Case Reports Intestinal Perforation Due to Cytomegalovirus Infection in Patients with AIDS MARRY B. KRAM, M.D., WILLIAM C. SHOEMAKER, M . D .
From the Department of Surgery, Los Angeles County King~Drew Medical Center, and the UCLA School of Medicine, Los Angeles, California
Kram HB, Shoemaker WC. Intestinal perforation due to cytomegalovirus infection in patients with AIDS. Dis Colon Rectum 1990;33:1037-1040.
Intestinal perforation due to cytomegalovirus (CMV) infection in patients with AIDS is the most common life-threatening condition requiring emergency celiotomy in these patients. The authors describe a patient with AIDS with intestinal perforation due to CMV infection, and review 14 additional cases reported in the English-language surgical literature. The diagnostic triad of pneumoperitoneum on x-ray, evidence or history of CMV infection, and AIDS occurred in 70 percent of patients. The most common site of intestinal perforation was the colon (53 percent), followed in frequency by the distal ileum (40 percent) and appendix (7 percent); perforation usually occurred between the distal ileum and splenic flexure of the colon. Colonoscopy, rather than sigmoidoscopy, is recommended as a screening examination in patients with AIDS suspected of having colonic ulceration due to CMV infection. Multiple biopsies of ulcerated tissue should be obtained. Gross and microscopic analyses of involved intestinal tissue reveal the characteristic findings of ulceration and CMV infection. Despite aggressive therapy, the operative mortality rate in patients with AIDS with intestinal perforation due to CMV infection was 54 percent and the overall mortality rate was 87 percent. Postoperative complications occurred in most patients and consisted mainly of systemic sepsis and pneumonia caused by Pneumocystis carinii infection. An increased awareness of this syndrome by physicians frequently called on to manage patients with AIDS is recommended. [Key words: AIDS; Cytomegalovirus; Intestinal perforation; Gastrointestinal hemorrhage] INTESTINAL PERFORATION DUE to cytomegalovirus (CMV) infection in the patient with AIDS was first reported in 1984.:'2 Three fatal cases were described,
Address reprint requests to Dr. Kram: Department of Surgery, Los Angeles County King/Drew Medical Center, 12021 S. Wilmington Ave., Los Angeles, California 90059.
including one case each of ileal, cecal, and transverse colon perforation. Since publication of these initial reports, 12 additional cases of intestinal perforation due to CMV infection in patients with AIDS have been described) -11 The incidence of this lethal condition may be greater than currently appreciated and probably will continue to increase as long as AIDS and CMV infection remain incurable. In this article, an additional case of fatal intestinal perforation due to CMV infection in a patient with AIDS is described, increasing the total number of cases reported in the English-language surgical literature to 15. In addition, a review of the literature was performed to better define diagnostic, therapeutic, and prognostic factors involved in the management of patients with this condition. Report
of a
Case
A 32-year-old male patient with AIDS presented to the emergency department complaining of rectal bleeding and vomiting blood of two days' duration. He denied any previous history of upper or lower gastrointestinal bleeding. However, his mental status was noted to be severely depressed, and he was confused and lethargic. On physical examination, his vital signs included a blood pressure of 68/palpable, heart rate of 140 beats/rain, respiratory rate of 20 breaths/min, and normal body temperature. His abdomen was distended and contained hypoactive bowel sounds. There was mild diffuse abdominal tenderness without rebound tenderness. Rectal examination revealed profuse anal condyloma acuminata and guaiac-positive stool.
