Shao Ping HUANG,*^ Yu Jie ZHAO,* Shui Hua LU,# Ji Lin CHENG,* Yan Ling FENG$

 *Gastroenterology Section, #Tuberculosis Section, $Pathology Department, Shanghai Public Health Clinical Center Affiliated to Fudan University, ^Endoscopy Research Institute Fudan University, Shanghai, China上海市公共卫生临床中心消化科黄绍萍

Correspondence to: Shui Hua LU, Shanghai Public Health Clinical Center Affiliated to Fudan  University, Jinshan District, Shanghai, China. Email: tubercle@shaphc.org

Abstract

Tuberculosis is the most common opportunistic infectious disease in HIV-infected subjects, and HIV infection is a high risk factor for tuberculosis, the convergence of HIV and tuberculosis is a disaster practically unequalled in medical history. This is a rare case report on the topic of pulmonary miliary tuberculosis and intestinal tuberculosis with AIDS. In this case, one month after the patient treated with HAART and anti-tuberculosis treatment, the number of CD4+ cell count increased and the symptoms improved, but the local intestinal lesion aggravated, which is commonly seen in IRIS. AIDS with intestinal tuberculosis locally aggravated is rare, and should be paid more attention.

Key Words：intestinal tuberculosis；HIV

People infected with human immunodeficiency virus (HIV) and Mycobacterium tuberculosis accounts for a number of 25 million worldwide. Tuberculosis is the most common opportunistic infectious disease in HIV-infected subjects, and HIV infection is a high risk factor for tuberculosis, the convergence of HIV and tuberculosis is a disaster practically unequalled in medical history(1). This is a rare case report on the topic of pulmonary miliary tuberculosis and intestinal tuberculosis with AIDS.

Cast report

A 38-year-old male was admitted on October 5, 2007 with a two-month history of intermittent abdominal pain, and had been treated with spasmolytic drugs without effect. A colonoscopy showed an annular bulging with about 1.0 × 1.6 cm ulcers, 40cm from the anus. The colonic lumen was narrowed and the histopathology indicated chronic inflammation with necrosis and granulation tissue. He had several sex partners, was found to have syphilis in May 2006, and had been treated for 15 days only. on September 12, 2007 he was known to have HIV infection and had been treated with antiviral drugs. On admission, vital signs were: T 37.6℃, P 86 / min, R 18 / min, BP 110/60mmHg (1 mmHg = 0.133kPa), being mentally clear, lymph nodes were not enlarged but with decreased breath sound over both lungs. His heart was normal and abdomen soft but with tenderness over left lower quadrant; liver and spleen were not palpate. Muscle strength, tendon reflexes were all normal. The Laboratory tests results Hb 110 g/L, PLT 77.30 × 109/L, RBC 3.70 × 1012/L, WBC 5.33 × 109/L. C-reactive protein 87.00 mg/L; IgA 1.97 g/L; IgG 30.30 g/L; serum albumin 32.3 g/L, ALT 60 U/L, AST 67 U/L; BUN 4.51 mmol/L, Cr 49.7 mmol/L; Cell-mediated immunity: CD4+ cell count 85 cell/μl; CD8+ cell count 591 cell/μl. B-ultrasound examination: hepatomegaly, splenomegaly and celiac lymphadenectasis, were present. Chest CT: bilateral pulmonary miliary tuberculosis. Abdominal CT: Lymphadenectasis was shown at porta hepatis. Colonoscopy displayed an ulcerative-proliferative mass at splenic flexure, adjacent to the mass involving the intestinal wall, was a 1.0×0.6 cm ulcer (Figure 1). Biopsy showed: chronic inflammation with atypical hyperplasia. Based on the clinical, laboratory and the histopathologic findings, a diagnosis of AIDS with pulmonary military tuberculosis and intestinal tuberculosis was made. HAART therapy and anti-tuberculosis treatment (isoniazid, rifampicin, Pyrazinamide and ethambutol) were given, one month afterwards, the patient’s general condition improved, fever subsided, part of pulmonary lesion absorbed, and CD4+ cell count increased up to 165 cell/μl, but abdominal pain became aggravated. A second colonoscopy showed the colonic lumen much narrowed and left hemicolon resection was performed. Typical tuberculous granuloma with caseous necrosis was shown in histopathology (shown in Figures 2, 3), and tissue culture showed the presence of tuberculosis. HAART therapy and anti-tuberculosis treatment had continued since then all symptoms improved after combination with anti-tuberculosis treatment. However, Since then the patient’s symptoms were gradually disappeared, and one month later, the patient was discharged without abdominal pain and other symptoms.

