1 Apr, 2025
ANKYLOSING SPONDYLITIS: DIAGNOSIS AND TREATMENTS
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ANKYLOSING SPONDYLITIS: DIAGNOSIS AND TREATMENTS

Prof. Dr. Sarita Khatkar

Geeta Institute of Pharmacy, Geeta University, Naultha, Panipat

Introduction

The axial skeleton is impacted by the frequent inflammatory rheumatic disease ankylosing spondylitis, which causes distinctive inflammatory back pain and can result in structural and functional deficits as well as a reduction in quality of life. Over the past ten years, new imaging methods and treatments have significantly altered how this condition is managed. It is yet unknown if the medications now on the market can limit structural damage and radiographic advancement. Additionally, physiotherapy and non-steroidal anti-inflammatory drug treatment continue to be crucial components of long-term care for individuals with ankylosing spondylitis. For individuals who are resistant to traditional treatment, the novel treatment options using tumor necrosis factor blockers appear to be a breakthrough. The primary subtype and consequence of an interconnected collection of rheumatic disorders currently known as spondyloarthrities is ankylosing spondylitis.

Clinical features of this category include enthesitis, inflammatory back pain, asymmetrical peripheral oligoarthrities (of the lower limbs mostly), and specific organ involvement, including anterior uveitis, psoriasis, and chronic inflammatory bowel disease. Rare side effects of ankylosing spondylitis include improper conduction and involvement of the aortic root. Ankylosing spondylitis, psoriatic spondyloarthrities, reactive spondyloarthrities, spondyloarthrities linked to inflammatory bowel illness, and undifferentiated spondyloarthrities are the five clinically distinct subgroups. The subgroups are genetically related; the MHC class I molecule HLA B27 is the most potent known contributing factor, however other factors are still unknown.

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EPIDEMIOLOGY

Young people are susceptible to ankylosing spondylitis, which often manifests around age 26. With a ratio of about 2 to 1.1, men are impacted more frequently than women. Approximately 80% of individuals have their first symptoms before the age of 30, and fewer than 5% do so beyond the age of 45.

  1. In a particular community, the incidence and prevalence of this disease are roughly correlated with the prevalence of HLA B27.

2 Eskimo and Haida Indian populations have the highest prevalence of HLA B27, which is also most common in northern nations and some tribes (up to 50% of instances). The prevalence of ankylosing spondylitis varies from 0·1% to 1·4%. Most of the statistics on this topic originate from Europe.

  1. HLA B27 is most common among Eskimo and Haida Indian populations, and it is also most common in northern countries and among some tribes (up to 50% of instances). Overall, the prevalence of ankylosing spondylitis ranges from 0·1% to 1·4%, with most data originating from Europe.
 

These variations are caused by a number of causes. Target population selection comes first, followed by screening criteria like back pain and diagnostic criteria to confirm the diagnosis, and finally, the prevalence of HLA B27 and the distribution of its subtypes, which vary among ethnically diverse populations. Those with a history of physically demanding professions, more comorbid diseases, and smoking have more functional limitations than patients with better educational attainment and a familial history of ankylosing spondylitis who have had the disease for 20 years. Functional outcomes are negatively correlated with the age at which symptoms first appear. Severe tarsitis is one among the many clinical signs that can appear in young people with Spondyloarthrities. Compared to female patients, male patients exhibit greater structural abnormalities, such as bamboo spines. Peripheral arthritis, enthesitis, anterior uveitis, and inflammatory back pain (panel 1) caused by sacroiliitis and inflammation at various locations in the axial skeleton are the main clinical features of this group, irrespective of the Spondyloarthrities subtype. However, it is uncommon to see symptoms in other organs, such the heart.

Ankylosing spondylitis is characterized by spinal stiffness and lack of motion, which may be caused by inflammation of the spine or structural damage. Signs of spinal inflammation include spondylitis, spondylodiscitis, and spondylarthritis. Osteoproliferation, not osteo destruction, is the primary source of structural alterations. The most distinctive characteristics of this illness are syndesmophytes and ankylosis, which appear on standard radiographs after a few months to several years. The burden of disease in the lower limbs is enhanced by low bone density, osteoporosis, and an elevated fracture rate, which may exacerbate the hyper kyphosis that is primarily observed in male patients.  About 20% of those with peripheral arthritis develop the condition, which is typically monoarticular or oligoarticular and mostly, though not entirely, affects the hip and shoulder joints. Although there is disagreement about what constitutes a serious disease, hip involvement is thought to be a poor prognostic indicator. Ethereal site inflammation occurs in a variety of places, including the spine, in addition to well-known sites like the Achilles tendon and the plantar fascia. Inflammation of the eyes in spondyloarthrities is mostly limited to the uvea and typically occurs unilaterally, however it might alternate between the two sides. Twelve Conjunctivitis can affect the eye in cases of reactive spondyloarthrities.

