"TB - Mindedness"-the only way to beat "the great mimicker": A case series with atypical presentation of female genital tuberculosis.

BACKGROUND: Incidence of Tuberculosis (TB) cases in India reported in 2019 is 193 per 1 lakh population [National Tuberculosis Elimination Plan (NTEP)]. In India, annual extra pulmonary TB burden is 20-25%, of which 4% of cases are of urogenital origin (Revised National TB Control Programme, 2019; World Health Organization, 2019). The Ministry of Health and Family Welfare has made a target of eliminating tuberculosis by 2025 under the NTEP by the process of identification, notification and treatment of cases. Tuberculosis being a leading cause of infertility in developing countries, employing best clinical practices and being "TB-minded" will also save the patient of enormous anxiety and uncertainity and also decrease the time gap between clinical presentation and diagnosis to optimize fertility outcome. METHODOLOGY: A prospective cohort study of cases presenting with unusual findings and ultimately being diagnosed as genital tuberculosis was conducted in the gynaecology OPD, AIIMS, New Delhi, from November 2020 to November 2021 (1 year). Patients were investigated judiciously, diagnosis made and followed up for their response to anti tuberculosis therapy (ATT). RESULTS: This data comprises of conglomerate of ten cases with unconventional exhibition of genital tuberculosis. 70% of the cases presented with pain lower abdomen not specifically related to menstrual cycle and often confused with IBD. Tubo ovarian mass (70%) mimicking as simple ovarian cyst, ovarian carcinoma or endometriosis was the most common clinical finding we came across.

Immune disturbances in female genital tuberculosis and latent genital tuberculosis.

BACKGROUND: Female genital tuberculosis (FGTB), an important clinical sub-type of extra-pulmonary tuberculosis (EPTB) is responsible for about 10% cases of infertility in India. Both FGTB and latent genital tuberculosis (LGTB) can cause infertility through blockage of fallopian tubes and through altered uterine endometrial receptivity. AIMS: This review tries to elucidates the role of various immune factors in FGTB and LGTB. CONTENT: Various immune disturbances are observed in FGTB and LGTB like growth factors and cytokines which inhibit implantation and several inflammatory signaling pathways like mitogen activated protein kinase (MAPK), natural killer (NK) cells, nuclear factor kappa-B (NF-KB), tumor necrosis factor (TNF), and toll like receptors (TLR) signaling are dysregulated. These altered immune factors and pathways may be detected in the endometrial biopsies at the early stages of disease before permanent damage. Prompt and adequate treatment with the four anti-tubercular drugs (rifampicin [R], isoniazid [H], pyrazinamide [Z], and ethambutol [E]) can increase pregnancy rates in some of these women. Assisted reproduction especially in-vitro fertilization and embryo transfer may be required for some women. IMPLICATIONS: Inflammatory pathways identified from the gene profiling have enabled development of potential biomarkers for early diagnosis of FGTB. Immunomodulation and novel biotechniques like stem cell transplantation, nanoparticles and host directed therapies are being tried in selected patients of FGTB and LGTB with promising results.

Female Genital Tuberculosis: Clinical Presentation, Current Diagnosis, and Treatment.

Female genital tuberculosis is a disease caused by Mycobacterium tuberculosis infection in the female reproductive tract. The disease burden among women leads to infertility is significant, especially in developing countries. The bacteria can spread from the lung into the reproductive organ through lymphatic or hematogenous. Many patients present with atypical symptoms, which mimic other gynecological conditions. Several investigations are needed to establish the diagnosis. Almost all cases of genital TB affect the fallopian tube and cause infertility in patients and endometrial involvement. Current treatment still relies on antituberculosis therapy with a combination of tubal surgery. The present review describes the epidemiological data, clinical presentation, diagnosis, and currently available treatment to cure the disease and for in vitro fertilization.

Immunohistochemical evaluation of infiltrating immune cells in endometrial biopsy of female genital tuberculosis.

