|Year : 2020 | Volume
| Issue : 5 | Page : 2-5
Spondyloarthritis in India
Anand N Malaviya
Department of Rheumatology, ISIC Superspecialty Hospital, Vasant Kunj, New Delhi, India
|Date of Web Publication||23-May-2020|
Prof. Anand N Malaviya
Flat 2015, Sector B.2, Vasant Kunj, New Delhi - 110 070
Source of Support: None, Conflict of Interest: None
Spondyloarthritis (SpA) is a family of systemic inflammatory rheumatic diseases that have been extensively reported and studied from India over the last >4 decades. The epidemiological studies estimate the prevalence of SpA to be 7–9 per 10,000 persons. There are a number of studies describing the clinical features of the different subsets of SpA showing the presence of all the clinical subtypes of SpA. Long-term follow-up studies are also available showing the variable progression of these subtypes. HLA-B27 and its subtypes are reported from India; its frequency in the Indian population is ~6% but >90% in ankylosing spondylitis (AS) with decreasing frequencies in other subtypes of SpA. The association of B*27:05 and B*27:04 with AS and SpA family of diseases has been confirmed in several studies. There have been several publications related to the immunopathogenesis of SpA showing evidence of sensitization to antigen fragments of enterobacteria leading to the perturbations in the innate and acquired immune system causing the diseases. “Slipped disc” and “tuberculosis” are the two most common misdiagnoses made by nonrheumatologists. An important observation was a steady decrease in the male: female ratio from 16 to 18:1 reported in the 1980s and 1990s down to 3:1 in most recent reports. This is likely to be due to increasing awareness and recognition of female SpA. An important observation has been a significantly higher proportion of peripheral arthritis reported among Indian axial SpA (axSpA) patients. It could be due to environmental exposure causing reactive arthritis type of onset that evolves into clinically recognizable SpA over time. In recent years, the reports on nonradiographic and radiographic axSpA categories have also appeared with similarities to that reported from the Western countries. This category showed the lowest male:female ratio (1.2:1) indicative of a much higher proportion of females in the nonradiographic axSpA category. The specific features related to the management were the widespread use of sulfasalazine for axSpA and much less use of biologicals, most likely due to financial reasons, in India.
Keywords: Ankylosing spondylitis, axial spondyloarthritis, India, peripheral spondyloarthritis, spondyloarthritis, undifferentiated spondyloarthritis
|How to cite this article:|
Malaviya AN. Spondyloarthritis in India. Indian J Rheumatol 2020;15, Suppl S1:2-5
| Introduction|| |
Spondyloarthritis (SpA) is a common inflammatory rheumatic disease in India, second only to rheumatoid arthritis (RA). The prevalence of SpA is linked to the prevalence of HLA-B27 in that population. Prevalence of HLA-B27 in India being ~6%, SpA is a common rheumatic disease in the country. This “Introductory” article summarizes a number of publications from India from 1970s onward covering the various aspects of the disease seen in adults including the clinical characteristics of ankylosing spondylitis (AS), broad category of seronegative SpA, certain specific features of the disease as seen in India; HLA-B27 in normal and in AS, SpA and its subtypes, the subtypes of HLA-B27 in the Indian population, genetic studies on non-HLA genes, and basic studies in its causation.
| Early Reports from India (The Late 1970s to 1980s) – spondyloarthritis, Unclassifiable (Undifferentiated) Spondyloarthritis, and HLA-B27 Status|| |
Detailed literature search (of the mainstream journals) did not find any publications on AS or SpA from India till 1977 when workers at PGIMER, Chandigarh, reported “HLA-B27 in AS in India.” However, the first report of the clinical characteristics of AS from India was in 1979 with the publication of two articles by the author's group from AIIMS, New Delhi., The first Indian report on patients with AS using the Rome criteria was published in 1984 by our group from AIIMS, New Delhi.