Instead of being illness presentations, inflammatory bowel disease-related skin involvement (psoriasis) and colitis can be thought of as fundamental subtype-defining entities with a distinct genetic foundation from HLA B27. But the spondyloarthrities have sometimes been considered a single disease with two main symptoms and a shared genetic basis (20).
Prognostic studies for ankylosing spondylitis are lacking. A substantial amount of radiographic progress is made in the first decade of the disease, according to two retrospective studies, and more recent studies have shown that the best predictor of future damage is structural damage at presentation. Amor and colleagues found that early onset and hip involvement are prognostic variables for the full range of spondyloarthrities, and they have been verified.

PATHOGENESIS

The cause of ankylosing spondylitis and related spondyloarthrities is uncertain. It is necessary to explain two key features: inflammation and the formation of new bone, especially in the spine. Although it is believed that inflammation is the first step in the formation of new bone, there is no clear connection between inflammation and osteo proliferation. Hereditary factors have a major role in spondyloarthrities, especially ankylosing spondylitis. HLA B27 is responsible for around one-third of this influence, with the remaining, largely undefinable amount coming from genes both inside and outside the MHC. Ninety to ninety-five percent of those with ankylosing spondylitis test positive for HLA 27and28; those who do have a five percent probability of developing the condition, and those who have relatives who test positive for HLA B27 have a far higher chance. On the other hand, most HLA B27-positive individuals remain healthy. In spondyloarthrities pathogenesis models, the potential interaction between bacteria and HLA B27 is essential. This approach is highly supported by the fact that reactive arthritis is caused by genitourinary Chlamydia trachomatis infections or enteritis caused by gram-negative enterobacteria, such as Shigella, Salmonella, Yersinia, and Campylobacter species. On the other hand, there is less proof that it causes infections in other spondyloarthrities. People with reactive arthritis have microbial antigens in their synovium, which suggests that their persistence may be essential for sustaining joint inflammation.

 Approximately 10–20% of patients with reactive arthritis who have HLA B27 go on to develop the full clinical picture of ankylosing spondylitis after 10–20 years. This link between Crohn’s disease, ankylosing spondylitis, and HLA B27 positivity lends more credence to the theory that bacteria may be a major factor in the pathophysiology of spondyloarthrities. Only 2·6% of individuals with Crohn’s disease who are HLA B27-negative go on to develop ankylosing spondylitis, compared to 54% of those who are HLA B27-positive. When the gut mucosa leaks as a result of inflammation from colitis, such as that observed in Crohn’s disease, the immune system interacts with gut microbes. The gut mucosa of about half of ankylosing spondylitis patients without Crohn’s disease has microscopic or macroscopic mucosal chronic lesions that mimic the condition. Finally, there is evidence supporting the importance of the B27-bacteria interaction from studies conducted on animals. HLA B27 transgenic rats have traits comparable to spondyloarthrities, however several transgene copies are needed to transmit disease. Environmental factors also play a role because gut flora plays a role in colitis and HLA B27 transgenic rats raised in a germ-free environment do not get sick. 34 It seems unlikely that microbial antigens in human spondyloarthrities will remain in usually associated locations, nevertheless, as PCR in sacroiliac joint samples did not reveal any possible bacteria.

Two cartilaginous components that have been studied as possible targets for the autoimmune response in ankylosing spondylitis are proteoglycan and collagen type II. Although the collagen-II-induced arthritis model and rheumatoid arthritis share similarities, animals inoculated with proteoglycan display traits of ankylosing spondylitis.
Patients with this disorder have ankylosis and damage as a result of mononuclear cells infiltrating the cartilaginous tissues of the sacroiliac joints and intervertebral discs. T-cell responses to aggrecan have also been reported in other forms of arthritis besides spondyloarthrities. Both CD4+43 and CD8+ T-cell responses to aggrecan and collagen-derived peptides have been demonstrated in peripheral blood and synovial fluid samples from individuals with ankylosing spondylitis.

