A 53 year old woman with a PMH of hypertension and bladder cancer, currently receiving direct BCG therapy, who presents with fever for the past 48 hours. Highest measured temperature was 101.8 F at home. She spoke with her urologist who advised her to go to the nearest emergency department. She endorses dysuria and hematuria. Last BCG treatment was one week ago. Her next treatment is tomorrow. She is worried that this fever will affect her treatment schedule.
Vitals - T: 38.4, HR: 78, BP: 143/92, O2: 99% RA
Physical exam - Well appearing with overall normal physical exam.
Work-up: Typical septic work-up including CBC, lactate, standard blood cultures, UA/UC, CXR.
Everything returned unremarkable with the exception of UA that was leukocyte esterase+, 10-15 WBC, few bacteria. Patient’s urologist was contacted to discuss desired disposition.
Outcome: Admitted to medicine with urology consult to follow labs and help decide on therapy. Add on AFB blood and urine cultures.
Discussion:
Live attenuated BCG vaccine is commonly used as intravesical therapy in conjunction with TURBT (transurethral resection of bladder tumor) for non-invasive urothelial cancers. Patient receive intravesical dosing once a week for 6 weeks and then once a week for three weeks at 3, 6, 12, 18, 24, 30 and 36 months. While it is not an immunosuppressive treatment that predisposes to neutropenia and subsequent infection, there are several serious infections side effects of the therapy itself.
Local - Cystitis, Proctitis, Epididymitis, Renal infections
Systemic - Sepsis, Hepatitis, Pneumonitis, Osteomyelitis, Arthritis, Endopthalmitis
Risk factors for infectious complications include:
Traumatic catheterization during BCG instillation
Receiving therapy too soon after urologic surgery
Concurrent non-BCG UTI
Older age
Immunosuppression (in some cases)
Of note, most cases will present within a couple weeks of therapy, but infectious complications have been reported up to years after last therapy.
Systemic infections can result in full septic response including hypotension and multiorgan failure. Because of this, patients on BCG therapy presenting with fever even in the absence of other symptoms or clinical instability should be admitted and monitored. Appropriate work-up includes AFB stain, culture, PCR of blood, urine and other relevant specimens. ID and urology consults are also recommended to help guide appropriate therapy.
Treatment generally depends on findings and clinical progression. For patients who present with localized infection it is often difficult to distinguish between BCG and non-BCG sources. Treatment should include either levofloxacin or INH. Response to initial treatment will determine duration which will be anywhere from two weeks to three months and may necessitate additional agents. For severe or disseminated infections, patient will receive multidrug anti-TB regimen +/- steroids for 6 months and should not receive further BCG therapies.
*Steroids are used as adjunctive therapy because there is some evidence that complications of BCG therapy are mediated by hypersensitivity reaction. However, steroids have been associated with development of the complication itself secondary to immunosuppression. For that reason, use of steroids should be left to ID consultants.
**PPE does not require N95 for handling BCG though it may be institutional preference/policy.
Alex Davic, MD is a current second year resident at Stony Brook Emergency Medicine.
References
Edited by Bassam Zahid, MD