Causes of mortality among inpatients with systemic lupus erythematosus in a tertiary care hospital in North India over a 10-year period.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder with significant morbidity and mortality. The present study was undertaken to identify the causes of in-hospital mortality of patients with SLE. METHODS: This was a retrospective study. The hospital records of patients with SLE who died between 1998 and 2007 were reviewed. Demographic details, organ involvement, treatment received and evidence of infection were recorded. Disease activity was calculated using the SLE Disease Activity Index. The cause of death of each patient was determined and this information was classified into either deaths caused primarily due to SLE, deaths caused due to infection or those that were multi-factorial. RESULTS: Seventeen patients with SLE who were diagnosed according to the revised American College of Rheumatology criteria died between 1998 and 2007. Fifteen of these patients were female and two were male. The median age was 25 years. The average duration of hospital stay was 10.29 days. Seven patients (41%) died of active SLE (three from pulmonary hemorrhage, two had renal failure, one had myocarditis and one had severe thrombocytopenia with upper gastrointestinal bleed), three patients (18%) died from infections (one contracted Staphylococcal septicemia, another contracted tuberculous meningitis and the third patient had Pseudomonas septicemia) and in seven patients (41%) the etiology was multi-factorial (these showed both active SLE and evidence of infection). In total 10 patients had evidence of infection, two of these were community-acquired and the rest were hospital-acquired. CONCLUSION: Active SLE and/or infection are the major causes of death in hospitalised patients with SLE. To reduce patient mortality improvements in supportive care for patients with active SLE and measures to prevent hospital-acquired infections are required.

Angioinvasive pulmonary mucormycosis presenting as multiple bilateral pulmonary nodules in a patient without obvious predisposing factors.

Pulmonary mucormycosis is a rare, frequently fatal, fungal infection. It is usually seen in the presence of various immunocompromised states, such as diabetes mellitus, haematological malignancy or renal transplantation. In the absence of underlying predisposing conditions, presentation with infiltrates, consolidation, cavitation and mass lesion have been reported. We describe a 50-year-old man who presented with cough and chest pain for six months. Chest radiograph and computed tomography showed bilateral multiple pulmonary nodules. Surgical lung biopsy revealed angioinvasive mucormycosis. He had complete recovery with amphotericin therapy.

Relapsing polychondritis in North India: a report of 10 patients.

OBJECTIVE: Relapsing polychondritis (RP) is a rare autoimmune disorder characterized by recurrent episodes of inflammation and destruction of cartilaginous tissues. We describe the outcome of 10 patients followed up at the Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, over the past 10 years. METHODS: All the patients fulfilling the diagnostic criteria suggested by McAdam et al (Medicine (Baltimore) 1976;55:193-215) and modified by Damiani and Levine (Laryngoscope 1979;89;929-46) were included in the study. Detailed clinical features, investigations, treatment given, and outcome were recorded on file. RESULTS: Six women and four men, mean age 48.1 years (range 26-65 years), met the criteria for diagnosis. The mean duration of symptoms, before diagnosis, was 27 months (range 1-72 months). Clinical features included auricular chondritis (100%), arthritis (80%), fever (50%), constitutional symptoms (50%), eye involvement (50%), hearing loss (40%), collapsed bridge of nose (30%), laryngotracheal involvement (20%), aortic dilatation (10%), and nephrotic syndrome (10%). Two patients had the MAGIC (mouth and genital ulcers with inflamed cartilage) syndrome. The number of episodes of cartilaginous inflammation varied from one to eight. Treatment included oral prednisolone (n = 9), intermittent 'pulse' cyclophosphamide (n = 2), and azathioprine (n = 2). One patient required tracheostomy and died later. The others are doing well. Mean duration of follow-up was 35.5 months (range 1-79 months). CONCLUSIONS: The diagnosis of this potentially lethal condition is frequently delayed. Our series suggests that clinical manifestations of RP are similar in Caucasian, Oriental, and Asian populations. Laryngotracheal involvement was seen less frequently in our patients.

Successful treatment of severe gastrointestinal involvement in adult-onset Henoch-Schönlein purpura.

Henoch-Schönlein purpura is a small vessel vasculitis which is uncommon in adults. The presentations of adult-onset disease are different from those seen in childhood. The commonly-recognised serious gastrointestinal complications of childhood are less well-documented in adults. We report three cases of adult-onset Henoch-Schönlein purpura with severe gastrointestinal involvement. All were men, aged 22, 35 and 42 years, respectively. Two of these patients had evidence of mesenteric ischaemia on computed tomography of the abdomen. All three patients were successfully treated with steroids.

Adherence to generic reverse transcriptase inhibitor-based antiretroviral medication at a Tertiary Center in North India.

