Clin J Gastroenterol (2014) 7:27–31 DOI 10.1007/s12328-013-0439-1
CASE REPORT
Peripartum genital tuberculosis presenting with ascites Serkan Dogan • Mehmet Celikbilek • Ulas¸ Serkan Topaloglu • Ozlem Canoz • Insu Yilmaz • Alper Yurci • Omer Ozbakir
Received: 3 September 2013 / Accepted: 11 November 2013 / Published online: 27 November 2013 Ó Springer Japan 2013
Abstract Extra-pulmonary tuberculosis may affect multiple sites within the body. The symptoms vary widely and diagnosis requires a high clinical suspicion. In rare cases, tuberculosis may be manifest in the genitalia, initially presenting as infertility. Here we report a clinical case of a 23-year-old female with peripartum genital tuberculosis who presented at 2 weeks after delivery with fever and increasing abdominal girth. Keywords Peripartum genital tuberculosis Genital tuberculosis Ascites
S. Dogan A. Yurci O. Ozbakir Department of Gastroenterology and Hepatology, Erciyes University, Medical School, Kayseri, Turkey S. Dogan (&) ¨ niversitesi Tıp Faku¨ltesi Hastanesi Gastroenteroloji Erciyes U Bilim Dalı, Talas, Kayseri, Turkey e-mail: [email protected] M. Celikbilek Department of Gastroenterology and Hepatology, Bozok University, Medical School, Yozgat, Turkey U. S. Topaloglu Department of Internal Medicine, Erciyes University, Medical School, Kayseri, Turkey O. Canoz Department of Pathology, Erciyes University, Medical School, Kayseri, Turkey I. Yilmaz Department of Chest, Erciyes University, Medical School, Kayseri, Turkey
Introduction Tuberculosis is a major cause of morbidity and mortality worldwide. Infection typically manifests in the lungs, but other sites within the body may become involved, each with a distinctive profile of symptoms and clinical manifestations [1]. Genital tuberculosis (GTB) may present as infertility with pelvic pain and the presence of a mass. Ascites or menstrual disturbances may also be present [2, 3]. Peripartum genital tuberculosis is exceedingly rare. Cheng et al. reported a clinical presentation of predominantly extrapulmonary tuberculosis in 22 of 29 patients with peripartum tuberculosis that had been asymptomatic during pregnancy. One patient in this study was diagnosed with genital tuberculosis that presented as peritonitis with a mass in the right side of the lower abdomen [4]. To the best of our knowledge, this is the first reported case of peripartum GTB presenting with severe ascites. Peripartum GTB should be considered in the diagnosis of female patients with no prior history of liver disease presenting with peripartum fever and ascites.
Case report A 23-year-old female with no clinically significant prior medical history presented to our clinic with a 10-day history of fatigue, weakness, fever, mild dyspnea with physical exertion, and increasing abdominal girth. The patient had given birth vaginally to a healthy child 10 days previously. No cough, expectoration, vomiting, diarrhea, or weight loss was noted. The patient had no prior history of tobacco or alcohol use, or the use of herbal products, illicit opiates, or intravenous drugs. She reported no recent travel. Family medical history was unremarkable.
