Colonic Histoplasmosis in Acquired Immunodeficiency Syndrome Report of Two Cases Bruce D. Graham, M.D., David S. McKinsey, M.D., Michael R. Driks, M.D., David L. Smith, M.D. From the Department of Colon-Rectal Surgery, and Department of Infectious Disease, Research Hospital, Kansas City, Missouri Graham BD, McKinsey DS, Driks MR, Smith DL. Colonic histoplasmosis in acquired immunodeficiency syndrome: report of two cases. Dis Colon Rectum 1991;34:185-190.
icopathologic features of gastrointestinal histoplasmosis are discussed.
CASE REPORT Patient 1
Colonic histoplasmosis is a rare entity. There have been four previous reported cases within the population of patients with human immunodeficiency virus (HIV) infection. Because of the increasing incidence of HIV infection within regions where histoplasmosis is endemic, this condition may become more common. Gastrointestinal
A 40-year-old white homosexual male with AIDS presented with a 2-month history of increasing diarrhea and a 2-week history of worsening abdominal pain and spiking high grade fever. Medications were zidovudine (AZT), mycostatin, and nebulized pentamidine. The patient was pale and cachectic with a temperature of 101.5~ Exam revealed a distended abdomen with hyperactive bowel tones. There was significant diffuse abdominal tenderness most marked in the LLQ, without rebound. There was a palpable spleen. Hemoglobin was 9.1 g/dl, leukocyte count 2,800/mm 3, with 60 percent polymorphonuclear leukocytes, 12 percent band forms, and 20 percent lymphocytes. Amylase was 49 units and glucose 113 mg/dl. Stool studies for pathogens, O and P, Yersinia, and Campylobacterwere negative. Clostriduim difficile toxin assay was positive. Rectal culture was positive for herpes simplex virus type II. Cryptosporidia oocysts were observed on modified acid fast stain of feces. The patient was placed on oral vancomycin, acyclovir, and metronidazole without improvement of symptoms. Flexible sigmoidoscopy revealed moderately edematous mucosa. Biopsies showed edema of the lamina propria. Special stains for mycobacteria and fungi were negative. CT scan of the abdom en revealed extensive mesenteric and retroperitoneal lymphadenopathy. (Fig. 1). Splenomegaly and an enlarged pancreas were also noted. Bone marrow biopsy revealed multiple lymphohistiocytic aggregates and noncaseating granulomas. Stains for mycobacteria and fungi were negative. Cultures of
histoplasmosis has protean clinical manifestations, and symptoms are often nonspecific. Any patient with HIV infection who has unexplained GI symptoms should undergo evaluation for possible histoplasmosis. Aggressive long-term amphotericin B therapy has been effective in HIV patients with histoplasmosis. Resection or diversion of symptomatic colonic strictures caused by histoplasmosis may be necessary in addition to medical therapy. [Keywords: AIDS histoplasmosis; Histoplasmosis colon; AIDS colitis]
istoplasmosis was first described by Darling 1 .in 1906. Gastrointestinal involvement was noted in two of Darling's z three reported cases. In 1942, Henderson and coworkers 3 emphasized the occurrence of enteritis and colitis in disseminated histoplasmosis. Since that time, over 77 cases of histoplasmosis with GI tract involvement have b e e n reported. This entity, however, is rarely recognized on initial presentation. There have been four cases of GI histoplasmosis in human immunodeficiency virus (HIV) infected patients d o cu men t e d since this condition was first reported by Haggerty and others in 1984. 4-6 We report the diagnostic and therapeutic approach to two AIDS patients with progressive disseminated histoplasmosis with colonic involvement. The clin-
H
Address reprint requests to Dr. Graham: 6420 Prospect, Suite T311, Kansas City, Missouri 64132. 0029/7828/91/4306-0319/$3.00 Diseases of the Colon & Rectum Copyright 9 1991 by The American Society of Colon & Rectal Surgeons
185
GRAHAM ETAL
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Dis Colon Rectum, February 1991
around the splenic flexure of the colon (Fig. 2). Colonscopy revealed inflamed, friable edematous mucosa at the splenic flexure. Biopsy of the lesion showed invasive budding yeasts (Fig. 3), lymphohistiocytic aggregates, granulation tissue and occasional noncaseating granulomas (Fig. 4). Blood
Figure 1. Computed tomography scan of abdomen in case 1. Notice very extensive lymphadenopathy within the mesentery and retroperitoneum.
