Osteoarticular side effects of BCG therapy

Although osteoarticular side effects of the Bacillus Calmette-Guérin (BCG) are rare compared to the number of administrations, BCG vaccination and cancer therapy are so widely used that the absolute number of cases is not negligible. Osteoarticular infection is an exceedingly rare complication of vaccination with the BCG. Intravesical BCG instillations used to treat superficial bladder cancer may cause arthralgia, reactive arthritis or osteoarticular infections. Intradermal BCG therapy used to treat a number of malignancies can cause osteoarticular infections or bilateral symmetric polyarthritis predominating in the wrists and fingers. In practice, when intravesical BCG instillation is followed by arthritis, hyperthermia is unhelpful for distinguishing septic arthritis from reactive arthritis. Arguments pointing to reactive arthritis include oligo- or polyarticular involvement and onset a few weeks (as opposed to a few months) after the last instillation. Nevertheless, joint fluid examination is in order to rule out septic arthritis. BCG-induced reactive arthritis usually responds well to nonsteroidal anti-inflammatory drugs. Osteoarticular infections related to BCG therapy should be treated by rifampin, isoniazid and ethambutol for 2 months, followed by rifampin and isoniazid for 10 months.     

Sepsis und Multiorganversagen nach BCG-Instillation bei Blasenkarzinom

Local Bacillus Calmette-Guerin (BCG) immunotherapy is an effective and widely used treatment for superficial bladder carcino-ma. Local side effects are frequent, where-as systemic side effects are rare, but more serious. Systemic BCG infection as a life-threatening complication of intravesical BCG instillation should be suspected in any patient who presents with persistent fever after BCG instillation for bladder cancer.A 62-year-old patient had been treated with 6 intravesical BCG instillations for recurrent, multifocal bladder carcinoma.4 weeks after the last instillation, he presented with fever, malaise and scleral icterus. Laboratory tests revealed abnormal li-ver function tests, panzytopenia and signs of coagulation disorder. Bone marrow biopsy and liver biopsy showed non-caseating granulomas. Systemic BCG infection was suspected and antituberculous therapy combined with steroids was started. The patient developed severe sepsis and suffered from multiple organ failure. Despite partial improvement, the course was complicated by intracranial sinus thrombosis, and the patient died two month after admission.     

Penile edema and meatal ulceration after intravesical instillation with Bacillus Calmette-Guérin

Bacillus Calmette-Guérin (BCG) bladder instillation is an accepted treatment modality in the management of superficial transitional cell carcinoma but is associated with frequent side effects. A report of intravesical BCG-induced penile edema and meatal ulceration that occurred in 2 patients is presented. During induction therapy, both patients complained of progressive penile edema. In 1 patient the edema appeared after the second instillation and in the other after the fourth instillation. Edema was associated with ensuing meatal ulceration and enlarged inguinal lymph nodes. BCG instillation was aborted, and oral antituberculous treatment was initiated. There was no report of external spillage during the administration of BCG or of genital or urethral trauma during catheterization. Patients were treated at different clinics but with BCG of the same strain and batch. Symptoms continued for 6 weeks until they abated. Both patients were managed with oral antituberculous drugs for a period of 3 months. Adverse effects of BCG intravesical administration affect several organs in the genitourinary system. The penis and urethra may also be involved, presenting as penile edema and meatal ulceration. Physicians who administer BCG must be familiar with the possible complications and their appropriate management.     

Evaluación de la incidencia,factores predictivos y consideraciones sobre el tratamiento de los granulomas genitourinarios asintomáticos después de la terapia intravesical con bacilo de Calmette-Guérin

