Inflammation of the female reproductive organs caused by Mycobacterium tuberculosis is known as genital tuberculosis, also referred to as tuberculous pelvic inflammatory disease. This condition includes ovarian tuberculosis, tubal tuberculosis, endometrial tuberculosis, cervical tuberculosis, vulvar and vaginal tuberculosis, and pelvic peritoneal tuberculosis. It is most commonly observed in women aged 20 to 40 years. However, recent trends indicate an increasing incidence in women aged 40 to 50 years.
Transmission Pathways
Genital tuberculosis is a manifestation of systemic tuberculosis and is often secondary to tuberculosis lesions in other parts of the body, such as pulmonary tuberculosis, intestinal tuberculosis, or peritoneal tuberculosis. Approximately 10% of pulmonary tuberculosis patients also have genital tuberculosis. The latency period for genital tuberculosis can be as long as 1 to 10 years, and in most cases, the primary site of infection has already resolved by the time genital tuberculosis is diagnosed. The common transmission pathways are as follows:
Hematogenous Dissemination
This is the most common route of transmission. During puberty, when reproductive organs are developing and have a rich blood supply, Mycobacterium tuberculosis can spread hematogenously. Following pulmonary tuberculosis infection, the internal reproductive organs can become infected within approximately one year. The bacteria initially invade the fallopian tube mucosa, which provides an environment conducive to latent infection, and then spread sequentially to the endometrium, ovary, and, less frequently, to the cervix, vagina, and vulva.
Direct Spread
Tuberculosis involving the peritoneum or intestines may directly spread to the internal reproductive organs.
Lymphatic Spread
Less common, this mode of transmission involves intestinal tuberculosis spreading to the internal reproductive organs via the lymphatic system.
Sexual Transmission
Extremely rare, this occurs when a male with urogenital tuberculosis transmits the infection through sexual activity, leading to ascending infection.
Pathology
Tubal Tuberculosis
This accounts for 90%–100% of female genital tuberculosis cases, meaning nearly all cases involve the fallopian tubes, with bilateral involvement being common. Tuberculous salpingitis can initially be classified into three types based on the infection route:
- Tuberculous Perisalpingitis: Numerous gray-white millet-sized nodules are present on the serosal surface of the fallopian tubes without involving the deeper muscular or mucosal layers.
- Tuberculous Salpingitis Interstitialis: This form arises from hematogenous spread, with scattered nodules initially forming in the submucosal or muscular layers, which may later invade the mucosa and serosa.
- Tuberculous Mucosal Salpingitis: Primarily affects the mucosa, often occurring at the distal end of the fallopian tubes.
As the disease progresses, depending on the bacterial virulence and host immunity, two pathological types emerge:
- Proliferative Adhesion Type: The most common type, accounting for approximately 80% of cases, characterized by thickened and hardened tubal walls. The fimbrial end becomes significantly swollen, resembling a pipe stem, although the tubal ostium may remain patent.
- Exudative Type: The presence of caseous necrosis in the tubal walls and adhesive mucosa leads to an accumulation of exudative material, causing severe tubal swelling and pyosalpinx formation.
Endometrial Tuberculosis
This commonly results from the spread of tubal tuberculosis and is present in 50%–80% of genital tuberculosis cases. Approximately half of patients with tubal tuberculosis also have endometrial tuberculosis. Early lesions are localized near the uterine cornua on both sides, without significant changes in uterine size or shape. As the condition advances, varying degrees of endometrial destruction occur, leading to scar tissue formation that may result in uterine cavity adhesions, deformation, and shrinking.
Ovarian Tuberculosis
Accounting for 20%–30% of genital tuberculosis cases, ovarian tuberculosis often originates from tubal tuberculosis. Due to the ovarian tunica albuginea, the disease typically remains localized to the ovarian surface, with deep ovarian involvement being rare. In fewer cases, hematogenous dissemination can lead to nodule formation and caseous necrotic abscesses deep within the ovary.
Cervical Tuberculosis
This is relatively uncommon, representing 10%–20% of genital tuberculosis cases. It may result from the spread of endometrial tuberculosis or from lymphatic or hematogenous dissemination. Lesions can present as either papillary hyperplasia or ulceration, which may resemble cervical cancer macroscopically.
Pelvic Peritoneal Tuberculosis
Often associated with tubal tuberculosis, pelvic peritoneal tuberculosis can be classified into two types based on lesion characteristics:
- Exudative Type: Characterized by diffuse gray-yellow nodules of varying sizes scattered on the peritoneal and serosal surfaces of pelvic organs. The exudate is a serous, straw-colored, clear fluid that accumulates within the pelvis and, in some cases, forms multiple encapsulated cysts due to adhesions.
- Adhesive Type: Adhesion is the predominant feature and involves thickened peritoneum tightly adherent to adjacent organs. The adhered tissue often undergoes caseous necrosis, increasing the risk of fistula formation.
Clinical Manifestations
The clinical presentation varies depending on the severity of the disease and the duration of the condition. Some patients may be asymptomatic, while others exhibit severe symptoms.