| HLA Status in Earlier Studies on Spondyloarthritis|| |
As already mentioned, the first report on HLA-B27 in AS was in 1977 from PGIMER, Chandigarh, with a 94% positivity rate. This was followed by two reports from our group in 1979 on patients with the broad group of “seronegative SpA.”, These two reports included not only AS but also other members of the SpA family e.g. Reiter's disease, psoriatic arthritis (PsA), “unclassifiable” group, along with some “disease controls” (Behcet's disease, inflammatory bowel disease (IBD)-related arthritis, reactive arthritis, RA with associated features of inflammatory back pain since childhood, nonspecific back pain) and some normal controls. The frequency of HLA-B27 was 74% and 87.5%, respectively. In the 1983 publication of the “unclassifiable” SpA, the frequency of HLA-B27 was 84% as against 6% in normal controls. These studies showed the frequency HLA-B27 to be the highest in patients with AS (~95%) but the frequency of HLA-B27 was much less in other diseases within the “SpA” family (e.g., only ~50% in PsA). These reports also established the frequency of HLA-B27 in normal controls in northern India to be ~6%, which is similar to that of the Western European population. In 1996, rheumatologists from Chennai also reported results on 177 patients with AS with an 86% positivity of HLA-B27. In summary, these early reports from different parts of India established that HLA-B27 positivity in patients with AS is high (80%–90%), almost similar to that reported in the Caucasian population.
| Axial Spondyloarthritis Reports in the 1990s|| |
In 1990, Achuthan et al. and, in 1994, Chandrasekaran et al. reported on the Indian patients with AS about the radiographic sacroiliitis and clinical spectrum. The age of onset of the symptoms was 26.4 years, with a male: female ratio of 18.7:1, highest ever reported.
In 1995, our group from AIIMS, New Delhi, reported the clinical and radiographic features in HLA-B27-positive persons (39 males and 25 females) having “unclassifiable” SpA; 92% of females and 74% of males had inflammatory back pain, clearly indicating that the disease is prevalent in females.
| Recent Reports: Before and After Publication of the 2009 Assessment of Spondyloarthritis International Society Classification Criteria for Axial Spondyloarthritis|| |
In 2009, our group restudied the clinical features of AS-SpA and the reasons for the delay in diagnosis using the modified-New York criteria., In the absence of any report on axial SpA (axSpA) using the 2009 Assessment of Spondyloarthritis International Society (ASAS) criteria, in 2014, we restudied 288 patients classifiable as axSpA using the ASAS criteria. The results were presented recently. One hundred and eighty-seven of the 288 patients had AS (mNY criteria). Another 101 remaining patients could, however, be classified as nonradiographic axSpA (nr-axSpA) using ASAS criteria. The male-to-female ratio was only 3.75:1, very different than the earlier reports using the mNY criteria. In this study the baseline disease activity, functional status and the spinal damage were reported using validated instruments namely 'Bath Ankylosing Spondylitis Disease Activity Index' (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Functional Index (BASFI) and the Bath Ankylosing Spondylitis Metrology Index (BASMAI); these values were 3.5, 2.86 and 2, respectively. As already mentioned, peripheral arthritis was much more common when compared to the Western figures. Acute anterior uveitis was the most common extra-articular feature, present in 25%–30%.
| Comparison of Patients With Ankylosing Spondylitis (Mny Criteria) and Nonradiographic Axial Spondyloarthritis (Assessment of Spondyloarthritis International Society Criteria) from India|| |
The author's group at the ISIC Super Speciality Hospital in Delhi reported on a comparison between patients with AS (radiographic, mNY criteria) and nr-axSpA (ASAS criteria)., A longer disease duration, onset with axial and sacroiliac joint (SIJ) symptoms, male predominance, predominant axial involvement, higher BASMI, and more syndesmophytes were noted in AS patients. Other parameters including age of onset, delay in diagnosis, BASDAI, BASFI, ASDAS, Maastricht AS Enthesitis Score, erythrocyte sedimentation rate, C-reactive protein, and HLA-B27 status showed no statistically significant difference between these two groups.
| Characteristics of the Isolated Peripheral Arthritis of Spondyloarthritis Without Axial Involvement|| |
The peripheral involvement in axial SpA has been mentioned in several studies. Most of these include psoriatic, inflammatory bowel-related, and reactive arthritis. However, there is very little known about “pure” peripheral arthritis in patients with SpA and no axial involvement and no evidence of psoriasis, IBD, or reactive arthritis. Recently, we published details of this category of SpA. In a total of 405 patients with SpA, 25 (6.2%) had this form of peripheral SpA. The male-to-female ratio was 2.6:1; the pattern of involvement was predominantly lower extremity asymmetrical large joint oligoarthritis in persons below the age of 40 years (60% were <30 years of age). Some had soft-tissue and/or extra-articular manifestations characteristic of SpA (36%) and family history (20%) of SpA spectrum of diseases. When compared to peripheral arthritis reported in axial axSpA/AS, root/central joint involvement was minimal in peripheral SpA.
