Advances in the diagnosis and treatment of female genital tuberculosis

  Inflammation of the female genitalia caused by Mycobacterium tuberculosis is called genital tuberculosis and is a manifestation of systemic tuberculosis, often secondary to other sites of tuberculosis such as pulmonary tuberculosis, intestinal tuberculosis, peritoneal tuberculosis, mesenteric tuberculosis, etc. About 10% of patients with pulmonary tuberculosis have genital tuberculosis. The incubation period of genital tuberculosis is long, up to 1-10 a. Most patients have healed their primary lesions by the time genital tuberculosis occurs. The common route of transmission is hematogenous, followed by direct transmission and, less commonly, lymphatic transmission. Tuberculosis bacilli can infect the internal genitalia within about 1 year after infection of the lungs. Since the mucosa of the fallopian tubes is conducive to latent infection of tuberculosis bacilli, Mycobacterium tuberculosis first invades the fallopian tubes and then spreads sequentially to the endometrium and ovaries. The tuberculosis bacilli first invade the fallopian tubes and then spread to the endometrium and ovaries in order. Peritoneal and intestinal tuberculosis may spread directly to the internal genitalia. Gastrointestinal tuberculosis can infect the internal genitalia through lymphatic transmission.  1. Diagnosis 1.1 Age of onset and history of the disease Most often occurs in sexually mature women between 20 and 40 years of age, but in recent years there has been a tendency to delay the onset of tuberculosis, and even postmenopausal women may develop tuberculosis. The history of tuberculosis is very important for the diagnosis of this disease. Genital tuberculosis. It is often secondary to tuberculosis in other parts of the body, such as pulmonary tuberculosis and intestinal tuberculosis. In addition, about 20% of patients with genital tuberculosis have a family history of tuberculosis. Therefore, patients should be asked in detail if they have a history of tuberculosis exposure and a history of tuberculosis in other organs of their own, especially if they have relatives with a history of tuberculosis who should be alert to the old.  1.2 Fallopian tubes 80%-90% of patients with tuberculosis of the ovaries are first diagnosed at the age of 20-40 years, and most of them have bilateral tubal involvement. Complete tubal obstruction accounted for 81.2%, incomplete obstruction for 9.3%, and patency for 9.5%, and the sites of obstruction were 80.0% at the uterine horn, 13.0% at the fallopian tube umbilicus, and 7.0% at the fallopian tube isthmus, in that order. The main clinical manifestations were infertility (45%-50%), pelvic pain (50%), systemic wasting symptoms (25%), and less often menstrual abnormalities when the endometrium was not invaded. Tubo-ovarian tuberculosis is usually asymptomatic and is often detected during infertility visits. 40%-50% of patients present with lower abdominal cramps due to extensive adhesions or combined tubo-ovarian abscesses caused by the lesion. During the active phase of tuberculosis, some patients may have systemic symptoms such as afternoon hypothermia and wasting. Menstrual disorders are rare in tubo-ovarian tuberculosis. The specificity of PPD is 85% and the sensitivity is only 55%. Localized diagnostic methods for tubo-ovarian tuberculosis rely on ultrasound, hysterosalpingography (HSG), laparoscopy and laparoscopic biopsy for histopathological examination. Pelvic ultrasound is the primary screening test for tubo-ovarian tuberculosis and usually shows a pelvic mass, sometimes combined with ascites, which is very similar to ovarian cancer and difficult to differentiate. HSG is the commonly used diagnostic method and can detect 45%-94% of tuberculosis patients and can also detect morphological abnormalities in the uterine cavity and fallopian tubes. The characteristic changes in patients with tubo-ovarian tuberculosis include a rigid tubular, bead-like appearance of the fallopian tubes, a dilated, smoke-bag-like appearance of the tubal jugular abdomen, distal tubal obstruction with a jagged profile, and bilateral horn obstruction. However, if tuberculosis has been diagnosed, HSG is not necessary to prevent the spread of the lesion. In recent years, laparoscopy has become a common and highly sensitive diagnostic modality. It allows direct visualization of the lesions in the pelvic and abdominal