1037
1038
Dis. Col. & Rect. December 1990
KRAM AND SHOEMAKER
Pertinent admission laboratory data revealed: hematocrit, 24 percent; white blood count, 27,500 mm ~ with 51 percent segs, 9 percent bands, 36 percent lymphs, and 4 percent monos; blood urea nitrogen, 75 mEq/L and creatinine, 4.5 mg/dl. Abdominal x-rays revealed an ileus pattern without free intraperitoneal air. After adequate fluid resuscitation and multiple blood transfusions, a computed tomography scan of the head was performed, which was unremarkable. Abdominal paracentesis was performed, which revealed cloudy fluid containing: white blood count, 740 mm 3, red blood count, 6800 mm 3, and protein greater than 700 mg/dl. Peritoneal fluid and blood cultures grew no organisms, but urine cultures grew greater than 105/ml Enterobacter cloaca and the patient was started on antibiotic therapy. An isotope labeled red blood cell nuclear scan was performed that revealed active bleeding from the distal ileum. This was followed by an isotope nuclear Meckel's scan, which was negative for Meckel's diverticulum. The patient continued to intermittently pass bloody stools with a drop in hematocrit level to 17 percent. After fluid resuscitation and blood transfusions, he underwent an exploratory celiotomy, which revealed approximately 700 ml of brownish peritoneal fluid and multiple localized areas of discoloration on the serosal surface of the small intestine extending from
the ligament of Treitz to the ileocecal valve. A small bowel resection with primary anastomosis was performed and included over 75 cm of distal jejunum and ileum. Pathologic examination of the resected small intestine revealed that the serosal discolorations coincided in location with multiple mucosal ulcers, the largest of which was 4.0 x 0.5 cm and was perforated. Microscopic analysis of the ulcerated tissue revealed chronic inflammation and full-thickness necrosis secondary to CMV infection. Postoperatively, the patient developed severe respiratory failure and septic shock, resulting in death on the first postoperative day.
Discussion
Data from the current article indicate that intestinal perforation due to CMV infection in the patient with AIDS is a life-threatening surgical emergency with a high operative mortality rate. A review of the English-language surgical literature revealed that 7 of 13 (54 percent) patients operated on for this condition died within one month of surgical treatment (Ta-
TABLE 1. Ch'nical Data of 15 Patients with AIDS with Intestinal Perforation due to Cytomegalovirus Infection Reported in the English-Language Surgical Literature
Author (Year)
X-ray
Findings
Surgical Procedure
Complications
Transverse colon perforation Terminal ileum perforation Multiple cecal perforations? Appendiceal perforation, periappendiceal abscess Terminal ileum perforation
Transverse colectomy, colostomy Small-bowel resection
Pneumocystis carinii pneumonia, sepsis Respiratory failure
Died*
None
Pneumocystis carinii pneumonia Wound infection
Died*
Died
Transverse colon perforation Terminal ileum perforation Transverse colon perforation Multiple ileal and jejunal perforations Colon perforation?
Transverse colectomy, colostomy Small-bowel resection
Pneumocystic carinii pneumonia, Toxoplasma gondii CNS infection Pneumocystis carinii pneumonia, sepsis Sepsis
Transverse colectomy, colostomy Small-bowel resection, jejunostomy, and mucous fistula Not mentioned
Blindness due to CMV infection Sepsis, muhiorgan failure
Died
Not mentioned
Died
Small-bowel resection, ileostomy and mucous fistula Sigmoid colectomy; colostomy Subtotal colectomy, ileostomy Ileostomy and mucous fistula Small-bowel resection
Lower gastrointestinal bleeding Not mentioned
Died*
None
Survived
Sepsis
Died
Respiratory failure, sepsis
Died*
Kram et al. (1984) I
Pneumoperitoneum
Frank and Raicht (1984) 2 Frank and Raicht (1984)2 Blackman et al. (1984) 3
Pneumoperitoneum
Freedman et al. (1985) 4
Pneumoperitoneum
Nugent and O'Connell (1986) 5 Burke et al. (1987) 6
Pneumoperitoneum
Robinson et al. (1987) 7 Houin et al. (1987) s
Not mentioned
Klatt and Shibata (1988) 9 Wexner et al. (1988) l~
Not mentioned Not mentioned
Terminal ileum perforation
Wexner et al. (1988) 1~ Wexner et al. (1988)x~ Burack et al. (1989) 11
Not mentioned Not mentioned
Multiple sigmoid colon perforation Rectal perforation
Pneumoperitoneum
Cecal perforation
Present report
Negative
Terminal ileum perforation
None Negative
Pneumoperitoneum
Pneumoperitoneum
* Died within one month of hospital admission. ? Autopsy findings.
