Mayo Clinic Vol. 65
Proceedings
ROCHESTER, MINNESOTA
JULY 1990
Hepatic Cyst Infection in Autosomal Dominant Polycystic Kidney Disease AMALIO TELENTI, M.D., Division of Infectious Diseases and Internal Medicine; VICENTE E. TORRES, M.D., Division of Nephrology and Internal Medicine; J O H N B. GROSS, Jr., M.D., Division of Gastroenterology and Internal Medicine; ROBERT E. VAN SCOY, M.D., Division of Infectious Diseases and Internal Medicine; MANUEL L. BROWN, M.D., ROBERT R. HATTERY, M.D., Department of Diagnostic Radiology To c h a r a c t e r i z e t h e s y n d r o m e o f h e p a t i c c y s t i n f e c t i o n i n a u t o s o m a l d o m i n a n t p o l y c y s t i c k i d n e y d i s e a s e (ADPKD) a n d t o r e v i e w i t s d i a g n o s i s a n d m a n a g e m e n t , w e r e t r o s p e c t i v e l y s t u d i e d five s u c h c a s e s i n p a t i e n t s from o u r i n s t i t u t i o n a n d n i n e d e t a i l e d c a s e r e p o r t s from t h e literature. T h e clinical m a n i f e s t a t i o n s w e r e a n a c u t e (58%) o r s u b a c u t e (42%) febrile i l l n e s s , typically a s s o c i a t e d w i t h t e n d e r n e s s i n t h e right u p p e r q u a d r a n t , l e u k o c y t o s i s , a v e r y h i g h e r y t h r o c y t e s e d i m e n t a t i o n rate, b u t m i n o r a b n o r m a l i t i e s of l i v e r f u n c t i o n t e s t s . B a c t e r e m i a w a s p r e s e n t i n 7 of 11 p a t i e n t s . E n t e r o b a c t e r i a c e a e g r e w i n p u r e c u l t u r e from t h e c y s t fluid i n 9 o f 12 p a t i e n t s . C o m p l e x c y s t s w e r e o b s e r v e d b y u l t r a s o n o g r a p h y (in four o f e i g h t patients), com p u t e d t o m o g r a p h y (in s i x o f n i n e ) , a n d m a g n e t i c r e s o n a n c e i m a g i n g (in t w o o f two). "'In l e u k o c y t e s c a n s w e r e p o s i t i v e i n all four p a t i e n t s i n w h o m t h e y w e r e d o n e , a n d "'Ga s c a n s w e r e p o s i t i v e i n o n l y o n e o f t h r e e p a t i e n t s . A n unfavorable o u t c o m e w a s o b s e r v e d i n s i x of s e v e n p a t i e n t s t r e a t e d w i t h o n l y a n t i b i o t i c s , i n c o n t r a s t w i t h o n e of s e v e n p a t i e n t s w h o r e c e i v e d a n t i b i o t i c s a n d e a r l y d r a i n a g e . In t w o p a t i e n t s , cip rofloxacin c y s t l e v e l s w e r e 2.3 a n d 4.8 t i m e s h i g h e r t h a n t h e l e v e l i n serum; i n a third p a t i e n t , c y s t l e v e l s r e m a i n e d i n t h e r a p e u t i c r a n g e 3 0 h o u r s after t h e l a s t d o s e of ciprofloxacin, a t w h i c h t i m e s e r u m l e v e l s w e r e u n d e t e c t a b l e . Clinical a n d laboratory f e a t u r e s a n d t h e u s e of m o d e m s c a n n i n g t e c h n i q u e s facilitate a p r o m p t d i a g n o s i s o f infection i n h e p a t i c c y s t s i n A D P K D . T h e t r e a t m e n t o f c h o i c e i s a c o m b i n a t i o n o f p e r c u t a n e o u s d r a i n a g e a n d antimicrobial t h e r a p y .
Hepatic cysts are common i n patients w i t h a u tosomal dominant polycystic kidney disease (ADPKD) but usually r e m a i n asymptomatic a n d do not substantially alter liver function or t h e natural history of t h e disease.^-^
Infection of hepatic cysts occurs in up to 3% of patients with A D P K D w h o h a v e end-stage renal failure b u t i n l e s s t h a n 1% of such patients before end-stage renal failure.^ Establishing the site of infection in a febrile patient with A D P K D and hepatic cysts can b e difficult because t h e s e
Address reprint requests to Dr. V. E. Torres, Division of Nephrology, Mayo Clinic, Rochester, MN 55905.
