. Effect on other lymphocyte subsets (CD3+, CD4+ and CD8+) was not marked. Pulse cyclophosphamide could therefore be an effective and less toxic form of treatment in patients with SLE having severe lupus nephritis, focal neurological lesions or vasculitis.