Appendectomy, abscess drainage
Small-bowel resection, right hemicolectomy
Outcome
Died*
Survived
Died Died*
Died*
Died
Volume 33 Number 12
INTESTINAL
ble 1). Furthermore, only 2 of 15 AIDS patients survived more than six months after intestinal perforation due to CMV infection, resulting in an overall mortality rate of 87 percent. Thus, the occurrence of this complication in the patient with AIDS carries grave prognostic significance, despite apparently adequate medical and surgical therapy. The fact that several authors 1'2'7'1~ have reported multiple patients with AIDS with intestinal perforation due to CMV infection indicates that its incidence is increasing and probabl~ greater than currently appreciated. Robinson et al." reported on two patients with AIDS with intestinal perforation due to CMV infection. However, one of the latter patients was the same patient reported previously. 1 On the other hand, Nugent and O'Connell 5 reported on one patient with AIDS with intestinal perforation due to CMV infection, as well as an additional patient who underwent emergency celiotomy and total colectomy for the treatment of toxic megacolon due to CMV colitis; the latter case may represent an early presentation of impending intestinal perforation due to CMV infection in which appropriate therapy prevented colonic perforation. Wexner et al.l~ reported on three patients with AIDS with intestinal perforation due to CMV infection, one of whom survived eight months after surgery. The diagnostic triad of pneumoperitoneum on xray, evidence or history of CMV infection, and AIDS appeared to be the most important factors involved in making a correct preoperative diagnosis of this condition. Nevertheless, despite the presence of this triad in 7 of 10 (70 percent) reported cases having x-ray examinations, the correct diagnosis was not made preoperatively in any of the patients. An increased awareness of this condition by physicians frequently called on to manage AIDS patients is recommended. This is further emphasized by the finding that patients with AIDS with intestinal perforation due to CMV infection frequently have only minimal abdominal tenderness, no fever, and a normal white blood cell count. 1'6 Any patient who presents with the diagnostic triad mentioned previously should be suspected of having intestinal perforation due to CMV infection until proven otherwise. Furthermore, in patients with AIDS who require emergency celiotomy, CMV infection is the most likely cause for their acute illness. Of the 38 AIDS patients who underwent emergency abd o m i n a l e x p l o r a t i o n r e p o r t e d in the Englishlanguage surgical literature, 1-1z 22 (58 percent) were found to have intra-abdominal pathology due to CMV infection as the cause for their acute illness, although the correct etiology was usually not realized preoperatively. Abdominal findings due to CMV in-
PERFORATION
1039
fection in these patients included intestinal perforation due to CMV infection (15 patients), CMV hemorrhagic proctocolitis (4 patients), CMV-induced toxic megacolon (1 patient), CMV cholecystitis (1 patient), and CMV hepatitis (1 patient); the most common abdominal findings not due to CMV infection were appendicitis (3 patients), cholecystitis (2 patients), and lymphoma (2 patients). The appearance of the perforated intestine due to CMV infection in patients with AIDS was characteristic and usually revealed multiple mucosal ulcerations with one or more full-thickness perforations through an ulcer base; multiple brownish discolorations on the serosal surface that corresponded in location with the mucosal ulcerations were also seen.t The microscopic appearance of these ulcers characteristically revealed inflammation and granulation tissue containing cells with enlarged nuclei showing the eosinophilic intranuclear inclusion bodies of CMV. 1 The site of intestinal perforation due to CMV infection in patients with AIDS was usually between the distal ileum and splenic flexure of the colon. Eight (53 percent) patients had colonic perforations, six (40 percent) had ileal perforations, and one (7 percent) had appendiceal perforation due to CMV infection. Thus, although CMV infection may involve the entire gastrointestinal tract, 4'13 areas involved with the most severe disease may be missed on routine sigmoidoscopic examination. Colonoscopy, rather than sigmoidoscopy, is recommended for screening patients with AIDS suspected of having colonic ulceration due to CMV infection. In addition, a thorough clinical and laboratory search for evidence of CMV infection in patients with AIDS with gastrointestinal ulcers should be p e r f o r m e d . Tissue diagnosis, when possible, should be performed, as serologic data relating to CMV antibodies may not reflect the true incidence of CMV infection of gastrointestinal tissue. 