Fifty two year old man of Chinese descent was admitted to hospital with epistaxis and bleeding per rectum. This was a consequence of a high international normalized ratio (INR) due to over-anticoagulation with warfarin. The language barrier impaired our ability to obtain a detailed history. It was incidentally noted that he had a swollen left knee and leg for about three months. It was initially thought to be a deep vein thrombosis and was treated with anti-coagulant, warfarin. A knee aspiration showed haemarthrosis which then required an ultrasound guided joint wash out. The knee aspirate was sent for microscopy, culture and sensitivity and initial results came back negative. The patient was discharged home with conservative treatment. Two week later, he represented to hospital with fever and worsening knee pain. Further detailed history through a trained translator brought to light that he had in fact been having recurrent asymmetrical polyarthritis for almost five years prior to migrating to the United Kingdom.
His blood results showed a mild anaemia with a haemoglobin of 10.0 G%, normal white cell count, normal neutrophil count and high inflammatory markers with a C-reactive protein (CRP) of 44. His erythrocyte sedimentation rate (ESR) was 62. He had a normal chest X-ray and normal urinalysis. His rheumatoid factor and anti-cyclic citrullinated protein antibody (anti-CCP) were negative. His HIV test which was performed at an early stage came back negative.
Clinical examination revealed swollen and tender joints in the right elbow, right wrist, left knee (Fig. 1) and left ankle which were consistent with active synovitis. He also had dactylitis (Fig. 2) in the left middle proximal interphalangeal joint. He was mildly pyrexial with a temperature of 37.8 degrees Celsius. His inflammatory markers were persistently high during his admission. Knee joint aspiration was repeated and samples were sent again for microscopy, culture and sensitivity for bacteria, viruses and mycobacterium tuberculosis.
A differential diagnosis of polyarticular septic arthritis had been considered and intravenous flucloxacillin two grams every six hours was initiated on the advice of the Microbiologist. The fever settled initially and there was a minimal improvement in his inflammatory markers. The intravenous antibiotic was continued for two weeks but there was no further improvement in his inflammatory markers and his fever returned. A concomitant tuberculosis infection was still considered a possibility despite the earlier negative results. A Mantoux test performed was also normal.
As the patient continued to have fevers and raised inflammatory markers despite the antibiotics, the possible alternative diagnosis of seronegative inflammatory arthritis was re-considered. Further investigations including a computerised tomographic (CT) scan of his chest and abdomen did not show any obvious pathology apart from small volume hilar lymphadenopathy. Magnetic resonance imaging (MRI) of his pelvis and sacroiliac joints showed no evidence of sacroilitis or a psoas abscess. In view of his mild anaemia, an upper gastrointestinal endoscopy was done which revealed a duodenal ulcer with positive helicobacter pylori. He was treated with eradication antibiotics therapy. As a series of blood cultures and urine cultures were negative, and there was no obvious clinical improvement, the antibiotics were stopped. The Orthopaedic team performed a synovial biopsy from his knee. The result showed granulomatous changes and the synovial tissue was sent for polymerase chain reaction (PCR). Sarcoidosis and tuberculosis were suggested as possible differential diagnosis.
After eight weeks in hospital, mycobacterium tuberculosis was grown from the initial synovial fluid sample taken from the knee. An isotope bone scan was performed and it has shown an increased uptake at the wrist, ribs, knees and ankles consistent with inflammatory changes. A diagnosis of multi-focal tuberculous osteomyelitis was made and standard quadruple therapy was initiated. Over the next two weeks, the fever settled and his acute phase markers also gradually improved. He was discharged after two weeks of initiating the anti-tuberculous treatment with an out-patient follow-up appointment.
One month after discharge, full sensitivity result from synovial fluid culture was available and it has shown that the patient was found to be resistant to Rifampicin, Isoniazid, and Ethambutol, but sensitive to Pyrazinamide, Amikacin, Moxifloxicin, Protionamide and Cycloserine. Given the complexity of treating multi-drug resistant tuberculosis, he was readmitted to a tertiary hospital where experts with experience in this area are available.
In this case series, the time from presentation to hospital to getting a correct diagnosis, was approximately eight weeks.