At least 95% adherence to medications is required for sustained response to antiretroviral therapy (ART). In resource constraint restrained settings it is not possible to use electronic methods to determine adherence. We determined adherence during the previous 4 weeks by the recall method in 200 patients (138 males) receiving generic triple drug reverse transcriptase inhibitor-based antiretroviral medications. They were administered a uniform questionnaire to determine the number of time they forgot or were unable to take their medications and the reasons thereof. One hundred and fifty received two and 50 took three pills daily. One hundred and forty-seven did not miss any dose. Fifty-three (26.5%) missed at least one dose during the preceding 4 weeks. Thirty-one took treatment on and off. Seven missed a dose in the preceding 3 days, nine more between the last 3 and 7 days, and six from 1 to 4 weeks. The major reasons for non-adherence were financial constraints, forgetting to take the medication, drug toxicity, lack of access to the drug, fear of getting immune to the benefit of the drug, and to avoid adverse effects. Non-adherence in 26.5% individuals could be an additional factor that can increase the risk of drug resistance.

Wegener's granulomatosis presenting as diabetes insipidus.

Pituitary gland involvement in Wegener's granulomatosis (WG) occurs most commonly in the form of central diabetes insipidus (CDI). However, CDI as a presenting manifestation of WG is very rare. We report two such cases; one of them had multi-organ involvement at presentation, while other developed it during follow-up. CDI was reversible following cytotoxic drug therapy in one of them.

Successful management of tubercular subretinal granulomas.

PURPOSE: To report the successful management of 12 eyes of 11 patients with tubercular subretinal granulomas. METHODS: Eleven consecutive patients with a presumed or confirmed diagnosis of tubercular subretinal granulomas were treated with four-drug anti-tuberculosis chemotherapy with concomitant oral corticosteroids. Two patients underwent pars plana vitrectomy. RESULTS: The study included seven males and four women with a median age of 30.5 years. Ten eyes responded well to medical management and a final visual acuity of 20/80 or better was achieved in eight of them. The eyes subjected to pars plana vitrectomy had a relatively worse outcome. CONCLUSIONS: Tubercular subretinal granulomas are amenable to medical management provided an early diagnosis is made and treatment is initiated promptly. Once the diagnosis of presumed or confirmed tuberculosis is established, surgical intervention should be avoided.

Prevention of opportunistic infections in HIV infection by pentoxiphylline.

BACKGROUND & OBJECTIVES: Levels of tumour necrosis factor (TNF) are increased in patients with HIV infection leading to increased apoptosis and reduced CD4 cell life. Pentoxiphylline is a TNF inhibitor with properties that might make it useful for the treatment of HIV infection. These include improved cell mediated immunity and inhibition of viral replication. We carried out this study to determine the therapeutic utility of pentoxiphylline in improving constitutional manifestations, preventing opportunistic infections and sustaining CD4 counts among asymptomatic HIV infected individuals (i.e., those with no opportunistic infection). METHODS: Individuals with HIV infection who were over 18 yr of age and free of opportunistic infections were recruited in the study and followed up 4 weekly. CD4 counts were measured using a flowcytometer using anti-human CD4 intervals. Pentoxiphylline was prescribed in a dose of 400 mg thrice daily. RESULTS: Thirty three (18 males) patients with HIV infection were studied. During their follow up (mean 12.5 +/- 5.6 months) one patient each developed cryptococcal meningitis and fibrocavitary tuberculosis. Weight increased from 51.3 +/- 7.4 kg at baseline to 55.3 +/- 7.4 kg (P<0.05). Malaise, fatigue and appetite improved in all those with these complaints, except the two with opportunistic infections. Mean CD4 counts were 184 +/- 36.4/microl at baseline and increased to 210 +/- 28.6/microl3 at four weeks (P<0.05). The patients had stable CD4 counts over the follow up period since then, i.e., within 25 per cent of the previous levels. INTERPRETATION & CONCLUSION: Pentoxiphylline therapy in HIV infected individuals, who were free of opportunistic infections, improved their body weight, minimized opportunistic infections, increased and sustained CD4 counts. Given the low cost of the drug it could be recommended for the use in individuals who are at a high risk of developing opportunistic infections.

Caspase 1 and caspase 8 in HIV infected patients with and without tuberculosis.