14 Moreover, the elevation of complement-fixing antibodies to CMV may be influenced by various factors, including blood transfusions.15 Although CMV infection in the patient with AIDS is incurable, the administration of ganciclovir has been reported to limit the progression of CMV infections of the gastrointestinal tract 16 and should be considered in patients with AIDS with extensive or nonhealing CMV intestinal ulcers. Significant postoperative complications occurred in most patients with AIDS with intestinal perforation due to CMV infection and were usually infectious in nature. Four patients had pneumonia caused by Pneumocystis carinii infection, which contributed to a fatal outcome, and six patients had overwhelming sepsis complicated by muhiorgan failure, which resulted in death. In conclusion, intestinal perforation due to CMV
1040
KRAM AND SHOEMAKER
infection is the m o s t c o m m o n life-threatening condition r e q u i r i n g e m e r g e n c y celiotomy in patients with AIDS. T h e diagnostic triad o f p n e u m o p e r i t o n e u m on x-ray, evidence or history o f C M V infection, a n d A I D S was p r e s e n t in 70 p e r c e n t o f r e p o r t e d patients with this condition. T h e most c o m m o n site o f intestinal p e r f o r a t i o n was the colon (53 percent), followed in f r e q u e n c y by the distal ileum (40 percent) a n d app e n d i x (7 percent); p e r f o r a t i o n characteristically occ u r r e d between the distal ileum a n d splenic flexure o f the colon. Colonoscopy, r a t h e r t h a n sigmoidoscopy, is r e c o m m e n d e d as a screening e x a m i n a t i o n in patients with A I D S suspected o f having colonic ulceration d u e to C M V infection a n d multiple biopsies o f ulcerated tissue s h o u l d be obtained. Gross a n d microscopic analyses o f involved intestinal tissue reveals the characteristic findings o f ulceration a n d C M V infection. T h e o p e r a t i v e mortality rate in patients with A I D S with intestinal p e r f o r a t i o n d u e to C M V infection was 54 p e r c e n t a n d the overall mortality rate was 87 percent, despite aggressive therapy. Postoperative complications o c c u r r e d in the majority o f patients and consisted mainly o f sepsis a n d p n e u m o n i a caused by P. carinii infection. An increased awareness o f this condition by physicians frequently called on to m a n age patients with A I D S is r e c o m m e n d e d . References
1. Kram HB, Hino ST, Cohen RE, DeSantis SA, Shoemaker WC: Spontaneous colonic perforation secondary to cytomegalovirus in a patient with acquired immune deficiency syndrome. Crit Care Med 1984; 12:469-71. 2. Frank D, Raicht RF: Intestinal perforation associated with cytomegalovirus infection in patients with acquired immune deficiency syndrome. Am J Gastroenterol 1984;79:201-4.
Dis. Col. & Rect. D. . . . ber 1990
3. Blackman E, Vimadalal S, Nash G: Significance of gastrointestinal cytomegalovirus infection in homosexual males. Am J Gastroenterol 1984;79:935--40. 4. Freedman PG, Weiner BC, Balthazar EJ: Cytomegalovirus esophagogastritis in a patient with acquired immunodeficiency syndrome. Am J Gastroenterol 1985;80:434-7. 5. Nugent P, O'Connell TX: The surgeon's role in treating acquired immunodeficiency syndrome. Arch Surg 1986; 121: 1117-20. 6. Burke G, Nichols L, Balogh K, et al: Perforation of the terminal ileum with cytomegalovirus vasculitis and Kaposi's sarcoma in a patient with acquired immunodeficiency syndrome. Surgery 1987;102:540-5. 7. Robinson G, Wilson SE, Williams RA: Surgery in patients with acquired imnmnodeficiency syndrome. Arch Surg 1987; 122: 170-5.