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Upon physical examination, blood pressure was 110/70 mmHg, pulse was 123 beats per min, temperature was 38.4 °C, and the respiratory rate was 24 breaths per min. Abdominal distension with shifting dullness was noted. Auscultation of the bilateral lung bases revealed cre´pitant raˆles. Other parameters of the physical examination were normal. Laboratory findings at admission revealed a relatively high percentage of neutrophils (69 %), hemoglobin of 10.8 g/dL, mean corpuscular volume of 77 fL, serum albumin of 2.3 g/dL, serum aspartate aminotransferase of 51 U/L, an erythrocyte sedimentation rate of 63 mm/h, serum C-reactive protein at 114 ng/L, Ca-125 at 599 U/mL, and a 24-h urine protein excretion of 180 mg/day. Other biochemical and coagulation parameters were within normal limits. Serological testing for Epstein– Barr virus, cytomegalovirus, and herpes simplex virus was
negative. The serum was negative for the presence of hepatitis A, hepatitis C, antibodies and human immunodeficiency virus (HIV) and hepatitis B surface antigen. Brucella agglutinin test, autoimmune diseases tests, and the purified protein derivative tuberculin test were all negative. A chest radiogram revealed left-sided pleural effusion and computed tomography (CT) of the chest indicated atelectasis in the left lung and the presence of effusion in the left pleural cavity. Abdominal ultrasonography indicated the presence of ascites. Transvaginal and pelvic ultrasound were normal except for the presence of ascites. CT examination of the abdomen and pelvis confirmed the presence of ascites without thickening of the peritoneal wall and a mild increase in liver echodensity (Fig. 1). Paracentesis was performed and the laboratory findings for the paracentesis fluid were white cell count, 410 cells/mL (10 % neutrophils, 80 % lymphocytes, 8 %
Fig. 1 CT scan and X-ray images of the patient. a Anteroposterior chest radiograph scan shows pleural fluid in the left lung; b CT scan of the chest after intravenous administration of contrast material
showing left pleural fluid (arrow) and lower lobe atelectasis; c CT scan of the abdomen with the presence of massive ascites throughout the abdomen (arrow); d CT scan of pelvis showing free fluid (arrow)
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histiocytes, and 2 % basophils); albumin, 1.8 g/dL [with a serum–ascites albumin gradient (SAAG) of 0.6 g/dL]; total protein, 3.9 g/dL; lactate dehydrogenase, 554 U/L; glucose, 56 mg/dL; and adenosine deaminase activity, 57 U/L. Gram staining of the paracentesis fluid was negative for the presence of microorganisms, as was bacterial culture. Staining for acid-fast bacilli was negative. Cytologic analysis of the fluid and of isolated cells was negative for malignancy. The initial diagnosis was suspected pneumonia. Ceftriaxone and clarithromycin treatment was initiated. On day 7, treatment with teicoplanin was initiated following the detection of methicillin-resistant Staphylococcus epidermidis that was sensitive to teicoplanin in blood cultures performed on days 3 and 5. Despite these interventions, fever persisted and abdominal girth increased. Low SAAG suggested a possible diagnosis of peritoneal carcinomatosis or tuberculosis. Peritoneoscopy was performed under general anesthesia to rule out the presence of a tumor and confirm the diagnosis of tuberculosis. The surface of both hemidiaphragms of the liver, the peritoneum, and the adnexal organs were examined directly. Peritoneoscopy revealed the presence of erythema, edema, and small amounts of white–yellow exudate on the fallopian tubes and peritoneum in the pelvic region. Biopsy specimens were collected from the right fallopian tube and peritoneum during the procedure. Examination by light microscopy revealed granulomas infiltrating the tubal wall. Caseation necrosis was present in some of the granulomas (Fig. 2).
29
A QuantiFeron-TB Gold (QFT-G) test indicated the presence of tuberculosis. Together, this lab result and the presence of granulomas confirmed the diagnosis of tuberculosis. The administration of teicoplanin was discontinued. The patient’s symptoms resolved gradually over a period of 2 weeks following treatment with isoniazid, pyrazinamide, rifampin, and ethambutol. Microbial culture and polymerase chain reaction of ascetic fluid was negative for mycobacteria at follow-up.