bone marrow, blood, and rectal tissue all grew Histoplasma capsulatum. The patient was then placed on amph0tericin B with rapid dramatic improvement. His fever, diarrhea, and abdominal pain resolved completely. He was treated with a 2,000mg initial course of intravenous amphotericin B and subsequently has received "maintenance" therapy with 50 mg of amphotericin B once weekly. His symptoms have not recurred after a follow-up period of 16 months. Patient 2 A 53-year-old white male homosexual and IV drug abuser presented with a 2-year history of intermittent diarrhea, constipation, and abdominal cramps. The patient had frequent dyspepsia but denied any fever or sweats. The patient noted a 40lb weight loss within 1 year. The patient was a chronic hepatitis B carrier and had significant chronic obstructed pulmonary disease. The patient was evaluated for these problems at another institution and underwent colonoscopy that showed an isolated segment of inflamed colon. Biopsies were not taken and he was given the diagnosis of Crohn's disease. Sulfasalazine therapy was started but there was no clinical response to treatment. Medications included zidovudine (AZT), sulfasalazine, mycostatin, megsterol acetate, and biweekly nebulized pentamidine treatments. On admission to our institution, physical exam revealed a pale cachectic male in no acute distress. The patient had mild tenderness to LUQ abdominal palpation. The leukocyte count was 2,300/mm 3, Hgb 8.7 g/dl. A barium enema showed three constricting lesions
Figure 2. Barium enema study from patient 2. Note multiple strictures of the left colon, and splenic flexure. There is proximal colonic dilation.
Figure 3. Colonic biopsy from patient 2. ;Note scattered invasive budding yeast forms.
Vol. 34, No. 2
COLONIC HISTOPLASMOSISIN AIDS
Figure 4. Colonic biopsy from patient 2. Note multiple noncaseating granulomas and lymphohistiocytic aggregates within granulation tissue. cultures by the Isolator technique (Dupont), were positive for Histoplasma capsulatum. Acute serum complement fixation antibody titer was 1:256 for H. capsulatum mycelial antigen. Greater than 1:8 is considered positive. The patient was treated with amphotericin B, and received 2,000 mg over a 2month period. There was initial symptomatic improvement, but the patient subsequently began having progressive obstructive symptoms. A transverse diverting loop colostomy was therefore performed. A large inflammatory mass was noted at the colonic splenic flexure. There was mild pericolic adenopathy. The remainder of the abdominal viscera were normal. The patient had an unremarkable postoperative course. The patient regained his appetite and weight, and returned to work. He has continued to receive biweekly amphotericin B infusions and is asymptomatic 8 months postoperatively. DISCUSSION
Histoplasma capsulatum is a soil dwelling saprophytic dimorphic fungus. It is found worldwide, however, it is especially concentrated in the Ohio, Missouri, and Mississippi river valleys. Histoplasma microconidia (spores) reach the alveoli after inhalation. Once exposed to core temperatures of 36~ or higher, the microconidia convert to the yeast phase and begin multiplication by binary fission. The organisms are ingested by macrophages but continue to multiply and occasionally spread to the bloodstream. With development of specific cell mediated immunity the macrophages can destroy the fungus. This leads to the formation
187
of granulomas. During the healing phase of the infection many of these granulomas develop central caseation, which may eventually lead to calcification. In patients with compromised immune status, containment of the organisms does not take place and progressive illness ensues throughout the reticuloendothelial system. This form of histoplasmosis is often referred to as the "infantile" form of the disease, because it was initially described in infants dying of the infectionT; however, progressive disseminated histoplasmosis also occurs in adults with underlying cellular immunodeficiency on the basis of malignancy or treatment with corticosteroids or cytotoxic chemotherapy. 8
icopathologic features of gastrointestinal histoplasmosis are discussed.