BACKGROUND: Female Genital Tuberculosis (FGTB) causes infertility in a large number of females in developing countries. Presence of granuloma on histopathological examination of endometrial samples is diagnostic of FGTB. But immunohistochemical evaluation of endometrial aspirates has not been explored before. AIM: To evaluate the immunohistochemical delineation of immune cells in FGTB. METHODS: 1515 infertile women from 20 to 35 years were enrolled and underwent endometrial aspiration (EA), which was subjected to microbiological and histopathological examination along with PCR. Patients positive for conventional tests like granulomas, acid fast bacilli, mycobacterial culture on LJ medium or liquid (MGIT) culture were started on antitubercular therapy. Conventional test negative but PCR positive patients were posted for laparoscopy. Immunohistochemistry (IHC) for LCA, CD68, CD3, CD4, CD8, CD 20, CD138, IFN gamma and IL10 were evaluated. RESULT: 38/1515 (2.5%) subjects tested positive for conventional methods. PCR-TB was positive in 615/1515 samples (40.59%). On IHC, the number of CD45 (LCA) positive immune cells (p = 0.03) and IFN gamma (p = 0.002) and IL10 expression (p = 0.012) at 1 + level were higher in the PCR positive samples. Laparoscopy done in 418/463 patients and 89/418 (21.3%) showed definitive findings of tuberculosis. CD3, CD4, CD8, CD20, CD68 and CD138 showed no correlation with PCR and laparoscopy. CONCLUSION: Increased IFN gamma and IL 10 expressing immune cells in PCR positive EA suggests subclinical early changes, and can be useful as a research tool but have no role in diagnosing FGTB.

Emerging progress on diagnosis and treatment of female genital tuberculosis.

Female genital tuberculosis (FGTB) is an infection caused by Mycobacterium tuberculosis and usually occurs secondary to pulmonary tuberculosis (TB) through the blood circulation, lymph circulation, or direct spreading from abdominal TB. FGTB is an uncommon type of TB that can destroy genital organs, and lead to menstrual disorders and infertility. The diagnosis of FGTB is often made by detection of acid-fast bacilli under microscopy, culture with endometrial biopsy, or histopathological examination of epithelioid granuloma on a biopsy. A multidrug anti-TB regimen is the major management of FGTB, including rifampicin, isoniazid, pyrazinamide, and ethambutol, while surgery is proposed in more deteriorated cases. However, the conception rate in infertile women with FGTB is still low, even after multidrug anti-TB therapy. Additionally, the risk of complications, such as ectopic pregnancy or miscarriage, remains high. In this review, we summarize the characteristics of FGTB, present current epidemiological data, and focus on its early diagnosis and effective management.

Genital tb-diagnostic algorithm and treatment.

Female genital tuberculosis (FGTB) is a common cause of infertility in India but its diagnosis remains elusive due to paucibacillary nature of disease. Traditional methods of diagnosis include demonstration of acid fast bacilli on endometrial or peritoneal biopsy or epithelioid granuloma on the biopsy or positive gene Xpert on the biopsy, but they are positive in small percentage of cases only missing diagnosis in many cases. Positive polymerase chain reaction (PCR) alone is not taken for diagnosis due to high false positivity. Diagnostic laparoscopy and hysteroscopy can detect many cases by direct demonstration of TB lesions. Composite reference standard is a useful method to diagnose FGTB. This review discusses various diagnostic modalities including endometrial or peritoneal biopsy to detect acid fast bacilli on microscopic or culture or epithelioid granuloma, role of PCR, role of radiological imaging (hysterosalpingography, ultrasound, CT scan, MRI and PET-CT scan) and role of endoscopic techniques (laparoscopy and hysteroscopy) in diagnosis of FGTB including role of composite reference standard. The International and National studies highlight the role of composite reference standard and its components like demonstration of AFB on microscopy or culture of endometrial or peritoneal biopsy or epithelioid granuloma or gene Xpert or PCR or latest tests like loop-mediated isothermal amplification (TB-LAMP) test and other newer molecular methods like Xpert Ultra for diagnosis of FGTB. It also detects role of endoscopy in FGTB and role of diagnostic algorithm for diagnosis of FGTB. Treatment is with four primary drugs (rifampicin, isoniazid, ethambutol and pyrazinamide) for two months followed by three drugs (rifampicin, isoniazid and ethambutol) daily orally for 4 months for drug sensitive FGTB. Shorter Multidrug-resistant TB (MDR-TB) regimen is given for Rifampicin resistant (RR)/MDR confined to only FGTB while longer all oral regimen is given for RR/MDR with or without additional drug resistance, HIV seropositives with FGTB or involvement of other sites or pulmonary TB (PTB) along with FGTB. Composite reference standard which combines various diagnostic modalities is a useful strategy to diagnose FGTB.