Discussion Tuberculosis remains a major cause of mortality worldwide despite increasing access to modern medical care [1]. The disease is most prevalent in developing regions. However, in recent years an increase in tuberculosis incidence have been observed in many Western countries due to the prevalence of HIV infection, immigration patterns, and the development of drug resistant stains of Mycobacterium tuberculosis [5, 6]. Tuberculosis is an infectious bacterial disease caused by M. tuberculosis and is most commonly manifest in pulmonary tissue. CT imaging characteristics of pulmonary tuberculosis include ground glass opacity, acinar nodules (\1 cm in diameter), consolidation, thickened wall cavity, branching linear structures with multiple contiguous branching sites, fibrosis, bronchial crowding, traction bronchiectasis, and granuloma[1 cm in diameter. Imaging
Fig. 2 a, b Photomicrographs showing granulomas infiltrating the fallopian tube. Arrows indicate tubal epithelium, arrowheads indicate granulomas (hematoxylin and eosin, 9100)
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of the present patient was not consistent with pulmonary tuberculosis and the presence of pleural effusion suggested possible ascites [7]. Tuberculosis may involve extra-pulmonary manifestations in other tissues including the pleura, lymph nodes, abdomen, genitourinary tract, skin, joints and bones, and meninges. The presence of extra-pulmonary tuberculosis is dependent upon numerous factors including race or ethnic background, age, M. tuberculosis strain, presence of comorbidities, and the use of immunomodulatory pharmaceuticals [1, 8]. GTB accounts for approximately 1 % of all cases of tuberculosis with extra-pulmonary involvement [9]. GTB has several possible etiologies including hematogenous dissemination from a primer inoculum in the lungs in woman (resulting in salpingitis) and dissemination to the epididymis and testes in men (resulting in prostatitis, urethritis, and epididymitis), and localized enteritis or peritonitis [10]. Male-to-female vaginal transmission of M. tuberculosis may occur through sexual intercourse in cases where the male exhibits active genitourinary tuberculosis [11]. The primary clinical features of female patients with GTB include infertility, pelvic pain, menstrual irregularities including postmenopausal bleeding, and vaginal discharge [2]. Uncommon symptoms of GTB included the presence of ascites, abdominal mass, tubo-ovarian abscess, and obscure abdominal distension. The classic systemic manifestations of disseminated tuberculosis, such as fever, weight loss, and night sweats, rarely occur in patients with HIV co-infection [12]. Active GTB is characterized by an initial exudative phase, days to months in duration, and ulceration of the wall of the fallopian tube. During this phase, the fallopian tubes appear enlarged and grossly edematous. This initial stage of the disease is followed by a secondary adhesive stage that may occur over months or years. During the adhesive phase tubercles form thick perisalpingeal adhesions that may lead to tubal blockage [13]. The most common etiologies of female infertility are ovulation disorders or dysfunction of the fallopian tubes; other causes include endometriosis, cervical defects, and uterine abnormalities. In GTB, adhesions result in chronic alteration of tubal function. In the present case the patient was reproductive, suggesting that the disease duration was minimal and had not sufficiently scarred the fallopian tubes to cause infertility. We applied the QFT-G test, an interferon-c release assay (IGRA) quantifying the release of interferon-c from cells in vitro for the detection of tuberculosis infection. Recent guidelines do not recommend the routine use of this type of assay in patients with suspected active tuberculosis [14]. IGRAs are primarily indicated for the screening and treatment of people at increased risk for latent tuberculosis.
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Lavender et al. suggested that IGRAs may be useful in excluding active tuberculosis disease, particularly in cases of extra-pulmonary disease, in patients residing in areas of low tuberculosis incidence. A negative IGRA test is highly predictive for the absence of active tuberculosis disease in these populations [15]. Further studies are required to determine the role of IGRAs in patients with suspected active tuberculosis. Our patient presented with extensive ascites and elevated CA 125 levels, for a test typically applied in the early detection of ovarian cancers. However, CA 125 may be elevated in certain benign conditions such as intraperitoneal inflammation. Patel et al. [16] reported that among 15 patients with abdominal tuberculosis, CA 125 levels were significantly increased in all patients. In our patient, serum levels of CA 125 gradually normalized over a period of 1–6 months with the application of anti-tuberculosis medication. After clinical and laboratory findings suggested the possible