Symptoms
Infertility
Infertility is a common reason for seeking medical attention in patients with genital tuberculosis. Genital tuberculosis is one of the frequent causes of primary infertility. Damage and adhesions in the fallopian tube mucosa often result in tubal occlusion. Even when the tubal lumen remains partially patent due to external adhesions, the damage to the mucosal cilia, stiffness of the tube, and restricted motility lead to loss of the tube’s transport function. Endometrial tuberculosis can also affect implantation and development of the fertilized egg, resulting in infertility.
Menstrual Irregularities
In the early stages, endometrial congestion and ulcers may cause excessive menstrual bleeding. In advanced stages, varying degrees of endometrial destruction often result in hypomenorrhea or amenorrhea. Most patients present during later stages.
Lower Abdominal Pain
Adhesions and inflammation from pelvic inflammatory disease may cause varying degrees of dull lower abdominal pain that worsens during menstruation.
Systemic Symptoms
During active disease, symptoms of tuberculosis, such as fever, night sweats, fatigue, anorexia, and weight loss, may be present. Mild cases may exhibit minimal systemic manifestations, sometimes limited to fever during menstruation, whereas severe cases may present with high fever and systemic toxic symptoms.
Signs
There is significant variability in clinical signs depending on the extent and severity of the disease. Many patients are diagnosed with pelvic tuberculosis during evaluations for infertility, such as diagnostic curettage, hysterosalpingography, or laparoscopy, without clear signs or symptoms. Severe pelvic tuberculosis is often associated with peritoneal tuberculosis, where abdominal palpation may reveal tenderness or signs of ascites. Encapsulated ascites may present as cystic masses with ill-defined, fixed borders.
The uterus often shows poor development and restricted mobility due to surrounding adhesions. If the adnexa are involved, palpable structures such as cord-like fallopian tubes or irregular, variably-sized adherent masses formed by the fallopian tubes and ovaries may be present. The masses are typically firm, nodular, and may contain calcifications.
Diagnosis
Most patients present with subtle symptoms and few positive physical signs, so diagnosis is often overlooked. A thorough medical history is essential, particularly in patients with primary infertility, hypomenorrhea, or amenorrhea, or in unmarried young women with low-grade fever, night sweats, pelvic inflammatory disease, or ascites. A history of tuberculosis exposure or past infections such as pulmonary tuberculosis, pleurisy, or intestinal tuberculosis should raise suspicion of genital tuberculosis. A definitive diagnosis requires confirmation through bacteriological or histological evidence. Frequently used diagnostic methods include the following:
Endometrial Pathology Examination
Endometrial biopsy is the most reliable method for diagnosing endometrial tuberculosis. The procedure is best performed during the premenstrual phase (one week before menstruation or within six hours after menstruation starts), as the endometrium is thickest, increasing the likelihood of detecting Mycobacterium tuberculosis. To prevent the dissemination of tuberculosis, intramuscular streptomycin (0.75g) and oral isoniazid (0.3g) are administered daily for three days prior and four days following the procedure.
Since endometrial tuberculosis often originates from tubal tuberculosis, special attention should be paid to sampling the endometrium near the uterine cornua. The presence of characteristic tuberculous granulomas on pathological examination confirms the diagnosis. A negative result, however, does not entirely rule out tuberculosis. If resources allow, part of the curettage sample can be cultured for Mycobacterium tuberculosis. If the uterine cavity is small, rigid, and there is no tissue obtained, endometrial tuberculosis should still be considered based on clinical history and symptoms, and further evaluation is warranted. For suspected cervical tuberculosis, a biopsy is recommended for confirmation.
Imaging Studies
Chest X-ray or CT
This can reveal tuberculosis lesions of varying sizes, stages, and locations.
Pelvic X-ray or CT
The presence of isolated calcifications suggests past pelvic lymph node tuberculosis.
Hysterosalpingography
This is best performed 2–3 days after menstruation ends, although it can be performed at any time in patients with amenorrhea. It is contraindicated in patients with inflammatory adnexal masses and fever. Pre- and post-procedure administration of anti-tuberculosis drugs such as streptomycin and isoniazid is recommended to prevent reactivation or spread of tuberculosis.
Detectable signs on hysterosalpingography include:
- Uterine cavity stenosis or deformation of varying degrees, with irregular serrated edges.
- Multiple strictures of the fallopian tubes, creating a "beaded" appearance, or narrow, rigid tubal lumens.
- Calcifications in pelvic lymph nodes, fallopian tubes, or ovaries.
- Retrograde flow of iodized oil into one or both venous plexuses, which suggests endometrial tuberculosis.
Although hysterosalpingography provides considerable diagnostic value, there is a risk of introducing caseous material or Mycobacterium tuberculosis into the peritoneum.
Ultrasonography
Transvaginal ultrasonography can identify encapsulated ascites, bilateral adnexal calcifications, omental thickening, and peritoneal thickening.
Laparoscopy
Laparoscopy enables direct visualization of milliary nodules on the uterine and fallopian serosal surface. It also allows the collection of peritoneal fluid for Mycobacterium tuberculosis culture or biopsy of the lesion for histological examination. Care is needed during the procedure to avoid intestinal injury.