cavity, understanding the condition of the fallopian tubes and ovaries, and simultaneous biopsy of the lesions at multiple points. Combined with methylene blue fluids, it can provide an accurate picture of the patency of the fallopian tubes and the site of obstruction. The morphologic features of laparoscopic tubal-ovarian tuberculosis include: (1) swelling, sclerosis, tortuosity, rigidity of the fallopian tubes and adhesions to the ovaries and surrounding tissues into a mass; (2) formation of extensive multilevel adhesions in the pelvis centered on the fallopian tubes; (3) detection of tuberculosis-specific pathologic products, including corn-like nodules, case-like necrotic material, cheese balls, and foci of calcification; (4) tubal fistulae and broken arms, and blue staining of the uterus on methylene blue fluids examination. Mycobacterium tuberculosis culture is the confirmatory method for tuberculosis, but the positive rate of mycobacterium tuberculosis culture is about 50%, and it takes 6-8 weeks, and rapid culture also takes 1 week. PCR or ligase chain reaction is a simple and rapid diagnostic method for detecting Mycobacterium tuberculosis DNA by taking the contents of the cavity, ascites or venous blood, with a sensitivity of 94.7%, but it is prone to false positives. The antacid staining test requires a higher concentration of bacteria in the tissues and has a lower positive rate than the Mycobacterium tuberculosis culture.  1.3 Endometrial tuberculosis and cervical tuberculosis Endometrial tuberculosis occurs mostly in young women. Most of the endometrial tuberculosis is infected via bloodstream, which can go through the fallopian tubes to the basal layer of the endometrium during the non-menstrual period, and can cause repeated endometrial infections with menstrual blood during the menstrual period. When tuberculosis invades the endometrium, due to the periodic shedding of the endometrium by menstruation, the lesions are usually confined to the endometrium in the form of corn-like nodules, and rarely invade the myometrium. After the endometrium is destroyed, scar formation can lead to uterine amenorrhea and uterine adhesions. Cervical tuberculosis is usually formed by the downward spread of endometrial tuberculosis, but can also be caused by hematogenous or lymphatic dissemination. The cervix may appear locally enlarged, hard, or ulcerated. The most common symptoms are infertility (55%), followed by pelvic pain (50%), poor general condition (25%), menstrual disorders (20%), and secondary amenorrhea (5.3%), hypomenorrhea (2.0%), and dysfunctional uterine bleeding (1.5%), as endometrial tuberculosis is often involved in the uterus and causes infertility. Only 1.0% of hysterectomy specimens were found to have tuberculosis. Cervical tuberculosis is relatively uncommon. Diagnosis of endometrial TB is made by diagnostic curettage and biopsy, HSG, bacterial culture of menstrual blood, laparoscopy, hysteroscopy, ultrasonography, and PPD. Diagnostic scraping pathology is the gold standard for the diagnosis of endometrial TB, but it is difficult to diagnose endometrial TB by this method alone because most cases have no specific symptoms. Some cases are often diagnosed on the basis of their non-specific symptoms, such as genital TB based on infertility, menstrual disorders, and pelvic pain as high-risk factors for TB. HSG is an effective method for diagnosing TB and is often used as the test of choice. In HSG, endometrial tuberculosis can show a variety of images, such as some non-specific changes, such as endometritis, pelvic pus, uterine adhesions, segregation, and uneven endometrium; some specific changes, such as narrow official cavity, bead-like abscess, unicornuate uterus, and “T”-shaped uterus, etc. The above changes, combined with changes in the fallopian tubes, can suggest the diagnosis of tuberculosis. Namavar et al. compared the diagnosis of genital tuberculosis by clinical symptoms and ancillary tests. 