presence of abdominal tuberculosis, we applied laparoscopy to confirm the diagnosis [17]. Tuberculosis peritonitis is characterized by multiple diffuse involvements of the visceral and parietal peritoneum described as white military nodules or plaques, enlargement of the lymph nodes, ascites, fibrinous strands, and omental thickening [18]. In other words, there are innumerable tubercles on the peritoneal surface. More than 90 % of cases are associated with ascites, which results from exudation of fluid from the abnormal peritoneal surfaces. About 10 % of patients with tuberculous peritonitis present with the dry form of tuberculous peritonitis, characterized by fibrosis and adhesions and no ascites. Due to the lack of characteristic laparoscopic appearance, together with other symptoms, we did not consider tuberculous peritonitis [19, 20]. In the present case, peritoneal implants were primarily observed on the pelvic side, likely resulting from contiguous spread of the infection from the adjacent fallopian tubes. Salpingitis may cause severe ascites. Wallace et al. described a case of acute chlamydial salpingitis with marked ascites. Additionally, fallopian tube serosa is derived from visceral peritoneum. Tuberculous salpingitis may cause marked ascites similar to tuberculous peritonitis [21]. Immune suppression is a necessary physiologic component of pregnancy that allows the pregnant mother to tolerate the presence of genetically distinct fetal tissue [22]. Pregnancy-associated immunosuppression may impair cellmediated immunity, resulting in a decreased immune response to certain infectious agents such as tuberculosis. Lymphocyte reactivity begins to normalize within 24 h after delivery and is completely recovered by the fourth postpartum week [23]. Restoration of the pathogen-specific cellular immune response following delivery may result in
Clin J Gastroenterol (2014) 7:27–31
acute immune reaction against pathogens that had not elicited an immune response during pregnancy, potentially resulting in deteriorating clinical symptoms. The clinical presentation of peripartum tuberculosis is predominantly extra-pulmonary and the associated mortality rate may be as high as 38 % [4]. The granulamotous lesions associated with tuberculosis during the postpartum period contained numerous inflammatory cells but few bacteria. This response may not provide ideal immunity, as indicated by the poor outcomes associated with peripartum tuberculosis infection [24]. In summary, tuberculosis infection may be asymptomatic during pregnancy as a result of immunosuppression required to restrain immune responses against the genetically distinct fetal tissue. Clinicians should be familiar with the features of this condition, which may form a complex clinical presentation. Peripartum genital tuberculosis should be evaluated in any patient presenting with acute deterioration with fever and ascites after other possible causes have been excluded. In the absence of a definitive microbiologic, serologic, cytological, molecular, and imaging diagnosis, it is critical to perform diagnostic laparoscopy in a timely manner to prevent morbidity and mortality. Acknowledgments We thanks to Dr. Kemal Deniz, Erciyes University, Deparment of Pathology and Dr. Nuri Tutar, Erciyes University, Department of Chest for their comments and recommendations. Disclosures Conflict of Interest: The authors declare that they have no conflict of interest. Human/Animal Rights: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 [5]. Informed Consent: Informed consent was obtained from all patients for being included in the study.
References 1. Global tuberculosis report 2012. Geneva: World Health Organization. http://www.who.int/tb/publications/global_report/en/. 2. Simon HB, Weinstein AJ, Pasternak MS, Swartz MN, Kunz L. Genitourinary tuberculosis: clinical features in a general hospital population. Am J Med. 1977;63:410–20. 3. Samal S, Gupta U, Agarwal P. Menstrual disorders in genital tuberculosis. J Indian Med Assoc. 2000;98:126–7. 4. Cheng VC, Woo PC, Lau SK, et al. Peripartum tuberculosis as a form of immunorestitution disease. Eur J Clin Microbiol Infect Dis. 2003;22(5):313–7 (Epub 2003 May 13, review). 5. Lawn SD, Zumla AI. Tuberculosis. Lancet. 2011;378(9785): 57–72. doi:10.1016/S0140-6736(10)62173-3 (Epub.2011.Mar.21).