Discussion

Active tuberculosis can be triggered by weakened immune function of the patient, it has become the second most common killer of patients with HIV/AIDS worldwide. The incidence of tuberculosis can be very high in Africa (356/100 000 population) and mortality (81/100 000), but being lower in America (incidence: 41/100 000, mortality: 5.9/100 000)(2). HIV is the highest single risk factor to boost tuberculosis disease in adults, and tuberculosis is able to occur early in the course of HIV infection. The clinical presentation of tuberculosis can be modified by immune suppression, which has a real influence on the prognosis of HIV infection (3). AIDS patients with secondary intestinal tuberculosis are rarely reported. Most of the intestinal tuberculous lesions are in ileocecum accounting for 80%, the remaining lie in ileum or colon which are mostly secondary to pulmonary tuberculosis, and will cause narrowing or obstruction in advanced stage, some of them can even result in adhesive ileus because of the complication of tuberculous peritonitis (4). The reason of intestinal tuberculosis being easy to be misdiagnosed in our patient was that both clinical and endoscopic features were atypical. The abdominal pain became aggravated but the patient’s general symptoms were improved after the combined treatment of HAART and anti-tuberculosis therapy. Intestinal tuberculosis mimics many other conditions such as Crohn’s disease, malignancy, and infectious diarrhea, and is often difficult to diagnose. Only when the biopsy found caseous necrosis or acid-fast bacilli at microscopy that precise diagnosis can be established. The increased prevalence of extra-pulmonary tuberculosis in HIV patients presents a particular diagnostic challenge,  the major factor hampering our ability to diagnose tuberculosis in HIV patients is lack of a sensitive, specific and rapid diagnostic test. The World Health Organization (WHO) Directly Observed Therapy Short Course (DOTS) Program relies on the microscopic identification of Mycobacterium tuberculosis. However, due to alteration of the normal host immune response to Mycobacterium tuberculosis in HIV patients, cavitation and transfer of Mycobacterium tuberculosis into respiratory secretions are markedly reduced. Indeed, smear-negative tuberculosis has been linked to poor treatment outcome, the increased prevalence of extra-pulmonary forms of tuberculosis in HIV-infected patients is a further challenge to the management of tuberculosis in resource-poor settings, where access to histopathology and advanced imaging tests are limited or absent. The lack of a reliable, rapid test for smear-negative tuberculosis not only means that we often miss the correct diagnosis, but also that patients often started on anti-tuberculosis therapy erroneously on the basis of clinical presentation alone (5). WHO has updated the guidelines for management of smear-negative and extra-pulmonary tuberculosis, and has provided algorithms for the management of smear-negative pulmonary and extra-pulmonary tuberculosis in HIV-prevalent communities. They highlight the need for HIV testing of all tuberculosis suspects rather than only confirmed tuberculosis cases. Furthermore, the diagnostic algorithms used for management of extrapulmonary tuberculosis are much clearer, providing more detailed advice on which tests to employ and improve the definitions of common extrapulmonary forms of the disease to aid the clinicians (6). Patients co-infected with HIV and Mycobacterium tuberculosis have a greatly increased risk of developing active tuberculosis (5).

In the course of anti-tuberculosis therapy, the abdominal pain of our patient became aggravated, the possible reason can be: ①emergence of complication; ②existence of drug-resistant tuberculosis (7); ③HAART treatment-related immune reconstitution inflammatory syndrome (IRIS). During the course of treatment, the CD4+ cell count increased from 85 cell/μl up to 165 cell/μl, this hints that IRIS may be the most possible cause. As we know, potent antiretroviral therapy can substantially reduce the likelihood of both opportunistic infections and progression of HIV infection to AIDS. Shortly after starting HAART, as many as 25% of the patients experience clinical worsening because of subclinical opportunistic pathogens or recurrence of previously disease. This phenomenon is commonly known as IRIS. One study has indicated that initiation of HAART therapy at 4-12 weeks of tuberculosis treatment in advanced AIDS may be safe and effective.(8). In this case, one month after the patient treated with HAART and anti-tuberculosis treatment, the number of CD4+ cell count increased and the symptoms improved, but the local intestinal lesion aggravated, which is commonly seen in IRIS. AIDS with intestinal tuberculosis locally aggravated is rare, and should be paid more attention.

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2. Nissapatorn V. Lessons learned about opportunistic infections in southeast Asia. Southeast Asian J Trop Med Public Health. 2008,39:625-641.

3. Dye, C. . Global epidemiology of tuberculosis. Lancet. 2006, 367,938–940.

4. Ramesh J, Banait GS, Ormerod LP.  Abdominal tuberculosis in a district general hospital: a retrospective review of 86 cases. QJM,2008,101:189 - 195.

5. World Health Organisation, Global tuberculosis control: surveillance, planning, financing. WHO Report 2005. Geneva, 2006.

6. World Health Organization. Improving the diagnosis and treatment of smear-negative pulmonary and extrapulmonary tuberculosis among adults and adolescents: recommendations for HIV-prevalent and resource-constrained settings. Geneva, Switzerland: World Health Organization.2006.

7. French CE, Glynn JR, Kruijshaar ME, et al. The association between HIV and antituberculosis drug resistance. Eur Respir J, 2008,32:718-725

8. Sungkanuparph S, Manosuthi W, Kiertiburanakul S, et al. Initiation of antiretroviral therapy in advanced AIDS with active tuberculosis: clinical experiences from Thailand. J Infect,2006;52：1-7

Figure 1. First colonoscopy shows an ulcerative proliferative mass 40 cm from the anus.

Figure 2. Tuberculous granuloma shown in the excised colon.