GENETICS

Although the main gene predisposing to ankylosing spondylitis is HLA B27, there is strong evidence that additional genes are also linked to vulnerability to the disorder. HLA B27 only contributes 20–30% of the total genetic risk for this disease, but the complete MHC contributes 40–50%, according to research (in twins). The concordance rate is 33 percent for dizygotic twin pairs and 63 percent for monozygotic twin pairs who are B27 positive. Those who have a first-degree relative with ankylosing spondylitis are also six to sixteen times more likely to get the disorder themselves than B27-positive individuals without a family history is. According to all of these results, non-B27 family factors have a major impact on the risk of developing this disease. Along with HLA B27, additional MHC genes, such as HLA B60 and HLA DR1, also seem to be associated with ankylosing spondylitis, however they are not highly important. Another possible gene identified in the MHC is TNFα, even though TNF polymorphisms are unlikely to have a major impact on patients with this illness.

Diagnosis:

Radiography

Sacroiliitis is a common symptom of ankylosing spondylitis, especially in the early stages of the condition. It has become a crucial tool for developing classification criteria because of its incredibly high occurrence in patients with ankylosing spondylitis. Since sacroiliac joint radiographs may appear normal in the early stages of the illness, structural changes may not be apparent for years for a considerable number of people.

Laboratory test

The two main laboratory indicators that could be crucial for a diagnosis of spondyloarthrities are HLA B27 and C-reactive protein. 76 However, the role of the erythrocyte sedimentation rate is less clear. HLA B27 has a crucial role in the early detection of spondyloarthrities. The performance of the HLA-B27 test depends on the population prevalence of HLA B27, which differs by race. While Chinese individuals might need subtyping since some subtypes (such HLA-B*2706) are not associated with ankylosing spondylitis, white patients do not need to have their HLA-B27 subtypes assessed. Laboratory measurements of inflammation and disease activity don’t really correlate. Only 50% of patients with this illness had increased levels of C-reactive protein.

Treatment or management

Ankylosing spondylitis treatment should be tailored to the patient’s preferences and expectations, the severity of symptoms, and the symptoms that the illness exhibits at the time of presentation. Monitoring a patient’s sickness should include imaging, laboratory testing, clinical features, and history. The frequency of monitoring should be determined by taking into account the intensity, symptoms, and drugs. A combination of pharmaceutical and non-pharmacological treatments, including education and physical therapy, is needed for the best results. Anti-TNF therapy should be administered in accordance with ASAS guidelines. Patients with refractory pain and disability who have radiographic evidence of advanced hip involvement must be evaluated for joint replacement. For certain patients who have symptoms and disabilities due to poor posture or an unstable spine, spinal surgery can be helpful.

Basic principles of treatment

In addition to physical therapy, non-pharmacological therapy includes education, self-help groups, and spa treatments.

NSAIDs

NSAIDs are an excellent treatment for ankylosing spondylitis patients. While a lack of response to NSAIDs may suggest a poor prognosis, even a positive response to these drugs has been demonstrated to be a diagnostic sign for spondyloarthrities.

Disease-modifying antirheumatic drugs

Peripheral arthritis caused by spondyloarthritis is relieved by sulfasalazine, but spinal pain is not. However, the duration of peripheral arthritis and the number of patients with the illness differ throughout trials.

TNF blockers

Three approved drugs are now available to treat ankylosing spondylitis:
1. The fully humanized monoclonal adalimumab, administered subcutaneously at a dose of 40 mg every other week;

  1. The 75 kD TNF receptor fusion protein etanercept, administered subcutaneously at a dose of 50 mg once weekly or 25 mg twice weekly; and
  2. The monoclonal chimeric antibody infliximab, administered intravenously at a dose of 3–5 mg per kg every 6–8 weeks (the recommended regimen is 5 mg/kg every 6–8 weeks).

Conclusion

Reducing symptoms, improving mobility, and preventing the disease from worsening are the objectives of AS treatment. Nonsteroidal anti-inflammatory drugs, or NSAIDs, are commonly used to relieve pain and inflammation. It has been demonstrated that biologic medications, such as TNF or IL-17 inhibitors, can effectively reduce inflammation and improve quality of life in patients with more severe conditions. While physical therapy is crucial for maintaining posture and spinal flexibility, regular exercise can help with pain management and overall mobility.

AS adverse effects that are often ignored include spine instability and neurological problems that could occur if treatment is not received. Early detection and treatment are essential to preventing progressive kyphotic abnormalities and their associated effects. Surgery may be necessary if there is severe pain, deformity, or neurological involvement, even if conservative treatment is still the cornerstone of AL management. It is necessary to comprehend how AL manifests and the available treatment options in order to improve patient outcomes in AS.

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