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.

Pathogenesis of spondyloarthritis (SpA) is multifactorial and still not understood entirely. The role of genetics including human leukocyte antigen B27 has been investigated extensively, which along with genome-wide association studies has helped us understand and postulate various theories. Environmental factors including gut dysbiosis, mechanical stress, and transduction have been implicated in the pathogenesis. Recently, the interleukin (IL)-17/IL-23 pathway has been major focus due to it being therapeutic target. Herein, we reviewed various recent developments and current concepts in the pathogenesis of SpA.

The association of spondyloarthritis (SpA) with human leukocyte antigen-B*27 (HLA-B*27) is one of the strongest known for a non-monogenic disease. How HLA-B*27 determines the aetiopathogenesis of SpA and disposes toward this group of disease has perplexed rheumatologists for decades. We searched through contemporary bibliographic databases for literature on the link between HLA-B*27 and different SpA, with special emphasis on ankylosing spondylitis. In this review, the structure and function relationship and subtypes of HLA-B*27 are discussed in the context. Then, three hypotheses on the pathological role of HLA-B*27 are presented. The first arthritogenic peptide hypothesis is based on molecular mimicry between the parts of the HLA-B*27 and epitopes of pathogenic Enterobacteriaceae. The second hypothesis is about the misfolding of the HLA-B*27 major chain, leading to endoplasmic reticulum (ER) stress and initiation of inflammation through the unfolded protein response. The third hypothesis deals with the formation of homodimers of the HLA-B*27 major chain on the cell surface, leading to the activation of natural-killer cells through the killer immunoglobulin-like receptors. Furthermore, discussed in the review are the epistatic factors such as ER-associated peptidase-1, role of microbiota, and the concept of autoinflammation in relation to HLA-B*27.

Spondyloarthritis (SpA) is an umbrella term for a group of inflammatory musculoskeletal conditions characterized by predominant involvement of the spine, the lower limb joints, and the entheses. The Assessment of SpA International Society (ASAS) group classifies SpA into axial SpA (axSpA) and peripheral SpA. axSpA was further divided into radiographic SpA and nonradiographic SpA. Classification criteria are meant for research purposes to enroll a homogeneous cohort, unlike diagnostic criteria, which are meant for diagnosing diseases in the community and therefore must include all the heterogeneous manifestations of a disease. Inflammatory low back pain is one of the most important features in history to be elicited in the diagnosis of axSpAs. It should not be used in isolation and always combined with other features of SpA. Magnetic resonance imaging (MRI) is the gold standard and is the only imaging modality capable of detecting both inflammatory and structural changes. A positive MRI finding should be interpreted in the relevant clinical context, and an alternative differential diagnosis for sacroiliitis should be considered if the clinical picture is atypical of SpA. The presence of HLA B 27 in isolation is neither diagnostic of SpAs nor its absence rules out the diagnosis. Erythrocyte sedimentation rate and C-reactive protein are the commonly used biomarkers in SpA but do not always correlate with disease activity. The ASAS criteria have been tested for its validity, though there were concerns regarding its specificity. In this narrative review various criteria available for classifying SpAs have been discussed and their strengths, weaknesses, and usefulness in the diagnosis of SpA in our everyday practice have been appraised . Various referral strategies and usefulness of these criteria and parameters in the Indian context have also been discussed.

The classification, monitoring, and early detection of axial spondyloarthritis poses significant challenges for health-care professionals owing to the etiology of the disorder. As no unique gold standard is set to confirm diagnosis, current practice relies on imaging the sacroiliac joint, focusing on features of inflammatory changes, and structural changes. New innovations and developments have resulted in significant improvements in the imaging of spondyloarthritis and have provided further development in the understanding of the disease. These recent imaging advances and their relevant pitfalls are discussed in this review.

Spondyloarthritis (SpA) comprises a group of related diseases which share similar pathogenesis and clinical manifestations. Although the occurrence of SpA spectrum disorders has been known for some time, it was only in the latter half of the twentieth century that the concept of SpA was formally defined. Advances in radiography and magnetic resonance imaging techniques have led to the development of classification criteria which have aided early diagnosis and effective management. This narrative review summaries the latest developments in our understanding of the concept of SpA.