Pregnancy in a patient with endometrial tuberculosis by in vitro fertilization: a case report.

Female genital tuberculosis is an important cause of infertility in developing countries where tuberculosis is endemic. However, the true incidence of genital tuberculosis is unknown because symptoms and signs are usually minimal, making its detection difficult. We herein report a case of subfertility due to endometrial tuberculosis. The patient had primary infertility and planned to utilize assisted reproductive technology because of bilateral fallopian tube obstruction. She underwent hysteroscopy and endometrial biopsy. The biopsy revealed epithelioid cells and multinuclear giant cells in the interstitium, and tuberculosis of the endometrium could not be excluded. Chest computed tomography showed secondary pulmonary tuberculosis in the upper left lung. A tuberculin test was positive, and a sputum culture of Mycobacterium tuberculosis was negative. The clinical diagnosis was secondary pulmonary tuberculosis. Considering the above findings in combination with the endometrial biopsy results, we concluded that the patient had endometrial tuberculosis. She underwent antituberculosis treatment for 6 months, after which the endometrial tuberculosis resolved and she achieved pregnancy by in vitro fertilization.

Endometritis granulomatosa por tuberculosis en mujer postmenopaúsica / Granulomatous tuberculosis endometritis in a posmenopausal woman

INTRODUCCIÓN: La tuberculosis (TBC) genital es una infección relativamente poco frecuente en la mujer. Afecta principalmente a mujeres menores de 40 años, y el motivo de consulta más usual es la esterilidad, de ahí la importancia de su diagnóstico precoz. CASO CLÍNICO clínico: Se presenta el caso de una paciente con dolor pélvico crónico que acude a nuestras consultas para valoración. Durante el estudio se toma biopsia dirigida de la cavidad endometrial diagnosticándose la presencia de granulomas no necrotizantes. Posteriormente se realiza un cultivo microbiológico que resulta positivo para micobacterias y se determina el DNA, mediante reacción en cadena de la polimerasa, de mycobacterium tuberculosis, como causante del cuadro. DISCUSIÓN: El diagnóstico definitivo de TBC requiere el aislamiento en cultivo del bacilo de Koch, aunque en los casos de TBC genital, al ser una entidad paucibacilar, puede no resultar positivo. En éste caso, sería suficiente el diagnóstico de presunción basado en la sospecha clínica y el hallazgo histológico de granulomas. CONCLUSIÓN: La tuberculosis genital es una entidad poco frecuente en nuestro medio, aunque es una causa importante de infertilidad femenina y su predominio generalmente se subestima debido a la naturaleza paucisintomática de la misma. El diagnóstico temprano y el tratamiento multidisciplinar son fundamentales.

INTRODUCTION: Genital tuberculosis (TB) is a relatively rare afection in women. It mainly affects women younger than 40 years, and the most frequent reason for consultation is sterility, therefore early diagnosis is important. CLINICAL CASE: We presented the case of a patient with chronic pelvic pain who comes to our consultations. During the study, we take an endometrial biopsy diagnosing the presence of non-necrotizing granulomas. Finally, we determined the mycobacterium tuberculosis DNA through the polymerase chain reaction and positive microbiological culture, as the cause of pathology. DISCUSSION: The definitive diagnosis of TB requires the isolation in culture of the Koch bacillus, although in genital TB cases, as it is a paucibacillary entity, it may not be positive. In this case, the presumptive diagnosis based on clinical suspicion and the histological granulomas would be enough. CONCLUSIONS: Genital tuberculosis is a rare entity in our environment, although it is an important cause of female infertility and its prevalence is generally underestimated due to its paucisymptomatic nature. Early diagnosis and multidisciplinary treatment are essential.