CASE REPORT Patient 1
Colonic histoplasmosis is a rare entity. There have been four previous reported cases within the population of patients with human immunodeficiency virus (HIV) infection. Because of the increasing incidence of HIV infection within regions where histoplasmosis is endemic, this condition may become more common. Gastrointestinal
A 40-year-old white homosexual male with AIDS presented with a 2-month history of increasing diarrhea and a 2-week history of worsening abdominal pain and spiking high grade fever. Medications were zidovudine (AZT), mycostatin, and nebulized pentamidine. The patient was pale and cachectic with a temperature of 101.5~ Exam revealed a distended abdomen with hyperactive bowel tones. There was significant diffuse abdominal tenderness most marked in the LLQ, without rebound. There was a palpable spleen. Hemoglobin was 9.1 g/dl, leukocyte count 2,800/mm 3, with 60 percent polymorphonuclear leukocytes, 12 percent band forms, and 20 percent lymphocytes. Amylase was 49 units and glucose 113 mg/dl. Stool studies for pathogens, O and P, Yersinia, and Campylobacterwere negative. Clostriduim difficile toxin assay was positive. Rectal culture was positive for herpes simplex virus type II. Cryptosporidia oocysts were observed on modified acid fast stain of feces. The patient was placed on oral vancomycin, acyclovir, and metronidazole without improvement of symptoms. Flexible sigmoidoscopy revealed moderately edematous mucosa. Biopsies showed edema of the lamina propria. Special stains for mycobacteria and fungi were negative. CT scan of the abdom en revealed extensive mesenteric and retroperitoneal lymphadenopathy. (Fig. 1). Splenomegaly and an enlarged pancreas were also noted. Bone marrow biopsy revealed multiple lymphohistiocytic aggregates and noncaseating granulomas. Stains for mycobacteria and fungi were negative. Cultures of
histoplasmosis has protean clinical manifestations, and symptoms are often nonspecific. Any patient with HIV infection who has unexplained GI symptoms should undergo evaluation for possible histoplasmosis. Aggressive long-term amphotericin B therapy has been effective in HIV patients with histoplasmosis. Resection or diversion of symptomatic colonic strictures caused by histoplasmosis may be necessary in addition to medical therapy. [Keywords: AIDS histoplasmosis; Histoplasmosis colon; AIDS colitis]
istoplasmosis was first described by Darling 1 .in 1906. Gastrointestinal involvement was noted in two of Darling's z three reported cases. In 1942, Henderson and coworkers 3 emphasized the occurrence of enteritis and colitis in disseminated histoplasmosis. Since that time, over 77 cases of histoplasmosis with GI tract involvement have b e e n reported. This entity, however, is rarely recognized on initial presentation. There have been four cases of GI histoplasmosis in human immunodeficiency virus (HIV) infected patients d o cu men t e d since this condition was first reported by Haggerty and others in 1984. 4-6 We report the diagnostic and therapeutic approach to two AIDS patients with progressive disseminated histoplasmosis with colonic involvement. The clin-
H
Address reprint requests to Dr. Graham: 6420 Prospect, Suite T311, Kansas City, Missouri 64132. 0029/7828/91/4306-0319/$3.00 Diseases of the Colon & Rectum Copyright 9 1991 by The American Society of Colon & Rectal Surgeons
185
GRAHAM ETAL
186
Dis Colon Rectum, February 1991
around the splenic flexure of the colon (Fig. 2). Colonscopy revealed inflamed, friable edematous mucosa at the splenic flexure. Biopsy of the lesion showed invasive budding yeasts (Fig. 3), lymphohistiocytic aggregates, granulation tissue and occasional noncaseating granulomas (Fig. 4). Blood
Figure 1. Computed tomography scan of abdomen in case 1. Notice very extensive lymphadenopathy within the mesentery and retroperitoneum.
