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An 18-year-old woman presents to the clinic with a 2-month history of generalized abdominal pain, nausea, decreased appetite, and increased abdominal girth. She is not exhibiting any abnormal urinary or bowel symptoms, but she does complain of an intermittent, low-grade fever that is sometimes accompanied by chills. There are no significant findings on the review of her past medical, surgical, and family histories. Her menstrual history reveals regular cycles. She is nulligravid but is sexually active and is not currently using any contraception. She has no known allergies and does not regularly take any medications.
On physical examination, she is 58 in (147.32 cm) in height and weighs 115 lb (52.2 kg). Her vital signs include an oral temperature of 99.5°F (37.5°C), a pulse rate of 106 bpm, and a blood pressure of 98/61 mm Hg. The patient appears to be in no acute distress. The examination of her chest, including auscultation of her heart and lungs, reveals no abnormalities. The peripheral pulses are palpable. The examination of her head and neck, as well as the neurologic examination, are normal. Her abdomen appears visibly distended and there is some degree of lower abdominal tenderness, but no guarding or rigidity is noted. No hepatomegaly or splenomegaly is found. The abdomen is dull to percussion and there is marked ascites, with shifting dullness. A large, doughy mass is found in the lower abdomen, which is tender on deep palpation. The mass is immobile, firm, does not move with breathing movements, and is nonpulsatile. The overlying skin is normal, with no erythema, pallor, or venous distention. The mass extends from the pelvis in the midline towards the umbilicus. On rectovaginal examination, the mass is found to be filling the pelvis to a size similar to that of a 20-week pregnancy. There is no evidence of cervical discharge, and the vulva, vagina, and cervix appear normal. The rest of the physical examination is normal.
Significant laboratory analyses include a hematocrit of 26.7% (0.267), a platelet count of 51 × 103/μL (51 × 109/L), and a white blood cell (WBC) count of 9.0 × 103/uL (9.0 × 109/L). Her carcinoembryonic antigen (CEA) level is less than 1 ng/mL (1 μg/L; normal range, 0-10 ng/mL), her human chorionic gonadotropin (hCG) value is less than 5 mIU/mL (5 IU/L; normal range for a nonpregnant woman, < 5 mIU/mL), her alpha-fetoprotein (AFP) level is 0.8 ng/mL (0.8 μg/L; normal range, 0-10 ng/mL), her lactate dehydrogenase (LDH) measurement is 534 U/L (normal range, 259-613 U/L), and her cancer antigen (CA) 125 level is 509 U/mL (509 kU/L; normal range, 0-35 U/mL). Her hepatic function tests are normal. Radiographs of the chest and an electrocardiogram (ECG) are ordered and found to be normal. Pelvic ultrasonography indicates a normal-sized uterus and endometrial stripe; it also shows a complex, midline pelvic mass of 11 × 9 cm in size, with both solid and cystic components (see Figure 1). Computed tomography (CT) scanning confirms the presence of a complex abdominopelvic mass with ascites. The patient is scheduled for an exploratory laparotomy with ovarian cystectomy, but she is also counseled for a hysterectomy and staging procedure, to which she consents. The gynecologic oncologist is aware of the surgery and is available if required.
At laparotomy, a large pelvic abscess is encountered and, subsequently, 1700 mL of turbid fluid is drained from the abscess cavity. The abscess extends from the pubic symphysis in the midline to the umbilicus. The small intestine appears to be seeded with small implants, all under 5 mm in diameter. Both fallopian tubes are noted to be grossly dilated, rigid, and have a rougher appearance externally, with the right tube appearing more grossly abnormal. Multiple constrictions are seen along the course of the right tube, with obstruction at the transition area between the isthmus and the ampulla. The uterus, ovaries, and appendix appear to be grossly normal. No abnormalities of the liver, kidneys, or stomach are found. Multiple biopsies and cultures are taken and sent for analysis. Frozen-section analysis demonstrates "granulomatous reaction compatible with tuberculosis". Surgery is terminated at this point, with the midline incision being closed without drains following extensive irrigation. All cultures come back negative for bacteria and fungi, with the exception of the abscess, which grows acid-fast bacilli on Lowenstein-Jensen medium in about 6 weeks. Testing for drug sensitivities shows no resistance to first-line tuberculosis agents. The biopsies reveal multiple caseating and noncaseating granulomas (see Figure 2 and 3), with organisms compatible with Mycobacterium tuberculosis on AFB staining (see Figure 4). A Gomori methenamine silver (GMS) stain examination is negative for fungal organisms. Postsurgery HIV tests are also negative; however, a PPD intradermal skin test (Mantoux test) is positive. The Health Department is notified.
