Clinical and experimental rheumatology, Jan 27, 2015
Enthesitis-related arthritis (ERA) is the most common form of juvenile idiopathic arthritis (JIA)... more Enthesitis-related arthritis (ERA) is the most common form of juvenile idiopathic arthritis (JIA) in the Asian and Indian populations. The presence of HLA-B27 has a strong association with JIA-ERA similar to that with adult ankylosing spondylitis (AS). The HLA-B27gene is highly polymorphic. Susceptibility to AS varies between different HLA-B27 subtypes; data on the relationship of susceptibility to JIA-ERA with HLA-B27 types are scant. In this study, we determined HLA-B27 subtypes in patients with JIA-ERA and AS to find out whether there is any difference in the HLA-B27 subtypes prevalent in these two diseases. Genomic DNA from 135 patients with JIA-ERA and 121 with AS was tested for the presence of HLA-B27. In patients testing positive, HLA-B27subtyping was done by sequencing a genomic region that contained second and third exons and the intervening intron of this gene; this method permitted identification of common HLA-B27 subtypes (HLA-B*27:01 to HLA-B*27:09). One hundred and sev...
C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene has been proposed as a... more C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene has been proposed as a pharmacogenomic marker for toxicity of methotrexate (MTX). We studied the relationship between the C677T gene polymorphism and toxicity and efficacy of MTX in patients with rheumatoid arthritis (RA) on folate supplementation. A total of 150 RA patients fulfilling American College of Rheumatology (ACR) criteria and on MTX treatment were evaluated. The mean age of the patients was 42.9 +/- 11.1 yr, mean disease duration was 7.65 +/- 5.2 yr and the mean duration of MTX treatment was 26.1 +/- 20.6 months. Genotype analysis of MTHFR gene was done by PCR and restriction enzyme method. Primary endpoint for treatment efficacy was change in disease activity score 28 (DAS28) from baseline. Drug toxicity was evaluated by blood count, renal and liver function tests and a standardized questionnaire. The mean DAS at baseline was 5.02 +/- 0.8. All patients received 10 mg/wk folic acid supplementation....
Background Data on outcome of ERA is scarce and there is lack of well-accepted tools. JADI is a n... more Background Data on outcome of ERA is scarce and there is lack of well-accepted tools. JADI is a newly described outcome measure in JIA that has not been evaluated in ERA. We studied outcome in ERA using JADI and correlated it with traditional outcome measures. Methods We studied 49 consecutive patients of ERA with age ≥ 5 years and duration ≥ 1 year. Along with JADI, we recorded enthesitis, lumbar spinal anterior flexion by modified Schober's method, presence of inflammatory backache, loss of school years, HAQ-S, growth and pubertal delay. Parent's/patient's and physician's global assessments on 100 mm visual analogue scale. Results The median age was 18.0 (10–27) years and the median duration of disease was 6.0 (1–17) years. All the patients were male and half (53.1%) were HLA B 27 positive. Fourteen had decreased anterior lumbar flexion movement and 32 had inflammatory backache. Active enthesitis was present in 63.3%. Functionally, mild, moderate and severe disabil...
Lymphomatoid granulomatosis (LG) is a rare systemic vasculitis caused by Epstein Barr virus induc... more Lymphomatoid granulomatosis (LG) is a rare systemic vasculitis caused by Epstein Barr virus induced transformation of the B-cells in a T-cell rich environment. The predominant clinical presentations are confined to the pulmonary system however; extra-pulmonary manifestations can sometimes be the main feature of the disease. Here in we describe a 52-year-old female who presented with symmetric polyarthritis and generalized stiffness for 7 months and papular lesions over extremities for 3 months duration. She in addition had generalized lymphadenopathy. Histopathological examination of the cutaneous lesions confirmed LG. Patient died despite therapy with cyclophosphamide and prednisolone. This is the first report of LG mimicking rheumatoid arthritis from India.