Introduction and objectivesAlthough the complications of intravesical BCG treatment are well described, asymptomatic genitourinary granulomas after BCG therapy have rarely been reported and management strategy for these conditions remains controversial. The objective of this study is to evaluate the incidence rate of asymptomatic genitourinary granuloma formation mimicking bladder cancer recurrence after intravesical bacillus Calmette-Guérin (BCG) therapy and to identify the diagnostic and treatment strategies according to patient conditions.Patients and methodsA retrospective review was conducted on 162 patients who underwent intravesical BCG therapy. For patients who developed granulomas, we evaluated the time interval between BCG instillation and the development of granuloma, the presence of acid-fast bacteria on pathology specimens, culture/polymerase chain reaction results, management strategies for the lesions, and clinical outcomes.ResultsAsymptomatic genitourinary masses developed in 14 patients, of whom 5 underwent histological examinations and all were confirmed to have granulomatous inflammation. The affected organs included the kidney, bladder, prostate, and penis. While four of the five patients did not receive treatment for their granulomas, one patient was administered antituberculous medication to prevent worsening of the lesion during the perioperative period of the scheduled cystoprostatectomy. None of the patients experienced worsening or recurrence of granulomatous lesions. Patients who developed asymptomatic masses (n =14) were significantly younger than those who did not (P=.0076) and multivariate analysis also showed that younger age was independently associated with the development of clinically suspicious lesions (P=.032); however, none of the parameters were associated with histologically confirmed granuloma formation.ConclusionsGenitourinary granulomas mimicking recurrence of carcinoma may develop in nearly 10% of patients after intravesical BCG therapy. Most patients can be managed without potentially toxic antituberculosis therapy.     

膀胱内灌注卡介苗的严重合并症及处理(18例病例报告并文献复习)

作者报告了168例卡介苗膀胱内灌注的患老中出现18例严重合并症,发生率为10.7％,其中泡性结角膜炎1例文献中尚未见报道,文章结合复习文献,讨论了卡介苗膀胱内灌注出现的局部及全身的合并症,掌握正确的灌注方法和恰当的灌注时间,积极早期的正确治疗能减少合并症的发生,但各种严重合并症的报道屡见增多,值得高度重视。     

Arthritis following intravesical instillation of BCG for urothelial cancers

BACKGROUND: Intravesical instillation of bacillus Calmette-Guerin (BCG) is efficient for prophylaxis of superficial bladder cancer and treatment for carcinoma in situ (CIS) of the upper urethelial cancer. However, the incidence of adverse effects is relatively high, and those include reactive arthritis. We retrospectively evaluated the incidence and the outcome of reactive arthritis following intravesical BCG therapy for urothelial cancers. PATIENTS AND METHODS: Intravesical instillations of BCC were performed in 192 cases (218 courses) between January 1998 and January 2002. BCG was instilled for prophylaxis of superficial bladder cancer recurrence in 170 (195 courses), treatment for CIS in 7 (8 course), and treatment for CIS in 7 (8 courses), and treatment for CIS in upper urinary tract in 15 (15 courses). RESULTS: Arthritis was recognized in 8 cases (3.7%, 8/218 courses), and 7 of them were identical to reactive arthritis following BCG therapy. Remaining 1 patient was diagnosed as rheumatoid arthritis (RA), and the relation between arthritis and intravesical BCG instillation was unclear. Mean number of BCG instillation was 5.6 (3-8 times). All reactive arthritis were occurred within 4 weeks after the last BCG instillation, i.e., BCG induced urinary tract infection, and 6 of them were polyarthritis. Concurrence of conjunctivitis was seen in one patient. HLA-B27 was negative in 4 examined patients. A nonsteroidal anti-inflammatory drug (NSAID) was used in all 8 patients, anti-tuberculous agents were used in 3, and prednisolone was added in 3, Arthritis was improved within 2 months in patients received prednisolone, however, it persisted longer than 3 months in patients without prednisolone. CONCLUSION: Arthritis was recognized in higher incidence than previous reports following intravesical instillation of BCG. All cases except one, diagnosed as RA, were diagnosed as reactive arthritis (Reiter's syndrome). However, correlation between HLA-B27 and arthritis was not clear in this study. Administration of steroidal drug was thought to improve arthritis in shorter duration.     

ＭＭＣ和ＢＣＧ交替灌注防治膀胱癌术后复发

目的：观察丝裂霉素Ｃ（ＭＭＣ）和卡介苗（ＢＣＧ）化学免疫预防膀胱癌术后复发的疗效。方法：对８６例浅表性膀胱癌患者术后应用ＭＭＣ２０mg和ＢＣＧ６０mg,每周１次进行交替膀胱藻注,共灌注１２次,以后每间隔３个月灌注１次,持续２年,结果：随记２．４－８年,平均４．８４年,肿瘤复发率为８．１％,结论：ＭＭＣ和ＢＣＧ交替膀胱灌注可减少膀胱癌术后复发率。     