Genital tuberculosis with peritonitis.Discussion
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Tuberculosis is a major world health problem, with a global prevalence estimated at 32%. In the United States, the percentage of cases occurring among foreign-born persons was 53% in 2003. Female genital tuberculosis is not uncommon in parts of the world where pulmonary tuberculosis is widespread. Tuberculosis is also associated with the HIV epidemic; in particular, extrapulmonary tuberculosis can be found in more than 50% of patients with concurrent AIDS.[1] Female genital tract infection may be contracted by hematogenous spread from a pulmonary nidus (the fallopian tube is the predominant site of infection) or the spread may be from gastrointestinal infection, characteristically from the ileocecal region by lymphatic spread to the right tube. Characteristically, the involvement of the fallopian tubes is bilateral (although asymmetric), with the tubes becoming thickened, swollen, and often with a roughened surface and adhesions. The tubes may also become obstructed, most often at the junction of the ampullary region with the isthmus and with multiple constrictions throughout the tubal length. The appearance of the tubes varies; in severe cases, they may be distended with caseous material. In milder cases, they may have only tubercles on the serosa. The fimbrial end of the tube is usually spared and remains patent with the fimbria everted, which produces the "tobacco pouch" appearance.[3] Distal tubal disease usually appears secondary to peritubal adhesions. These adhesions disrupt the delicate anatomical relationship between the tube and the ovary and interfere with normal ovulation. Spread from the tubes to the endometrium is common, but the ovaries do not usually show signs of involvement. In addition, involvement of the cervix, vagina, and vulva is uncommon. Tuberculous peritonitis is a variant of genital tuberculosis that results from initial miliary dissemination during primary bacteremia or secondarily during reactivation of pulmonary or extrapulmonary disease. Genital and peritoneal diseases are coexistent in up to 50% of cases.
The characteristic tuberculous granuloma consists of a central area of caseous necrosis surrounded by concentric layers of modified epithelial cells and with multiple Langerhans giant cells, all of which is surrounded by a peripheral zone of lymphocytes, monocytes, and fibroblasts. There may be calcified lymph nodes or irregular calcifications of the adnexa.
The clinical manifestations of genital/peritoneal tuberculosis include abdominal pain, abdominal swelling, persistent low-grade fever, weight loss, malaise, and fatigue. Menstrual disturbances initially include increased and irregular bleeding. Amenorrhea is usually evidence of advanced endometritis, which is secondary to spread from a primary focus in the tubes. Infertility is the most common complaint, and up to 85% of women with tuberculous salpingitis or genital tuberculosis never get pregnant. Symptoms are usually present for weeks or months, and there may be a history of infected individuals with recent close contact with an infected person, such as other family members. Patients may have a personal history of pulmonary or extrapulmonary disorders, such as pleurisy, erythema nodosum, renal disease, and/or bone disease. A physical examination may be unremarkable except for mild weight loss. Ascites is present in up to 97% of cases of tuberculous peritonitis. The abdomen can feel "doughy" and with irregular masses, which may be calcified and visible on abdominopelvic radiographs. A pelvic examination often shows findings similar to nontuberculous pelvic inflammatory disease; however, the bilateral masses are usually less tender and less uniform in consistency. The findings of bilateral inflammatory masses in a virginal female or of ascites in an adolescent, respectively, should raise suspicion for genital or peritoneal tuberculosis.[3,4,5]
In this patient, the presence of a pelvic mass with ascites and an elevated CA 125 led to the erroneous presumptive diagnosis of an ovarian malignancy; however, pelvic/peritoneal tuberculosis may be associated with elevated serum and peritoneal fluid CA 125 levels, and should always be kept in mind with such presentations. These levels can return to normal after successful drug therapy. Other conditions may cause granulomas with giant cells, including sarcoidosis, actinomycosis, and foreign-body reactions. Actinomyces, an anaerobic gram-positive bacterium, is only occasionally a cause of pelvic organ infection, usually in the presence of a long-standing intrauterine device. Sarcoidosis rarely involves pelvic organs, and this patient's ethnicity makes sarcoidosis a highly unlikely diagnosis (it is more common in African-Americans).[5]