Rheumatology Principles & Practice, a comprehensive rheumatology textbook, edited by Dr Ashit Syn... more Rheumatology Principles & Practice, a comprehensive rheumatology textbook, edited by Dr Ashit Syngle & Dr SD Deodhar . It brings together the academic and clinical experience of more than 60 contributors from across the world. It has been the brain child of Dr Ashit Syngle and the culmination of his three years labor of love. The highlights of the book are: • It covers a range of topics within rheumatology and offers diagnostic and management options. • It is comprehensively illustrated with original photos and contains algorithms and multiple choice questions. • A unique interactive DVD supplements the book It is an ideal book for graduate and post graduate medical students, interns, physicians, orthopaedicians, dermatologists, ophthalmologists, paediatricians, practitioners, physiotherapists, researchers and a valuable asset for libraries.
Conventional radiologic modalities provide details only about the anatomic aspect of the various ... more Conventional radiologic modalities provide details only about the anatomic aspect of the various structures of the spine. Frequently the structures that show abnormal morphology may not be the cause of low back pain (LBP). Functional imaging in the form of bone scan along with single photon emission computerized tomography (SPECT/CT) may be helpful in identifying structures causing pain, whether morphologically normal or not. The objective of this study is to evaluate the role of bone scan with SPECT/CT in management of patients with LBP. This is randomized double-blinded controlled study performed on 80 patients with LBP aged 20 to 80 years, ASA physical status I to III. Patients were randomized into bone scan and control groups consisting of 40 patients each. On the basis of the clinical features and radiologic findings a clinical diagnosis was made. After making a clinical diagnosis, the patients in bone scan group were subjected to bone scan with SPECT/CT. On the basis of the finding of the bone scan and SPECT/CT, a new working diagnosis was made and intervention was performed according to the new working diagnosis. Diagnostic blocks in the control group were given based on clinical diagnosis. Controlled comparative diagnostic blocks were performed with local anesthetic. The pain score just after the diagnostic block and at the time of discharge (approximately 4 h later) was recorded; the pain relief was recorded in percentage. In both the groups, sacroilitis was the most common diagnosis followed by facet joint arthropathy. The number of patients obtaining pain relief of >50% was significantly higher in the bone scan-positive group as compared with the control group. Three new clinical conditions were identified in the bone scan group. These conditions were multiple myeloma, avascular necrosis of the femoral head, and ankylosing spondylitis. Bone scan with SPECT/CT was found to complement the clinical workup of patients with LBP. Inclusion of bone scan with SPECT/CT in LBP management protocol can help in making a correct diagnosis. At times it might bring out some new information that may be vital for further management of the patients with LBP.
There is a paucity of data regarding the outcome of pregnancy from the Indian subcontinent. There... more 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.
In chronic arthritis cartilage and bone destruction occur as a consequence of synovial inflammati... more In chronic arthritis cartilage and bone destruction occur as a consequence of synovial inflammation. It is mainly mediated by matrix metalloproteinases and RANKL-OPG pathways. Data on synovial fluid levels of these mediators in enthesitis related arthritis subtype (ERA) of JIA are not available. MMP-1, MMP-3, TIMP, sRANKL and OPG levels were measured in synovial fluid from patients with ERA and compared with other arthritides, polyarticular (Poly) JIA, RA and osteoarthritis (OA). sRANKL was detectable in 25/41 of ERA patients, 4/16 of Poly JIA patients. Median SF sRANKL level in patients with ERA was higher as compared to OA (p < 0.001) and poly JIA (p < 0.05) but were comparable to RA. The median OPG level in ERA was lower as compared to OA (p < 0.001), comparable to RA but was higher than poly JIA (p < 0.001). sRANKL/OPG ratio was significantly higher in ERA and Poly JIA compared to OA (p < 0.0001, p < 0.0001 respectively). The median MMP3 levels in ERA (74 microg/ml) was lower as compared to poly JIA (410 microg/ml; p < 0.0001) and RA (340 ug/ml; p < 0.0001) but was comparable to OA (107 microg/ml). The median level of ProMMP1 in ERA (0.70 microg/ml) was lower as compared to RA (2.9 microg/ml; p < 0.0001) and poly JIA but was elevated as compared to OA patients (0.1 microg/ml; p < 0.0001). TIMP1 levels in ERA were higher than poly JIA and RA patients. MMP3/TIMP1 ratio was lower in ERA compared to polyarticular JIA patients (p < 0.05). Ours is the first study reporting elevated sRANKL and reduced OPG levels and elevated sRANKL/OPG ratio in SF of children with JIA resulting in a mileu associated with bone loss. In addition, ERA patients had lower MMP level as well as MMP/TIMP ratio as compared to poly JIA which may partly explain lesser degree of joint damage seen in ERA as compared to poly JIA.
