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International publications of interest from India (September–November 2009)
Indian Journal of Rheumatology 2009 December Volume 4, Number 4; pp. 176–178
PG Forum
International publications of interest from India (September–November 2009) V Arya
1. Sharma NL, Mahajan VK, Ranjan N, Sharma VC, Gupta M. Systemic sclerosis sine scleroderma and calcinosis cutis: report of a rare case. Clin Rheumatol 2009 Oct 17. [Epub ahead of print] The authors describe a 17-year-old girl with systemic sclerosis sine scleroderma who was diagnosed initially as seronegative juvenile rheumatoid arthritis. She developed progressively increasing disc-like masses of calcinosis over the gluteal regions, knee, elbow, and ankle joints fixed to the overlying skin associated with malaise, anorexia, and weight loss. There was no Raynaud’s phenomenon, dysphagia, dyspnoea, sclerodermatous skin, sclerodactyly, telangectasias, or muscle tenderness/weakness. Digital pitted scars, elevated anticentromere antibody values, esophageal hypomotility, and fluffy calcification in subdermal soft tissues in gluteal regions and around wrist, hip, knees, heels, and ankle joints (without affecting the underlying structures) were detected. Therapy with diltiazem and magnesium/aluminum antacids was useful in resolving calcinosis. This case highlights a rare presentation of scleroderma. 2. Dhir V, Lawrence A, Aggarwal A, Misra R. Fibromyalgia is common and adversely affects pain and fatigue perception in North Indian patients with Rheumatoid Arthritis. J Rheumatol 2009 Oct 15. [Epub ahead of print] This cross-sectional study was aimed at assessing the prevalence and effects of fibromyalgia (FM) in North Indian patients with RA and associations of RA with disease activity. The study included 200 RA patients and an equal number of controls. FM was present in 15% of patients with RA compared to 2.5% of controls. RA patients with FM did not differ from those without FM in terms of age, gender, current disease-modifying agents,
or steroid use. RA patients with FM had higher disease activity and worse functional disability. The number of tender and swollen joints was higher in patients with FM, but correlated poorly with each other. RA patients with FM had higher pain and fatigue scores but were not different in the quality of life or mood. This study addresses a neglected aspect of rheumatoid arthritis: co-existing fibromyalgia and its adverse impact on RA. 3. Gupta R, Deepanjali S, Kumar A, Dadhwal V, Agarwal SK, Pandey RM, Chaturvedi PK. A comparative study of pregnancy outcomes and menstrual irregularities in northern Indian patients with systemic lupus erythematosus and rheumatoid arthritis. Rheumatol Int 2009 Oct 14. [Epub ahead of print] The authors designed this study to evaluate the menstrual, fertility, and pregnancy outcomes in patients with systemic lupus erythematosus compared to those with rheumatoid arthritis (RA) and also to study the effect of cyclophosphamide therapy on menstrual cycles in patients with SLE. Four hundred and twenty patients with SLE (210) and RA (210) were interviewed using a standard questionnaire and available medical records used. After disease-onset, the chances of adverse pregnancy outcomes were significantly more in patients with SLE compared to RA [OR = 5.17 (2.13–12.52); P ≤ 0.001]. Compared to the National average in India, the average number of living children is lesser in patients with RA (2.39 + /− 1.39, P = 0.002), and in patients with SLE (1.44 + /− 1.35, P = 0.001). A younger age at diagnosis and cyclophosphamide therapy were found to be independently associated with menstrual irregularities after disease-onset. This study explores an important aspect in patients with SLE and RA – pregnancy outcomes and menstrual abnormalities. Since these diseases are predominantly seen in women, this study reminds us to pay
Department of Medicine, PGIMER and Dr. R.M.L. Hospital, New Delhi, India.