31 6. Liu Y, Weinberg MS, Ortega LS, Painter JA, Maloney SA. Overseas screening for tuberculosis in US-bound immigrants and refugees. N Engl J Med. 2009;360(23):2406–15. doi:10.1056/ NEJMoa0809497. 7. Tozkoparan E, Deniz O, Ciftci F, et al. The roles of HRCT and clinical parameters in assessing activity of suspected smear negative pulmonary tuberculosis. Arch Med Res. 2005;36(2): 166–70. 8. Zumla A, Raviglione M, Hafner R, von Reyn CF. Tuberculosis. N Engl J Med. 2013;368(8):745–55. doi:10.1056/NEJMra12 00894. 9. Arora R, Rajaram P, Oumachigui A, Arora VK. Prospective analysis of short course chemotherapy in female genital tuberculosis. Int J Gynecol Obstet. 1992;38(4):311–4. 10. Christensen WI. Genitourinary tuberculosis: review of 102 cases. Medicine (Baltimore). 1974;53:377–90. 11. Duggal S, Duggal N, Hans C, Mahajan RK. Female genital TB and HIV co-infection. Indian J Med Microbiol. 2009;27:361–72. 12. Mondal SK. Histopathologic analysis of female genital tuberculosis: a fifteen-year retrospective study of 110 cases in eastern India. Turk Patoloji Derg. 2013;29(1):41–5. doi:10.5146/tjpath. 2013.01146. 13. Scott JR, Gibbs RS, Karlan BY, Haney AF, editors. Danforth’s obstetrics and gynecology. 9th ed. Philadelphia: Lippincott Williams and Wilkins; 2003. p. 600–3. 14. Horsburgh CR Jr, Rubin EJ. Clinical practice. Latent tuberculosis infection in the United States. N Engl J Med. 2011;364(15):1441–8. doi:10.1056/NEJMcp1005750. 15. Lavender TW, Barrett A, Magee J, Ong EL. Interferon-c release assays in the diagnosis of active tuberculosis disease in a lowincident setting: a 5-year review of data. Clin Microbiol Infect. 2013. doi:10.1111/1469-0691.12129 (Epub ahead of print). 16. Patel SM, Lahamge KK, Desai AD, Dave KS. Ovarian carcinoma or abdominal tuberculosis?-A diagnostic dilemma: study of fifteen cases. J Obstet Gynaecol India. 2012;62(2):176–8. doi:10. 1007/s13224-012-0163-7 (Epub 2012 Jun 1). 17. Clancy C, Bokhari Y, Neary PM, Joyce M. Diagnosing peritoneal tuberculosis. BMJ Case Rep. 2013. doi:10.1136/bcr-2013009871. 18. Taˆrcoveanu E, Dimofte G, Bradea C, et al. Peritoneal tuberculosis in laparoscopic era. Acta Chir Belg. 2009;109(1):65–70. 19. Bhargava DK, Shriniwas, Chopra P, Nijhawan S, Dasarathy S, Kushwaha AK. Peritoneal tuberculosis: laparoscopic patterns and its diagnostic accuracy. Am J Gastroenterol. 1992;87:109–12. 20. Manohar A, Simjee AE, Haffejee AA, Pettengell KE. Symptoms and investigative findings in 145 patients with tuberculous peritonitis diagnosed by peritoneoscopy and biopsy over a five year period. Gut. 1990;31:1130–2. 21. Wallace TM, Hart WR. Acute chlamydial salpingitis with ascites and adnexal mass simulating a malignant neoplasm. Int J Gynecol Pathol. 1991;10(4):394–401. 22. Yip L, McCluskey J, Sinclair R. Immunological aspects of pregnancy. Clin Dermatol. 2006;24(2):84–7. 23. Covelli H, Wilson R. Immunologic and medical considerations in tuberculin-sensitized pregnant patients. Am J Obstet Gynecol. 1978;132:256–9. 24. Singh N, Perfect JR. Immune reconstitution syndrome and exacerbation of infections after pregnancy. Clin Infect Dis. 2007;45(9):1192–9 (Epub 2007 Sep 21).
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CASE REPORT
Peripartum genital tuberculosis presenting with ascites Serkan Dogan • Mehmet Celikbilek • Ulas¸ Serkan Topaloglu • Ozlem Canoz • Insu Yilmaz • Alper Yurci • Omer Ozbakir
Received: 3 September 2013 / Accepted: 11 November 2013 / Published online: 27 November 2013 Ó Springer Japan 2013
Abstract Extra-pulmonary tuberculosis may affect multiple sites within the body. The symptoms vary widely and diagnosis requires a high clinical suspicion. In rare cases, tuberculosis may be manifest in the genitalia, initially presenting as infertility. Here we report a clinical case of a 23-year-old female with peripartum genital tuberculosis who presented at 2 weeks after delivery with fever and increasing abdominal girth. Keywords Peripartum genital tuberculosis Genital tuberculosis Ascites
S. Dogan A. Yurci O. Ozbakir Department of Gastroenterology and Hepatology, Erciyes University, Medical School, Kayseri, Turkey S. Dogan (&) ¨ niversitesi Tıp Faku¨ltesi Hastanesi Gastroenteroloji Erciyes U Bilim Dalı, Talas, Kayseri, Turkey e-mail: [email protected] M. Celikbilek Department of Gastroenterology and Hepatology, Bozok University, Medical School, Yozgat, Turkey U. S. Topaloglu Department of Internal Medicine, Erciyes University, Medical School, Kayseri, Turkey O. Canoz Department of Pathology, Erciyes University, Medical School, Kayseri, Turkey I. Yilmaz Department of Chest, Erciyes University, Medical School, Kayseri, Turkey
Introduction Tuberculosis is a major cause of morbidity and mortality worldwide. Infection typically manifests in the lungs, but other sites within the body may become involved, each with a distinctive profile of symptoms and clinical manifestations [1]. Genital tuberculosis (GTB) may present as infertility with pelvic pain and the presence of a mass. Ascites or menstrual disturbances may also be present [2, 3]. Peripartum genital tuberculosis is exceedingly rare. Cheng et al. reported a clinical presentation of predominantly extrapulmonary tuberculosis in 22 of 29 patients with peripartum tuberculosis that had been asymptomatic during pregnancy. One patient in this study was diagnosed with genital tuberculosis that presented as peritonitis with a mass in the right side of the lower abdomen [4]. To the best of our knowledge, this is the first reported case of peripartum GTB presenting with severe ascites. Peripartum GTB should be considered in the diagnosis of female patients with no prior history of liver disease presenting with peripartum fever and ascites.
