Q J Med 2001; 94: 719
© 2001 Association of Physicians
Correspondence |
Systemic reactions after intravesical BCG instillation for bladder cancer
Department of Internal Medicine B
Department of Internal Medicine and Nutrition Hôpitaux Universitaires de Strasbourg France
Sir,
Systemic reactions after BCG (bacillus Calmette-Guerin) have seldom been described.1 We report two such cases, and show the potential efficacy of quinolone antibiotics.
The first patient was a 70-year-old man with sepsis syndrome, bone marrow and liver involvement (non-caseating epitheloid granulomas) after intravesical BCG administration for bladder carcinoma (second treatment 5 days before the admission).2 He had features of Gram-negative bacterial sepsis with fever (38.5 °C), chills and hypotension (TA<80/60 mmHg). Laboratory tests showed CRP >180 mg/l, white cell count <0.4x109/l, platelet count <50x109/l, gGT >4N (normal) and aspartate aminotransferase (ASAT) >6N. All cultures (blood, urine, liver and bone marrow) were negative for Mycobacterium bovis. A favourable outcome was obtained after 3 weeks of ofloxacin (400 mg/day). One year after this episode, the patient remains cured.
The second patient was a 62-year-old man with severe sepsis syndrome, that appeared 12 days after the fifth treatment of intravesical BCG for superficial bladder cancer. Like the first patient, he also had high fever (40 °C) and collapses, and also presented with moderate jaundice. Laboratory tests showed CRP >120 mg/l, fibrinogen >6 g/l, neutrophils count <2.4x109/l, hepatic cytolysis (ASAT>4N) and total bilirubin >45 µmol/l. All cultures (blood, urine, liver and bone marrow) and immunological tests (anti–DNA and ANCA antibodies) were negative, but bone marrow biopsy showed non-caseating granulomas (no M. bovis was found). Empirical therapy with 4 weeks of ofloxacin (400 mg/day) and steroid (prednisone 0.5 mg/kg/day) led to a favourable outcome.
High-grade fever, septicaemia and hepatitis or pulmonary granulomas are reported in <1% of all cases of BCG therapy (vaccination, immunotherapy in bladder cancer).3,4 Extensive systemic granulomas (as in our first case) are exceptional.1 The pathogenic mechanisms of such systemic complications are complex: dissemination of mycobacteria and/or host immunological reaction (mediated by cytokines).3 In this setting, anti-tuberculous drugs should be considered, and corticosteroid therapy may be proposed (as in the second case).4,5 In vitro, M. bovis is susceptible to all anti-tuberculous drugs (except pyrazinamide) and to quinolone. In animals, the combination of isoniazid and rifampicin for 6 months improves the outcome,5 but many physicians would administer at least three anti-tuberculous drugs, including ethambuthol.3 Anecdotal data in humans,3 as in the case of Mooren et al.,1 support this concept. Meanwhile, there are no conclusive data as regards optimal therapy.3 Our reports illustrate that in some cases,2 a favourable outcome may be obtained with a short course (3–4 weeks) of oral ofloxacine.
References
1.
Mooren FC, Lerch MM, Ullerich H, Bürger H, Domschke W. Systemic granulomatous disease after intravesical BCG instillation. Br Med J2000; 320:219.
2. Andrès E, Kuhnert C, Perrin AE, Averous G, Ruellan A, Goichot B, et al. Syndrome septicémique et granulomatose médullaire dans les suites d’une instillation intra-vésicale de BCG en traitement d'un cancer de la vessie. Presse Med1999; 28:1753–4.
3.
Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises: a 57-year-old man with fever and jaundice after intravesical instillation of bacille Calmette-Guerin for bladder cancer. N Engl J Med1998; 339:831–7.
4. Lamm DL, van der Meijden PM, Morales A, Brosman SA, Catalona WJ, Herr HW, et al. Incidence and treatment of complications of bacillus Calmette-Guerin intravesical therapy in superficial bladder cancer. J Urol1992; 147:596–600.[Web of Science][Medline]
5. Dehaven JI, Traynellis C, Riggs DR, Ting E, Lamm DL. Antibiotic and steroid therapy of massive bacillus Calmette-Guerin toxicity. J Urol1992; 147:738–42.[Medline]
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