International publications of interest from India
attention to the gynaecological and obstetric issues encountered in this patient population. 4. Sharma A, Kumar S, Wanchu A, Lal V, Singh R, Gupta V, Singh S, Gupta A. Successful treatment of hypertrophic pachymeningitis in refractory Wegener’s granulomatosis with rituximab. Clin Rheumatol 2009 Oct 3. [Epub ahead of print] This is a report of a patient with refractory Wegener’s granulomatosis (WG) with CNS involvement which responded to rituximab. The patient presented with nodular scleritis. Three months later, she developed headache, vision loss with complete ophthalmoplegia, and relative afferent papillary defect. MRI of the brain showed thickened dura along anterior temporal region and enlargement of right cavernous sinus. C ANCA and PR 3 ELISA were positive. Non-contrast CT scan of orbit and paranasal sinuses showed soft tissue swelling of the right orbit along with mucosal thickening of right maxillary sinus. HRCT of the thorax revealed bilateral upper lobe nodules. She responded to 3 days of methylprednisolone pulses and 1 g pulse cyclophosphamide but had multiple relapses while receiving high dose oral steroids and pulse cyclophosphamide. She was then given four infusions of rituximab (375 mg/m2) at weekly intervals following which she had complete remission. She relapsed after 6 months but responded to repeat rituximab infusion. 5. Gambhir D, Lawrence A, Aggarwal A, Misra R, Mandal SK, Naik S. Association of tumor necrosis factor alpha and IL-10 promoter polymorphisms with rheumatoid arthritis in North Indian population. Rheumatol Int 2009 Sep 25. [Epub ahead of print] The authors studied the association between promoter polymorphisms of TNF alpha and IL-10 gene with susceptibility, age of disease onset and disease severity in North Indian patients with rheumatoid arthritis (RA). SNPs at position −308 and −863 of TNF gene and −819/ −592 and −1082 position of IL-10 gene were determined in 222 patients and 208 healthy controls using RFLP or ARMS method. Polymorphism TNF −308A was less prevalent among the patients (1.7%) than controls (4.9%, OR: 0.32, 95% CI: 0.13−0.76). Among female patients, IL-10 −592A allele associated with higher baseline disease activity scores (5.77 +/− 1.99) than −592C (5.57 +/− 1.19; P = 0.04). Female patients carrying allele A of TNFalpha −863 had earlier age of onset of RA (33.99 + /− 9.6 years) than those with allele C (36.15 + /− 11.21 years; P = 0.043). The authors conclude that allele A at TNF alpha -308 locus provides protection against RA in North Indian population while another TNF allele A at −863 position had weak association with earlier onset of disease in female patients. On the other
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hand promoter polymorphisms of IL-10 did not affect susceptibility but polymorphism at −819/−592A was associated with higher disease activity scores at baseline. This study provides valuable insights into the genetic predisposition to RA and its SNP correlates. 6. Sharma A, Kumar S, Wanchu A, Sharma K, Sharma N, Singh R, Bambery P, Singh S, Varma S. Clinical characteristics and predictors of mortality in 67 patients with primary pyomyositis: a study from North India. Clin Rheumatol 2009 Sep 8. [Epub ahead of print] This was a retrospective study in which patients admitted with the diagnosis of primary pyomyositis from January 2000 to June 2007 were included. Their demographic details, clinical and laboratory data, Sequential Organ Failure Assessment (SOFA) score at presentation, treatment instituted, complications encountered, and hospital outcome were recorded. Sixty-seven patients (42 males and 25 females) were included. Median age at the time of presentation was 37 years (interquartile range = 25−50 years). Common presenting symptoms were myalgias [50 (74.62%)] and fever [49 (73.13%)]. Twenty-six patients had underlying predisposing medical conditions. The commonest muscle group involved was iliopsoas in 31 (46.26%) patients. Methicillin-sensitive Staphylococcus aureus was the commonest organism isolated from the pus. Twenty-eight patients developed sepsis and seven died. On univariate analysis, there was a statistically significant association between higher SOFA score, lower Glasgow coma scale, higher pulse rate, lower blood pressure, raised blood urea, raised serum creatinine, higher serum glutamic pyruvate transaminase, raised total bilirubin at presentation, and development of sepsis during hospital stay with mortality. This study is the largest case series of pyomyositis from India. The authors have highlighted the clinical features and predictors of mortality in these patients. As expected, Staphylococci were the commonest organisms isolated from pus and features suggestive of organ dysfunction and sepsis predicted mortality. 7. Rajasekhar L, Habibi S, Sudhakar P, Gumdal N. Lymphatic obstruction as a cause of extremity edema in systemic lupus erythematosus. Clin Rheumatol 2009 Sep 1. [Epub ahead of print] The authors report lymphatic obstruction involving all four limbs as a cause of extremity edema in a patient with SLE. Lymphedema has previously not been reported in SLE. 8. Gupta R, Thabah MM, Gupta S, Shankar S, Kumar A. Clinical significance of antiphospholipid antibodies in Indian scleroderma patients. Rheumatol Int 2009 Aug 23. [Epub ahead of print]
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Indian Journal of Rheumatology 2009 December; Vol. 4, No. 4
This study was undertaken to assess the prevalence of antiphospholipid antibodies in Indian SSc patients and to correlate them with clinical and immunological features. Seventy-two patients were recruited prospectively from 2002 to 2006. Nineteen patients had diffuse cutaneous SSc and 53 had limited disease. Seven patients (9.7%) were positive for aPL antibodies in their sera. Only one
Arya
patient had clinical features of antiphospholipid antibody syndrome and manifested with recurrent abortions and deep vein thrombosis. She was positive for aCL, LA and anti-beta2 glycoprotein-I antibodies. Four patients were only aCL (IgG) positive in moderate titres and one each had only aCL (IgM) and LAC positivity. None of the clinical parameters showed an association with aPL antibody.