8. Houin HP, GruenbergJC, Fisher EJ, Mezger E: Multiple small bowel perforations secondary to cytomegalovirus in a patient with acquired immunodeficiency syndrome. Henry Ford Hosp Med J 1987;35:17-9. 9. Klatt EC, Shibata D: Cytomegalovirus infection in the acquired immunodeficiency syndrome. Clinical and autopsy findings. Arch Pathol Lab Med 1988; 112:540--4. 10. Wexner SD, Smithy WB, Trillo C, Hopkins BS, Dailey TH: Emergency colectomy for cytomegalovirus ileocolitis in patients with the acquired immune deficiency syndrome. Dis Colon Rectum 1988;31:755-61. 11. Burack JH, Mandel MS, Bizer LS: Emergency abdominal operations in the patient with acquired immunodeficiency syndrome. Arch Surg 1989;124:285-6. 12. Potter DA, Danforth DN, Macher AM, Longo DL, Stewart L, Masur H: Evaluation of abdominal pain in the AIDS patient. Ann Surg 1984;199:332-9. 13. Rosen P, Armstrong D, Rice N: Gastrointestinal cytomegalovirus infection. Arch Intern Med 1973;132:274-6. 14. Farmer GW, Vincent MM, Fuccillo DA, et al: Viral investigations in ulcerative colitis and regional enteritis. Gastroenterology 1973;65:8-18. 15. Prince AM: A serologic study of cytomegalovirus infections associated with blood transfusions. N Engl J Med 1971; 284:1125-31. 16. Collaborative DHPG Treatment Study Group: Treatment of serious cytomegalovirus infections with 9-(1,3-dihydroxy-2propoxymethyl) guanine in patients with AIDS and other immunodeficiencies. N Engl J Med 1986;314:801-5.
From the Department of Surgery, Los Angeles County King~Drew Medical Center, and the UCLA School of Medicine, Los Angeles, California
Kram HB, Shoemaker WC. Intestinal perforation due to cytomegalovirus infection in patients with AIDS. Dis Colon Rectum 1990;33:1037-1040.
Intestinal perforation due to cytomegalovirus (CMV) infection in patients with AIDS is the most common life-threatening condition requiring emergency celiotomy in these patients. The authors describe a patient with AIDS with intestinal perforation due to CMV infection, and review 14 additional cases reported in the English-language surgical literature. The diagnostic triad of pneumoperitoneum on x-ray, evidence or history of CMV infection, and AIDS occurred in 70 percent of patients. The most common site of intestinal perforation was the colon (53 percent), followed in frequency by the distal ileum (40 percent) and appendix (7 percent); perforation usually occurred between the distal ileum and splenic flexure of the colon. Colonoscopy, rather than sigmoidoscopy, is recommended as a screening examination in patients with AIDS suspected of having colonic ulceration due to CMV infection. Multiple biopsies of ulcerated tissue should be obtained. Gross and microscopic analyses of involved intestinal tissue reveal the characteristic findings of ulceration and CMV infection. Despite aggressive therapy, the operative mortality rate in patients with AIDS with intestinal perforation due to CMV infection was 54 percent and the overall mortality rate was 87 percent. Postoperative complications occurred in most patients and consisted mainly of systemic sepsis and pneumonia caused by Pneumocystis carinii infection. An increased awareness of this syndrome by physicians frequently called on to manage patients with AIDS is recommended. [Key words: AIDS; Cytomegalovirus; Intestinal perforation; Gastrointestinal hemorrhage] INTESTINAL PERFORATION DUE to cytomegalovirus (CMV) infection in the patient with AIDS was first reported in 1984.:'2 Three fatal cases were described,
Address reprint requests to Dr. Kram: Department of Surgery, Los Angeles County King/Drew Medical Center, 12021 S. Wilmington Ave., Los Angeles, California 90059.
including one case each of ileal, cecal, and transverse colon perforation. Since publication of these initial reports, 12 additional cases of intestinal perforation due to CMV infection in patients with AIDS have been described) -11 The incidence of this lethal condition may be greater than currently appreciated and probably will continue to increase as long as AIDS and CMV infection remain incurable. In this article, an additional case of fatal intestinal perforation due to CMV infection in a patient with AIDS is described, increasing the total number of cases reported in the English-language surgical literature to 15. In addition, a review of the literature was performed to better define diagnostic, therapeutic, and prognostic factors involved in the management of patients with this condition. Report
of a
Case
A 32-year-old male patient with AIDS presented to the emergency department complaining of rectal bleeding and vomiting blood of two days' duration. He denied any previous history of upper or lower gastrointestinal bleeding. However, his mental status was noted to be severely depressed, and he was confused and lethargic. On physical examination, his vital signs included a blood pressure of 68/palpable, heart rate of 140 beats/rain, respiratory rate of 20 breaths/min, and normal body temperature. His abdomen was distended and contained hypoactive bowel sounds. There was mild diffuse abdominal tenderness without rebound tenderness. Rectal examination revealed profuse anal condyloma acuminata and guaiac-positive stool.
