A 61-year-old Caucasian gentleman who was known to suffer from schizophrenia, learning disability, atrial flutter, congestive heart failure and epilepsy on a rehabilitation ward for a humeral fracture, was noted to have recurrent episodes of high fever which had been present for months. He had been treated with antibiotics on a number of occasions targeting a lower respiratory tract infection despite no symptoms or obvious consolidations on the chest X-Ray at the general hospital prior to being transferred to the rehabilitation hospital. There the patient was treated for suspected infective endocarditis in view of vegetation seen on transthoracic Echocardiogram (ECHO) which then resulted negative on a trans-oesophageal ECHO.

The fevers resolved for two months but then started once again in a cyclical pattern and lasted for over 2 months while the patient was at the rehabilitation hospital. During this time, the patient was noted to deteriorate significantly, becoming bed-bound with occasional tantrums. The patient denied symptoms such as myalgias, sore throat, headache, back pain, dysuria, blurred vision, oral ulceration, eye pain or arthralgias throughout this time, although history taking was limited and difficult due to the learning disability. He had no recent history of travelling and did not have contact with any animals prior to admission for rehabilitation, other than his pet dog. Review of body systems was negative. The patient was on sodium valproate, carbamezapine, phenytoin, digoxin, bumetanide and olanzapine. He was allergic to ceftazidime and gentamycin. He had no significant family history. On physical examination the patient had temperatures of 39 degrees Celcius with a blood pressure of 102/74mmHg and tachycardia of 120 beats/minute. The chest, cardiovascular, abdominal and neurological examinations were all normal on assessment. He had a small healing sacral sore. On one occasion, a non-puritic maculopapular rash over the sternum with Koebner effect was noted which resolved over an hour. The patient denied any tenderness of the joints and no lymph nodes were palpable. There was no evidence of synovitis.

The patient had a number of blood cultures which were all negative, including samples for mycology. Multiple urine samples were negative as was a wound swab from the sacral sore. C-Reactive Protein (CRP) was elevated at 400mg/L (Normal 0-5mg/L), erythrocyte sedimentation rate (ESR) at 120 mm/hr (normal 12-16mm/hr) with ferritin levels of 380ug/L (normal 22-328). The patient had a slight leukocytosis with a white cell count of 12.05 (normal up to 11.4 x109/l) with neutrophilic predominance of more than 80% (10.52 (normal range up to 7.2 x109/l)), a normocytic anaemia and thrombocytosis. Liver function tests were minimally deranged with a gamma-glutamyltransferase of 254 U/l (normal 8-61 U/l), alkaline phosphatase of 86 U/l (normal 40 -129 U/l) and alanine transaminase of 15 U/l (within normal limits). Hepatitis screen, HIV and autoimmune screen were all negative. Antinuclear antibodies, double stranded-DNA, extractable nuclear antigen and rheumatoid factor antibodies were negative pointing against a diagnosis of Rheumatoid arthritis or systemic lupus erythomatosum. Galactomannan antigen test was also negative. Anti-epileptic drug levels were all within range. Serum protein electrophoresis and serum albumin were within normal limits.

The patient received intravenous co-amoxiclav for 10 days followed by 10 days of piperacillin - tazobactam and 4 days of meropenem and teicoplanin yet he remained febrile and with raised inflammatory markers. A computed topography of the thorax, abdomen and pelvis showed small bibasal consolidations associated with pleural effusions and a large pericardial effusion yet no signs of lymphadenopathy or alternate pathology such as tuberculosis. The case was discussed with respiratory physicians in view of the bilateral pleural effusions. Pleural fluid analysis was not performed as the risks of thoracocentesis were believed to outweigh the benefits given that the patient was poorly compliant and in frail condition at the time.  

A trans-oesophageal echocardiogram was performed which excluded infective endocarditis. Echocardiogram showed normal left ventricular dimensions with normal systolic function, in the presence of mild mitral regurgitation. A moderate pericardial effusion was also noted. A pericardial tap was not deemed necessary at the time as the effusion was not causing any symptoms or haemodynamic compromise.  The patient was started on colchicine to no effect and was thus discontinued after a number of weeks. This was started since Familial Mediterranean Fever was one of the differential diagnoses being considered and lack of response to colchicine refuted this diagnosis. Haematological conditions including leukaemia and lymphomas were excluded on the basis of absence of laboratory and physical findings. The infectious disease specialists were consulted and Coxiella burnetti antigen was taken and was found to be negative. No further tests to exclude tuberculosis were deemed necessary by the infectious disease specialists at the time given the patient’s history and lack of suggestive features on imaging, absence of haemoptysis, sputum production and shortness of breath which was not in keeping with mycobacterial infection.

A tentative diagnosis of polycyclic systemic variant of adult-onset Still’s disease was made according to Yamaguchi criteria. The patient was given 7 doses of intravenous hydrocortisone (100mg three times a day regimen) followed by 30mg prednisolone daily. The patient improved clinically and remained afebrile while on steroids. CRP decreased to 29 and the ESR to 80. Chest X-ray taken after 7 days of steroids showed resolution of the pleural effusions and consolidations. The patient improved clinically and was able to mobilise. Psychological improvement was also noted. Since the patient required high doses of steroids to keep the inflammatory markers under control (60mg/ day), Methotrexate was then introduced as a steroid-sparing agent at a dose of 7.5mg/ week. Normalisation of inflammatory markers was noted by this time. The patient continued improving and over time managed to regain dependence in activities of daily living.