Patients are often on dialysis a n d are i m m u n o suppressed, a n d multiple s i t e s of infection are
Mayo Clin Proc 65:933-942, 1990
933
9·Μ
HEPATIC CYST INFECTION IN POLYCYSTIC KIDNEY DISEIASE
possible. Single case reports of hepatic cyst infection in A D P K D have been published,' '' but the syndrome has not been characterized. Herein we describe five cases of hepatic cyst infection in A D P K D that we identified in our patient popu lation, and we s u m m a r i z e our findings together with those from nine cases published in the medical literature. MATERIAL A N D METHODS B e t w e e n 1978 and 1988 at our institution, five patients with A D P K D had hepatic cyst infec tions. A D P K D w a s defined as the presence of bilateral polycystic kidneys and a family history consistent with autosomal dominant inheritance or bilaterally enlarged and polycystic kidneys with exclusion of other disorders associated with renal cysts. The clinical records of t h e s e patients were thoroughly reviewed. In addition, the available sonograms, computed tomograms, magnetic resonance images, and gallium and indium scans were reviewed by three of the authors with respect to findings that suggested the presence of an infected cyst. In one of these patients, who underwent segmental hepatectomy, and in two additional patients without substantiated cyst infection, who underwent segmental hepatectomy, the levels of antibiotics in serum and in cyst fluid were determined. Nine case reports of patients with A D P K D and infected hepatic c y s t s ' " were identified by a M E D L I N E computer search. FINDINGS The clinical and laboratory data from the five patients from our institution are summarized in Table 1. These data were pooled with those from nine reported cases of hepatic cyst infection and A D P K D in Tables 2 through 4. Clinical Manifestations.—The 10 women and 4 m e n ranged in age from 32 to 71 years old (mean age, 57 years). The features at the time of initial examination are summarized in Table 2. All the patients had fever and abdominal pain or tenderness. Four patients had undergone renal transplantation and were immunosuppressed. No patient had a prior history of confirmed hepatic cyst infection although the clinical his
Mayo Clin Proc, J u l y 1990, Vol 65
tory w a s suggestive of infection in four patients: one with a history of probable recurrent renal and hepatic cyst infections; another who had had two episodes of Escherichia coli bacteremia of unknown source during a 4-year period; a third with a history of recurrent unexplained episodes of fever and chills and pain in the right upper quadrant for 24 years; and a fourth who had had an episode of unexplained fever 3 months before the current admission. Seven of 12 pa tients had had symptoms for 7 days or less, whereas the other 5 patients had a febrile illness that had persisted from 2 weeks to 3 months. Presumed sources of the bacteria that caused the hepatic cyst infections were identified in only 6 of the 14 patients: 4 patients had recently undergone an abdominal surgical procedure or manipulation, and 2 patients had the same pathogen isolated from the infected cyst and from the bile or urine. Laboratory Tests.—Leukocytosis or a shift to the left in the blood smear w a s the most common laboratory abnormality (Table 2). The erythrocyte sedimentation rate exceeded 100 m m in 1 hour in four of the five patients in whom it w a s determined. Increased values were found for the alkaline phosphatase level in 5 of 13 patients, serum bilirubin concentration in 2, and aspartate aminotransferase activity in 1. Microbiologic Data.—Cultures of blood or cyst fluid (or both) were positive in 12 of 14 patients (Table 3). In the two patients with negative cultures, cysts containing purulent material were found at laparotomy. In one of the two patients. Gram stain of the foul-smell ing cyst content demonstrated gram-positive cocci. The second patient w a s receiving antibiot ics at the time of drainage of the cyst. In five patients, cultures of both cyst fluid and blood were positive and showed the same isolate. All isolates were Enterobacteriaceae except for the isolation of Haemophilus parainfluenzae in one patient. In some patients, cultures of cyst fluid were positive despite the use of broadspectrum antibiotics for up to 25 days before drainage. Imaging Procedures.—In all five patients in our series, computed tomographic scans were
HEPATIC CYST INFECTION IN POLYCYSTIC KIDNEY DISEASE
Mayo Clin Proc, J u l y 1990, Vol 65
935
Table 1—Clinical a n d Laboratory Data, Treatment, and O u t c o m e in F i v e P a t i e n t s With Autosomal Dominant P o l y c y s t i c Kidney D i s e a s e and H e p a t i c Cyst Infection D i a g n o s e d at t h e Mayo Clinic B e t w e e n 1978 and 1988*
Clinical manifestations Fever Pain Laboratory data WBC (nl, 4,100-10,900/mm'') Neutrophils (nl, 46-747() ESR (nl, 38.3°C 37.8-38.3°C 7-day course Abdominal pain or tenderness (or both) Right upper quadrant Right flank Diffuse Extension to shoulder Extension to back Laboratory data Leukocytosis or "left-shift" maturation (normal, 4,100-10,900 leukocytes/mm'.