卡介苗联合白细胞介素-2膀胱灌注预防膀胱癌复发机理的研究

目的探讨卡介苗（ＢＣＧ）联合白细胞介素－２（ＩＬ－２）膀胱灌注预防膀胱癌复发的机理。方法对３５例膀胱移行细胞癌术后患者分别行ＢＣＧ和ＢＣＧ加ＩＬ－２膀胱灌注,随访１４～２２个月,复发率分别为３１．２５％和２１．０５％。结果应用ＩＬ－２加ＢＣＧ膀胱灌注６周后,外周血天然杀伤细胞激活因子（ＮＫＣＦ）活性明显增强,在ＮＫＣＦ活性与ＩＬ－２活性间有显著正相关变化。结论ＩＬ－２加ＢＣＧ膀胱灌注预防膀胱癌复发作用明显优于单纯用ＢＣＧ,ＩＬ－２和ＢＣＧ两者间有免疫促进和协同作用。     

Photodynamic Diagnosis (5-Aminolevulinic Acid) of Transitional Cell Carcinoma After Bacillus Calmette-Guérin Immunotherapy and Mitomycin C Intravesical Therapy

Background

Photodynamic diagnosis (PDD) is a technique that enhances the detection of occult bladder tumors during cystoscopy using a fluorescent dye.

Objective

To study the differential effects of bacillus Calmette-Guérin (BCG) and mitomycin C (MMC) intravesical therapy on the false-positive rate of PDD of bladder cancer.

Design, setting, and participants

This study included 552 procedures and 1874 biopsies.

Intervention

Tumors were resected and biopsies were taken from suspicious areas, under guidance of white-light endoscopy and 5-ALA (5-aminolevulinic acid)–induced fluorescence cystoscopy.

Measurements

The influence of intravesical BCG immunotherapy and intravesical MMC chemotherapy on pyuria, inflammation, and PDD specificity was examined in univariate analyses.

Results and limitations

BCG significantly results in inflammation (odds ratio [OR]: 1.53, p = 0.002), leukocyturia (OR: 1.84, p = 0.034), and false positives in PDD (OR: 1.49, p = 0.001). However, a single BCG instillation within 3 mo before PDD is most likely not associated with increased false-positive rates (OR: 0.35, p = 0.26). Leukocyturia normalizes within 6 wk after the last BCG instillation, but PDD specificity is reduced up to 3 mo.

Conclusions

BCG is an important predictor for false positives in PDD (5-ALA). More than one BCG instillation within 3 mo before fluorescence cystoscopy decreases the specificity of PDD.     

Safety and efficacy of intensive instillation of low-dose pirarubicin vs. bacillus Calmette-Guérin in patients with high-risk non-muscle-invasive bladder cancer

ObjectivesTo evaluate the safety and efficacy of intensive intravesical instillation of low-dose pirarubicin (THP) for 6 times vs. bacillus Calmette-Guérin (BCG) without maintenance therapy after transurethral resection of bladder tumor (TURBT) in patients with primary high-risk non-muscle-invasive bladder cancer (NMIBC).Materials and MethodsWe retrospectively evaluated 370 patients with primary high-risk NMIBC who underwent TURBT from November 1993 to April 2019. The patients were divided into 2 groups: patients treated with intravesical instillation of BCG without maintenance therapy (BCG group) and intensive intravesical instillation of low-dose (20 mg) THP for 6 times within 10 days after TURBT (THP group). Safety was assessed using the Common Terminology Criteria for Adverse Events version 5.0. Background-adjusted multivariate analyses were performed to evaluate the effect of intensive intravesical instillation of low-dose THP on oncological outcomes, including intravesical recurrence-free survival (RFS), upper urinary tract RFS, muscle-invasive bladder cancer-free survival, metastasis-free survival, cancer-specific survival, and overall survival.ResultsOf the 370 patients with primary high-risk NMIBC, 180 (49%) and 190 (51%) were stratified into the BCG and THP groups, respectively. The incidence rate of adverse events of any grade in the BCG group was significantly higher than that in the THP group (P < 0.001). In the background-adjusted multivariate analyses, no significant differences were observed in oncological outcomes between the BCG and THP groups.ConclusionsIntensive intravesical instillation of low-dose THP for 6 times may be one of the treatment options in view of safety and efficacy after TURBT in patients with primary high-risk NMIBC.     