Tuberculosis and ovarian malignancy: Sometimes mimics, sometimes coexists.

Tuberculosis is a disease prevalent all over the world with India contributing to a larger share. Pulmonary tuberculosis presents with generalized symptoms of malaise, low grade fever and cough. On the other hand, genital tuberculosis presents with a variety of symptoms in each age group and is often underdiagnosed and missed. In an unmarried female, the usual presentations are menstrual complaints or presence of a solid cystic mass and ascites. In reproductive age group, patients may present with primary or secondary infertility or rarely with tubo-ovarian masses with peritoneal deposits, omental thickening and lymph node enlargement, hence mimicking ovarian carcinoma. In postmenopausal females, it can present as postmenopausal bleeding, leucorrhea or pyometra giving suspicion of endometrial carcinoma. We hereby report two cases operated with provisional diagnosis of ovarian malignancy but final histopathology ruled out malignancy in first and confirmed coexistence of malignancy and tuberculosis in another.

First case report of tuberculous meningitis secondary to endometrial tuberculosis following a clandestine abortion.

Tuberculous meningitis (TBM) is a medical emergency: it is the most severe, lethal and disabling clinical form of tuberculosis. We report the case of a 44-year-old woman who had undergone a clandestine abortion six weeks before admission. One week later, she had abnormal vaginal discharge. Three weeks prior to admission, headache, hyperpyrexia and mental alteration were added. At admission, a transvaginal ultrasound showed abnormalities of the uterine cavity. Sepsis and endometritis were diagnosed, and a hysterectomy was scheduled. During preoperative evaluation, meningeal signs were found. The first lumbar puncture (LP) showed a lymphomononuclear pleocytosis, hypoglycorrhachia and hyperproteinorrachia. After five days treatment with ceftriaxone, vancomycin and dexamethasone, only partial recovery occurred. A second LP showed AFB and PCR confirmed Mycobacterium tuberculosis. The histopathology of endometrial biopsy confirmed endometrial tuberculosis. Therapeutic response to anti-tuberculous treatment and corticosteroids was excellent. No other cause of immunosuppression apart from pregnancy was found. To the best of our knowledge, this is the first report of TBM secondary to endometrial tuberculosis and highlights an unusual clinical scenario in which severe and disseminated forms of TB could be present. TBM during and after pregnancy is rare, but compared with TBM in non-pregnant women, it has a poorer prognosis. Early diagnosis and treatment can be lifesaving in this life-threatening disease.

Vulvar tuberculosis.

Genital tuberculosis (TB) in women is a chronic disease with low-grade symptoms. Genital tract tuberculosis is usually secondary to extragenital TB. The fallopian tubes are most commonly affected, and along with endometrial involvement, it causes infertility in such patients. Involvement of the cervix and the vulva is very rare. We present one such rare case of vulvar tuberculosis presented with a large ulcer diagnosed on histopathology and treated with antitubercular chemotherapy.

Endometrial Tuberculosis a Treatable Cause of Infertility.

We present a case of 29 years lady with secondary infertility and amenorrhea. Her clinical findings were normal. Her hormone assays and ultrasonography was normal. She underwent hysteroscopy which showed atrophic endometrium and PCR for mycobacterium tuberculosis was sent which was reported positive for Mycobacterium tuberculosis. She was diagnosed as a case of Endometrial tuberculosis. Anti tuberculosis therapy was started for six months. After the completion of medical therapy she spontaneously conceived and delivered a healthy full term baby. Tuberculosis is a major public health problem among developing country like Nepal.

Peritoneal and upper genital tract tuberculosis.

