DISSEMINATED TUBERCULOSIS INVOLVING LUNGS, LYMPH NODES, AND GASTRO-INTESTINAL TRACT COMPLICATED BY RECTOVESICAL/URETHRAL FISTULA.
This patient developed mycobacterial infection of the lungs, gastrointestinal tract and diffuse lymphadenopathy. At the time of his initial presentation he denied any HIV risk factors as was stated in the clinical history, but because of the known association between disseminated mycobacterial infection and HIV infection HIV ELISA and Western blot tests were preformed and both were positive. His CD4 count was also markedly low.
This patient had two important risk factors for developing disseminated tuberculosis such as immigration from underdeveloped country and immunosuppression due to coinfection with HIV. Other populations at risk for extrapulmonary tuberculosis include, the urban poor, prisoners and elderly nursing home residents.
Extrapulmonary involvement occurs in only 15% of patients with tuberculosis. This rate is increased in patients coinfected with HIV, who have a 50% incidence of extrapulmonary disease (pleura, lymph nodes, bones, gastrointestinal tract, or genitourinary tract). Abdominal tuberculosis can involve the omentum, intestinal tract, liver, spleen, female genital tract, and peritoneum. It is caused by both Mycobacterium tuberculosis and M bovis. Active pulmonary disease is present in less than 50% of patients. Any portion of the alimentary tract from mouth to anus may be involved, although lesions proximal to the terminal ileum are extremely unusual. The most frequent sites of involvement are the ileocecal region and rectum. The pathologic reaction is hypertrophic or ulcerative. Hypertrophic tuberculous enteritis results in stenosis, and the symptoms and signs are those of obstruction. The ulcerative form causes abdominal pain, alternating constipation and diarrhea. Complications include intestinal obstruction, hemorrhage, fistula formation, and bacterial overgrowth with malabsorption. Fistulas in intestinal tuberculosis occur in up to 44% of patients and may result from either secondary bacterial invasion or the sequelae of the confined perforation.
The diagnosis of intestinal tuberculosis can be difficult, since less than half of patients have an abnormality on chest x-ray and active pulmonary tuberculosis is evident in only 14% of patients. The PPD skin test may be negative, especially in patients with weight loss or AIDS. The differential diagnosis includes Crohn's disease, carcinoma, and intestinal amebiasis. CT of the abdomen and pelvis is the most sensitive diagnostic test and has advantages for evaluating bowel wall involvement patterns, extraluminal space, and changes in other organs. It can demonstrate retroperitoneal, mesenteric and peripancreatic lymphadenopathy (the most common finding). Other findings include hepatosplenomegaly, intestinal wall thickening, most commonly in the ileo-cecal region, irregular serosal surface, ascities, intrasplenic and intrahepatic masses, and pleural effusions. However, CT has limitations for demonstrating mucosal ulcerations or strictures and these abnormalities can be assessed by barium study. Paracentesis can be utilized in patients with ascities, but AFB smears are positive on ascitic fluid in 5% of patients, and cultures are positive in 20%; therefore, negative AFB smears and cultures are not helpful in excluding tuberculous peritonitis. Laparoscopy is the optimal method for establishing the diagnosis, allowing a presumptive visual diagnosis in more than 85% of cases. Suggestive findings include scattered whitish nodules over the visceral and parietal peritoneum and adhesions between adjacent organs. Biopsy by colonoscopy, laparoscopy, or even laparotomy is needed to establish the diagnosis by demonstrating caseating granulomas and acid-fast bacilli. Bacteriologic evaluation of biopsy specimens should also be performed. Biopsies will document the presence of caseating granulomas in more than 85% of cases. AIDS patients often demonstrate extremely large number of acid-fast bacilli invading the full thickness of the intestinal wall, presumably due to impaired T-cell function. Microscopic examination of intestinal deposits in our patient showed only small amount of granulomas and no multinucleated giant cells. Granulomas form in the area of local persistence of antigen, antigen-specific T cells, and activated macrophages. CD 4 T cells are necessary for activation of macrophages. Since patients with HIV lack CD 4 T cells, it is not surprising that they do not develop granulomas and multinucleated giant cells. Granulomas can be beneficial in that they wall off and prevent the spread of microorganisms.
Antituberculosis chemotherapy with a prolonged course of multiple antituberculous antibiotics is the mainstay of management. Due to the increased prevalence of multiple drug-resistant strains of tuberculosis, especially in HIV-infected patients, culture and sensitivity studies of the appropriate specimens are imperative. Ether Rifampin, Rifabutin or Streptomycin- based therapy should be initiated. If INH resistance is documented, the INH should be discontinued, and the remaining three drugs should be continued for at least 6- to 9-month short-course regimens. The concomitant use of rifampin (RIF) with protease inhibitors or NNRTIs is contraindicated owing to pharmacologic interactions. Two weeks are needed after discontinuation of rifampin before therapy with a PI or NNRTI is begun. Rifabutin (RFB) or streptomycin-based regiments can be substituted for rifampin-based regimen if the patient is also taking PIs or NNRTIs, or when feasible, therapy for HIV-1 might be delayed. Monitoring for RFB toxicity (arthralgias, uveitis, leukopenia) is necessary. Surgery is required if the diagnosis is uncertain, if disease is resistant to chemotherapy, or if complications develop. Some surgeons recommend early operation because medical treatment results in healing by fibrosis with resultant intestinal obstruction. Although corticosteroids have been recommended for prevention of severe scarring, documentation of benefit is lacking. Resection is the preferred surgical procedure, and bypass is done only if abscesses or fistulas are present. The prognosis is good if the patient is operated on in the early stages of the illness This patient underwent ileostomy regarding his rectovesical fistula and was initially treated with four antituberculous agents: Rifabutin, Isoniazid, Ethambutol, and Pyrazinamide. He was also started on anti-HIV regimen: Combivir and Indinavir. After sensitivity results came back Isoniazid was discontinued. Potential toxicities of these medications were monitored.
In conclusion, TB remains one of the leading causes of death in developing countries and its resurgence in developed countries warrants our attention. Extrapulmonary TB has a broad spectrum of clinical manifestations that may be referable to almost any organ system and should be considered in the differential diagnosis of patients with sterile pyuria, chronic diarrhea and intestinal obstruction.
Contributed by Irina Pauhkar, MD and A. William Pasculle, ScD