Case report A 23-year-old female with no clinically significant prior medical history presented to our clinic with a 10-day history of fatigue, weakness, fever, mild dyspnea with physical exertion, and increasing abdominal girth. The patient had given birth vaginally to a healthy child 10 days previously. No cough, expectoration, vomiting, diarrhea, or weight loss was noted. The patient had no prior history of tobacco or alcohol use, or the use of herbal products, illicit opiates, or intravenous drugs. She reported no recent travel. Family medical history was unremarkable.
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Upon physical examination, blood pressure was 110/70 mmHg, pulse was 123 beats per min, temperature was 38.4 °C, and the respiratory rate was 24 breaths per min. Abdominal distension with shifting dullness was noted. Auscultation of the bilateral lung bases revealed cre´pitant raˆles. Other parameters of the physical examination were normal. Laboratory findings at admission revealed a relatively high percentage of neutrophils (69 %), hemoglobin of 10.8 g/dL, mean corpuscular volume of 77 fL, serum albumin of 2.3 g/dL, serum aspartate aminotransferase of 51 U/L, an erythrocyte sedimentation rate of 63 mm/h, serum C-reactive protein at 114 ng/L, Ca-125 at 599 U/mL, and a 24-h urine protein excretion of 180 mg/day. Other biochemical and coagulation parameters were within normal limits. Serological testing for Epstein– Barr virus, cytomegalovirus, and herpes simplex virus was
negative. The serum was negative for the presence of hepatitis A, hepatitis C, antibodies and human immunodeficiency virus (HIV) and hepatitis B surface antigen. Brucella agglutinin test, autoimmune diseases tests, and the purified protein derivative tuberculin test were all negative. A chest radiogram revealed left-sided pleural effusion and computed tomography (CT) of the chest indicated atelectasis in the left lung and the presence of effusion in the left pleural cavity. Abdominal ultrasonography indicated the presence of ascites. Transvaginal and pelvic ultrasound were normal except for the presence of ascites. CT examination of the abdomen and pelvis confirmed the presence of ascites without thickening of the peritoneal wall and a mild increase in liver echodensity (Fig. 1). Paracentesis was performed and the laboratory findings for the paracentesis fluid were white cell count, 410 cells/mL (10 % neutrophils, 80 % lymphocytes, 8 %
Fig. 1 CT scan and X-ray images of the patient. a Anteroposterior chest radiograph scan shows pleural fluid in the left lung; b CT scan of the chest after intravenous administration of contrast material
showing left pleural fluid (arrow) and lower lobe atelectasis; c CT scan of the abdomen with the presence of massive ascites throughout the abdomen (arrow); d CT scan of pelvis showing free fluid (arrow)
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histiocytes, and 2 % basophils); albumin, 1.8 g/dL [with a serum–ascites albumin gradient (SAAG) of 0.6 g/dL]; total protein, 3.9 g/dL; lactate dehydrogenase, 554 U/L; glucose, 56 mg/dL; and adenosine deaminase activity, 57 U/L. Gram staining of the paracentesis fluid was negative for the presence of microorganisms, as was bacterial culture. Staining for acid-fast bacilli was negative. Cytologic analysis of the fluid and of isolated cells was negative for malignancy. The initial diagnosis was suspected pneumonia. Ceftriaxone and clarithromycin treatment was initiated. On day 7, treatment with teicoplanin was initiated following the detection of methicillin-resistant Staphylococcus epidermidis that was sensitive to teicoplanin in blood cultures performed on days 3 and 5. Despite these interventions, fever persisted and abdominal girth increased. Low SAAG suggested a possible diagnosis of peritoneal carcinomatosis or tuberculosis. Peritoneoscopy was performed under general anesthesia to rule out the presence of a tumor and confirm the diagnosis of tuberculosis. The surface of both hemidiaphragms of the liver, the peritoneum, and the adnexal organs were examined directly. Peritoneoscopy revealed the presence of erythema, edema, and small amounts of white–yellow exudate on the fallopian tubes and peritoneum in the pelvic region. Biopsy specimens were collected from the right fallopian tube and peritoneum during the procedure. Examination by light microscopy revealed granulomas infiltrating the tubal wall. Caseation necrosis was present in some of the granulomas (Fig. 2).
