• 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-Hypotension-Altered 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 historyHypertension since 10 years ago.

Diabetes mellitus since 5 years ago.History 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 8.7Plt 77000 24000 22000Na=135 K=4 Ca=9 P=4PBS= Toxic granulation: 1+ Shistocyte :neg Blood culture : neg

AST=198 109 ALT=226 124

ALKph=206 403

Bil(D:8.2 3.6 T:14.9 6.3)

PT=17 13.5 PTT=49 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:110 179 75

Cr:3.6 4.7 2.8

Paraclinic evaluations

Abdomio –pelvic sonography was normalEchocardiography : EF=60% PAP=NL

No evidence of PTEBMA & BIOPSY : Hypercellular marrow

with increased megakaryocyte Negetive for granulomatous inflammation

PPD test:neg

Doppler sonography of lower extremites: normal

Chest x Ray was normal

EKG: 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 non-muscle 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 of testicle

Painful 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

SepsisThe 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-malaise-dyspnea

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 is the most common presentation .

Reactive arthritis: predominantly involves lower

extremitis. usually 2 weeks after instillation occurs.it

associated with genitourinary symptoms. in one

study 55% had HLA B27.

Septic arthritis can due to 1)Bacterial infection

(monoarthritis) 2)M.bovis infection(polyarthritis)

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 Cr=1.6

AST=36 ALT=34 Alk ph=138

References:

• UP-TO-DATE version:21-3

• Brazillian journal of urology (SEP-OCT) 2013 (page 488-502)

• European urology supplement 2012 (page 542-547)

• Journal of urology 2008 (page 1-5) American urological association.

• Journal of urology 2010 (page 596-600) printed in USA.