1037
1038
Dis. Col. & Rect. December 1990
KRAM AND SHOEMAKER
Pertinent admission laboratory data revealed: hematocrit, 24 percent; white blood count, 27,500 mm ~ with 51 percent segs, 9 percent bands, 36 percent lymphs, and 4 percent monos; blood urea nitrogen, 75 mEq/L and creatinine, 4.5 mg/dl. Abdominal x-rays revealed an ileus pattern without free intraperitoneal air. After adequate fluid resuscitation and multiple blood transfusions, a computed tomography scan of the head was performed, which was unremarkable. Abdominal paracentesis was performed, which revealed cloudy fluid containing: white blood count, 740 mm 3, red blood count, 6800 mm 3, and protein greater than 700 mg/dl. Peritoneal fluid and blood cultures grew no organisms, but urine cultures grew greater than 105/ml Enterobacter cloaca and the patient was started on antibiotic therapy. An isotope labeled red blood cell nuclear scan was performed that revealed active bleeding from the distal ileum. This was followed by an isotope nuclear Meckel's scan, which was negative for Meckel's diverticulum. The patient continued to intermittently pass bloody stools with a drop in hematocrit level to 17 percent. After fluid resuscitation and blood transfusions, he underwent an exploratory celiotomy, which revealed approximately 700 ml of brownish peritoneal fluid and multiple localized areas of discoloration on the serosal surface of the small intestine extending from
the ligament of Treitz to the ileocecal valve. A small bowel resection with primary anastomosis was performed and included over 75 cm of distal jejunum and ileum. Pathologic examination of the resected small intestine revealed that the serosal discolorations coincided in location with multiple mucosal ulcers, the largest of which was 4.0 x 0.5 cm and was perforated. Microscopic analysis of the ulcerated tissue revealed chronic inflammation and full-thickness necrosis secondary to CMV infection. Postoperatively, the patient developed severe respiratory failure and septic shock, resulting in death on the first postoperative day.
Discussion
Data from the current article indicate that intestinal perforation due to CMV infection in the patient with AIDS is a life-threatening surgical emergency with a high operative mortality rate. A review of the English-language surgical literature revealed that 7 of 13 (54 percent) patients operated on for this condition died within one month of surgical treatment (Ta-
TABLE 1. Ch'nical Data of 15 Patients with AIDS with Intestinal Perforation due to Cytomegalovirus Infection Reported in the English-Language Surgical Literature
Author (Year)
X-ray
Findings
Surgical Procedure
Complications
Transverse colon perforation Terminal ileum perforation Multiple cecal perforations? Appendiceal perforation, periappendiceal abscess Terminal ileum perforation
Transverse colectomy, colostomy Small-bowel resection
Pneumocystis carinii pneumonia, sepsis Respiratory failure
Died*
None
Pneumocystis carinii pneumonia Wound infection
Died*
Died
Transverse colon perforation Terminal ileum perforation Transverse colon perforation Multiple ileal and jejunal perforations Colon perforation?