Anemia in rheumatoid arthritis (RA) is multi-factorial. We studied the prevalence and type of ane... more Anemia in rheumatoid arthritis (RA) is multi-factorial. We studied the prevalence and type of anemia and its correlation with disease variables in RA patients. Among patients with RA anemia was defined as hemoglobin <or= 11 g/dl in females and <or= 12 g/dl in males. Iron-deficiency anemia (IDA) was defined as serum ferritin <or= 50 microg/dl. Disease activity was assessed by modified Disease Activity Score (DAS28). Of the 214 patients (183 females) anemia was found in 151 [70.6% (anemia of chronic disease--ACD in 51.6%, IDA in 48.4%)]. Except 13 all patients with anemia had active disease. mDAS-28 was higher (5.23) in anemic patients as compared to non-anemic patients (3.83; P < 0.005). Further, it was higher in patients with ACD (5.69) as compared to IDA (4.7; P < 0.001). In patients with ACD mDAS-28 had an inverse correlation with hemoglobin (r = -0.258, P < 0.05) and a positive correlation with serum ferritin (r = 0.359, P < 0.001). At 1 year 37.74% of patients with anemia had recovered. Anemia is a frequent extra-articular manifestation in RA. Significant IDA is present in nearly half the patients. Partial response to iron replacement suggests a component of ACD in these patients. Anemic patients with ACD had more active disease as compared with non-anemic patients or those with IDA.
Clinical and experimental rheumatology, Jan 27, 2015
Enthesitis-related arthritis (ERA) is the most common form of juvenile idiopathic arthritis (JIA)... more Enthesitis-related arthritis (ERA) is the most common form of juvenile idiopathic arthritis (JIA) in the Asian and Indian populations. The presence of HLA-B27 has a strong association with JIA-ERA similar to that with adult ankylosing spondylitis (AS). The HLA-B27gene is highly polymorphic. Susceptibility to AS varies between different HLA-B27 subtypes; data on the relationship of susceptibility to JIA-ERA with HLA-B27 types are scant. In this study, we determined HLA-B27 subtypes in patients with JIA-ERA and AS to find out whether there is any difference in the HLA-B27 subtypes prevalent in these two diseases. Genomic DNA from 135 patients with JIA-ERA and 121 with AS was tested for the presence of HLA-B27. In patients testing positive, HLA-B27subtyping was done by sequencing a genomic region that contained second and third exons and the intervening intron of this gene; this method permitted identification of common HLA-B27 subtypes (HLA-B*27:01 to HLA-B*27:09). One hundred and sev...
C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene has been proposed as a... more C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene has been proposed as a pharmacogenomic marker for toxicity of methotrexate (MTX). We studied the relationship between the C677T gene polymorphism and toxicity and efficacy of MTX in patients with rheumatoid arthritis (RA) on folate supplementation. A total of 150 RA patients fulfilling American College of Rheumatology (ACR) criteria and on MTX treatment were evaluated. The mean age of the patients was 42.9 +/- 11.1 yr, mean disease duration was 7.65 +/- 5.2 yr and the mean duration of MTX treatment was 26.1 +/- 20.6 months. Genotype analysis of MTHFR gene was done by PCR and restriction enzyme method. Primary endpoint for treatment efficacy was change in disease activity score 28 (DAS28) from baseline. Drug toxicity was evaluated by blood count, renal and liver function tests and a standardized questionnaire. The mean DAS at baseline was 5.02 +/- 0.8. All patients received 10 mg/wk folic acid supplementation....