PG Forum
International publications of interest from India (September–November 2009) V Arya
1. Sharma NL, Mahajan VK, Ranjan N, Sharma VC, Gupta M. Systemic sclerosis sine scleroderma and calcinosis cutis: report of a rare case. Clin Rheumatol 2009 Oct 17. [Epub ahead of print] The authors describe a 17-year-old girl with systemic sclerosis sine scleroderma who was diagnosed initially as seronegative juvenile rheumatoid arthritis. She developed progressively increasing disc-like masses of calcinosis over the gluteal regions, knee, elbow, and ankle joints fixed to the overlying skin associated with malaise, anorexia, and weight loss. There was no Raynaud’s phenomenon, dysphagia, dyspnoea, sclerodermatous skin, sclerodactyly, telangectasias, or muscle tenderness/weakness. Digital pitted scars, elevated anticentromere antibody values, esophageal hypomotility, and fluffy calcification in subdermal soft tissues in gluteal regions and around wrist, hip, knees, heels, and ankle joints (without affecting the underlying structures) were detected. Therapy with diltiazem and magnesium/aluminum antacids was useful in resolving calcinosis. This case highlights a rare presentation of scleroderma. 2. Dhir V, Lawrence A, Aggarwal A, Misra R. Fibromyalgia is common and adversely affects pain and fatigue perception in North Indian patients with Rheumatoid Arthritis. J Rheumatol 2009 Oct 15. [Epub ahead of print] This cross-sectional study was aimed at assessing the prevalence and effects of fibromyalgia (FM) in North Indian patients with RA and associations of RA with disease activity. The study included 200 RA patients and an equal number of controls. FM was present in 15% of patients with RA compared to 2.5% of controls. RA patients with FM did not differ from those without FM in terms of age, gender, current disease-modifying agents,
or steroid use. RA patients with FM had higher disease activity and worse functional disability. The number of tender and swollen joints was higher in patients with FM, but correlated poorly with each other. RA patients with FM had higher pain and fatigue scores but were not different in the quality of life or mood. This study addresses a neglected aspect of rheumatoid arthritis: co-existing fibromyalgia and its adverse impact on RA. 3. Gupta R, Deepanjali S, Kumar A, Dadhwal V, Agarwal SK, Pandey RM, Chaturvedi PK. A comparative study of pregnancy outcomes and menstrual irregularities in northern Indian patients with systemic lupus erythematosus and rheumatoid arthritis. Rheumatol Int 2009 Oct 14. [Epub ahead of print] The authors designed this study to evaluate the menstrual, fertility, and pregnancy outcomes in patients with systemic lupus erythematosus compared to those with rheumatoid arthritis (RA) and also to study the effect of cyclophosphamide therapy on menstrual cycles in patients with SLE. Four hundred and twenty patients with SLE (210) and RA (210) were interviewed using a standard questionnaire and available medical records used. After disease-onset, the chances of adverse pregnancy outcomes were significantly more in patients with SLE compared to RA [OR = 5.17 (2.13–12.52); P ≤ 0.001]. Compared to the National average in India, the average number of living children is lesser in patients with RA (2.39 + /− 1.39, P = 0.002), and in patients with SLE (1.44 + /− 1.35, P = 0.001). A younger age at diagnosis and cyclophosphamide therapy were found to be independently associated with menstrual irregularities after disease-onset. This study explores an important aspect in patients with SLE and RA – pregnancy outcomes and menstrual abnormalities. Since these diseases are predominantly seen in women, this study reminds us to pay
Department of Medicine, PGIMER and Dr. R.M.L. Hospital, New Delhi, India.