Aim To present diagnostic and therapeutic possibilities for genital and peritoneal tuberculosis, mimicking to other pathological conditions, mainly, ovarian cancer. Methods Transabdominal and transvaginal ultrasound, computerized tomography, Ca125 and HE 4, ROMA- index (Risk of Ovarian Maligancy Algorithm index) and diagnostic laparoscopy were performed in order to diagnose genital tuberculosis in a female patient. Results: A 23-year-old woman from Morocco presented with intermitting abdominal pain, unintentional weight loss and primary infertility. There was no positive family history for breast or ovarian cancer and no history of previous tuberculosis (TB). Elevated CA-125 level, HE 4 normal, ROMA-Index of 13.2 % suggested high risk for epithelial ovarian cancer (EOC). Ultrasound revealed free fluid, dilated fallopian tubes and a cystic mass near the right ovary. Suspecting fallopian tube or ovarian cancer, we performed exploratory laparoscopy, revealing adhesions, multiple miliary nodes and dilated fallopian tubes. Histological investigation revealed granulomatous abscessing salpingitis with suspicion of genital TB, so antituberculous therapy was administered with success. Conclusion Female genital tuberculosis is very rare but important in differential diagnosis and should be kept in mind regarding suspected fallopian tube or ovarian carcinoma to prevent women from extensive surgery. An algorithm for possible differentiation between peritoneal/female genital TB and EOC may be helpful in clinical setting.

[Rare location of tuberculosis: endometrial tuberculosis]. / Une localisation rare de la tuberculose: la tuberculose endométriale.

Tuberculosis is a public health problem, especially in the developing countries. Bacillary pulmonary tuberculosis is the most common form of tuberculosis while genital tuberculosis is rare and underdiagnosed. We here report a case of endometrial tuberculosis. The study involved a 72-year old female patient with SC hemoglobinopathy consulting her gynecologist because of chronic leukorrhea. Cytobacteriologic assessment of vaginal swabs showed Streptococcus agalactatiae. Despite suitable antibiotic therapy, the evolution was marked by the persistence of leukorrhea. Pelvic ultrasonography objectified thickened endometrium, appearing as hyperechoic at the base of the uterus. This was suggestive of endometrial cancer. Anatomo-pathological examination of endometrial curettage samples showed granulomatous endometritis suggesting follicular tuberculosis. Outcome was favorable under antituberculosis treatment. In TB endemic areas, genital tuberculosis is not exceptional and should be suspected in patients with chronic leukorrhea despite suitable treatment.

Multicentre evaluation of Xpert MTB/RIF assay in detecting urinary tract tuberculosis with urine samples.

Genitourinary tuberculosis (GUTB) accounts for up to 40% of extrapulmonary tuberculosis cases. Rapid tests for GUTB are urgently needed because it is often associated with delayed health-care seeking, leading to serious consequences. This study evaluated the performance of the Xpert MTB/RIF assay in the rapid diagnosis of urinary tract tuberculosis (UTB) and rifampicin-resistant tuberculosis with urine specimens. In all, 302 patients were included from four hospitals in China. Suspected UTB patients were tested with Xpert, smear, and MGIT 960 culture. Drug susceptibility testing (DST) was conducted for culture-positive cases. The performance of the assays was evaluated against MGIT 960 culture and a composite reference standard (CRS). Among all participants, 150 (49.7%) had CRS-positive UTB, of whom 36 (24.0%) were culture-confirmed. Against culture, Xpert and smear achieved a sensitivity of 94.4% (95% CI: 81.3-99.3%) and 22.2% (95% CI: 10.1-39.2%), respectively. Against CRS, the sensitivity of Xpert, smear and culture was 41.3% (95% CI: 33.4-49.7%), 7.3% (95% CI: 3.7-12.7%), and 24.0% (95% CI: 17.4-31.6%). Xpert had better performance than smear and culture in detecting UTB from urine samples and could be considered for the diagnosis of UTB. Moreover, Xpert showed better performance than MGIT 960-based DST using urine culture.

[Pseudotumoral tuberculosis of the cervix]. / Tuberculose pseudo tumorale du col de l'utérus.