Systemic and local immunomodulatory effects of intravesical BCG therapy in patients with superficial urinary bladder carcinomas

PURPOSE: The aim of the present study was to elucidate whether only local, or also systemic immunomodulatory effects may be induced by intravesical BCG therapy of superficial urinary bladder cancer. MATERIALS AND METHODS: A total of 37 patients with stages Ta to T1b superficial transitional cell bladder carcinomas received 6 weekly BCG instillations after transurethral resection of the tumor. In a first group of 19 patients blood was taken before each BCG instillation and 6 weeks after the last one. In a second group of 18 patients blood and urine was taken before and 2, 6, and 24 hours after each BCG instillation. In the mitogen-stimulated whole blood cell cultures and in the urine samples the levels of the cytokines IL-1beta, IL-2, IL-10, TNF-alpha and IFN-gamma were determined by enzymoimmunological tests. Additionally, in all plasma and urine samples the levels of TNF-p75-receptor (TNF-p75-R) were measured. RESULTS: Comparison of ex vivo leukocyte cytokine production in the blood cell cultures of the patients of group I revealed no significant change in the levels of the cytokines. In contrast, TNF-p75-R plasma levels increased significantly during the experimental time of 12 weeks (p < or =0.01). In the blood cell cultures of the group II patients a different daytime variation of cytokine production was seen, compared to the 19 healthy controls. After BCG instillation the normal peak cytokine production in the evening was suppressed. A significant rise in plasma TNF-p-75-R levels was measured 24 hours after BCG instillation (p < or =0.05). In the urine of these patients significantly higher levels of all measured cytokines and TNF-p75-R were observed 6 to 24 hours after the instillation. CONCLUSIONS: The results suggest that besides the well known local immune activation, BCG instillation also leads to a modulation of peripheral immune mechanisms.     

Safety and immunoresponse study of intravesical instillation of Taipei-NIPM bacillus Calmette-Guérin.

The intravesical instillation of bacillus Calmette-Guérin (BCG) has proved to be an effective modality for prophylaxis of recurrent superficial bladder cancer and treatment of carcinoma in situ. The domestic BCG, named Taipei-NIPM, which is produced by the National Institute of Preventive Medicine, has been used as an anti-TBC vaccine in Taiwan for decades. In this study, we have investigated the safety and immune response in animals after intravesical BCG treatment to test its feasibility in future clinical application. Weekly instillation of BCG (1 mg/ml, 5-8 x 10(7) CFU/mg) for 6 instillations could induce lymphocytic infiltration, submucosal fibrosis, and granulomatous reaction after 4 weeks with mild decrease of bladder weight and high incidence of hematopyuria (75%). No changes in appetite, body weight, and splenic weight were noticed in the chronically treated rats. A delayed hypersensitivity test through foot pad swelling measurement reached 80% positive rates at 2 weeks. Cystometric study revealed a mild decrease in bladder capacity (33.3%) at 2 weeks and of contractile pressure of the urinary bladder in rats receiving BCG instillations. In addition, increase in lymphocytic infiltration by natural killer (NK) cells against YAC-1 cells could be detected after BCG treatment and this was related to dosage of BCG. The urothelial damage by cauterization and the number of instillations could also enhance NK cell activity. Low toxicity and high safety of intravesical instillation of the domestic BCG are demonstrated by this pilot animal study. This information on local and systemic immune responses can provide a solid base for future efficacy of BCG immunotherapy in bladder cancer patients using this domestic strain BCG.     

Intravesical bacillus Calmette-Guerin (BCG) in the treatment of superficial bladder cancer. Prospective randomized study for prophylactic effect

We report the results of prospective randomized study which was designed to evaluate prophylactic effects of intravesical bacillus Calmette-Guerin (BCG) in the treatment of superficial transitional cell carcinoma of the bladder. A total of 44 cases who had no previous treatment of bladder cancer were randomly assigned to BCG or control groups after TUR. BCG group (23 cases) received intravesical instillation of 80 mg BCG (Tokyo strain) at one week intervals for 6 weeks, at two week intervals for 12 weeks, and at one month intervals for 20 months. In BCG groups, 3 cases had recurrence at 6 months and 1 case at 9 months, while the other 19 cases had no recurrent disease for 3 to 34 months (average 20.3 months) of follow-up. Control group (21 cases) had no further treatment after TUR. In control group, recurrence was seen at 3 months in 3 cases, at 6 months in 5 cases, at 9 months in 2 cases, at 12 months in 3 cases and at 21 months in 1 case. Only 7 cases in the control group were free of recurrence for 8 to 45 months (average 32.3 months) of follow-up. One and two year-recurrence rates in BCG group (18.4%, 18.4%) was significantly (p less than 0.01) lower than those in control group (63.2%, 68.9%). Among the complications of intravesical BCG were cystitis (76.2%), low grade fever (13.0%), and several days' persistent gross hematuria (13.0%). Most of these signs were self-limited and only in 2 cases instillation of BCG was discontinued.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ruptured mycotic abdominal aortic aneurysm secondary to Mycobacterium bovis after intravesical treatment with bacillus Calmette-Guérin