Transverse colectomy, colostomy Small-bowel resection
Pneumocystic carinii pneumonia, Toxoplasma gondii CNS infection Pneumocystis carinii pneumonia, sepsis Sepsis
Transverse colectomy, colostomy Small-bowel resection, jejunostomy, and mucous fistula Not mentioned
Blindness due to CMV infection Sepsis, muhiorgan failure
Died
Not mentioned
Died
Small-bowel resection, ileostomy and mucous fistula Sigmoid colectomy; colostomy Subtotal colectomy, ileostomy Ileostomy and mucous fistula Small-bowel resection
Lower gastrointestinal bleeding Not mentioned
Died*
None
Survived
Sepsis
Died
Respiratory failure, sepsis
Died*
Kram et al. (1984) I
Pneumoperitoneum
Frank and Raicht (1984) 2 Frank and Raicht (1984)2 Blackman et al. (1984) 3
Pneumoperitoneum
Freedman et al. (1985) 4
Pneumoperitoneum
Nugent and O'Connell (1986) 5 Burke et al. (1987) 6
Pneumoperitoneum
Robinson et al. (1987) 7 Houin et al. (1987) s
Not mentioned
Klatt and Shibata (1988) 9 Wexner et al. (1988) l~
Not mentioned Not mentioned
Terminal ileum perforation
Wexner et al. (1988) 1~ Wexner et al. (1988)x~ Burack et al. (1989) 11
Not mentioned Not mentioned
Multiple sigmoid colon perforation Rectal perforation
Pneumoperitoneum
Cecal perforation
Present report
Negative
Terminal ileum perforation
None Negative
Pneumoperitoneum
Pneumoperitoneum
* Died within one month of hospital admission. ? Autopsy findings.
Appendectomy, abscess drainage
Small-bowel resection, right hemicolectomy
Outcome
Died*
Survived
Died Died*
Died*
Died
Volume 33 Number 12
INTESTINAL
ble 1). Furthermore, only 2 of 15 AIDS patients survived more than six months after intestinal perforation due to CMV infection, resulting in an overall mortality rate of 87 percent. Thus, the occurrence of this complication in the patient with AIDS carries grave prognostic significance, despite apparently adequate medical and surgical therapy. The fact that several authors 1'2'7'1~ have reported multiple patients with AIDS with intestinal perforation due to CMV infection indicates that its incidence is increasing and probabl~ greater than currently appreciated. Robinson et al." reported on two patients with AIDS with intestinal perforation due to CMV infection. However, one of the latter patients was the same patient reported previously. 1 On the other hand, Nugent and O'Connell 5 reported on one patient with AIDS with intestinal perforation due to CMV infection, as well as an additional patient who underwent emergency celiotomy and total colectomy for the treatment of toxic megacolon due to CMV colitis; the latter case may represent an early presentation of impending intestinal perforation due to CMV infection in which appropriate therapy prevented colonic perforation. Wexner et al.l~ reported on three patients with AIDS with intestinal perforation due to CMV infection, one of whom survived eight months after surgery. The diagnostic triad of pneumoperitoneum on xray, evidence or history of CMV infection, and AIDS appeared to be the most important factors involved in making a correct preoperative diagnosis of this condition. Nevertheless, despite the presence of this triad in 7 of 10 (70 percent) reported cases having x-ray examinations, the correct diagnosis was not made preoperatively in any of the patients. An increased awareness of this condition by physicians frequently called on to manage AIDS patients is recommended. This is further emphasized by the finding that patients with AIDS with intestinal perforation due to CMV infection frequently have only minimal abdominal tenderness, no fever, and a normal white blood cell count. 1'6 Any patient who presents with the diagnostic triad mentioned previously should be suspected of having intestinal perforation due to CMV infection until proven otherwise. Furthermore, in patients with AIDS who require emergency celiotomy, CMV infection is the most likely cause for their acute illness. Of the 38 AIDS patients who underwent emergency abd o m i n a l e x p l o r a t i o n r e p o r t e d in the Englishlanguage surgical literature, 1-1z 22 (58 percent) were found to have intra-abdominal pathology due to CMV infection as the cause for their acute illness, although the correct etiology was usually not realized preoperatively. Abdominal findings due to CMV in-
PERFORATION
1039