29
A QuantiFeron-TB Gold (QFT-G) test indicated the presence of tuberculosis. Together, this lab result and the presence of granulomas confirmed the diagnosis of tuberculosis. The administration of teicoplanin was discontinued. The patient’s symptoms resolved gradually over a period of 2 weeks following treatment with isoniazid, pyrazinamide, rifampin, and ethambutol. Microbial culture and polymerase chain reaction of ascetic fluid was negative for mycobacteria at follow-up.
Discussion Tuberculosis remains a major cause of mortality worldwide despite increasing access to modern medical care [1]. The disease is most prevalent in developing regions. However, in recent years an increase in tuberculosis incidence have been observed in many Western countries due to the prevalence of HIV infection, immigration patterns, and the development of drug resistant stains of Mycobacterium tuberculosis [5, 6]. Tuberculosis is an infectious bacterial disease caused by M. tuberculosis and is most commonly manifest in pulmonary tissue. CT imaging characteristics of pulmonary tuberculosis include ground glass opacity, acinar nodules (\1 cm in diameter), consolidation, thickened wall cavity, branching linear structures with multiple contiguous branching sites, fibrosis, bronchial crowding, traction bronchiectasis, and granuloma[1 cm in diameter. Imaging
Fig. 2 a, b Photomicrographs showing granulomas infiltrating the fallopian tube. Arrows indicate tubal epithelium, arrowheads indicate granulomas (hematoxylin and eosin, 9100)
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of the present patient was not consistent with pulmonary tuberculosis and the presence of pleural effusion suggested possible ascites [7]. Tuberculosis may involve extra-pulmonary manifestations in other tissues including the pleura, lymph nodes, abdomen, genitourinary tract, skin, joints and bones, and meninges. The presence of extra-pulmonary tuberculosis is dependent upon numerous factors including race or ethnic background, age, M. tuberculosis strain, presence of comorbidities, and the use of immunomodulatory pharmaceuticals [1, 8]. GTB accounts for approximately 1 % of all cases of tuberculosis with extra-pulmonary involvement [9]. GTB has several possible etiologies including hematogenous dissemination from a primer inoculum in the lungs in woman (resulting in salpingitis) and dissemination to the epididymis and testes in men (resulting in prostatitis, urethritis, and epididymitis), and localized enteritis or peritonitis [10]. Male-to-female vaginal transmission of M. tuberculosis may occur through sexual intercourse in cases where the male exhibits active genitourinary tuberculosis [11]. The primary clinical features of female patients with GTB include infertility, pelvic pain, menstrual irregularities including postmenopausal bleeding, and vaginal discharge [2]. Uncommon symptoms of GTB included the presence of ascites, abdominal mass, tubo-ovarian abscess, and obscure abdominal distension. The classic systemic manifestations of disseminated tuberculosis, such as fever, weight loss, and night sweats, rarely occur in patients with HIV co-infection [12]. Active GTB is characterized by an initial exudative phase, days to months in duration, and ulceration of the wall of the fallopian tube. During this phase, the fallopian tubes appear enlarged and grossly edematous. This initial stage of the disease is followed by a secondary adhesive stage that may occur over months or years. During the adhesive phase tubercles form thick perisalpingeal adhesions that may lead to tubal blockage [13]. The most common etiologies of female infertility are ovulation disorders or dysfunction of the fallopian tubes; other causes include endometriosis, cervical defects, and uterine abnormalities. In GTB, adhesions result in chronic alteration of tubal function. In the present case the patient was reproductive, suggesting that the disease duration was minimal and had not sufficiently scarred the fallopian tubes to cause infertility. We applied the QFT-G test, an interferon-c release assay (IGRA) quantifying the release of interferon-c from cells in vitro for the detection of tuberculosis infection. Recent guidelines do not recommend the routine use of this type of assay in patients with suspected active tuberculosis [14]. IGRAs are primarily indicated for the screening and treatment of people at increased risk for latent tuberculosis.