Bacillus Calmette-Guérin (BCG) is a live attenuated strain of Mycobacterium bovis that has proven effective in the treatment of early-stage bladder cancer. Although intravesical therapy with BCG is generally considered safe, serious complications including hematuria, granulomatous pneumonitis, hepatitis, and life-threatening BCG sepsis are well known. BCG-related vascular infections are rarely reported. We present a case of a ruptured abdominal aortic aneurysm secondary to M bovis infection 2 years after intravesical instillation of BCG and review the related literature.     

Epididymo-orchitis caused by intravesically instillated bacillus Calmette-Guérin: Genetically proven using a multiplex polymerase chain reaction method

The intravesical instillation of bacillus Calmette-Guérin (BCG) is a standard therapy for superficial bladder carcinoma. Tuberculosis-like inflammation in the genitourinary tract is a serious complication of BCG. It can occur after a long interval from the cessation of the intravesical BCG therapy. If inflammation occurs, it is necessary to test whether the BCG strain has caused it or another mycobacterium species has. However, there has never been a report that proves BCG causes the inflammation, because BCG is difficult to differentiate from other strains of Mycobacterium bovis and other members of the Mycobacterium tuberculosis complex by conventional tests, including regular polymerase chain reaction (PCR). We first present a case of epididymo-orchitis, which developed 31 months after the cessation of BCG therapy, detected using a multiplex PCR method as having been caused by BCG. Our report illustrates the efficacy of this method to detect the responsible microbe that is thought to be transmitted from the instillated BCG strain.     

膀胱癌经尿道电切除术后吡柔比星膀胱灌注预防复发临床观察

目的:探讨吡柔比星膀胱内灌注预防膀胱癌术后复发的疗效、安全性。方法:45例膀胱癌经尿道电气化术后患者分2组,分别用吡柔比星和卡介苗定期行膀胱内灌注,随访10～33个月,了解灌注后肿瘤复发情况及并发症。结果:卡介苗组复发率为13.6%(3/22),副反应率为81.8%(18/22);吡柔比星复发率为13.0%(3/23),副反应率为91.3%(21/23),两组肿瘤复发率、并发症无显著差异,但卡介苗严重副反应高于吡柔比星(P<0.05)。结论:吡柔比星膀胱灌注预防膀胱癌复发的有效率与卡介苗相同,但严重副反应明显减少,是一种有效的药物。     

Management of hepatic granulomatous tuberculosis complicating intravesical BCG for superficial bladder cancer

Intravesical bacille Calmette-Guérin (BCG) therapy is the most effective treatment for high-risk superficial bladder cancer. Severe systemic complications are rare, but may occur in approximately 1% of cases. We report a severe complication of intravesical BCG: a disseminated Mycobacterium bovis infection with biopsy-proven granulomatous hepatitis in a patient with bladder cancer. We also elaborate on the different management alternatives.     

膀胱内灌注纤维蛋白溶解抑制药物对卡介苗抗膀胱癌复发作用影响的临床研究

目的探讨膀胱内灌注纤维蛋白溶解抑制药物增强卡介苗（BCG）预防膀胱癌术后复发的疗效。方法将208例浅表性膀胱移行细胞癌（BTCC）患者术后随机分成5组，A组44例，定期膀胱内灌注BCG100～120mg＋氨甲苯酸（PAMBA）0．1g＋生理盐水，B组4l例，灌注BCG50～60mg＋PAMBA0.1g＋生理盐水，C组4l例，灌注BCG100～120mg＋氨基己酸（EACA）2．0g＋生理盐水，D组39例，灌注BCG50～60mg＋EACA2．0g＋生理盐水，E组43例，灌注BCG100～120mg＋生理盐水。每周1次，6次后每月1次。灌注后每3个月作膀胱镜检查，必要时取活检明确肿瘤有无复发。结果随访4～58个月，平均22个月，A～E组BTCC复发率分别为10．3％、8．6％、9．7％、9．7％和29．7％。A、B、C、D各组抗BTCC复发的疗效均明显优于E组（对照组），差异有统计学意义（P〈0．05）；B、D组预防BTCC术后复发的效果与A、C组比较差异无统计学意义。结论膀胱内灌注纤维蛋白溶解抑制药物PAMBA、EACA可增强BCG预防膀胱癌术后复发的疗效，BCG剂量减半后，疗效不降低。     

