Tuberculous Endometritis: Etiology, Clinic, Diagnosis and Treatment

Tuberculosis (TB) is a life-threatening chronic granulomatous inflammatory disease caused by Mycobacterium tuberculosis. Genital TB in women is more common between the ages of 18 and 35.

3D Model of endometrium damaged by Mycobacterium tuberculosis:

Endometrium damaged by Mycobacterium tuberculosis

Synechiae in the uterine cavity formed as a result of endometritis

Tuberculous endometritis: posterior uterine wall

Tuberculous endometritis is a specific inflammation of the endometrium of the uterus caused by mycobacterial lesions of the mucous membrane. This disease develops slowly, is often asymptomatic in the early stages and can lead to irreversible changes in the uterus, which in turn can affect a woman’s reproductive function.

Manifestation of the disease, as a rule, is not associated with the onset of sexual activity. The onset of sexual activity may cause an exacerbation and transform a latent process into a reactive one. Isolated uterine involvement occurs in 10-15% of cases. In most cases, the uterus is affected together with the tubes (50-55%). The endometrium is most often affected (50-60%), in which tubercles characteristic of tuberculous lesions are formed.

The uterine mucosal glands near the tubercles are destroyed. If only the functional layer of the uterine mucosa is affected, the endometrium, together with the tubercles and mycobacteria, is rejected during the first menstruation, resulting in spontaneous cure. If the tuberculous process goes to the basal layer and deeper, the process of self-healing becomes more difficult.

Transmission route of tuberculous endometritis

The emergence of genital tuberculosis is more often associated with reactivation of mycobacterial infection from systemic distribution of mycobacterium during primary infection by hematogenous route. Direct transmission of mycobacteria between sexual partners has been established. Spread from other intra-abdominal foci is rare.

Clinical picture

Manifestation of genital tuberculosis is varied and depends on the general condition and resistance of the organism. In most cases, the disease develops slowly, without any characteristic symptoms. Later it acquires a chronic, often recurrent course, especially when the uterine appendages and pelvic peritoneum are affected. Less often the disease begins acutely, accompanied by a significant rise in temperature, abdominal pain, with phenomena of irritation of the peritoneum. It has been established that a rapid onset of the disease in genital tuberculosis is observed in cases of mixed infection.

Common symptoms include:

• Subfebrile fever;
• Weakness;
• A growing decline in strength;
• Rapid fatigue;
• Poor appetite and sleep;
• Night sweats;
• Weight loss;
• Dry skin.

On the genital side, patients complain of menstrual irregularities of the menstrual cycle type:

• Amenorrhea;
• Hypomenorrhea;
• Oligomenorrhea.

However, in the initial stages, women of reproductive age may be diagnosed with abnormal uterine bleeding. Patients also report low back and lower abdominal pain, and less frequently abnormal vaginal discharge, dyspareunia and infertility. In cases of self-healing, especially in childhood or puberty, scarring occurs as a result of healing, with partial or complete obliteration of the uterine cavity and atrophy of the endometrium, causing persistent primary amenorrhea.

Infertility develops in 60-95% of women as a result of genital tuberculosis. Primary infertility is more common than secondary infertility. The cause of infertility in tuberculosis is more often a lesion of the Fallopian tubes and less often – the lesion of the uterine mucosa. The diagnosis can be established after separate diagnostic scraping and culture for mycobacterial culture or PCR-diagnosis.

Diagnosis of tuberculous endometritis

1. Histological examination

Histologic examination reveals perivascular infiltrates, fibrosis or caseous decay of tuberculin tubercle tubercles.

2. Cytologic examination

The use of cytologic examination of uterine cavity contents and cervical smears, which detects giant Langhans cells specific for tuberculosis, is relevant. Caseous necrosis is rare and is usually diagnosed in severe forms. It reveals an ulcerative lesion of the uterine mucosa, which is more often diffuse and progresses to the caseous form, penetrating into the thickness of the muscular wall of the uterus.

3. Pyometra

Pyometra forms when curd-purulent decay accumulates in the uterine cavity in cases of obliteration of the internal pharynx.

4. Microbiological diagnostic methods

Microbiological methods are considered to be the most reliable diagnostic methods. Seeding of material from the uterine cavity is performed at least 3 times on dense artificial nutrient media. Also, the diagnosis of mycobacteria is possible using a highly sensitive and specific PCR method. However, this method has difficulties in interpretation and implementation, since the material for the study can lead to false-negative results. It is worth saying that sowing menstrual discharge for mycobacterial culture more often shows a positive result than biopsy samples.