BACKGROUND: Caspase 8 is involved in apoptosis mediated by Fas and p55 tumor necrosis factor receptor ligation in HIV infection. Apoptosis is partially mediated by interleukin-1beta-converting enzyme (caspase-1). AIMS: We determined apoptosis, using caspase-1 and caspase-8, among patients with HIV infection, with and without tuberculosis (TB), those with TB alone and healthy individuals. SETTING AND DESIGN: Cross-sectional analysis of caspase-1 and caspase-8 among patients with HIV infection, with and without TB, those with TB alone and healthy individuals. MATERIALS AND METHODS: Nineteen HIV infected patients with TB (HIV+/TB+) and 20 with HIV infection without TB (HIV+/TB-) were studied. Fifteen individuals with TB alone were disease controls (HIV-/TB+) and 20 were healthy controls (HIV-/TB-). Caspases were measured by single-step ELISA using commercially available monoclonal antibodies. STATISTICAL ANALYSIS: Two-way ANOVA and Pearson's correlation coefficient. RESULTS: Mean CD4 counts of HIV+/TB+ were lower than HIV+/TB- (p<0.05). OD value of caspase 1 in HIV+/TB+ was 0.295+0.05, while that in HIV+/TB- it was 0.302+0.18. It was 0.293+0.07 in HIV-/TB+ and in HIV-/TB- the values were 0.287+0.06. OD value of caspase 8 in HIV+/TB+ was 0.307+ 0.07, lower than HIV+/TB- (0.927+0.25). It was 0.008+0.03 in HIV-/TB+ and in HIV-/TB-, 0.074+0.004. Values of caspase 8 in patients with HIV infection (with/without TB) were higher than those with TB alone or healthy individuals (p<0.01). Levels of caspase 8 in HIV+/TB- were higher than patients with HIV+/TB+ (p<0.01). CONCLUSION: Levels of caspase-1 are not different irrespective of presence or otherwise of TB and HIV infection. Fas-related apoptosis is higher in HIV infection. With concomitant TB, levels of caspase 8 were lower as compared with those without TB.

Beta2 microglobulin as a surrogate marker for HIV infection: good correlation with CD4 counts.

To determine if beta-2 microglobulin (beta2M) levels were elevated in our HIV infected patient population and if it could be used as a surrogate marker for disease progression. Thirty-eight HIV infected individuals and 26 age and sex-matched controls were studied. Measurement of CD4 cell count was carried out on a flowcytometer using anti-human CD4 monoclonal antibody and beta2M was measured by an enzyme immunoassay. Mean levels of HIV infected individuals were 1.29 +/- 0.52 mg/L and were significantly higher than 0.74 +/- 0.07 mg/L, the value of controls (p value <0.01). There was a negative correlation between CD4 counts and beta2M levels (r-value-0.79, p value <0.001). Beta2M levels in HIV infected individuals who have no opportunistic infection are elevated and these levels correlate with the CD4 counts. Beta2M can be used for the clinical follow-up of patients with HIV infection.

Acute pancreatitis following propoxyfur (Baygon) ingestion.

Elevation of serum amylase and blood glucose is not uncommon following anticholinesterase poisoning. We report a young male who developed acute cholinergic crisis and acute pancreatitis following propoxyfur (Baygon) ingestion and recovered completely with conservative management.

Reduced apoptosis by pentoxiphylline among patients with HIV infection.

BACKGROUND: Apoptosis is a significant cause of CD4(+) T cell death. Caspase 8 (FLICE) is involved in apoptosis mediated by Fas and p55 tumor necrosis factor (TNF) receptor ligation. It is also partially mediated by interleukin-1beta (IL-1beta)-converting enzyme (ICE; caspase 1). We and others have shown that pentoxiphylline inhibits TNF-alpha. We used it among patients with HIV infection to determine if 24 weeks of therapy altered the levels of caspase 1 and caspase 8. PATIENTS AND METHODS: Nineteen HIV-infected patients having no opportunistic infection at the time of recruitment were administered pentoxiphylline 400 mg thrice daily for 24 weeks. Caspase levels were measured using a single-step ELISA using commercially available monoclonal antibodies against caspase 1 and caspase 8. RESULTS: Mean CD4 counts of the patients were 202.6+/-111.6 (/mm(3)). Mean OD value of caspase 1 among patients before therapy was 0.302+/-0.197 and was higher than that of controls (0.287+/-0.064), but this was not statistically significant. Following 24 weeks of therapy with pentoxiphylline, the OD value declined significantly to 0.164+/-0.028 among patients (p<0.001). Mean OD value of caspase 8 among patients prior to therapy was 0.927+/-0.249. This was significantly higher than that of controls, whose level was 0.0074+/-0.004 (p<0.001). Following 24 weeks of therapy with pentoxiphylline, the OD value declined to 0.199+/-0.064 among patients and this was significantly lower than the value at the start of treatment (p<0.001). CONCLUSION: Therapy with pentoxiphylline for 24 weeks is associated with a decline in the levels of caspase 1 and caspase 8. Since the drug is known to produce TNF inhibition, this might result in reduced apoptosis and an improved CD4 lymphocyte survival.

