Ayurvedic medicine offers a good alternative to glucosamine and celecoxib in the treatment of symptomatic knee osteoarthritis: a randomized, double-blind, controlled equivalence drug trial.

OBJECTIVE: To demonstrate clinical equivalence between two standardized Ayurveda (India) formulations (SGCG and SGC), glucosamine and celecoxib (NSAID). METHODS: Ayurvedic formulations (extracts of Tinospora cordifolia, Zingiber officinale, Emblica officinalis, Boswellia serrata), glucosamine sulphate (2 g daily) and celecoxib (200 mg daily) were evaluated in a randomized, double-blind, parallel-efficacy, four-arm, multicentre equivalence drug trial of 24 weeks duration. A total of 440 eligible patients suffering from symptomatic knee OA were enrolled and monitored as per protocol. Primary efficacy variables were active body weight-bearing pain (visual analogue scale) and modified WOMAC pain and functional difficulty Likert score (for knee and hip); the corresponding a priori equivalence ranges were ±1.5 cm, ±2.5 and ±8.5. RESULTS: Differences between the intervention arms for mean changes in primary efficacy variables were within the equivalence range by intent-to-treat and per protocol analysis. Twenty-six patients showed asymptomatic increased serum glutamic pyruvic transaminase (SGPT) with otherwise normal liver function; seven patients (Ayurvedic intervention) were withdrawn and SGPT normalized after stopping the drug. Other adverse events were mild and did not differ by intervention. Overall, 28% of patients withdrew from the study. CONCLUSION: In this 6-month controlled study of knee OA, Ayurvedic formulations (especially SGCG) significantly reduced knee pain and improved knee function and were equivalent to glucosamine and celecoxib. The unexpected SGPT rise requires further safety assessment. TRIAL REGISTRATION: Clinical Drug Trial Registry-India, www.ctri.nic.in, CTRI/2008/091/000063.

Pulmonary arterial hypertension complicating adult-onset Still's disease.

Adult-onset Still's disease (AOSD) is a rare condition diagnosed by a combination of clinical and laboratory features and after ruling out other conditions. Pulmonary manifestations, apart from pleuritis, are uncommon and pulmonary arterial hypertension (PAH) in extremely uncommon. We have described a case of AOSD with severe PAH. There have been rare reports of PAH occurring in AOSD in the literature. Probably, this manifestation may have been understudied, being confined to cases which are symptomatic. A larger study to look at the asymptomatic occurrences of PAH in AOSD may help in unraveling the mystery of this disease.

Evaluating higher doses of Shunthi - Guduchi formulations for safety in treatment of osteoarthritis knees: A Government of India NMITLI arthritis project.

BACKGROUND: Results of an exploratory trial suggested activity trends of Zingiber officinale-Tinopsora cordifolia (platform combination)-based formulations in the treatment of Osteoarthritis (OA) Knees. These formulations were "platform combination+Withania somnifera+Tribulus terrestris" (formulation B) and "platform combination+Emblica officinale" (formulation C). This paper reports safety of these formulations when used in higher doses (1.5-2 times) along with Sallaki Guggul and Bhallataka Parpati (a Semecarpus anacardium preparation). MATERIALS AND METHODS: Ninety-two patients with symptomatic OA knees were enrolled in a 6 weeks investigator blind, randomized parallel efficacy 4-arm multicenter drug trial. The 4 arms were (I) formulation B, 2 t.i.d.; (II) formulation B, 2 q.i.d.; (III) platform combination+Sallaki Guggul; (IV) Bhallataka Parpati+formulation C. A detailed enquiry was carried out for adverse events (AE) and drug toxicity as per a priori check list and volunteered information. Laboratory evaluation included detailed hematology and metabolic parameters. Patients were examined at baseline, first and fourth weeks, and on completion. Standard statistical program (SPSS version 12.5) was used for analysis. RESULTS: None of the patients reported serious AE or withdrew due to any drug-related toxicity. Mild gut-related (mostly epigastric burning) AE was reported. A mild increase in liver enzymes [serum glutamic pyruvate transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT)] without any other hepatic abnormality was reported in 2 patients (group IV). Other laboratory parameters remained normal. The mean improvement in active pain visual analog scale (1.4, CI 0.5-2.22), WOMAC (functional activity questionnaire) pain score (1.37, CI 0.22-2.5), and urinary C-TAX (cartilage collagen breakdown product) assay was maximum (NS) in group IV. Lower dose group I showed numerically superior improvement compared with higher dose group II. CONCLUSION: The results suggested that despite higher doses, standardized Ayurvedic formulations demonstrated a good safety profile. An improved efficacy and likely chondroprotective effect was shown by group IV intervention. A confirmatory drug trial with adequate power and sample size was planned based on the learning from this trial.