Hysteroscopy
Hysteroscopy assists in diagnosing endometrial tuberculosis by providing a direct view of the lesion location, severity, and uterine structural changes. Biopsy under hysteroscopy improves diagnostic accuracy. To prevent the dissemination of tuberculosis, intraoperative uterine distension pressure should be minimized, and anti-tuberculosis drugs should be administered postoperatively.
Mycobacterium tuberculosis Detection
Menstrual blood, curettage samples, or peritoneal fluid can be examined for Mycobacterium tuberculosis using various methods:
- Smear and acid-fast staining to identify Mycobacterium tuberculosis.
- Culturing the bacteria, which is accurate but time-consuming (typically 1–2 months).
- Molecular techniques such as PCR, which are rapid and convenient but may yield false-positive results.
- Animal inoculation, which is complex, time-intensive, and difficult to implement widely.
Tuberculin Skin Test
A positive tuberculin test indicates prior or current infection with Mycobacterium tuberculosis. A strongly positive result suggests active lesions, though the test cannot pinpoint the lesion's location. A negative result typically indicates the absence of prior infection.
Interferon-Gamma Release Assays (IGRAs)
This diagnostic method includes the QuantiFERON-TB test and the T-SPOT.TB test, the latter having the highest sensitivity and specificity.
Additional Laboratory Tests
Indicators such as increased lymphocytes in the white blood cell differential (contrasting with purulent pelvic inflammatory disease) and elevated erythrocyte sedimentation rates during active disease may support, but not confirm, a tuberculosis diagnosis. These tests are nonspecific and primarily supplementary.
Differential Diagnosis
Tuberculous pelvic inflammatory disease should be differentiated from sequelae of pelvic inflammatory disease, endometriosis, and ovarian malignancies, particularly epithelial ovarian cancer. In cases where the diagnosis remains challenging, laparoscopy or exploratory laparotomy may be performed to confirm the diagnosis.
Treatment
The treatment principles include the primary use of anti-tuberculosis medication, supplemented by rest and nutritional support, with surgical intervention considered when necessary.
Anti-Tuberculosis Pharmacotherapy
Anti-tuberculosis drug therapy is effective in approximately 90% of female genital tuberculosis cases. The selection, administration, and duration of anti-tuberculosis medications for genital tuberculosis generally follow the protocols established for pulmonary tuberculosis. Treatment should adhere to the principles of early initiation, combination therapy, consistent administration, appropriate dosing, and completion of the full course.
For patients with rifampin-sensitive or rifampin-resistance status unknown, first-line anti-tuberculosis drugs (isoniazid, rifampin, rifapentine, pyrazinamide, ethambutol, and streptomycin) are recommended in most cases, with preference given to fixed-dose combination formulations to simplify treatment.
For rifampin-resistant patients, treatment regimens include:
- Long-course therapy: An 18–20 month regimen consisting of at least four effective anti-tuberculosis drugs is recommended. Specific regimens are available for patients sensitive to or resistant to fluoroquinolones.
- Short-course therapy: A standardized 9–11 month regimen that combines seven anti-tuberculosis drugs may be prioritized for eligible patients.
Supportive Therapy
Acute-phase patients are generally advised to rest for at least three months. Chronic-phase patients may engage in limited work or study but should maintain a balance between activity and rest. Adequate nutrition and appropriate physical exercise are recommended to improve physical fitness.
Surgical Treatment
Surgery may be indicated under the following circumstances:
- Pelvic masses that have reduced in size with drug therapy but have not completely resolved.
- Persistent or recurrent disease that does not respond to treatment, or when differentiation from malignancies in the pelvis or abdomen remains difficult.
- Large pelvic masses or substantial encapsulated fluid collections.
- Severe endometrial tuberculosis with extensive damage to the endometrium, which does not respond to drug therapy.
Pre- and post-operative anti-tuberculosis pharmacotherapy is necessary to prevent the spread of infection during surgery and to improve post-operative outcomes. Surgical extent is determined by the patient's age and the location of the lesions. In older patients, total hysterectomy with bilateral salpingo-oophorectomy is often appropriate. In younger women, ovarian function should be preserved whenever possible. For patients with lesions confined to the fallopian tubes and a strong desire for fertility, bilateral salpingectomy with preservation of the ovaries and uterus may be performed.
Extensive and dense adhesions caused by genital tuberculosis frequently complicate surgery. Pre-operative bowel preparation is crucial, and special attention must be paid to anatomical structures during surgery to minimize the risk of injury.
Prognosis
Although standardized anti-tuberculosis pharmacotherapy achieves good clinical outcomes for genital tuberculosis, the post-treatment pregnancy success rate is very low. Assisted reproductive technology may be considered for patients desiring pregnancy.
Prevention
Preventive measures include strengthening physical fitness, ensuring appropriate vaccination with Bacille Calmette-Guérin (BCG), and actively preventing and treating conditions such as pulmonary tuberculosis, lymph node tuberculosis, and intestinal tuberculosis.