Tuberculosis of the cervix is rare and can mimick cervical cancer. Patients are paucisymptomatic and the disease is characterized by an insidious evolution, hence the delay in diagnosis. Common symptoms are non-specific contributing to therapeutic delay and increasing the risk of infertility which is perhaps inevitable. We report a case of tuberculosis of the cervix whose diagnosis given first wasn't obvious. Indeed, a patient was referred to our Department with suspected cervical cancer. Suspected diagnosis of cancer was then retained based on the presence of vaginal bleeding on contact and abdominopelvic CT scan results showing cervical cancer. Biopsy was indicated in order to confirm the diagnosis histologically. Anatomo-pathological examination objectified epitheliogigantocellular granuloma with caseous necrosis, supporting cervical tuberculosis. The other examinations were negative. The patient received TB treatment which led to healing. Diagnosis and treatment of tuberculosis of the cervix is often based on presumptive elements, hence the importance of anatomo-pathological examination.

Endometrial Tuberculosis: Hysteroscopic Findings of a Clinical Case.

Endometrial tuberculosis is a rare diagnosis in the postmenopausal period, and it can mimic a carcinoma. The present article describes the case of a 54-year-old female patient with weight loss, abdominal pain, and ascites. An ultrasonography showed endometrial thickening, and a video hysteroscopy revealed a uterine cavity with formations with cotton aspect covering the entire endometrial surface and the tubal ostia. An anatomopathological evaluation diagnosed endometrial tuberculosis. The treatment was with a standardized therapeutic scheme (ethambutol, isoniazid, pyrazinamide and rifampicin), and the patient evolved with clinical improvement and normal uterine cavity at hysteroscopy. Considering the lack of pathognomonic hysteroscopic findings of the disorder, it is important to disclose the images of the case.

A tuberculose endometrial é um diagnóstico raro na pós-menopausa e pode mimetizar um carcinoma. O presente artigo descreve o caso de uma paciente de 54 anos com perda de peso, dor abdominal e ascite. A ultrassonografia mostrou espessamento endometrial, e a histeroscopia por vídeo revelou uma cavidade uterina com formações que apresentavam aspecto de algodão cobrindo toda a superfície endometrial e os óstios tubários. Uma avaliação anatomopatológica diagnosticou tuberculose endometrial. O tratamento foi com esquema terapêutico padronizado (etambutol, isoniazida, pirazinamida e rifampicina), e a paciente evoluiu com melhora clínica e cavidade uterina normal na histeroscopia. Considerando a falta de achados histeroscópicos patognomônicos do distúrbio, é importante divulgar as imagens do caso.

Endometrial tuberculosis: hysteroscopic findings of a clinical case / Tuberculose endometrial: Achados histeroscópicos de um caso clínico

Abstract Endometrial tuberculosis is a rare diagnosis in the postmenopausal period, and it can mimic a carcinoma. The present article describes the case of a 54-year-old female patient with weight loss, abdominal pain, and ascites. An ultrasonography showed endometrial thickening, and a video hysteroscopy revealed a uterine cavity with formations with cotton aspect covering the entire endometrial surface and the tubal ostia. An anatomopathological evaluation diagnosed endometrial tuberculosis. The treatment was with a standardized therapeutic scheme (ethambutol, isoniazid, pyrazinamide and rifampicin), and the patient evolved with clinical improvement and normal uterine cavity at hysteroscopy. Considering the lack of pathognomonic hysteroscopic findings of the disorder, it is important to disclose the images of the case.

Resumo A tuberculose endometrial é um diagnóstico raro na pós-menopausa e podemimetizar um carcinoma. O presente artigo descreve o caso de uma paciente de 54 anos com perda de peso, dor abdominal e ascite. A ultrassonografia mostrou espessamento endometrial, e a histeroscopia por vídeo revelou uma cavidade uterina com formações que apresentavam aspecto de algodão cobrindo toda a superfície endometrial e os óstios tubários. Uma avaliação anatomopatológica diagnosticou tuberculose endometrial. O tratamento foi com esquema terapêutico padronizado (etambutol, isoniazida, pirazinamida e rifampicina), e a paciente evoluiu com melhora clínica e cavidade uterina normal na histeroscopia. Considerando a falta de achados histeroscópicos patognomônicos do distúrbio, é importante divulgar as imagens do caso.