Comparable efficacy of standardized Ayurveda formulation and hydroxychloroquine sulfate (HCQS) in the treatment of rheumatoid arthritis (RA): a randomized investigator-blind controlled study.

Hydroxychloroquine sulfate (HCQS) is a popular disease-modifying antirheumatic drug (DMARD) despite modest efficacy and toxicity. Ayurveda (ancient India medicinal system) physicians treat rheumatoid arthritis (RA) with allegedly safer herbal formulations. We report a head-to-head comparison in an exploratory drug trial. The objective is to compare standardized Ayurvedic formulations and HCQS in the treatment of RA. One hundred twenty-one patients with active moderately severe RA (ACR 1988 classified) were randomized into a 24-week investigator-blind, parallel efficacy, three-arm (two Ayurvedic and HCQS) multicenter drug trial study; polyherb (Tinospora cordifolia and Zingiber officinale based) and monoherb (Semecarpus anacardium). Study measures included joint counts (pain/tenderness and swelling), pain visual analogue scale, global disease assessments, and health assessment questionnaire. Oral meloxicam (fixed-dosage schedule) was prescribed to all patients during the initial 16 weeks. Patients on prednisolone could continue a fixed stable dose (<7.5 mg daily). Rescue oral use of paracetamol was permitted and monitored. All groups matched well at baseline. An intent-to-treat analysis (ANOVA, significance P < 0.05) did not show significant differences by treatment groups. In the polyherb, monoherb, and HCQS arms, 44%, 36%, and 51%, respectively, showed ACR 20 index improvement. Several efficacy measures improved significantly in the HCQS and polyherb groups with no difference between the groups (corrected P). However, the latter was individually superior to monoherb. Only mild adverse events (gut and skin, and none withdrew) were reported with no differences between the groups. Forty-two patients dropped out. This preliminary drug trial controlled for HCQS demonstrated a standardized Ayurvedic polyherb drug to be effective and safe in controlling active RA. A better-designed study with a longer evaluation period is recommended.

Posterior reversible encephalopathy syndrome in systemic lupus erythematosus.

OBJECTIVE: To study the clinical profile of posterior reversible encephalopathy syndrome (PRES) in patients with systemic lupus erythematosus (SLE) and analyze the risk factors and outcomes associated with it. METHODS: We identified patients with SLE and PRES from January 2006 to October 2010. Data were collected on demographic details, lupus characteristics, PRES-related features, laboratory abnormalities, treatment details, and outcomes. RESULTS: We studied 13 patients (all female) ages 14-37 years (median 23 yrs; 4 were aged < 18 yrs with juvenile SLE). Duration of lupus ranged from 1.5 to 36 months (median 6 mo). Six patients had PRES as a part of their initial presentation of lupus. All had active lupus and hypertension; 9 had nephritis. Four patients were on treatment with cyclophosphamide therapy when they developed PRES. Antihypertensives and antiepileptics were the mainstay of treatment along with supportive care. Immunosuppressive therapy was guided by lupus-related major organ manifestations. Two patients had focal neurological deficits; one had persistent hemiparesis at followup. One patient died. CONCLUSION: PRES occurs in young lupus patients and in the early part of the disease. Focal deficits are not uncommon. It can be the presenting manifestation of lupus. Management is predominantly symptomatic. Immunosuppression is directed by other major organ manifestations. Early diagnosis and appropriate management is productive.

A Randomized Controlled Exploratory Evaluation of Standardized Ayurvedic Formulations in Symptomatic Osteoarthritis Knees: A Government of India NMITLI Project.