41 cases were diagnosed with female genital tuberculosis (72.03% endometrial, 34.03% tubal, 12.9% ovarian, 2.4% cervical) by histological specimens, and the initial 10 cases were diagnosed with lower abdominal masses, tubo-ovarian cysts, and cysts. The initial 10 cases were diagnosed with genital tuberculosis due to lower abdominal masses, tubo-ovarian cysts, irregular vaginal bleeding and open surgery or curettage respectively; the remaining 3l cases (75.6%) were diagnosed with tuberculosis based on infertility. This indicates that although adjuncts help in diagnosis, in most cases, diagnosis is mostly based on symptoms, with infertility being the most closely related to tuberculosis. The early stage of cervical tuberculosis shows papillary hyperplasia followed by ulceration with sharp margins, yellow base, caseous necrosis and absence of cervical appearance. Since endometrial tuberculosis and cervical tuberculosis have no specific symptoms, in clinical practice, attention should be paid to differentiate them from cervical cancer, endometrial cancer, endometriosis, etc. In young women in the acute stage, they should be differentiated from acute pelvic inflammatory disease.  1.4 Tuberculous peritonitis is a chronic, diffuse peritoneal infection caused by Mycobacterium tuberculosis infection, and is currently the most common chronic peritonitis in clinical practice, accounting for about 5% of tuberculosis, second only to pulmonary and intestinal tuberculosis, with an increasing trend in incidence in recent years. The disease is most common in young adults aged 20-40 years. The disease is caused by direct spread or rupture of foci of mesenteric tuberculosis, intestinal tuberculosis, tubal tuberculosis and appendiceal tuberculosis in 80% of the abdominopelvic cavity. The pathological subtypes are exudative (ascites), adhesive (dry), caseous and mixed, with the first two types being more common.1 The diagnosis is based on: (1) women of childbearing age with a history of tuberculosis or other organ tuberculosis; (2) fever, malaise, poor appetite and wasting; (3) the triad of abdominal distention, ascites and pelvic mass is the most common clinical manifestation and sign of tuberculous peritonitis; (4) ascites is mostly straw yellow exudate with protein The specific gravity was mostly between 1.016 and 1.020, and the rivalta test was positive. The white blood cell count was >0.5X109/L, with a predominance of lymphocytosis. In a few cases, ascites is celiac, bloody or cholesterol. Mycobacterium tuberculosis examination of ascites, either by smear or culture, has an extremely low positive rate. ⑤ X-ray examination may reveal peritoneal thickening, intra-abdominal adhesions, and calcified shadows. (6) B-type ultrasonography shows free ascites in the abdominal cavity. In a small amount of ascites, a band-like anechoic zone appears between the right lateral margin and diaphragm and between the liver and kidney space; in a larger amount of ascites, an anechoic zone appears in front of the liver, which changes accordingly with the change of body position; when the amount of ascites increases further, an anechoic zone of ascites is seen in the abdominal cavity with small light dots or multiple thin light bands inside, and the anechoic zone of ascites is confined or separated. The peritoneal echogenic thickening, the mass is an adhesive gas-containing mass with strong echogenicity of floating intestinal gas, multiple intestinal loops are floating in the anechoic zone of ascites with adhesions, but with low mobility and passive motion, and single or multiple limited cystic masses with anechoic zones are seen in the abdominal cavity, the edges are still clear, and unevenly distributed light spots or light clusters are seen in the questions. (7) CT and MRI examinations can accurately show ascites, but the scan shows vague images of nodules and exudates of tuberculous peritonitis similar to peritoneal involvement in malignancy, so it is difficult to differentiate. ⑧ A positive PPD is helpful for diagnosis, but a negative one does not negate the presence of tuberculosis. (9) Laparoscopy is used in suspicious cases where the diagnosis cannot be established by the above tests and there is no extensive abdominal adhesions, so that the peritoneum and intra-abdominal lesions can be viewed directly, while the lesion tissue is taken for pathological diagnosis and ascites is taken for bacterial examination. ⑩Dissection is used when the intra-abdominal lesions are severely adherent and it is difficult to distinguish them from ovarian cancer or other tumors, which is the most reliable diagnostic method used in clinical practice. In addition, in 1989, Ronay et al. first reported 2 cases of elevated serum CA125 in tuberculous peritonitis. Elevated serum CA125 is no longer a tumor marker for malignant tumors such as ovarian cancer, but can also be elevated in non-neoplastic diseases.  