Detection of interleukin 2 in the urine of patients with superficial bladder tumors after treatment with intravesical BCG

Adjuvant intravesical BCG therapy is an effective means of treating superficial bladder tumors. The mechanism by which BCG mediates antitumor activity is not known; however, clinical and animal studies suggest that immunological responsiveness to BCG antigens correlates with antitumor activity. In this report the detection of interleukin 2 (IL-2, a lymphokine produced in response to BCG) in urine specimens of patients treated with intravesical BCG is reported. Patients with superficial transitional cell carcinoma of the bladder received intravesical BCG once each week for six weeks. No intradermal injections were administered. Urine specimens were obtained prior to BCG instillation and four, eight and 24 hours afterwards. The specimens were dialysed, concentrated five-fold and assayed for the presence of IL-2 in a biological assay using an IL-2 dependent cultured T-cell line. IL-2 was detected in urine but not serum after intravesical BCG instillation. IL-2 was characterized by absorption against an IL-2-dependent T cell line and neutralization by monoclonal anti-IL-2 antibodies. No IL-2 was detected in specimens obtained prior to BCG instillation or from donors with no detectable bladder pathology. One of 10 urine specimens from patients with urinary tract infections had detectable IL-2 levels. IL-2 production generally peaked during the fourth to sixth intravesical BCG treatment. Production was short-term in that IL-2 levels peaked four to eight hours after BCG instillation and were rarely (six of 54 specimens) observed 24 hours after instillation. Mean IL-2 levels were higher in patients who were rendered tumor free after BCG therapy but statistical significance was not achieved. Ten of 12 patients (83%) who responded to BCG therapy had urine IL-2 levels greater than or equal to 1.6 units/ml. at least once during the six week treatment period while two of six (33%) patients not responding to therapy had similar urine IL-2 levels. These results show that intravesical BCG therapy induces the production of lymphokines including IL-2. The presence of BCG-induced lymphokines may be associated with anti-tumor activity.     

Serious complications of intravesical bacillus Calmette-Guerin therapy in patients with bladder cancer]

Side effects and serious complications of intravesical bacillus Calmette-Guérin (BCG) therapy were reviewed in 120 patients with transitional cell carcinoma of the urinary bladder from October, 1983 to June, 1989 at Hirosaki University Hospital. As local side effects, 102 patients (85.0%) had bladder irritability with frequency and/or micturition pain, and 46 patients (38.3%) had hematopyuria. As systemic side effects, fever in 43 patients (35.8%), elevation of serum GOT, GPT in 9 patients (7.5%), and malaise in 3 patients (2.5%) were seen. Serious complications were observed in 7 patients. 4 patients had a severely contracted bladder with decreased compliance less than 50 ml, 2 patients had persistent arthritis and one patient had interstitial pneumonia. In all 4 patients with a contracted bladder partial cystectomy was performed before or after intravesical BCG therapy, and three of them received more than ten times instillation of BCG. It was suggested that contracted bladder most likely occurred after frequent BCG instillations in addition to decreased bladder compliance. Contracted bladder was irreversible in 2 patients. Histopathologically, there was marked fibrosis in the muscular layer of the bladder without tuberculous inflammatory changes. It might depend on the severity of fibrosis in the muscular layer whether contracted bladder was reversible or not. Persistent arthritis was nonspecific inflammation with negative culture results for mycobacteria in the joint fluid in 2 patients. In one patient with interstitial pneumonia, fiberoptic bronchoscopy with transbronchial lung biopsy demonstrated marked fibrosis of alveolar septums and increased lymphocyte count without tuberculous inflammatory changes. The pathogenesis of this complications is considered to be a hypersensitivity reaction to BCG.