The multidisciplinary "New Millennium Indian Technology Leadership Initiative" Arthritis Project was undertaken to validate Ayurvedic medicines. Herbal formulations in popular use were selected by expert consensus and standardized using modern tools. Our clinical strategy evolved from simple exploratory evaluations to better powered statistically designed drug trials. The results of the first drug trial are presented here. Five oral formulations (coded A, B, C, D and E), with a common base of Zingiber officinale and Tinospora cordifolia with a maximum of four plant extracts, were evaluated; with placebo and glucosamine as controls. 245 patients suffering from symptomatic OA knees were randomized into seven arms (35 patients per arm) of a double blind, parallel efficacy, multicentric trial of sixteen weeks duration. The groups matched well at baseline. There were no differences for patient withdrawals (17.5%) or adverse events (AE) of mild nature. Intention-to-treat efficacy analysis, demonstrated no significant differences (P < .05) for pain (weight bearing) and WOMAC questionnaire (knee function); placebo response was high. Based on better pain relief, significant (P < .05) least analgesic consumption and improved knee status, "C" formulation was selected for further development. Controlled exploratory drug trials with multiple treatment arms may be used to economically evaluate several candidate standardized formulations.

Low body mass index is adversely associated with radiographic joint damage in Indian patients with early rheumatoid arthritis.

OBJECTIVE: Various factors affect joint damage in rheumatoid arthritis (RA). The influence of body mass index (BMI) is not adequately known. As BMI is potentially modifiable, we studied its influence on radiological joint damage in patients with RA. METHODS: Treatment-naive patients with early RA (< 24 mo) were included. Demographic data were collected along with swollen joint count (SJC), tender joint count (TJC), erythrocyte sedimentation rate (ESR), and IgM-rheumatoid factor (IgM-RF). Radiographs of hands and feet were obtained. BMI and Disease Activity Score for 28-joint count (DAS28-ESR) were calculated. Joint damage was assessed using the Simplified Erosions Narrowing Score (SENS). RESULTS: A total of 101 patients were studied (81 women; mean age 41.91 ± 11.99 yrs). Mean disease duration was 10.77 ± 6.73 months; 55 patients (54.5%) were IgM-RF-positive. Mean BMI was 22.82 ± 4.66 kg/m(2) with 24 (23.8%) patients having low, 42 (41.6%) normal, and 35 (34.7%) high BMI. Mean SENS score was 16.81 ± 11.10; mean DAS28 was 6.23 ± 0.96. Significant correlation was noted between SENS and DAS28 (r = 0.28; p < 0.005). There was significant negative correlation between BMI and SENS (r = -0.509; p < 0.0005). In patients with low BMI, mean SENS (26.62 ± 13.45) was significantly higher than in patients with normal (15.88 ± 8.38; p < 0.001) and high BMI (11.20 ± 7.32; p < 0.001). Patients with normal BMI also had significantly higher SENS scores than those with high BMI (p < 0.05). One-way ANOVA did not reveal significant differences in DAS28 between groups. SENS was significantly higher in the IgM-RF-positive group (19.55 ± 11.36) than in the IgM-RF-negative group (13.54 ± 9.94; p < 0.01); DAS28 was not different between the 2 groups (6.22 ± 0.98 vs 6.26 ± 0.96, respectively). Within the 2 IgM-RF groups, a significant negative correlation was seen between BMI and SENS. Multiple regression analysis revealed RF, DAS28, and BMI were independently associated with SENS. BMI accounted for 23.04% of the variance in SENS independent of DAS28 and IgM-RF. CONCLUSION: Low BMI is adversely associated with joint damage in patients with early RA.

Stenotrophomonas maltophilia: a very rare cause of tropical pyomyositis.

Pyomyositis is a purulent infection of skeletal muscles that arise from hematogenous spread associated with abscess formation. Most often caused by Staphylococcus aureus in more than 90-95% of cases but other rare organisms can cause this infection. Herein we report a rare case of strenotrophomonas maltophilia as a cause of pyomyositis which is a rare occurrence, especially in immunocompetent adults. Strenotrophomonas is a multidrug-resistant aerobic non-fermentative, non-sporulating, gram-negative bacillus which usually produces nosocomial infections, but community-acquired infections are also rarely reported. This a first case report of strenotrophomonas maltophilia causing pyomyositis in an immunocompetent adult.

The prevalence and associations of sleep disturbances in patients with systemic lupus erythematosus.