2. Treatment 2.1 Treatment principle Preferred chemotherapy, in strict compliance with the principles of early, combined, appropriate, regular and full course, to develop a reasonable chemotherapy regimen and prevent the occurrence of drug resistance: surgical treatment is only used in patients whose masses do not disappear after drug treatment, recurrent symptoms, poor efficacy, prolonged course of treatment, adhesions, and postoperative continuation of anti-tuberculosis treatment.  2.2 Treatment regimen 2.2.1 Prophylactic treatment isoniazid 300 mg daily and vitamin B6 50 mg daily taken together for 3-6 months, with an efficiency of 60%-90%, even up to 98%.  2.2.2 Treatment of active tuberculosis ① According to the protocol in the “Guidelines for the Implementation of China’s Tuberculosis Prevention and Control Plan”, intensive phase: isoniazid 0.6 g, rifampin 0.6 g, ethambutol 1.25 g, bisacodyl 2.0 g, once every other day for 2 months; continuation phase I isoniazid 0.6 g , rifampin 0.6 g, once every other day for 4 months. (2) According to the clinical standard chemotherapy regimen, intensive phase: isoniazid 0.3 g, rifampin 0.45 g, ethambutol 0.75 g, and bisazinamide 1.5 g (or streptomycin 0.75 g intramuscularly) once daily for 2 months; continuation phase: isoniazid 0.3 g, rifampin O.45 g, and ethambutol 0.75 g once daily for 4 months. All the above doses are for patients weighing 50 kg or more, and those less than 50 kg should be measured by body weight.  2.3 Specific treatment regimen 2.3.1 Treatment regimen for tubo-ovarian tuberculosis The standard clinical chemotherapy regimen is available. The American Thoracic Society recommends the use of a standard short course chemotherapy regimen of isoniazid and rifampin for 6 months, with the addition of pyrazinamide for the first 2 months, and reports that the efficiency of genital tuberculosis drug therapy can reach 95%. In general, tubo-ovarian tuberculosis drug therapy is effective, and surgical treatment is considered as an option only in the following cases: (i) tubo-ovarian abscess or pelvic tuberculous abscess has formed and cannot be eradicated by drugs or the mass has increased with conservative treatment; (ii) large encapsulated effusion or massive ascites; (iii) unsatisfactory results of regular adequate anti-tuberculosis treatment and formation of drug-resistant lesions; (iv) severe persistent dysmenorrhea that is not relieved by conservative treatment; (v) persistent sinus tract. The American Thoracic Society states that surgical treatment of genital tuberculosis is only indicated for giant ovarian tubal abscess formation. Tuboplasty is feasible for patients with fertility requirements, but the results are poor, and tubectomy is feasible for those without fertility requirements.  2.3.2 Treatment options for endometrial and cervical tuberculosis often coexist with other sites of tuberculosis, and endometrial tuberculosis is rarely treated alone, often requiring systemic therapy plus pharmacological antituberculosis treatment for 3-6 months. Surgery is indicated for patients with uterine adhesions with fertility requirements, with hysteroscopic release of uterine adhesions under B- or even laparoscopic supervision and postoperative adjuvant therapy (placement of intrauterine device, larger doses of sex hormone therapy), but with limited improvement in reproductive function.  2.3.3 Treatment options for tuberculous peritonitis Anti-tuberculosis treatment is the main approach and can be done with a clinical standard chemotherapy regimen with appropriate rest and increased nutrition. Surgical treatment is firstly to clarify the diagnosis and secondly to remove the lesion, which can shorten the treatment time and improve the cure rate of tuberculosis. The scope of surgery should be determined by the age of the patient and the size of the lesion. 45 years of age or older, regardless of the severity of the disease, total hysterectomy and double adnexal resection are recommended to avoid recurrence. In women of childbearing age, the ovaries should be preserved as much as possible, and if the patient wishes to preserve the uterus, the uterus should be preserved if the endometrial tuberculosis lesions have been cured. In more severe cases, if the ovaries and fallopian tubes are densely adherent and form large masses that cannot be separated surgically, total hysterectomy with bilateral adnexal resection should be performed regardless of age.