Chapter

48
Genitourinary
Tuberculosis in Female

INTRODUCTION
Female genital tuberculosis, though known to have existed for centuries, was
first described by Morgagni in 1744 during an autopsy on a 20-year-old girl
known to have died of TB peritonitis.1 It is almost always secondary to a focus
elsewhere in the body. Large number of patients may remain asymptomatic
and the finding of the disease may be incidental. This chapter aims to review
epidemiology, pathogenesis, clinical features, diagnosis and management of
female genital tuberculosis.

EPIDIMIOLOGY
Fallopian tubes are the first and most commonly affected genital organs,
followed by endometrium, ovary and cervix.2 There has been some change in
trends in incidence of disease that has been observed in recent times, reasons
responsible are improvement in economic standards in developed countries
and global pandemic of the HIV infection. However, trend in developing
countries are different. Incidence has been different in various parts of
world ranging from 10.3% in India to being less than 1% in USA.3,4 It has been
observed that the worldwide incidence of genital TB in infertile women to be
5–10% whereas it has been estimated to range from 1–26.7% in several parts of
India.5,6 Sutherland described endometrial TB in 10 out of 1000 patients with
abnormal uterine bleeding.7 Schaefer reported that 80–90% of his patients
were between 20 and 40 years of age.8 However, further studies have shown
a changing trend in the age at diagnosis. The mean age was 28.2 years in the
initial decades as compared to 38.9 years observed in last decade in one of
the studies. It has been reported from India that 68–69% of genital TB were
between 20 and 30 years of age.
 Genitourinary Tuberculosis in Female 567

PATHOGENESIS
It is always secondary to primary tuberculosis infection elsewhere in the
body. Although pulmonary tuberculosis is most commonly responsible but
extrapulmonary organs can also be the source of infection.9 The primary
focus is found to be quiescent or healed by the time the genital lesion
becomes evident. Many years may get evolved between the primary focus and
appearance of genital TB. In 50% patients with genital TB, chest involvement
is common. Hematogenous/lymphatic spread is the most common mode of
transmission.

Fallopian Tube Tuberculosis

Fallopian tube is the most frequently involved part of genital tract seen in
90% of patients.2,8 Ampullary portion is most commonly involved followed by
isthmus and involvement of interstitial portion is rare. Bilateral involvement is
more common. Various types of tubercular salpingitis have been recognized-
tubercular endosalpingitis, tubercular exosalpingitis interstitial tubercular
salpingitis.

TB of Ovaries
Ovarian involvement occurs in 15–25% cases.2 It most often results from direct
extension of the disease from the fallopian tubes. Clinically, these conditions
present as tubo-ovarian mass or cyst.

Endometrial TB
Endometrial infiltration by tuberculosis is usually secondary to tubal
involvement. It has been reported that endometrium is involved in 50–80%
cases of genital TB.10,11 A study was conducted in 156 hospitalized female
patients of pulmonary tuberculosis and tuberculous endometritis was
associated with 11.5% of patients.12 The uterus may appear normal, but the
endometrium may show giant cell microscopically. In more advanced cases,
caseating material collects in the uterine cavity which may lead to pyometra.
This is more commonly noted in postmenopausal women who have a
stenosed cervix. Adhesions within the uterine cavity lead to formation of
synechia. Rarely an abscess may also occur in myometrium.

TB of Cervix
TB of cervix may be seen in 5–15% cases of genital tuberculosis.2 Cervix mostly
gets involved by downward spread of the disease from the endometrium.
Microscopic examination reveals granulomatous inflammation.
Inflammatory atypia with frequent hyperplastic, mucosal changes may also
be seen along with caseation.
568 Clinical Tuberculosis: Diagnosis and Treatment

TB of Vagina, Vulva and Bartholin Gland

TB of vulva and vagina has been observed in 1% of cases and is usually
secondary to involvement of other parts of genital tract.2 However,
transmission of the disease by a male partner with involvement of epididymis
or seminal vesicles has been reported.13 Lesions may present as hypertrophic
form and sometimes non-healing ulcers resembling malignancy for which
histopathological examination is required for confirmation of diagnosis.
There may be many different forms of skin lesions on the vulva including TB
verrucosa cutis, lupus vulgaris, scrofuloderma and erythema indurata.

CLINICAL PRESENTATION OF FEMALE

GENITAL TUBERCULOISIS
The most frequent presenting symptoms are primary and secondary infertility
reported in 35–60% cases. Menorrhagia and secondary amenorrhea is
reported in 40% and 10% patients respectively or even postmenopausal
bleeding can occur. Lower abdominal or pelvic pain which is non-
characteristic, chronic or dull aching in nature and occasionally it may
be acute starting with tubercular peritonitis or by tubo-ovarian mass or
pelvic inflammatory disease. Persistent and abnormal vaginal discharge
seen in endocervical TB or TB of cervix and vagina. Amenorrhea was the
most common menstrual complaint observed in 18 female patients having
pulmonary tuberculosis with associated tuberculous endometritis.12 Rarely
patients may present with non-healing wounds/sinus/fistula, spontaneous
vesico-vaginal fistulas and hour-glass bladder. No physical sign on abdominal
or pelvic examination is characteristic of genital TB. Minimal induration in
adnexal areas on both sides is most commonly noted finding during pelvic
examination. Bilateral tubo-ovarian masses, especially in nullipara or
unmarried girls in the absence of fever should raise a suspicion of genital TB.2
Presence of ascites or doughy feel of abdomen with pyrexia and menstrual
abnormalities should also raise the suspicion.