Human immunodeficiency virus infection in a patient with systemic lupus erythematosus.

We describe a 47 years lady with systemic lupus erythematosus (SLE) who was infected with human immunodeficiency virus (HIV), due to transfusion either by blood or platelet concentrate. There was a near remission in the disease and during the course of follow up she developed cryptococcal meningitis. The approach to the diagnosis of HIV infection in a patient with SLE, the effect of SLE on the virus and vice versa and some management issues in this setting are discussed.

Fatal 2,4-D (ethyl ester) ingestion.

2,4-D (2,4-dichlorphenoxyacetic acid) is widely used in agriculture and forestry to destroy broad leaved weeds (herbicide). It has a moderate mammalian toxicity and human poisoning has rarely been reported except following ingestion with suicidal intent. We report two young adults who ingested it with suicidal intent, developed neurological, cardiac, hepatic and renal toxicity and died.

Paucity of anti-hepatitis C virus antibodies in the serum of Indian patients with Sjogren's syndrome and inflammatory myositis.

Several extrahepatic manifestations have been associated with infection with Hepatitis C virus (HCV) infection. It has been associated with Sjogren's syndrome (SS) and inflammatory myositis (IM). The objective was to look at the prevalence of anti-HCV antibodies in the serum of SS and IM patients of Indian origin. Individuals satisfying the European Economic Community criteria for the diagnosis of SS and those satisfying the criteria of Bohan and Peter for the diagnosis of IM were recruited in the study. Routine evaluation for liver functions was made. Anti-HCV antibodies were tested by a third generation ELISA, using microplate HCV3.0 ELISA. Of the 23 patients with SS studied, 14 had extraglandular features. The commonest were anaemia and arthritis in six each, followed by in lymphopenia in two. One patient each had interstitial lung disease, hypothyroidism and chronic active hepatitis. Twenty-two patients with IM were studied alongside. None of the patients had abnormal liver functions. One patient with primary SS tested positive for anti-HCV antibodies. None of the patients with inflammatory myositis tested positive for anti-HCV antibodies. The presence of anti-HCV antibodies in our cohort of patients with SS and IM is low and more in keeping with the generally low prevalence of the infection in the Indian population.

Paradoxical reaction in HIV and tuberculosis coinfection.

Occurrence of paradoxical reaction following institution of antiretroviral therapy to patients with HIV and tuberculosis coinfection who are already on antitubercular therapy is distinctly uncommon. In this report we describe one such case and emphasize that such a reaction does not imply discontinuation of therapy.

Clinical characteristics of serpiginous choroidopathy in North India.

PURPOSE: To describe clinical characteristics of serpiginous choroidopathy in the North Indian population. DESIGN: Retrospective cohort-based study. METHODS: Records of 86 patients who obtained a diagnosis of serpiginous choroidopathy at presentation or after a minimal follow-up of 2 years were retrieved. Group I included 62 patients who were diagnosed as having serpiginous choroidopathy at the initial presentation. Group II included 20 patients who initially presented as having multifocal placoid pigment epitheliopathy resembling acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and had progressed over years to serpiginous choroidopathy, while group III had 4 patients with mixed presentations. Statistical analysis was done using the chi-square and Mann-Whitney U test. A review of the clinical, historical, fundus photographic, and fluorescein angiographic features was performed. The demographic and clinical features, number of recurrences, final visual acuity, and final description of healed lesions were documented. RESULTS: The median age at presentation was 30 years in group I, 29 years in group II, and 31 years in group III. The disease was bilateral in five (15%) patients in group I, 12 (60%) in group II, and all four in group III. All the affected eyes in groups II and III and 58 eyes (87%) in group I had recurrences over 2 to 8 years of follow up. Compared with group I, group II was characterized by more bilaterality (P =.001), less central foveal involvement (P =.001), better final visual acuity (P =.001), the presence of healed multifocal scars (P =.001), and less subretinal fibrosis (P =.02). Four patients in group III showed mixed features. CONCLUSIONS: Serpiginous choroidopathy in our population was seen in young patients and had three distinct presentations that seemed to affect the choriocapillaris primarily. Our patients appeared to have a variation of serpiginous choroidopathy, typical of the Asian-Indian population, that had some important differences from that reported in Caucasians.

Linear scleroderma and autoimmune hemolytic anaemia.

Coexistence of localized scleroderma with other autoimmune disorders is not seen frequently. It has been reported to occur with myasthenia gravis, hemiatrophy and systemic lupus erythematosus. In this report we describe an association wherein linear scleroderma coexisted with autoimmune haemolytic anaemia.