| Other Diseases of the Spondyloarthritis Family|| |
The first publication on PsA from India was in 1984 by our group  from AIIMS, New Delhi, and from Chennai., In general, the clinical profile conformed to what is reported in the literature, i.e., disease of young-middle age, with slight preponderance of males, psoriasis antedating arthritis (mean interval of ~2.5 years) in ~50%–60%, polyarticular presentations varied in different studies from 25% to 98%, mono/oligoarticular enthesopathic SpA 1.8%–50% (HLA-B20 50%–60%), distal interphalangeal joint 2%–4%, and mutilans pattern seen in <1%–12.7%. Only 25% showed the involvement of SIJs. The joints involved were most of the small and large joints in the extremities, asymmetrically.
In another study of 141 patients with PsA using theClassification Criteria for Psoriatic Arthritis (CASPER) criteria from southern India, SpA was reported in 29 (20.6%).
Our group was the first in India to describe 36 patients with Reiter's syndrome in 1983. The following clinical features were recorded: male: female ratio of 4:1 and median duration at presentation in males and females of 5.5 and 6.5 years, respectively. The median age of onset was 24 and 28 years in males and females, respectively. The disease onset was in the second and third decades of life in 75%. Inflammatory back pain was reported in 69%, mono- or oligoarthritis mainly affecting large joints in the lower extremities with significant asymmetry in 83%.
Inflammatory bowel disease-associated arthritis
In 2012, the Indian Society of Gastroenterology (ISG) Task Force reported on the clinical spectrum of IBD. Arthralgia/arthritis was reported in 33% of 745 patients with ulcerative colitis (UC) and 26% of 409 Crohn's disease (CD) patients. Back pain was reported in 31% and 36% of UC and CD, respectively, but its character was not described. Pokharna et al. from Bikaner reported 46 patients with UC among whom there was 1 patient with peripheral arthritis and anterior ileitis in 2 patients.
Acute anterior uveitis
Mehra et al. from AIIMS, Delhi, reported that the most frequent HLA phenotype in AS/SpA-associated uveitis in Indian patients was A9-B27. This was in contrast to the American Caucasians and African Americans in whom uveitis was associated with A2-B27 phenotype. Another report on 89 patients with endogenous uveitis (80 with acute anterior uveitis) showed the presence of HLA-B27 in 56.3%.
| Immunological and Immunopathological Studies on Axial Spondyloarthritis from India|| |
After a few rather rudimentary studies in the 1980s and 1990s, further evidence on the immunology of SpA had been reported from across India.,,,, The results can be encapsulated as follows: demonstration of fragments of antigens (lipoproteins) related to several Gram-negative bacteria and Salmonella More Details genus-specific DNA, novel peptides having similarities with outer membrane proteins from arthritogenic bacteria bound to HLA-B*27.05, in the joint of the patients; antigen-specific lymphoproliferative responses against enteric bacteria; innate immune gene dysregulation involvement in antigen presentation; scavenger function, chemotaxis, and possible activation of the toll-like receptors (TLRs) by endogenous ligands causing persistence of the disease even in the absence of infection; studies of endogenous ligands for TLR4; absence of specific polymorphisms in TLR2 and TLR4 among these patients; upregulation of TLRs and their adaptors that may lead to uncontrolled inflammation and tissue injury; stimulation of TLRs on binding with their ligands causing increased pro-inflammatory cytokines; and matrix metalloproteinases by fibroblast-like synoviocytes from the synovial fluid of children.