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Lavender et al. suggested that IGRAs may be useful in excluding active tuberculosis disease, particularly in cases of extra-pulmonary disease, in patients residing in areas of low tuberculosis incidence. A negative IGRA test is highly predictive for the absence of active tuberculosis disease in these populations [15]. Further studies are required to determine the role of IGRAs in patients with suspected active tuberculosis. Our patient presented with extensive ascites and elevated CA 125 levels, for a test typically applied in the early detection of ovarian cancers. However, CA 125 may be elevated in certain benign conditions such as intraperitoneal inflammation. Patel et al. [16] reported that among 15 patients with abdominal tuberculosis, CA 125 levels were significantly increased in all patients. In our patient, serum levels of CA 125 gradually normalized over a period of 1–6 months with the application of anti-tuberculosis medication. After clinical and laboratory findings suggested the possible presence of abdominal tuberculosis, we applied laparoscopy to confirm the diagnosis [17]. Tuberculosis peritonitis is characterized by multiple diffuse involvements of the visceral and parietal peritoneum described as white military nodules or plaques, enlargement of the lymph nodes, ascites, fibrinous strands, and omental thickening [18]. In other words, there are innumerable tubercles on the peritoneal surface. More than 90 % of cases are associated with ascites, which results from exudation of fluid from the abnormal peritoneal surfaces. About 10 % of patients with tuberculous peritonitis present with the dry form of tuberculous peritonitis, characterized by fibrosis and adhesions and no ascites. Due to the lack of characteristic laparoscopic appearance, together with other symptoms, we did not consider tuberculous peritonitis [19, 20]. In the present case, peritoneal implants were primarily observed on the pelvic side, likely resulting from contiguous spread of the infection from the adjacent fallopian tubes. Salpingitis may cause severe ascites. Wallace et al. described a case of acute chlamydial salpingitis with marked ascites. Additionally, fallopian tube serosa is derived from visceral peritoneum. Tuberculous salpingitis may cause marked ascites similar to tuberculous peritonitis [21]. Immune suppression is a necessary physiologic component of pregnancy that allows the pregnant mother to tolerate the presence of genetically distinct fetal tissue [22]. Pregnancy-associated immunosuppression may impair cellmediated immunity, resulting in a decreased immune response to certain infectious agents such as tuberculosis. Lymphocyte reactivity begins to normalize within 24 h after delivery and is completely recovered by the fourth postpartum week [23]. Restoration of the pathogen-specific cellular immune response following delivery may result in
Clin J Gastroenterol (2014) 7:27–31
acute immune reaction against pathogens that had not elicited an immune response during pregnancy, potentially resulting in deteriorating clinical symptoms. The clinical presentation of peripartum tuberculosis is predominantly extra-pulmonary and the associated mortality rate may be as high as 38 % [4]. The granulamotous lesions associated with tuberculosis during the postpartum period contained numerous inflammatory cells but few bacteria. This response may not provide ideal immunity, as indicated by the poor outcomes associated with peripartum tuberculosis infection [24]. In summary, tuberculosis infection may be asymptomatic during pregnancy as a result of immunosuppression required to restrain immune responses against the genetically distinct fetal tissue. Clinicians should be familiar with the features of this condition, which may form a complex clinical presentation. Peripartum genital tuberculosis should be evaluated in any patient presenting with acute deterioration with fever and ascites after other possible causes have been excluded. In the absence of a definitive microbiologic, serologic, cytological, molecular, and imaging diagnosis, it is critical to perform diagnostic laparoscopy in a timely manner to prevent morbidity and mortality. Acknowledgments We thanks to Dr. Kemal Deniz, Erciyes University, Deparment of Pathology and Dr. Nuri Tutar, Erciyes University, Department of Chest for their comments and recommendations. Disclosures Conflict of Interest: The authors declare that they have no conflict of interest. Human/Animal Rights: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 [5]. Informed Consent: Informed consent was obtained from all patients for being included in the study.
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