intravesical instillation of bacillus calmette - guerin ( bcg ) is an established option for the treatment and prophylaxis of non - muscle - invasive bladder cancer .
low - grade fever and irritative bladder symptoms are common side - effects of intravesical bcg instillation therapy . penile lesions or balanitis as complications of bcg treatment
, we present a patient who underwent intravesical treatment with bcg and subsequently developed penile lesions and bilateral inguinal lymphadenopathy .
the pathologic diagnosis was pta , g2 transitional cell carcinoma and carcinoma in situ ( who 1973 ) .
he was offered six weeks of bcg instillation ( oncotice , tice strain , administered intravesically after reconstitution in 50 ml saline ) .
the patient was unable to complete the treatment cycles consecutively due to severe irritative symptoms ; hence at the second and fourth week , treatment cycles were cancelled for a period of one week and his symptoms were treated with antibiotics and antispasmodics .
he was administered five cycles of bcg at full dose , atraumatically , by a staff urologist using a 12fr hydrophilic nelaton catheter .
one week after the last instillation the patient reported penile swelling and tenderness , itching at suprapubic areas .
two days later , he presented with a penile lesion and indurated lesions at the suprapubic area .
physical examination demonstrated two areas of painless indurated lesions at the pubic area and shallow ulceration on the penil shaft [ figures 1a and b ] and bilateral palpable inguinal lymphadenopathy .
chest x - ray was unremarkable and computed tomography ( ct ) of abdomen revealed bilateral inguinal adenopathy ( maximal length of diameter 1 cm on the left and 1,5 on the right side ) .
laboratory data showed slight elevation of c - reactive protein and erythrocyte sedimentation rate , and otherwise blood chemistry was normal .
polymerase chain reaction ( pcr ) for urine tubercle bacilli was negative , and thereafter urine cultures were also negative for mycobacterium .
( a , b ) penile ulcerated lesion and papule at pubic area before treatment ; ( c , d ) appearance at three months ( c ) and six months ( d ) after treatment the patient underwent diagnostic biopsy from the papules of pubic areas and cystoscopy at the same time .
cystoscopy showed several erythematous areas in the bladder and cold - cut biopsy was obtained from these areas .
pathology of the bladder biopsies revealed acute and chronic inflammation with granulomatous changes ; there was no evidence of malignancy .
the pathologic examination of biopsy samples from endurated pubic lesions demonstrated granulomatous inflammation with caseous necroses [ figure 2 ] and multinucleated giant cells of langhans type , which was compatible with bcg - induced granulomatous skin infection .
histological appearance of granulomatous inflammation with caseous necroses ( h and e , 10 ) intravesical bcg instillation therapy was discontinued and the patient was given a three - drug antitubercular regimen including rifampicin , isoniazid , and pyrazinamide .
the total treatment course was six months , with discontinuation of pyrazinamide after two months .
complete resolution of penile , pubic lesions and inguinal adenopathy was achieved at six months of treatment [ figures 1c and d ] .
follow - up cystoscopy showed no evidence of tumor recurrence and ct of abdomen and chest x - ray were unremarkable .
side - effects of bcg usually occur when bcg is given immediately after transurethral resection of a bladder tumor , or when the patient had a traumatic catheterization or concurrent cystitis during intravesical instillation .
use of immunosuppressive agents or genetic factors may also play significant role . during the instillation cycles of bcg ,
urine culture was negative however this may not preclude urinary tract infection and may have predisposed to bcg side - effects .
although catheterization was atraumatic in the present case unnoticed trauma during catheterization could have played a role in the bcg toxicity determined in our patient .
although our patient had no co - morbidities such as diabetes or immunosupression , his older age may have been a factor for the progression of side - effects .
granulomatous reaction associated with bcg treatment is known to occur in the bladder , epididymis , prostate , kidney , lung and liver .
however , occurrence of balanitis is uncommon and only a few cases of balanitis associated with bcg instillation have been reported .
granulomatous balanitis symptoms include penile edema , papules and ulcers , occasionally associated with inguinal lymphadenopathies as in our case .
therefore , clinical diagnoses are made in the majority of cases by histopathology and by the history of bcg therapy .
although the stain and culture were negative for mycobacterium , given the recent history of intravesical instillation of bcg , these lesions likely represent dissemination of inoculums .
the mechanism of infection presumably occurred via direct inoculation of the penis during the instillation of bcg , followed by dissemination to the superficial inguinal lymph nodes .
histological appearances of these changes typically show epithelioid granuloma with central necroses and giant cells of langhans type as determined in our case . as
bcg - induced penile ulcer and adenopathy is a rare complication of intravesical bcg therapy , treatment for this disease is not yet standardized .
however , modern short - course anti - tuberculosis drug regimens for genitourinary tuberculosis are also recommended for the treatment of such cases . according to the world health organization
anti - tuberculous drug treatment is based on an initial two - month intensive phase of treatment with three or four drugs with rifampicin , isoniazid , pyrazinamide , and ethambutol to destroy almost all tubercle bacilli .
treatment is followed by a four - month continuation phase with only two drugs , rifampicin and isoniazid . in our case ,
adverse effects of bcg intravesical administration affect several organs in the genitourinary system and can disseminate to distant organs .
the clinician must be alert to any complaints the patient has after treatment , and investigate accordingly .
physicians should be aware of the possibility of bcg - induced granulomatous balanitis and concomitant adenopathy .
when these clinical features appear in patients , adequate therapy should be started as soon as possible .
we consider that immediate antituberculous therapy should be commenced to achieve prompt resolution and management of clinical findings .
 intravesical bacillus calmette - gurin ( bcg ) is widely used as an adjuvant therapy in the treatment of non - muscle - invasive bladder cancer . 
 bcg is generally well tolerated , though localized and systemic infectious complications may occur . 
 infection of the glans and inguinal adenopathy are rare local complications of intravesical bcg therapy . 
 traumatic urethral catheterization is one of the main causes . 
 we report the case of a 75-year - old male who developed granulomatous balanitis and enlarged inguinal lymph nodes after five cycles of intravesical bcg treatment for transitional cell carcinoma of the bladder . 
 histology revealed giant cell granuloma . 
 oral antituberculous treatment was initiated with subsequent full recovery of penile lesions and adenopathy . 
 physicians who administer bcg must be familiar with the possible complications and their adequate management and should inform patients about the side - effects accordingly . 