International publications of interest from India
attention to the gynaecological and obstetric issues encountered in this patient population. 4. Sharma A, Kumar S, Wanchu A, Lal V, Singh R, Gupta V, Singh S, Gupta A. Successful treatment of hypertrophic pachymeningitis in refractory Wegener’s granulomatosis with rituximab. Clin Rheumatol 2009 Oct 3. [Epub ahead of print] This is a report of a patient with refractory Wegener’s granulomatosis (WG) with CNS involvement which responded to rituximab. The patient presented with nodular scleritis. Three months later, she developed headache, vision loss with complete ophthalmoplegia, and relative afferent papillary defect. MRI of the brain showed thickened dura along anterior temporal region and enlargement of right cavernous sinus. C ANCA and PR 3 ELISA were positive. Non-contrast CT scan of orbit and paranasal sinuses showed soft tissue swelling of the right orbit along with mucosal thickening of right maxillary sinus. HRCT of the thorax revealed bilateral upper lobe nodules. She responded to 3 days of methylprednisolone pulses and 1 g pulse cyclophosphamide but had multiple relapses while receiving high dose oral steroids and pulse cyclophosphamide. She was then given four infusions of rituximab (375 mg/m2) at weekly intervals following which she had complete remission. She relapsed after 6 months but responded to repeat rituximab infusion. 5. Gambhir D, Lawrence A, Aggarwal A, Misra R, Mandal SK, Naik S. Association of tumor necrosis factor alpha and IL-10 promoter polymorphisms with rheumatoid arthritis in North Indian population. Rheumatol Int 2009 Sep 25. [Epub ahead of print] The authors studied the association between promoter polymorphisms of TNF alpha and IL-10 gene with susceptibility, age of disease onset and disease severity in North Indian patients with rheumatoid arthritis (RA). SNPs at position −308 and −863 of TNF gene and −819/ −592 and −1082 position of IL-10 gene were determined in 222 patients and 208 healthy controls using RFLP or ARMS method. Polymorphism TNF −308A was less prevalent among the patients (1.7%) than controls (4.9%, OR: 0.32, 95% CI: 0.13−0.76). Among female patients, IL-10 −592A allele associated with higher baseline disease activity scores (5.77 +/− 1.99) than −592C (5.57 +/− 1.19; P = 0.04). Female patients carrying allele A of TNFalpha −863 had earlier age of onset of RA (33.99 + /− 9.6 years) than those with allele C (36.15 + /− 11.21 years; P = 0.043). The authors conclude that allele A at TNF alpha -308 locus provides protection against RA in North Indian population while another TNF allele A at −863 position had weak association with earlier onset of disease in female patients. On the other
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hand promoter polymorphisms of IL-10 did not affect susceptibility but polymorphism at −819/−592A was associated with higher disease activity scores at baseline. This study provides valuable insights into the genetic predisposition to RA and its SNP correlates. 6. Sharma A, Kumar S, Wanchu A, Sharma K, Sharma N, Singh R, Bambery P, Singh S, Varma S. Clinical characteristics and predictors of mortality in 67 patients with primary pyomyositis: a study from North India. Clin Rheumatol 2009 Sep 8. [Epub ahead of print] This was a retrospective study in which patients admitted with the diagnosis of primary pyomyositis from January 2000 to June 2007 were included. Their demographic details, clinical and laboratory data, Sequential Organ Failure Assessment (SOFA) score at presentation, treatment instituted, complications encountered, and hospital outcome were recorded. Sixty-seven patients (42 males and 25 females) were included. Median age at the time of presentation was 37 years (interquartile range = 25−50 years). Common presenting symptoms were myalgias [50 (74.62%)] and fever [49 (73.13%)]. Twenty-six patients had underlying predisposing medical conditions. The commonest muscle group involved was iliopsoas in 31 (46.26%) patients. Methicillin-sensitive Staphylococcus aureus was the commonest organism isolated from the pus. Twenty-eight patients developed sepsis and seven died. On univariate analysis, there was a statistically significant association between higher SOFA score, lower Glasgow coma scale, higher pulse rate, lower blood pressure, raised blood urea, raised serum creatinine, higher serum glutamic pyruvate transaminase, raised total bilirubin at presentation, and development of sepsis during hospital stay with mortality. This study is the largest case series of pyomyositis from India. The authors have highlighted the clinical features and predictors of mortality in these patients. As expected, Staphylococci were the commonest organisms isolated from pus and features suggestive of organ dysfunction and sepsis predicted mortality. 7. Rajasekhar L, Habibi S, Sudhakar P, Gumdal N. Lymphatic obstruction as a cause of extremity edema in systemic lupus erythematosus. Clin Rheumatol 2009 Sep 1. [Epub ahead of print] The authors report lymphatic obstruction involving all four limbs as a cause of extremity edema in a patient with SLE. Lymphedema has previously not been reported in SLE. 8. Gupta R, Thabah MM, Gupta S, Shankar S, Kumar A. Clinical significance of antiphospholipid antibodies in Indian scleroderma patients. Rheumatol Int 2009 Aug 23. [Epub ahead of print]
178
Indian Journal of Rheumatology 2009 December; Vol. 4, No. 4
This study was undertaken to assess the prevalence of antiphospholipid antibodies in Indian SSc patients and to correlate them with clinical and immunological features. Seventy-two patients were recruited prospectively from 2002 to 2006. Nineteen patients had diffuse cutaneous SSc and 53 had limited disease. Seven patients (9.7%) were positive for aPL antibodies in their sera. Only one
Arya
patient had clinical features of antiphospholipid antibody syndrome and manifested with recurrent abortions and deep vein thrombosis. She was positive for aCL, LA and anti-beta2 glycoprotein-I antibodies. Four patients were only aCL (IgG) positive in moderate titres and one each had only aCL (IgM) and LAC positivity. None of the clinical parameters showed an association with aPL antibody.