Background Data on outcome of ERA is scarce and there is lack of well-accepted tools. JADI is a n... more Background Data on outcome of ERA is scarce and there is lack of well-accepted tools. JADI is a newly described outcome measure in JIA that has not been evaluated in ERA. We studied outcome in ERA using JADI and correlated it with traditional outcome measures. Methods We studied 49 consecutive patients of ERA with age ≥ 5 years and duration ≥ 1 year. Along with JADI, we recorded enthesitis, lumbar spinal anterior flexion by modified Schober's method, presence of inflammatory backache, loss of school years, HAQ-S, growth and pubertal delay. Parent's/patient's and physician's global assessments on 100 mm visual analogue scale. Results The median age was 18.0 (10–27) years and the median duration of disease was 6.0 (1–17) years. All the patients were male and half (53.1%) were HLA B 27 positive. Fourteen had decreased anterior lumbar flexion movement and 32 had inflammatory backache. Active enthesitis was present in 63.3%. Functionally, mild, moderate and severe disabil...
Lymphomatoid granulomatosis (LG) is a rare systemic vasculitis caused by Epstein Barr virus induc... more Lymphomatoid granulomatosis (LG) is a rare systemic vasculitis caused by Epstein Barr virus induced transformation of the B-cells in a T-cell rich environment. The predominant clinical presentations are confined to the pulmonary system however; extra-pulmonary manifestations can sometimes be the main feature of the disease. Here in we describe a 52-year-old female who presented with symmetric polyarthritis and generalized stiffness for 7 months and papular lesions over extremities for 3 months duration. She in addition had generalized lymphadenopathy. Histopathological examination of the cutaneous lesions confirmed LG. Patient died despite therapy with cyclophosphamide and prednisolone. This is the first report of LG mimicking rheumatoid arthritis from India.
Rheumatology Principles & Practice, a comprehensive rheumatology textbook, edited by Dr Ashit Syn... more Rheumatology Principles & Practice, a comprehensive rheumatology textbook, edited by Dr Ashit Syngle & Dr SD Deodhar . It brings together the academic and clinical experience of more than 60 contributors from across the world. It has been the brain child of Dr Ashit Syngle and the culmination of his three years labor of love. The highlights of the book are: • It covers a range of topics within rheumatology and offers diagnostic and management options. • It is comprehensively illustrated with original photos and contains algorithms and multiple choice questions. • A unique interactive DVD supplements the book It is an ideal book for graduate and post graduate medical students, interns, physicians, orthopaedicians, dermatologists, ophthalmologists, paediatricians, practitioners, physiotherapists, researchers and a valuable asset for libraries.
Conventional radiologic modalities provide details only about the anatomic aspect of the various ... more Conventional radiologic modalities provide details only about the anatomic aspect of the various structures of the spine. Frequently the structures that show abnormal morphology may not be the cause of low back pain (LBP). Functional imaging in the form of bone scan along with single photon emission computerized tomography (SPECT/CT) may be helpful in identifying structures causing pain, whether morphologically normal or not. The objective of this study is to evaluate the role of bone scan with SPECT/CT in management of patients with LBP. This is randomized double-blinded controlled study performed on 80 patients with LBP aged 20 to 80 years, ASA physical status I to III. Patients were randomized into bone scan and control groups consisting of 40 patients each. On the basis of the clinical features and radiologic findings a clinical diagnosis was made. After making a clinical diagnosis, the patients in bone scan group were subjected to bone scan with SPECT/CT. On the basis of the finding of the bone scan and SPECT/CT, a new working diagnosis was made and intervention was performed according to the new working diagnosis. Diagnostic blocks in the control group were given based on clinical diagnosis. Controlled comparative diagnostic blocks were performed with local anesthetic. The pain score just after the diagnostic block and at the time of discharge (approximately 4 h later) was recorded; the pain relief was recorded in percentage. In both the groups, sacroilitis was the most common diagnosis followed by facet joint arthropathy. The number of patients obtaining pain relief of >50% was significantly higher in the bone scan-positive group as compared with the control group. Three new clinical conditions were identified in the bone scan group. These conditions were multiple myeloma, avascular necrosis of the femoral head, and ankylosing spondylitis. Bone scan with SPECT/CT was found to complement the clinical workup of patients with LBP. Inclusion of bone scan with SPECT/CT in LBP management protocol can help in making a correct diagnosis. At times it might bring out some new information that may be vital for further management of the patients with LBP.
