Arthritis as a complication of intravesical BCG vaccine

BMJ 1994; 308 doi: https://doi.org/10.1136/bmj.308.6944.1638 (Published 18 June 1994) Cite this as: BMJ 1994;308:1638
  1. M Devlin,
  2. A Deodhar,
  3. M Davis
  1. Duke of Cornwall Rheumatology Unit, Royal Cornwall Hospital (City), Truro TR1 2HZ.

    EDITOR, - In their editorial on treating superficial bladder cancer with intravesical BCG vaccine1 Neeraj Sharma and Stephen Prescott do not mention the important, though rare, complication of arthritis.*RF 2-4* We describe a case of asymmetric oligoarthritis in a patient treated with intravesical BCG vaccine.

    After an episode of painless haematuria in April 1992 a 40 year old man was diagnosed as having a moderately differentiated transitional cell carcinoma of the bladder. At cystoscopy all visible tumour was resected. Repeat cystoscopy, however, showed recurrence, with the development of extensive satellite lesions. A six week course of weekly treatment with intravesical BCG vaccine was started in November. The first three instillations were each followed by influenza-like symptoms, which responded to antipyretic agents. After the fourth treatment he developed fever (38°C), bilateral conjunctivitis, periorbital oedema, and arthralgia of the left shoulder. Over the next two days his right fourth toe, right knee, both ankles, and right fourth proximal interphalangeal joint became painful, tender, and swollen.

    Laboratory investigations showed a normal full blood count, but the C reactive protein concentration and erythrocyte sedimentation rate were 180 mg/l and 84 mm in the first hour respectively. Blood and urine cultures yielded negative results. A chest x ray film was normal. Isoniazid and prednisolone 30 mg were started. No clinical improvement was observed.

    Further serological investigations excluded infective causes of reactive arthritis. A test for rheumatoid factor yielded a negative result and serum uric acid concentration was normal, but he was positive for HLA B-27. The isoniazid was stopped and prednisolone withdrawn, and diclofenac was started. He improved progressively and with regular physiotherapy returned to full mobility within a month.

    The incidence of arthralgia after intravesical instillation of BCG vaccine is quoted to be 0.5-1% of treated patients.3,4 Bilaterally symmetric polyarthritis affecting the hands, wrists, and knees generally develops a few days to five months after the first instillation.2 Further instillations aggravate the arthritis. Laboratory investigations yield non- specific findings, and examination of synovial fluid or a synovial biopsy specimen does not show infection with the Calmette-Guerin bacillus. Because of the absence of diagnostic tests, attention to the sequence of events in history taking is of paramount importance.

    The pathophysiology of this condition is believed to be a reactive immunogenic response to the BCG antigen, the same response that is essential for BCG vaccine's therapeutic effect on the bladder cancer. As immunotherapy with BCG vaccine becomes more commonly used more cases of this new form of reactive arthritis are likely to occur.


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