bone marrow, blood, and rectal tissue all grew Histoplasma capsulatum. The patient was then placed on amph0tericin B with rapid dramatic improvement. His fever, diarrhea, and abdominal pain resolved completely. He was treated with a 2,000mg initial course of intravenous amphotericin B and subsequently has received "maintenance" therapy with 50 mg of amphotericin B once weekly. His symptoms have not recurred after a follow-up period of 16 months. Patient 2 A 53-year-old white male homosexual and IV drug abuser presented with a 2-year history of intermittent diarrhea, constipation, and abdominal cramps. The patient had frequent dyspepsia but denied any fever or sweats. The patient noted a 40lb weight loss within 1 year. The patient was a chronic hepatitis B carrier and had significant chronic obstructed pulmonary disease. The patient was evaluated for these problems at another institution and underwent colonoscopy that showed an isolated segment of inflamed colon. Biopsies were not taken and he was given the diagnosis of Crohn's disease. Sulfasalazine therapy was started but there was no clinical response to treatment. Medications included zidovudine (AZT), sulfasalazine, mycostatin, megsterol acetate, and biweekly nebulized pentamidine treatments. On admission to our institution, physical exam revealed a pale cachectic male in no acute distress. The patient had mild tenderness to LUQ abdominal palpation. The leukocyte count was 2,300/mm 3, Hgb 8.7 g/dl. A barium enema showed three constricting lesions
Figure 2. Barium enema study from patient 2. Note multiple strictures of the left colon, and splenic flexure. There is proximal colonic dilation.
Figure 3. Colonic biopsy from patient 2. ;Note scattered invasive budding yeast forms.
Vol. 34, No. 2
COLONIC HISTOPLASMOSISIN AIDS
Figure 4. Colonic biopsy from patient 2. Note multiple noncaseating granulomas and lymphohistiocytic aggregates within granulation tissue. cultures by the Isolator technique (Dupont), were positive for Histoplasma capsulatum. Acute serum complement fixation antibody titer was 1:256 for H. capsulatum mycelial antigen. Greater than 1:8 is considered positive. The patient was treated with amphotericin B, and received 2,000 mg over a 2month period. There was initial symptomatic improvement, but the patient subsequently began having progressive obstructive symptoms. A transverse diverting loop colostomy was therefore performed. A large inflammatory mass was noted at the colonic splenic flexure. There was mild pericolic adenopathy. The remainder of the abdominal viscera were normal. The patient had an unremarkable postoperative course. The patient regained his appetite and weight, and returned to work. He has continued to receive biweekly amphotericin B infusions and is asymptomatic 8 months postoperatively. DISCUSSION
Histoplasma capsulatum is a soil dwelling saprophytic dimorphic fungus. It is found worldwide, however, it is especially concentrated in the Ohio, Missouri, and Mississippi river valleys. Histoplasma microconidia (spores) reach the alveoli after inhalation. Once exposed to core temperatures of 36~ or higher, the microconidia convert to the yeast phase and begin multiplication by binary fission. The organisms are ingested by macrophages but continue to multiply and occasionally spread to the bloodstream. With development of specific cell mediated immunity the macrophages can destroy the fungus. This leads to the formation
187
of granulomas. During the healing phase of the infection many of these granulomas develop central caseation, which may eventually lead to calcification. In patients with compromised immune status, containment of the organisms does not take place and progressive illness ensues throughout the reticuloendothelial system. This form of histoplasmosis is often referred to as the "infantile" form of the disease, because it was initially described in infants dying of the infectionT; however, progressive disseminated histoplasmosis also occurs in adults with underlying cellular immunodeficiency on the basis of malignancy or treatment with corticosteroids or cytotoxic chemotherapy. 8
