Immunological conundrum – A paradoxical reaction in tuberculosis

INTRODUCTION

As per the 2023 Global Report on Tuberculosis, India is the leading country in the world, contributing to 27% of the overall incidence of tuberculosis.^[1] India has witnessed a record high increase in notifications by 13% as compared to 2021, approximately 172 cases/lakh population.^[1] Tuberculosis continues to remain a burden on India’s healthcare system and significantly contributes to mortality and morbidity of India’s population. Despite numerous studies on tuberculosis, the ever-changing forms of the disease have become a serious challenge for healthcare workers. A paradoxical response in tuberculosis is the clinical or radiological worsening of pre-existing tubercular lesions or the development of new lesions during anti-tubercular treatment. This is due to the host immune reaction, a form of molecular mimicry. One such paradoxical response is seen in Poncet’s disease. Poncet’s disease is a form of reactive arthritis seen in active tuberculosis infection.^[2] This is due to molecular mimicry between the host cartilage and the tubercular antigens.^[2] It was first described by Antonin Poncet in 1897.^[3] There are not enough studies on the current incidence of Poncet’s disease despite the high incidence of tuberculosis in India. The main reason could be due to under-reporting of the cases, mainly because there is no uniform, standard diagnostic criteria for Poncet’s disease. We report to you a child with abdominal tuberculosis presenting to us with large joint swelling and pain, diagnosed to have Poncet’s disease.

CASE REPORT

A 16-year-old girl with abdominal tuberculosis on anti-tubercular therapy for 1 month had c/o pain and swelling in B/L knee and ankle joints for 1 week. The child was initially evaluated outside where total leucocyte count was elevated with lymphocytic predominance, serum uric acid was mildly elevated (8 mg/dL, reference range: 3–7 mg/dL), Vitamin B12 (261 pg/mL, reference range: 200–800 pg/dL) and folic acid (6.1 ng/dL, reference range: 3–18 ng/dL) were within normal limits. The child was suspected to have gouty arthritis secondary to pyrazinamide and ethambutol. These two drugs were temporarily discontinued. Tablet febuxostat, a xanthine oxidase inhibitor, was started. Nonsteroidal anti-inflammatory drugs (NSAIDs)-etoricoxib and thiocolchicoside were also added. The child presented to our hospital with persistent symptoms despite the above measures. Initial blood workup was done s/o haemoglobin and C-reactive protein within the normal limits. However, the erythrocyte sedimentation rate was 40 (elevated). She also had B/L lower limb paraesthesia. She also had B/L lower limb paraesthesia. Repeat uric acid levels were reported to be normal (6 mg/dL). Initially suspecting paraesthesia secondary to pyridoxine deficiency, the pyridoxine dose was increased from 100 mg/day to 200 mg/day. Gabapentin and Vitamin B12 supplements were started.

Nerve conduction studies were normal. Radio-imaging of the knee joint was done s/o mild effusion without any erosions of the joint [Figure 1]. The child also had a history of strongly positive Mantoux tests. In view of polyarthritis of lower limbs and typical history, Poncet’s disease was considered. Rheumatoid arthritis (RA) factor and anti-nuclear antibody were negative. Magnetic resonance imaging knee was considered but not done due to financial constraints. The child was treated with a short course of oral steroids (prednisolone) for 6 weeks at 60 mg/day and NSAIDs. Pyrazinamide and ethambutol were gradually restarted. The child showed symptomatic improvement over the course of hospital stay. The child was discharged on anti-tuberculosis treatment (ATT) and counselled for strict adherence. On follow-up, currently, the child is in the 5^th month of anti-tubercular therapy and complete resolution of symptoms is noted. As the child was asymptomatic and also due to financial constraints, no further follow-up investigations were done. Gouty arthritis is a close differential of Poncet’s disease after the start of anti-tubercular therapy. Peripheral neuropathy due to isoniazid was also another differential. As the child’s symptoms are completely resolved on re-starting ATT and steroids, Poncet’s disease is a likely diagnosis. If symptoms recur at all, juvenile idiopathic arthritis can still be a differential. Sepsis workup was negative and as the child eventually improved on ATT and steroids, septic arthritis was ruled out.

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Figure 1:

(a-b) X-ray of knee joints suggestive of mild effusion with no erosion.

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DISCUSSION

Poncet’s disease is an immune reaction to molecular mimicry between tubercular antigen and host cartilage.^[2] It commonly presents as polyarthritis but can also present as oligoarthritis. It is non-erosive inflammatory arthritis. It is extra-articular as there is no bacteriological involvement of the joints. It is usually seen in extrapulmonary tuberculosis at the start of anti-tubercular therapy and resolves within 6–12 months. The child in our case report is also a case of abdominal tuberculosis presenting with polyarthritis. Cartridge-based nucleic acid amplification test (sputum) was negative in the child. Sharma and Pinto’s diagnostic criteria for Poncet’s disease can be used to diagnose Poncet’s disease^[3] [Table 1]. It comprises essential, major and minor criteria. The essential criteria include inflammatory non-erosive arthritis after excluding other causes. Major criteria include concurrent extra-articular tuberculosis and complete response to anti-tubercular therapy. Minor criteria include Mantoux positivity, hypersensitivity phenomenon and absence of sacroiliac and axial involvement. There is an increased association of Poncet’s disease with Mantoux positivity. As in our case, the child was strongly positive for Mantoux, and an induration area of 20 mm was noted. Poncet’s disease responds to steroids and NSAIDs. In refractory cases, methotrexate and anti-tumour necrosis factor biologics can be considered.^[4] However, the treatment of Poncet’s disease is the continuation of anti-tubercular therapy which eventually results in the resolution of symptoms. Poncet’s disease is a diagnosis of exclusion. Hence, other causes of inflammatory arthritis have to be ruled out. The closest differential is tubercular arthritis.

Unlike Poncet’s disease, tubercular arthritis is usually monoarticular and causes erosion of the joints. On synovial fluid aspiration, tubercular bacilli can be detected which is not seen in Poncet’s disease. In our case, synovial biopsy was not done as the history was typical. Another differential is gouty arthritis. As Poncet’s disease usually occurs on the commencement of anti-tubercular therapy, it can easily be mistaken for gouty arthritis secondary to pyrazinamide and ethambutol. Gouty arthritis is usually monoarticular and is associated with hyperuricaemia. There is deposition of the uric acid crystals in the joint space and erosions of the joint. The great toe is most commonly involved. Gouty arthritis can be treated with xanthine oxidase inhibitors. It is also advisable to rule out RA before considering Poncet’s as both have a similar presentation. The diagnosis of Poncet’s disease becomes important because the usual immunosuppressive drugs that are considered in other inflammatory arthritis can worsen the existing tuberculosis in the body and result in disseminated tuberculosis.^[5]

CONCLUSION

Poncet’s Disease is a rare occurrence yet an important differential of atypical presentation of not so rare disease in India-Tuberculosis.