The diagnosis is best established by successful culture of the organism and demonstrating the acid-fast bacilli with the Ziehl-Neelsen staining technique. Samples tested may be derived from peritoneal fluid, biopsies, pus from the abscess, sputum, urine, and/or menstrual fluid. Histopathologic diagnosis is usually based on premenstrual endometrial biopsy samples or biopsies obtained at laparoscopy or laparotomy (as in this case). Imaging studies are nonspecific and the findings include high-density ascites (which appear more radiopaque rather than radiolucent because the ascitic fluid is thick, usually as a result of blood or a proteinaceous exudate), adenopathy, adnexal masses, and omental and mesenteric thickening. Hysterosalpingography may show characteristic tubal changes, including "pipe-stem" appearance and multiple fistulae; however, unlike in chronic pelvic inflammatory disease, the fimbriae are uninvolved. Further evaluation should include HIV status, chest radiography, and renal tract assessment (because 10% of patients with genital lesions have renal tuberculosis and vice versa). Positive cultures should be tested for drug resistance against all first line agents.[3] Nucleic acid amplification tests (eg, polymerase chain reaction) have been approved in the United States for the diagnosis of tuberculosis in patients with positive sputum smears with high positive and negative predictive value but, in sputum-negative patients, the positive predictive value is only about 50%. Ultimately the diagnosis of tuberculosis involves a synthesis of clinical and laboratory findings.[6]
Response to drug therapy is excellent for all forms of genital tuberculosis. Surgery is reserved for large tuboovarian abscesses, abscesses refractory to antituberculous treatment, persistent adnexal masses, persistent pain, and drug resistance. Multidrug-resistant strains of tuberculosis (MDR-TB) are defined as those resistant to at least isoniazid and rifampin. The leading risk factors for these strains are coexistent HIV, improper drug selection, inappropriate or incomplete treatment, patient noncompliance with the treatment, or infection spread by an individual who carries a resistant strain. Since sensitivity results may take 6-8 weeks, it is customary to start treatment with multidrug regimens that are modified when results become available. If genital tuberculosis is encountered unexpectedly at operation (as in this case), only biopsy should be performed, as procedures after 3-4 months of drug therapy are technically easier and less prone to complications (especially fistulae). For the same reason, surgery should be delayed until an adequate course of medical therapy has been delivered, whenever possible. Drug therapy should be prolonged for 18-24 months as required.[3] In adults, however, most forms of extra pulmonary tuberculosis can be cured with 6 months of chemotherapy, although the clinical response should guide decisions on treatment duration.[7]
In this patient, treatment with rifampin, ethambutol, isoniazid, and pyrazinamide is promptly initiated. Characteristically after laparotomy, the ascites did not recur and her clinical progress was satisfactory. Two months after surgery, she had made remarkable progress, and treatment was continued with the same drugs, as the organism was sensitive to all 4 agents. Her prognosis was quite good, but unfortunately her prospects for spontaneous pregnancy were poor, as evidenced by the massive scarring in and around her fallopian tubes. The rarity of a successful uterine pregnancy with genital tuberculosis is borne out by a recent report from India in which 9 of 56 treated patients conceived; of these, 8 suffered spontaneous abortions and only 1 had a successful pregnancy.[8] In these cases, however, successful pregnancies have been reported with in vitro fertilization.
A patient with known tuberculosis exposure complains of a several-month history of fevers, progressive abdominal pain, and increasing girth. The patient is found to have a heterogeneous pelvic mass by ultrasonography. What is the recommended first step for diagnosis and/or treatment?
Biopsy of mass.
If genital tuberculosis is suspected, only biopsy should be performed, as procedures after 3-4 months of drug therapy are technically easier and less prone to complications (especially fistulae). For the same reason, surgery should be delayed until an adequate course of medical therapy has been delivered, whenever possible. Empiric treatment based on suspicion alone is not recommended, as a potentially harmful delay in appropriate treatment may occur if the mass is from a different infectious cause or from malignancy, for example. Blood and sputum cultures are unlikely to be beneficial.
When examining a patient with genital tuberculosis, which of the following choices would be the best for confirming a diagnosis of tuberculosis?
Culture with examination on Ziehl-Neelsen staining.
