Discussion of the case
The 58-year-old male was having oligoarthritis involving knees and ankle of two-months duration. Previous surgical exploration revealed an infected right tibial synovial sheath which was managed on antibiotics. Though partial improvement was noted, the pain relapsed in both the knees and ankles. Ultrasound showed the tenosynovial effusion of flexor and peroneal sheath and subcutaneous edema. The synovial histopathology was not performed.
Investigations revealed elevated ESR and CRP with positive ANA, anti-Ro-52, and RF. The patient fulfilled the 2010 ACR/EULAR guidelines for the diagnosis of RA. However, certain findings do not support the diagnosis. Ultrasound scan of soft tissue suggested tenosynovitis rather than arthritis and the previous surgery exploration was indicative of an infection, which resolved on a one-week course of antibiotics. However, histopathology confirmation or culturing was not performed to further evaluate the cause of infection.
In a non-diabetic patient, the incidence of two joint infections is unusual. Since the RF and ANA were positive, the condition was diagnosed as RA and the patient was managed on methotrexate and hydroxychloroquine sulfate. Initially, the patient responded well to the treatment, but after three months, the pain and swelling in the ankle increased, while the knee returned to normal. The three-month follow-up revealed normal counts, but the inflammation persisted, suggesting an additional cause for inflammation. The possibilities include partially treated or chronic infection and refractory rheumatoid synovitis. At this point, further, work-up using MRI or CT is advisable to identify the inflammatory site and bony changes. Alternatively, microbiological and other analyses of aspirated synovial fluid should be conducted. A positive ANA, RF, and antibodies directed against extractable nuclear antigens (ENA) can also be seen in patients with tuberculosis. Hence, the possibility of mycobacterial infection needs to be confirmed through PCR if the results are not concurring with other infections.
A study involving patients with active tuberculosis has reported significantly elevated levels of anti-ds DNA (32% vs. 2.5%), anti-Sm (38% vs. 0%), anti-RNP (15% vs. 0%), anti-Ro (64% vs. 10%), anti-ACA-IgG (59% vs. 0%) and anti-ACA-IgM (47% vs. 7.7%) compared to controls (P < 0.05). 1
Even though knee pain and swelling reduced, given recurring synovitis and increased pain in the ankle, the possibility of a different cause for ankle synovitis needs to be considered. The needle aspiration of the joint yielded, cloudy synovial fluid, and the analysis suggested a cell count of 6000/ cu mm, with predominant lymphocyte. The protein level was high and PCR for mycobacterium was positive, while AFB stained negative. Quantiferon test for mycobacterium was also positive.
Final Diagnosis
Tuberculosis arthritis with undifferentiated connective tissue disease (UCTD)
Follow-up
The patient was managed on anti-tubercular therapy (ATT) for one year along with hydroxychloroquine. The ankle swelling and pain reduced by the end of 3 months and the inflammatory parameters settled, but the minimal knee pain persisted.
Learning points
- Synovial biopsy should always be subjected to HPE and if suspected for evaluation of mycobacterial disease.
- Infectious arthritis should be considered as a differential diagnosis in patients with failed treatment responses.
- ANA can be sometimes misguiding, especially in chronic infective arthritis.
Reference
- Elkayam O, Caspi D, Lidgi M, Segal R. The International Journal of Tuberculosis and Lung Disease. 2007; 11(3): 306-310.