The aim of this study was to analyze sleep complaints in patients with systemic lupus erythematosus (SLE) and to determine its prevalence and associations. Fifty outpatients with SLE and an equal number of age- and sex-matched controls were included in the study. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) in both cases and controls. Depressed mood, functional disability and pain severity were assessed in patients using standardized questionnaires. Disease severity, cumulative damage and presence of fibromyalgia were determined by clinical examination. Bivariate associations between sleep quality and disease-related variables as well as demographic variables were calculated. A series of hierarchical regression analyses were computed to determine the independent determinant of sleep quality. PSQI scores were significantly higher in patients with SLE. Prevalence of sleep disturbance was 62%. Functional disability, disease activity and depressed mood correlated positively with sleep disturbances. 36% of the patients satisfied ACR criteria for fibromyalgia. In multiple regression analyses disease activity was found to be an independent determinant of sleep quality. The prevalence of poor sleep quality in patients with SLE was higher than it is generally perceived to be. Functional disability, disease activity and depressed mood contributed significantly to sleep disturbances in SLE.

Systemic lupus erythematosus and dermatomyositis with symptomatic bilateral sacroiliitis: an unusual and interesting association.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune connective-tissue disease with a complex phenotype and varying disease course. Although SLE often causes a polyarticular synovitis, there are only a few case reports of abnormalities of the synovial lined sacroiliac joints. We report a case with an overlap syndrome of SLE and dermatomyositis who subsequently developed bilateral symptomatic sacroiliitis. We conclude that sacroiliitis, although rare, can occur in patients with active SLE as a manifestation of the disease per se.

Cutaneous vasculitis as a presenting manifestation of acute myeloid leukemia.

One of the rare causes of secondary vasculitides is malignancy. Hematological malignancies produce secondary vasculitis more frequently than solid malignancies. Here in we report a case of acute myeloid leukemia presenting with anti-neutrophil cytoplasmic antibody-positive vasculitis. This case highlights the importance of looking for underlying malignancies, especially leukemias in patients presenting with features of systemic vasculitides.

Melioidosis--an unusual cause of septic arthritis.

Melioidosis is an infection caused by Burkholderia pseudomallei. It is an important human pathogen in the tropical area. The clinical manifestations are protean with multisystem involvement. Septic arthritis and prostatic abscess are rare but well-recognized forms of the disease. Herein we report a case of melioidosis presenting with a rare combination of septic arthritis, prostatic abscess, and septicemia.

Kimura's disease--an unusual cause of lymphadenopathy in children.

Kimura's disease is a rare inflammatory disorder of unknown cause primarily seen in young Asian males. The disease is characterized by a triad of painless subcutaneous masses in the head or neck region, blood and tissue eosinophilia, and markedly elevated serum immunoglobulin E levels. We describe a 3-year-old Indian boy with Kimura's disease who presented with generalized lymphadenopathy. The diagnosis was based on the characteristic histopathologic findings after surgical excision in conjunction with peripheral eosinophilia and elevated serum immunoglobulin E levels.

Multiple peripheral arterial and aortic aneurysms in Behcet's syndrome: a case report.

Behcet's syndrome is an inflammatory disorder of unknown cause, characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions. Behcet's syndrome with predominant vascular involvement is known as vasculo-Behcet. Arterial complications occur in only 1 to 7% of patients with Behcet's syndrome. In most reports, arterial lesions are isolated. We report a case of Behcet's syndrome that, over 6 years, developed multiple aneurysms in peripheral arteries and aorta without any coexisting venous thrombosis. An increased awareness of Behcet's syndrome and its vascular complications is essential. This is highlighted by the fact that our patient had to undergo four surgeries and many years of diagnostic uncertainty before reaching at the final diagnosis.

Active necrotizing cerebral vasculitis in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multisystemic disease with varied clinical manifestations. Focal cortical brain infarcts and CNS infections are the most common neuropathological features reported in most studies. This report describes a 32-year-old woman who had repeated episodes of strokes over 5 years. In view of polyarthritis, oral ulcers, presence of high titres of serum antinuclear antibodies, high titres of double-stranded DNA and strokes, she was treated as SLE. Despite prolonged immunosuppressive therapy with azathioprine and pulse cyclophosphamide, she succumbed to a brainstem stroke. Complete body autopsy showed multiple cerebral cortical and brainstem infarcts with fibrinoid necrosis of the vessel wall. Renal infarction with healed vasculitis and systemic vasculitis involving small vessels was seen. Extensive thrombosis was remarkable by its absence. Active necrotizing vasculitis of cerebral and renal vessels is a rare complication of SLE, which contributed to a fatal outcome in this patient.