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• A 62-year-old man was diagnosed with bladder TCC since 7 month ago .A tumoral TUR was performed and intravesical BCG instillations once a week for 4 weeks were started . One day after the last cycle ;the patient was referred to the hospital because of : Chills-Fever-Dyspnea-HypotensionAltered of LOC & icter. He was admitted to ICU immediately and took corticosteroid & hydration for 24 hours. After 24 hours ; he became alert and his blood pressure was normal ;but fever and chills continued . He was referrerd to gastrointestinal ward with : icter- fever &chills for more investigations Past medical history Hypertension Diabetes History since 10 years ago. mellitus since 5 years ago. of hematuria since 8 month ago. Opium addict. Heavy smoker until 7 years ago. Tab- Atenolol 100 mg daily. Cap-tamsulosin Qhs No familial and allergy history Physical examination Sclera was icteric No lymphadenopathy Lungs bilateral were clear Heart sounds were normal without murmur Abdomen was normal no organomegaly No edema-cyanosis-clubbing Neuromuscular examinations was normal. General appearance(After 24 hours): An old man nearly obese ‘ alert’ not ill & toxic. he was icteric Vital sign at the first visit: BP=70/p HR:110 T:38.1 RR:18 O2sat:95% Laboratory tests WBC 9.1 5.6 2.8 Hb 15.1 12.5 8.7 Plt 77000 24000 22000 Na=135 K=4 Ca=9 P=4 PBS= Toxic granulation: 1+ Shistocyte :neg Blood culture : neg AST=198 109 ALT=226 ALKph=206 Bil(D:8.2 PT=17 124 403 3.6 T:14.9 13.5 PTT=49 6.3) 39 INR=1.7 1 HBSAg: neg HCVAb: neg HBCAb :neg HIV Ab:neg U/A(pro= neg WBC =2-4 RBC=3-5 Bact-) Urine 24h(vol=3900 pr=257 cr=1833) LDH=618 Serum Alb=4 TP=6.4 BS=243 ESR=10 Urea:110 Cr:3.6 179 4.7 75 2.8 Paraclinic evaluations Abdomio –pelvic sonography was normal Echocardiography : EF=60% PAP=NL No evidence of PTE BMA & BIOPSY : Hypercellular marrow with increased megakaryocyte Negetive for granulomatous inflammation PPD test:neg Doppler Chest EKG: sonography of lower extremites: normal x Ray was normal normal sinus rhythm. Problem list: A 62 –year –old man Known case of TCC of bladder since 7 month ago. He was taken intravesical BCG instillation weekly after TUR After the last dose(fourth dose) he admitted in hospital with: Fever-Chills - Hypotension - Dyspnea -Altered of LOC and icter He was referred to gastrointestinal field after 24 hours management in ICU fore more investigations. Differential diagnosis Hypoglycemia Overdose of opiate Uremia Infections(Septicemia -Meningitis- BCG sepsis) Pulmonary embolism Hypoxia or Hypercarbia Siezure CVA MI and CHF Anaphylactic shock Hepatic encephalopathy Syncopal attack About Bacille -Calmette-Gu’erin(B.C.G) B.C.G has been used for more than 90 years with safety records as a vaccine against TB that derivated from live mycobacterium bovis.(M.bovis is slow-growing aerobic bacterium and the causative agent of tuberculosis in cattle). Intravesical B.C.G used about 35 years ago for nonmuscle bladder cancer. B.C.G has been shown the most effective agent against superficial bladder tumors. B.C.G therapy prevents or reduce tumor recurrence. Indications of intravesical BCG Indications for intravesical B.C.G Papillary or flat Tis.(carcinoma in situ) Papillary tumors as non invasive .tumors confined to urothelium(Ta) Superficially invasive.tumors invading the lamina properia(T1) Mechanism of intravesical BCG 1) An immune mechanism of BCG induced antitumor activity(cytotoxic effect)an intact immune system particularly the cellular system is required for antitumor activity. 2)Infiltration of bladder wall by immunocompetent cells together with secretion of cytokines into the urine part the intense local immune activation. Complications of intravesical BCG Localized complications of BCG BCG cystitis Granulomatous prostatitis &Epididymitis Hematuria Swelling Painful of testicle urination Systemic complications of BCG Chills-Fever-Cough-Body pain-Weakness-Vomiting-Flulike symptoms Acute renal failure-Granulomatous nephritis-Mesangial GN Arthralgia - Reactive arthritis - septic arthritis - Osteomyelitis Hepatitis-Hepatic granuloma –granulomatous collangitis Serious allergic reactions(Intractable anaphylaxia) F.U.O-Night sweats-Anorexia-Fatigue-Weight loss Hematologic disorders Mycotic aneurysms Loss of vision in elderly patients due to endophtalmitis Respiratory disorders(ARDS-Pneumonitis-Cough) BCG sepsis & septic shock Pityriasis rosea like rash Systemic complications of BCG treatment Sepsis The classic sepsis syndrome can occur with: Fever-Hypotension-DIC & respiratory failure. These manifastations are probably due to high levels of cytokines released directly into the bloodstream as part of the hypersensivity response(so called cytokine storm) Hepatitis Granulomatous hepatitis is early or late complication of BCG intravesical instillations that presents with :fever-jaundice in the first week after BCG instillation Hepatitis represents similar to granulomatous hepatitis with: (fever-jaundice and anorexia) Pneumonitis Milliary nodular or interstitial pattern on routine chest X-R or CT scan Accompanied by fever-malaisedyspnea Usually occurs with sepsis Osteomyelitis Usually involves spine due to spread from urinary tract through Batson’s plexus Presents with low back pain-motor weakness-rigors-sweats Arthralgia & Arthritis Arthralgia Reactive extremitis. is the most common presentation . arthritis: usually predominantly involves lower 2 weeks after instillation occurs.it associated with genitourinary symptoms. in one study 55% had HLA B27. Septic arthritis can due to 1)Bacterial (monoarthritis) 2)M.bovis infection(polyarthritis) infection Hematologic complications Anemia due to chronic disease Leukopenia Coagulopathy disorders such as DIC or Thrombocytopenia Pancytopenia due to granulomatous reaction Coclusions about complications of BCG 1-Hypersensivity reactions gained based upon the presence of granuloma and absence of organism (Hepatitis-prostatitis-bone marrow involvement…….) 2-Ungoing active infection due to M-bovis spreading Southern medical journal.2008;101(1):91-95 The journal of urology .printed in USA .March 2010. page:598 Active infection(BCGosis or BCG sepsis) BCGosis occur following systemic absorption of BCG into blood stream via disturbed mucosa due to traumatic catheterization and recent bladder tumor resection. If fever exceeding 38.5’c lasting over 24hours despite antipyretic therapy or recorded fever higher than 39.5’c should prompt a hight clinical suspicion of BCGosis In this patient fever &chills were discontinued after two days.He felt wellbeing .icter diminished and laboratory tests nearly improved and discharged after one week He was followed for two month by urologist and nephrologist. The last laboratory tests: WBC=4600 HB=12.9 Plt=211000 Urea=24 AST=36 ALT=34 Cr=1.6 Alk ph=138 References: • UP-TO-DATE version:21-3 • Brazillian journal of urology • European urology supplement 2012 • Journal of urology 2008 (page 1-5) American urological association. • Journal of urology 2010 (page 596-600) printed in USA. (SEP-OCT) 2013 (page 488-502) (page 542-547)