| Disease Associations With HLA-b27 Subtypes|| |
As already discussed, there is a strong association of AS/SpA with HLA-B27 subtypes.,, Additionally, a report dorm Delhi has also reported a higher relative risk of some additional antigens including A11, Aw30, A28, Bw63, Bw41, B37 and Bw35 have been reported from Delhi. Southern Indian patients with AS showed a predominant association with B*27:05 and B*27:04. In summary, the most AS-associated B27 subtypes in Asian Indians are B*27:05, B*27:02, B*27:04, and B*27:07. In Indian patients with PsA, HLA-B27 has been reported to be 11.3%, a figure that is lower than 19%–30% reported from other regions of the world.,
| Conclusion|| |
Although earlier studies showed a variable presentation of SpA in India, recent studies show more concordance with a Western population with few uncommon manifestations. It becomes imperative for future researchers to review the genetics and clinical profile with newer imaging modalities to understand the evolution of SpA.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Malaviya AN, Singh RR, Kapoor SK, Sharma A, Kumar A, Singh YN. Prevalence of rheumatic diseases in India: Results of a population survey. Jour Ind Rheumatol Assoc 1994;2:13-7.
Malaviya AN, Sawhney S, Mehra NK, Kanga U. Seronegative arthritis in South Asia: An up-to-date review. Curr Rheumatol Rep 2014;16:413.
Sengupta S, Sehgal S, Aikat BK, Deodhar SD, James DC. HLA B27 in ankylosing spondylitis in India. Lancet 1977;1:1209-10.
Malaviya AN, Mehra NK, Adhar GC, Jindal K, Bhargava S, Batta RK, et al
. HLA B27 in patients with seronegative spondarthritis. J Rheumatol 1979;6:413-6.
Malaviya AN, Mehra NK, Adhar GC, Jindal K, Bhargava S, Batta RK, et al
. The clinical spectrum of HLA-B27 related rheumatic diseases in India. J Assoc Physicians India 1979;27:487-92.
Prakash S, Mehra NK, Bhargava S, Vaidya MC, Malaviya AN. Ankylosing spondylitis in India. Ann Rheum Dis 1984;43:381-5.
Khan MA. Update on spondyloarthropathies. Ann Intern Med 2002;136:896-907.
Madhavan R, Chandrasekaran AN, Parthiban M, Achutan K, Porkodi R, Rajendran CP. HLA profile of seronegative spondyloarthropathies in a referral hospital in South India. J Ind Rheumatol Assoc 1996;4–3:91-5.
Achuthan K, Porkodi R, Ramakrishnan S, Krishnamurthy V, Madhavan R, Parthiban M, et al
. Pattern of rheumatic diseases in south India. V. Ankylosing spondylitis. A clinical and radiological study. J Assoc Physicians India 1990;38:774-6.
Chandrasekaran AN, Porkodi R, Achutan K, Madhavan R, Parthiban M. Spectrum of clinical and immunological features of systemic rheumatic disorders in a referral hospital in south India: Primary ankylosing spondylitis. J Ind Rheumatol Assoc 1994;2-4:149-52.
Uppal SS, Pande I, Singh G, Kailash S, Kakker R, Kumar A, et al
. Profile of HLA-B27-related 'unclassifiable' seronegative spondyloarthropathy in females and its comparison with the profile in males. Br J Rheumatol 1995;34:137-40.
Aggarwal R, Malaviya AN. Clinical characteristics of patients with ankylosing spondylitis in India. Clin Rheumatol 2009;28:1199-205.
Aggarwal R, Malaviya AN. Diagnosis delay in patients with ankylosing spondylitis: Factors and outcomes—an Indian perspective. Clin Rheumatol 2009;28:327-31.
Malaviya AN Rawat R, Gogia SB, Arya V. Axial-spondyloarthritis (ax-SpA) from single rheumatology clinic in New Delhi-I: Demography, HLA B27 status, spinal indices, delay in diagnosis and classification. Ind Jour Rheumatol 2014;9 (suppl 1):S47-8.
Malaviya AN, Kalyani A, Rawat R. Is radiographic axial SpA a distinct subset with more severe axial involvement? Comment on the article by Deodhar et al
. Arthritis Rheumatol 2015;67:856.
Malaviya AN, Kalyani A, Rawat R, Gogia SB. Comparison of patients with ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA) from a single rheumatology clinic in New Delhi. Int J Rheum Dis 2015;18:736-41.