There is a paucity of data regarding the outcome of pregnancy from the Indian subcontinent. There... more 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.
In chronic arthritis cartilage and bone destruction occur as a consequence of synovial inflammati... more In chronic arthritis cartilage and bone destruction occur as a consequence of synovial inflammation. It is mainly mediated by matrix metalloproteinases and RANKL-OPG pathways. Data on synovial fluid levels of these mediators in enthesitis related arthritis subtype (ERA) of JIA are not available. MMP-1, MMP-3, TIMP, sRANKL and OPG levels were measured in synovial fluid from patients with ERA and compared with other arthritides, polyarticular (Poly) JIA, RA and osteoarthritis (OA). sRANKL was detectable in 25/41 of ERA patients, 4/16 of Poly JIA patients. Median SF sRANKL level in patients with ERA was higher as compared to OA (p < 0.001) and poly JIA (p < 0.05) but were comparable to RA. The median OPG level in ERA was lower as compared to OA (p < 0.001), comparable to RA but was higher than poly JIA (p < 0.001). sRANKL/OPG ratio was significantly higher in ERA and Poly JIA compared to OA (p < 0.0001, p < 0.0001 respectively). The median MMP3 levels in ERA (74 microg/ml) was lower as compared to poly JIA (410 microg/ml; p < 0.0001) and RA (340 ug/ml; p < 0.0001) but was comparable to OA (107 microg/ml). The median level of ProMMP1 in ERA (0.70 microg/ml) was lower as compared to RA (2.9 microg/ml; p < 0.0001) and poly JIA but was elevated as compared to OA patients (0.1 microg/ml; p < 0.0001). TIMP1 levels in ERA were higher than poly JIA and RA patients. MMP3/TIMP1 ratio was lower in ERA compared to polyarticular JIA patients (p < 0.05). Ours is the first study reporting elevated sRANKL and reduced OPG levels and elevated sRANKL/OPG ratio in SF of children with JIA resulting in a mileu associated with bone loss. In addition, ERA patients had lower MMP level as well as MMP/TIMP ratio as compared to poly JIA which may partly explain lesser degree of joint damage seen in ERA as compared to poly JIA.
Anemia in rheumatoid arthritis (RA) is multi-factorial. We studied the prevalence and type of ane... more Anemia in rheumatoid arthritis (RA) is multi-factorial. We studied the prevalence and type of anemia and its correlation with disease variables in RA patients. Among patients with RA anemia was defined as hemoglobin <or= 11 g/dl in females and <or= 12 g/dl in males. Iron-deficiency anemia (IDA) was defined as serum ferritin <or= 50 microg/dl. Disease activity was assessed by modified Disease Activity Score (DAS28). Of the 214 patients (183 females) anemia was found in 151 [70.6% (anemia of chronic disease--ACD in 51.6%, IDA in 48.4%)]. Except 13 all patients with anemia had active disease. mDAS-28 was higher (5.23) in anemic patients as compared to non-anemic patients (3.83; P < 0.005). Further, it was higher in patients with ACD (5.69) as compared to IDA (4.7; P < 0.001). In patients with ACD mDAS-28 had an inverse correlation with hemoglobin (r = -0.258, P < 0.05) and a positive correlation with serum ferritin (r = 0.359, P < 0.001). At 1 year 37.74% of patients with anemia had recovered. Anemia is a frequent extra-articular manifestation in RA. Significant IDA is present in nearly half the patients. Partial response to iron replacement suggests a component of ACD in these patients. Anemic patients with ACD had more active disease as compared with non-anemic patients or those with IDA.
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