fection in these patients included intestinal perforation due to CMV infection (15 patients), CMV hemorrhagic proctocolitis (4 patients), CMV-induced toxic megacolon (1 patient), CMV cholecystitis (1 patient), and CMV hepatitis (1 patient); the most common abdominal findings not due to CMV infection were appendicitis (3 patients), cholecystitis (2 patients), and lymphoma (2 patients). The appearance of the perforated intestine due to CMV infection in patients with AIDS was characteristic and usually revealed multiple mucosal ulcerations with one or more full-thickness perforations through an ulcer base; multiple brownish discolorations on the serosal surface that corresponded in location with the mucosal ulcerations were also seen.t The microscopic appearance of these ulcers characteristically revealed inflammation and granulation tissue containing cells with enlarged nuclei showing the eosinophilic intranuclear inclusion bodies of CMV. 1 The site of intestinal perforation due to CMV infection in patients with AIDS was usually between the distal ileum and splenic flexure of the colon. Eight (53 percent) patients had colonic perforations, six (40 percent) had ileal perforations, and one (7 percent) had appendiceal perforation due to CMV infection. Thus, although CMV infection may involve the entire gastrointestinal tract, 4'13 areas involved with the most severe disease may be missed on routine sigmoidoscopic examination. Colonoscopy, rather than sigmoidoscopy, is recommended for screening patients with AIDS suspected of having colonic ulceration due to CMV infection. In addition, a thorough clinical and laboratory search for evidence of CMV infection in patients with AIDS with gastrointestinal ulcers should be p e r f o r m e d . Tissue diagnosis, when possible, should be performed, as serologic data relating to CMV antibodies may not reflect the true incidence of CMV infection of gastrointestinal tissue. 14 Moreover, the elevation of complement-fixing antibodies to CMV may be influenced by various factors, including blood transfusions.15 Although CMV infection in the patient with AIDS is incurable, the administration of ganciclovir has been reported to limit the progression of CMV infections of the gastrointestinal tract 16 and should be considered in patients with AIDS with extensive or nonhealing CMV intestinal ulcers. Significant postoperative complications occurred in most patients with AIDS with intestinal perforation due to CMV infection and were usually infectious in nature. Four patients had pneumonia caused by Pneumocystis carinii infection, which contributed to a fatal outcome, and six patients had overwhelming sepsis complicated by muhiorgan failure, which resulted in death. In conclusion, intestinal perforation due to CMV
1040
KRAM AND SHOEMAKER
infection is the m o s t c o m m o n life-threatening condition r e q u i r i n g e m e r g e n c y celiotomy in patients with AIDS. T h e diagnostic triad o f p n e u m o p e r i t o n e u m on x-ray, evidence or history o f C M V infection, a n d A I D S was p r e s e n t in 70 p e r c e n t o f r e p o r t e d patients with this condition. T h e most c o m m o n site o f intestinal p e r f o r a t i o n was the colon (53 percent), followed in f r e q u e n c y by the distal ileum (40 percent) a n d app e n d i x (7 percent); p e r f o r a t i o n characteristically occ u r r e d between the distal ileum a n d splenic flexure o f the colon. Colonoscopy, r a t h e r t h a n sigmoidoscopy, is r e c o m m e n d e d as a screening e x a m i n a t i o n in patients with A I D S suspected o f having colonic ulceration d u e to C M V infection a n d multiple biopsies o f ulcerated tissue s h o u l d be obtained. Gross a n d microscopic analyses o f involved intestinal tissue reveals the characteristic findings o f ulceration a n d C M V infection. T h e o p e r a t i v e mortality rate in patients with A I D S with intestinal p e r f o r a t i o n d u e to C M V infection was 54 p e r c e n t a n d the overall mortality rate was 87 percent, despite aggressive therapy. Postoperative complications o c c u r r e d in the majority o f patients and consisted mainly o f sepsis a n d p n e u m o n i a caused by P. carinii infection. An increased awareness o f this condition by physicians frequently called on to m a n age patients with A I D S is r e c o m m e n d e d . References
1. Kram HB, Hino ST, Cohen RE, DeSantis SA, Shoemaker WC: Spontaneous colonic perforation secondary to cytomegalovirus in a patient with acquired immune deficiency syndrome. Crit Care Med 1984; 12:469-71. 2. Frank D, Raicht RF: Intestinal perforation associated with cytomegalovirus infection in patients with acquired immune deficiency syndrome. Am J Gastroenterol 1984;79:201-4.
Dis. Col. & Rect. D. . . . ber 1990
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