5. Hysteroscopy

Hysteroscopy as a diagnostic method has limited application.

6. Standardized tuberculin test and interferon gamma release assay (IGRA)

Injection of tuberculin to assess the immune response. This is an additional method that alone cannot be used to establish or exclude the diagnosis of tuberculosis. Blood can also be tested for levels of interferon-γ, which is produced in response to mycobacterial antigens. This test is an alternative to skin testing.

7. Diagnosis based on the totality of the clinical examination

If there is no possibility of histologic and bacteriologic examination, the diagnosis is established on the basis of the totality of the results of clinical examination. X-ray examination (hysterosalpingography) plays the leading role in this case.

8. Radiologic examination

Radiographs show features typical of genital tuberculosis:

• Intrauterine synechiae;
• Displacement of the uterine body as a result of spreading adhesions;
• Obliteration of the internal pharynx;
• A distinct change in the pipes;
• Expansion of the outlet portions of the tubes;
• The presence of limited pipe expansions;
• Lack of tubal peristalsis;
• Visualization of irregular contours and unclear differentiation of the fimbrial section of the tubes.

9. Review radiography

Pathologic shadows are visualized during the review radiography of the pelvic organs. They are represented by calcinates in the tubes, ovaries, lymph nodes, foci of caseous decay.

10. Ultrasound

Ultrasound examination of the pelvic organs is also possible, but a highly qualified specialist is needed to make a diagnosis.

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Treatment of tuberculous endometritis

Chemotherapy with antituberculosis drugs is the therapy of choice. The intensity and duration of treatment is determined by the clinical form, prevalence and phase of the disease. Inappropriate treatment can cause the development of drug resistance of the bacterium, which leads to a worsening of the pathologic process.

Drugs in the first (basic) class include:

• Rifampicin;
• Streptomycin;
• Isoniazid;
• Pyrazinamide;
• Ethambutol.

Drugs from the reserve group are prescribed to patients with drug-resistant forms. The reserve group includes:

• Aminoglycosides;
• Fluoroquinolones;
• Oxazolidinones;
• Bedaquiline;
• Cycloserine.

Antituberculosis therapy has significantly reduced the use of surgical treatment, which is now used for certain indications. The main indications for surgical treatment are:

• Presence of tuboovarian inflammatory conglomerates;
• Lack of effect of conservative therapy after 9 months of treatment;
• Fistula formation;
• Proliferation of adhesions with impaired development of pelvic organ dysfunction.

Tuberculosis treatment guidelines recommend a minimum of 6 months of treatment, provided pyrazinamide is taken during the first 2 months of treatment and the body is receptive to therapy.

Surgical therapy usually consists of a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Surgery should be performed at least 6 weeks after initiation of antituberculosis therapy, as antimicrobial therapy facilitates the extent of surgery and reduces the risk of perioperative complications.

Treatment in pregnancy

Untreated TB poses a greater risk to a pregnant woman and her fetus than cured TB. Treatment should be started when the likelihood of TB is medium to high.

Features:

• Children born to women with untreated TB may have a lower birth weight than children born to women without TB, and in rare cases the child may be born with TB.
• Drugs used to treat TB penetrate the placenta but have no harmful effects on the fetus.
• Most pregnant women can delay treatment of latent TB infection until 2-3 months after delivery to avoid taking unnecessary medications during pregnancy.
• For women who are at high risk of latent tuberculosis infection progressing to tuberculosis disease, especially those who have had recent contact with a person with infectious tuberculosis, treatment of latent tuberculosis infection should not be delayed solely because of pregnancy, even during the first trimester.

Treatment regimens for tuberculosis in pregnant women

Drugs that are contraindicated in pregnant women:

• Streptomycin;
• Kanamycin;
• Amikacin;
• Capreomycin;
• Fluoroquinolones.

Pregnant women being treated for drug-resistant tuberculosis should be counseled regarding the risk to the fetus because of the known and unknown risks associated with back-up-line antituberculosis drugs.

Treatment during breastfeeding

Breastfeeding is not contraindicated in women being treated with first-line antituberculosis drugs because the concentrations of these drugs in breast milk are too low to cause toxicity in the newborn.

For the same reason, drugs in breast milk are not an effective treatment for tuberculosis or latent tuberculosis infection in newborns. Rifampicin may cause orange staining of body fluids, including breast milk. Orange staining of body fluids is expected and harmless.