34-year-old male with lower limb arthritis back pain, weight loss, and joint pain and stiffness

Case discussion

The 34-year-old male with lower limb arthritis back pain, weight loss, and joint pain and stiffness (not very severe). The patient had persistently elevated inflammatory parameters and swelling over heels. Since the results of RF, ANA, Schober's test, and other parameters were normal, the clinical probabilities could be: Seonegative spondyloarthropathy (SpA) especially ankylosing spondylitis or undifferentiated SpA, Atypical rheumatoid arthritis. and Infective conditions like brucellosis and tuberculosis.

The back pain of the patient is not clinically qualified to categorize as inflammatory back pain (IBP). The pain and stiffness were minimal. As per the first set of criteria for IBP proposed by Calin et al. in 1977, the patient should satisfy the following 5 features:

1. Insidious onset
2. Age at onset < 40 years
3. Duration of back pain >3 months
4. Pain associated with morning stiffness
5. Improvement with exercise.

IBP is considered to be present if at least 4 of the 5 aforementioned features are fulfilled (sensitivity 95%; specificity 76% in patients with mechanical low back pain). ¹ According to the newly proposed criteria, the back pain in young to middle-aged adults (50 years old) should qualify the following individual parameters:  1. Morning stiffness of 30 minutes duration 2. Improvement with exercise but not with rest 3. Awakening during the second half of the night due to back pain 4. Alternating buttock pains.² The post-test analysis indicates a sensitivity of 70.3% and a specificity of 81.2%. The recently published ASAS criteria consider five features namely: 1. Age at onset <40 years 2. Insidious onset 3. Improvement with exercise 4. No improvement with rest, and 5. Pain at night (with improvement upon getting up). This showed a sensitivity of 77.0% and specificity of 91.7% if at least four five parameters are present.³ In the present case, there was no such documentable history of inflammatory back pain. However, in the presence of asymmetric back pain, due consideration should be given to the sensitivity of criteria in a real-time scenario. As per the published literature, the sensitivity ranges from 40-75%. Hence it is necessary to explore the possibility of sacroiliitis in the current case.

Enthesitis

Inflammation of muscle and tendon insertions is an early manifestation of SpA. Enthesitis and dactylitis are important manifestations of PsA and other spondyloarthropathies .⁴The presence of enthesitis is noted in approximately 50% of SpA patients and is often associated with severe disease. In a published cohort of 1505 from Brazil, 54% of the patients with SpA, with a mean of 2.12 ± 2.98 affected with enthesitis. There was a statistical association between the presence of enthesitis and axial symptoms (buttock pain, cervical pain, and hip pain), and peripheral symptoms (lower limb arthritis, number of painful and swollen joints; p < 0.05). Additionally, enthesitis could be one of the leading manifestations of SpA.⁵ Enthesitis should be considered in the presence of ankle pain and should be distinguished from true ankle arthritis and enthesitis. Ankle joints are supported by many enthesis and ligaments that are either attached directly or cross over the bones and joints. Clinical examination to distinguish enthesitis from joint involvement is essential. In the present case, clinical examination suggests the involvement of both entheses as well as joints. Enthesitis has been described as the primary pathology of SpA and it is commonly noted late in rheumatoid and other arthritis.⁶

Arthritis and the disease pattern

The patient had symmetrical polyarthritis, predominantly involving the lower limbs. One of the characteristic features of arthritis, as defined by ESSG, is asymmetric oligoarthritis (Table 3). Symmetric lower limb arthritis is less frequent in adults. In a series from India, more than 65% of the patients had symmetric arthritis with more than 90.6% involving lower limbs.⁷ Although the presentation is most commonly asymmetrical and oligoarticular in nature, a small percentage can present with symmetric polyarthritis. Symmetric large joints can also be affected in rheumatoid arthritis. The criteria for classifying RA are the presence of more than 6 joints, but predominantly large joints (less critical), and having a score of one according to new ACR-EULAR 2010 criteria for RA (Table 4).⁸  However, it is significant to evaluate the levels of anti-CCP. In the present case, the presence of inflammatory parameters at a high level and negative rheumatoid factor were suggestive of SpA, however, it needs to be explored further to confirm the diagnosis.

Table 3: ACR-EULAR 2010 criteria for RA

Table 4: ESSG criteria for characterizing SpA

ASAS classification criteria for axial and peripheral spondyloarthritis⁹

Fig 1 (A) ASAS classification criteria for axial spondyloarthritis.

Fig 2 (B) ASAS classification criteria for peripheral spondyloarthritis.

Recommendations for further evaluation

Though the signs and symptoms are not adequate to consider IBP, radiological evaluation for evidence of sacroiliitis is necessary. The age, gender, and minimum back pain were suggestive of possible sacroiliitis. Sacroiliitis may be often asymptomatic.¹⁰ Despite inconsistent symptoms in males with atypical inflammatory arthritis, clinically classifying it as either RA or SpA will assist in characterizing the diagnosis. X-ray of the pelvis, CT scan, and preferably MRI will assist in confirming sacroiliitis. However, unilateral sacroiliitis may be seen in one-third of patients who may not fulfil definite criteria of ESSG to consider it as SpA and it is recommended to be classified as unclassified sacroiliitis. HLA B27 will help in defining SpA, but it is not a part of the ESSG criteria for classification.

In view of symmetric arthritis, the exclusion of RA is essential. Anti-CCP test will help to exclude the diagnosis. In the presence of anti-CCP, the chance of the patient having RA is 80%, even if the patient did not fulfill ACR criteria at the point of presentation. ¹¹

The weight loss needs to be evaluated carefully, as the patient lost 15 Kg in 6 months. It can also happen in cases with inflammatory arthritis. Stool examination for evidence of occult blood and any features of inflammatory bowel disease like pus cells and other inflammatory cells should be evaluated. If there is a clinical clue, a colonoscopy will help in excluding inflammatory bowel disease. Asymptomatic sacroiliitis and lower limb arthritis are common in IBD. Diarrhea may not be a dominant symptom in 10-30% of the patients especially those with ulcerative colitis.¹²

Conclusion

Altogether, we must consider the diagnosis in the current case as seronegative SpA, either unclassified or a probable associated inflammatory bowel disease.  RA can be excluded based on further evaluation.

Further investigation showed that HLA B 27 and anti-CCP were negative, and the X-ray of the pelvis and the colonoscopy findings were normal. Evaluations by USG abdomen, and chest X-ray were normal. The conclusion was undifferentiated SpA.

Final Diagnosis

Unclassified spondyloarthritis