Proceedings
ROCHESTER, MINNESOTA
JULY 1990
Hepatic Cyst Infection in Autosomal Dominant Polycystic Kidney Disease AMALIO TELENTI, M.D., Division of Infectious Diseases and Internal Medicine; VICENTE E. TORRES, M.D., Division of Nephrology and Internal Medicine; J O H N B. GROSS, Jr., M.D., Division of Gastroenterology and Internal Medicine; ROBERT E. VAN SCOY, M.D., Division of Infectious Diseases and Internal Medicine; MANUEL L. BROWN, M.D., ROBERT R. HATTERY, M.D., Department of Diagnostic Radiology To c h a r a c t e r i z e t h e s y n d r o m e o f h e p a t i c c y s t i n f e c t i o n i n a u t o s o m a l d o m i n a n t p o l y c y s t i c k i d n e y d i s e a s e (ADPKD) a n d t o r e v i e w i t s d i a g n o s i s a n d m a n a g e m e n t , w e r e t r o s p e c t i v e l y s t u d i e d five s u c h c a s e s i n p a t i e n t s from o u r i n s t i t u t i o n a n d n i n e d e t a i l e d c a s e r e p o r t s from t h e literature. T h e clinical m a n i f e s t a t i o n s w e r e a n a c u t e (58%) o r s u b a c u t e (42%) febrile i l l n e s s , typically a s s o c i a t e d w i t h t e n d e r n e s s i n t h e right u p p e r q u a d r a n t , l e u k o c y t o s i s , a v e r y h i g h e r y t h r o c y t e s e d i m e n t a t i o n rate, b u t m i n o r a b n o r m a l i t i e s of l i v e r f u n c t i o n t e s t s . B a c t e r e m i a w a s p r e s e n t i n 7 of 11 p a t i e n t s . E n t e r o b a c t e r i a c e a e g r e w i n p u r e c u l t u r e from t h e c y s t fluid i n 9 o f 12 p a t i e n t s . C o m p l e x c y s t s w e r e o b s e r v e d b y u l t r a s o n o g r a p h y (in four o f e i g h t patients), com p u t e d t o m o g r a p h y (in s i x o f n i n e ) , a n d m a g n e t i c r e s o n a n c e i m a g i n g (in t w o o f two). "'In l e u k o c y t e s c a n s w e r e p o s i t i v e i n all four p a t i e n t s i n w h o m t h e y w e r e d o n e , a n d "'Ga s c a n s w e r e p o s i t i v e i n o n l y o n e o f t h r e e p a t i e n t s . A n unfavorable o u t c o m e w a s o b s e r v e d i n s i x of s e v e n p a t i e n t s t r e a t e d w i t h o n l y a n t i b i o t i c s , i n c o n t r a s t w i t h o n e of s e v e n p a t i e n t s w h o r e c e i v e d a n t i b i o t i c s a n d e a r l y d r a i n a g e . In t w o p a t i e n t s , cip rofloxacin c y s t l e v e l s w e r e 2.3 a n d 4.8 t i m e s h i g h e r t h a n t h e l e v e l i n serum; i n a third p a t i e n t , c y s t l e v e l s r e m a i n e d i n t h e r a p e u t i c r a n g e 3 0 h o u r s after t h e l a s t d o s e of ciprofloxacin, a t w h i c h t i m e s e r u m l e v e l s w e r e u n d e t e c t a b l e . Clinical a n d laboratory f e a t u r e s a n d t h e u s e of m o d e m s c a n n i n g t e c h n i q u e s facilitate a p r o m p t d i a g n o s i s o f infection i n h e p a t i c c y s t s i n A D P K D . T h e t r e a t m e n t o f c h o i c e i s a c o m b i n a t i o n o f p e r c u t a n e o u s d r a i n a g e a n d antimicrobial t h e r a p y .
Hepatic cysts are common i n patients w i t h a u tosomal dominant polycystic kidney disease (ADPKD) but usually r e m a i n asymptomatic a n d do not substantially alter liver function or t h e natural history of t h e disease.^-^
Infection of hepatic cysts occurs in up to 3% of patients with A D P K D w h o h a v e end-stage renal failure b u t i n l e s s t h a n 1% of such patients before end-stage renal failure.^ Establishing the site of infection in a febrile patient with A D P K D and hepatic cysts can b e difficult because t h e s e
Address reprint requests to Dr. V. E. Torres, Division of Nephrology, Mayo Clinic, Rochester, MN 55905.