Malaviya AN, Agrawal N, Patil NS. Clinical characteristics of peripheral spondyloarthritis without psoriasis, inflammatory enteropathy or preceding infection, from a single rheumatology clinic in northern India. Clin Rheumatol 2017;36:2613-8.
Malaviya AN, Dasgupta B, Tiwari SC, Khan KM, Pasricha JS, Mehra NK. Psoriatic arthritis: A clinical and immunological study in 20 cases from India. J Assoc Physicians Ind 1984;32:403-5.
Rajendran CP, Ledge SG, Rani KP, RadhaMadhavan R. Psoriatic arthritis. J Assoc Physicians Ind 2003;51:1065-8.
Shah NM, Mangat G, Balakrishnan C, Joshi VR. Psoriatic arthritis-A study of 102 patients. J Indian Rheumatol Assoc 1995;3:133-6.
Mithun CB, Antony PT, Mariaselvam CM, Negi VS. Clinical and immunogenetic characteristics of psoriatic arthritis: A single-centre experience from South India. Internet J Rheumatol Clin Immunol 2013;1:OA1.
Prakash S, Mehra N, Bhargava S, Malaviya A. Reiter's disease in north India: A clinical and immunogenetic study. Rheumatol Int 1983;3:101-4.
Makharia GK, Ramakrishna BS, Abraham P, Choudhuri G, Misra SP, Ahuja V, et al
. Survey of inflammatory bowel diseases in India. Indian J Gastroenterol 2012;31:299-306.
Pokharna RK, Kabra PK, Sharma R, Kochar DK. Extraintestinal manifestations of idiopathic ulcerative colitis in northwestern India. Indian J Gastroenterol 2004;23:89-90.
] [Full text]
Mehra NK, Khan MA, Vaidya MC, Malaviya AN, Batta RK. HLA antigens in acute anterior uveitis and spondyloarthropathies in Asian Indians and their comparison with American whites and blacks. J Rheumatol 1983;10:981-4.
Mishra MN, Bharucha KM. HLA-B27 association with uveitis in an Asian Indian population. Iran J Immunol 2011;8:85-9.
Prakash S, Bansal R, Rajagopalan P, Malaviya AN. Immunological studies in seronegative spondyloarthropathies. Br J Rheumatol 1983;22:146-50.
Madhavan R, Porkodi R, Rajendran CP, Chandrasekaran AN, Umadevi KR, Alamelu R. IgM, IgG, and IgA response to enterobacteria in patients with ankylosing spondylitis in southern India. Ann N
Y Acad Sci 2002;958:408-11.
Singh AK, Aggarwal A, Chaurasia S, Misra R. Identification of immunogenic HLA-B*27:05 binding peptides of salmonella outer membrane protein in patients with reactive arthritis and undifferentiated spondyloarthropathy. J Rheumatol 2013;40:173-85.
Myles A, Tuteja A, Aggarwal A. Synovial fluid mononuclear cell gene expression profiling suggests dysregulation of innate immune genes in enthesitis-related arthritis patients. Rheumatology (Oxford) 2012;51:1785-9.
Rahman MT, Myles A, Gaur P, Misra R, Aggarwal A. TLR4 endogenous ligand MRP8/14 level in enthesitis-related arthritis and its association with disease activity and TLR4 expression. Rheumatology (Oxford) 2014;53:270-4.
Myles A, Aggarwal A. Lack of association of single nucleotide polymorphisms in toll-like receptors 2 and 4 with enthesitis-related arthritis category of juvenile idiopathic arthritis in Indian population. Rheumatol Int 2013;33:417-21.
Thomas R, Philip J, Banerjee M. Association of an extended haplotype of HLA class I alleles and their flanking microsatellites with spondyloarthropathies in South Indian patients. Hum Immunol 2006;67:318-23.
Prakash S, Mehra NK, Bhargava S, Malaviya AN. HLA B27 related 'unclassifiable' seronegative spondyloarthropathies. Ann Rheum Dis 1983;42:640-3.
Eder L, Chandran V, Pellet F, Shanmugarajah S, Rosen CF, Bull SB, et al
. Human leucocyte antigen risk alleles for psoriatic arthritis among patients with psoriasis. Ann Rheum Dis 2012;71:50-5.
Brown MA. Genetics of ankylosing spondylitis. Curr Opin Rheumatol 2010;22:126-32.
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