Uveitis is the inflammation of the middle layer of the eye, the Uvea. Spondyloarthropathies are systemic disorders with common clinical and pathological features. Uveitis is an important and frequent extraarticular manifestation of spondyloarthropathies. Recently, there has been a remarkable enhancement in the management of uveitis with the approval of biologics. This review discusses epidemiology, clinical features and management of uveitis associated with spondyloarthropathies.

Psoriatic arthritis (PsA) is a chronic, systemic inflammatory arthritis with symptoms spanning six domains including peripheral arthritis, enthesitis, dactylitis, axial disease, psoriasis, and nail disease. The classification of disease has been refined over recent years following the development of criteria such as ClASsification of PsA criteria. In addition to classification, treatment options for PsA have continued to expand over recent years, with the development of monoclonal antibody therapies targeting the underlying immunological mediators involved in PsA such as interleukin (IL)-17, tumor necrosis factor-alpha, and IL-23. Therapies have shown that robust treatment in patients, achieving tight disease control, improves outcomes and overall quality of life. This review provides a broad overview of the epidemiology, classification, and treatment of PsA.

Inflammatory bowel disease (IBD) is seen in up to 14% of patients with spondyloarthritis (SpA) with a lower prevalence seen in the Asian population. Conversely, SpA is the most common extraintestinal manifestation in IBD, with prevalence ranging from 10% to 39%. Apart from the strong Class I human leukocyte antigen B27 link for both diseases, several new shared genetic risk loci are identified from genome-wide association studies. Demonstrable mucosal inflammation of gut is present in most of the patients with SpA, even in the absence of clinically overt IBD. Mucosal inflammation leads to disruption of the epithelial barrier and activation of antigen-presenting cells and T-helper cells, which then home to synovium to cause inflammation maintaining the gut synovial axis. Several putative gut bacteria are implicated in the pathogenesis of SpA. IBD must be suspected in all patients of SpA presenting with abdominal pain, diarrhea, unexplained weight loss, anemia, or other malabsorption features. Fecal calprotectin is emerging as a noninvasive screening tool for detecting clinically silent IBD in patient with SpA. Several therapeutic targets have emerged in the last few years based on the understanding of the pathogenic mechanism and have considerably changed the management of both IBD and SpA.

The role of sulfasalazine in pure axial spondyloarthritis (axial SpA) is claimed to be almost non-existent, due to very low-quality evidence from available literature. Guidelines recommend early institution of biologic therapy if one fails 2 NSAIDs sequentially in optimal doses over 4 weeks. As NSAIDs are effective in about 70% cases, the remaining 30% patients would require biologics within the first few weeks of onset of illness. With each passing year, a significant percentage of the remaining patients would require biologics due to NSAID failure. Relapse rates after discontinuation of TNFα inhibitors at 1-year followup is almost 100%, implying lifelong therapy with biologics. Cochrane metaanalysis reveals that ASAS 40 response (40% improvement in pain, function, and inflammation) is in the range of 25%-40% for various biologics over 24 weeks. Considering that in a country with a per Capita GDP of just Rs 1.44 lakhs/ year, where 80% of people have to meet their medical expenses out of pocket and the cheapest anti TNFs cost over Rs 2 lakhs per annum, the western guidelines are clearly impractical in Indian context. In this review article, we present a contrarian view on the use of Sulfasalazine in axial SpA. We look at the available data on Sulphasalazine with a different perspective and arrive at different conclusions. We also explore the role of other innovative strategies in the management of axial SpA and suggest alternate algorithms catering to the Indian scenario.

The management of axial spondyloarthritis (axSpA) has been completely transformed since the introduction of biologic therapies. Tumor necrosis factor inhibitors (TNFis) were the first effective drug therapies in people affected with axSpA who had previously failed to respond to nonsteroidal anti-inflammatory drugs. Currently, there are five TNFis licensed for the treatment of established axSpA, traditionally known as ankylosing spondylitis or radiographic axSpA, with four of them also available for use in the nonradiographic axSpA disease group. More recent developments comprise new drugs designed to block the interleukin-17 or JAK inflammatory pathways. The high cost associated to these drugs has been the main limiting factor for their use and availability at global level, a problem that will, in part, be addressed with the recent introduction of biosimilars, with comparable efficacy and safety profile at lower cost. The fast arrival of so many “kids on the block” poses many challenges for the clinician in order to choose the right drug for each patient and brings the need for feasible, well-validated biomarkers of treatment response to the forefront of research in axSpA.