Patients are often on dialysis a n d are i m m u n o suppressed, a n d multiple s i t e s of infection are
Mayo Clin Proc 65:933-942, 1990
933
9·Μ
HEPATIC CYST INFECTION IN POLYCYSTIC KIDNEY DISEIASE
possible. Single case reports of hepatic cyst infection in A D P K D have been published,' '' but the syndrome has not been characterized. Herein we describe five cases of hepatic cyst infection in A D P K D that we identified in our patient popu lation, and we s u m m a r i z e our findings together with those from nine cases published in the medical literature. MATERIAL A N D METHODS B e t w e e n 1978 and 1988 at our institution, five patients with A D P K D had hepatic cyst infec tions. A D P K D w a s defined as the presence of bilateral polycystic kidneys and a family history consistent with autosomal dominant inheritance or bilaterally enlarged and polycystic kidneys with exclusion of other disorders associated with renal cysts. The clinical records of t h e s e patients were thoroughly reviewed. In addition, the available sonograms, computed tomograms, magnetic resonance images, and gallium and indium scans were reviewed by three of the authors with respect to findings that suggested the presence of an infected cyst. In one of these patients, who underwent segmental hepatectomy, and in two additional patients without substantiated cyst infection, who underwent segmental hepatectomy, the levels of antibiotics in serum and in cyst fluid were determined. Nine case reports of patients with A D P K D and infected hepatic c y s t s ' " were identified by a M E D L I N E computer search. FINDINGS The clinical and laboratory data from the five patients from our institution are summarized in Table 1. These data were pooled with those from nine reported cases of hepatic cyst infection and A D P K D in Tables 2 through 4. Clinical Manifestations.—The 10 women and 4 m e n ranged in age from 32 to 71 years old (mean age, 57 years). The features at the time of initial examination are summarized in Table 2. All the patients had fever and abdominal pain or tenderness. Four patients had undergone renal transplantation and were immunosuppressed. No patient had a prior history of confirmed hepatic cyst infection although the clinical his
Mayo Clin Proc, J u l y 1990, Vol 65
tory w a s suggestive of infection in four patients: one with a history of probable recurrent renal and hepatic cyst infections; another who had had two episodes of Escherichia coli bacteremia of unknown source during a 4-year period; a third with a history of recurrent unexplained episodes of fever and chills and pain in the right upper quadrant for 24 years; and a fourth who had had an episode of unexplained fever 3 months before the current admission. Seven of 12 pa tients had had symptoms for 7 days or less, whereas the other 5 patients had a febrile illness that had persisted from 2 weeks to 3 months. Presumed sources of the bacteria that caused the hepatic cyst infections were identified in only 6 of the 14 patients: 4 patients had recently undergone an abdominal surgical procedure or manipulation, and 2 patients had the same pathogen isolated from the infected cyst and from the bile or urine. Laboratory Tests.—Leukocytosis or a shift to the left in the blood smear w a s the most common laboratory abnormality (Table 2). The erythrocyte sedimentation rate exceeded 100 m m in 1 hour in four of the five patients in whom it w a s determined. Increased values were found for the alkaline phosphatase level in 5 of 13 patients, serum bilirubin concentration in 2, and aspartate aminotransferase activity in 1. Microbiologic Data.—Cultures of blood or cyst fluid (or both) were positive in 12 of 14 patients (Table 3). In the two patients with negative cultures, cysts containing purulent material were found at laparotomy. In one of the two patients. Gram stain of the foul-smell ing cyst content demonstrated gram-positive cocci. The second patient w a s receiving antibiot ics at the time of drainage of the cyst. In five patients, cultures of both cyst fluid and blood were positive and showed the same isolate. All isolates were Enterobacteriaceae except for the isolation of Haemophilus parainfluenzae in one patient. In some patients, cultures of cyst fluid were positive despite the use of broadspectrum antibiotics for up to 25 days before drainage. Imaging Procedures.—In all five patients in our series, computed tomographic scans were
HEPATIC CYST INFECTION IN POLYCYSTIC KIDNEY DISEASE
Mayo Clin Proc, J u l y 1990, Vol 65
935
Table 1—Clinical a n d Laboratory Data, Treatment, and O u t c o m e in F i v e P a t i e n t s With Autosomal Dominant P o l y c y s t i c Kidney D i s e a s e and H e p a t i c Cyst Infection D i a g n o s e d at t h e Mayo Clinic B e t w e e n 1978 and 1988*
Clinical manifestations Fever Pain Laboratory data WBC (nl, 4,100-10,900/mm'') Neutrophils (nl, 46-747() ESR (nl, 38.3°C 37.8-38.3°C 7-day course Abdominal pain or tenderness (or both) Right upper quadrant Right flank Diffuse Extension to shoulder Extension to back Laboratory data Leukocytosis or "left-shift" maturation (normal, 4,100-10,900 leukocytes/mm'.