DIAGNOSIS
Genital TB is an elusive diagnosis and a high index of suspicion is the first
step of the diagnostic process. A careful history with specific mention of
previous exposure to or active TB is of prime importance. One has to rely
on imaging and histopathology as genital TB is a paucibacillary disease.
Endometrial biopsy for histopathological examination and mycobacterial
culture remain the most commonly used procedures for the diagnosis of
female genital TB. Laparoscopy, hysterosalpingography, ultrasonography
of pelvic organs, CT scan and MRI are other investigations advised if the
endometrial biopsy is inconclusive. However, diagnostic hysteroscopy and
laparoscopy have emerged as the most useful investigations.
 Genitourinary Tuberculosis in Female 569

Endometrial Biopsy
Endometrial tissue obtained by biopsy, curette or dilatation of the cervix
and curettage of endometrium is useful for the diagnosis of TB, performed
best before the menstrual phase as lesions are located close to endometrium
during this period.2 Diagnosis of TB is established in 50–76% patients. Other
findings such as dilatation of glands, destruction of epithelium and presence
of inflammatory cells apart from granulomas and caseation necrosis on
histopathology. A negative result does not rule out pelvic involvement
suggesting involvement of adjacent organs.

Mycobacterial Isolation
Endometrial biopsy specimen, menstrual blood, cervical and vaginal
secretions, tubal biopsy material or peritoneal fluid obtained during
diagnostic laparoscopy have been subjected to mycobacterial smear and
culture examination.

Plain Radiograph
Tuberculosis can affect any part of the female genital tract but more
commonly involves the fallopian tubes.14,15 Hydrosalpinx and pyosalpinx
are usually large and may appear as soft tissue masses on plain abdominal
radiographs. The pyosalpinx may be calcified. Tuberculous tubo-ovarian
abscesses may calcify, are observed on either side of the pelvis and sometimes
appear as well-defined homogeneous masses, occasionally with areas of
increased density presumably due to the granuloma. Serpiginous or linear
calcification can occur in the tubes.

Hysterosalpingography
Hysterosalpingographic (HSG) findings may suggest a diagnosis. HSG
appearances vary as widely as the pathologic changes observed in this
condition.16 Tubal involvement is almost always bilateral but the degree of
involvement varies between the two sides. HSG may demonstrate a flask-
shaped dilatation of the fallopian tubes due to obstruction at the fimbria.
Occasionally, the obstruction is at the uterine end of the tube; therefore, the
tubes are not depicted. HSG may demonstrate sacculation with infiltration
of contrast material resembling salpingitis isthmica nodosa. Infiltration
around the tube, which creates a cloud-like appearance of the delicate sinus
tracts, has also been described. A characteristic HSG feature suggestive of
tuberculosis has been described; in which irregular contrast distribution
occurs resembling a cotton-wool plug. Focal irregularity and areas of
calcification may occur within the lumen of the fallopian tubes. Obstruction
of the fallopian tubes is not pathognomonic for tuberculosis and may occur
with other pathology. In end-stage disease, the tubes become rigid, lack
peristalsis and resemble pipe-like conduits. Within the endometrial cavity,
570 Clinical Tuberculosis: Diagnosis and Treatment

tuberculous endometritis findings include adhesions, which may vary

from very thin to very thick synechiae. In end-stage disease, the uterine
cavity may be obliterated completely. Within the pelvis calcified lymph
nodes and ovaries may be observed. Blockage of the fallopian tubes is not
pathognomonic for tuberculous salpingitis and may occur as a result of
previous ectopic pregnancy, iatrogenic and developmental causes, pelvic
inflammatory disease, and other forms of infective processes of the genital
tract. In one series of 15 patients with genital tuberculosis and peritonitis, 12
patients had wet peritonitis and 3 had dry (adhesive) peritonitis. An adnexal
mass was present in 93%, peritoneal thickening in 69%, omental thickening
in 61%, and endometrial involvement in 83%. Associated ascites may be
septated, particulated, and/or loculated.

Laparoscopy and Hysteroscopy

These procedures are essential in the diagnostic work-up of patients with
infertility. Pelvic organs and peritoneal surfaces are directly visualized. It also
helps in confirmation of tubal patency. Despite normal physical examination,
several abnormalities can be detected in about 60% of the cases during
laparoscopy.17 The frequent use of these methods has led to diagnose large
number of cases of genital TB among women with infertility and chronic
pelvic pain.

Ultrasonography
Sonographic findings may suggest genitourinary tuberculosis in the appro-
priate clinical setting and findings may help eliminate the treatment choices
using renal surgery or hysterectomy for benign disease. Demonstration of
bilateral, predominantly solid, adnexal masses containing scattered small
calcifications is highly indicative of TB involvement.18 In patients with female
genital tract tuberculosis, awareness of sonographic changes associated
with the infection may improve diagnostic accuracy and avoid clinical mis-
management and surgical explorations in genital infections associated with
wet-type (peritonitis) tuberculosis.19

Computed Tomography (CT)

CT-scan can reveal many findings suggestive of genital tuberculosis such as
low density ascites, adenopathy, presence of multiple pelvic lesions, hepatic,
adrenal and splenic lesions. All the features are suspected for TB especially
encountered in young patients suffering from infertility, however possibility
of malignancy cannot be ruled out.18

Magnetic Resonance Imaging (MRI)

MRI has been increasingly used for evaluation of pelvic and other abdominal
masses and particularly useful in localizing soft tissue abnormalities in
patients with the disease.20
 Genitourinary Tuberculosis in Female 571

Polymerase Chain Reaction (PCR)

The PCR is a useful supporting test for the diagnosis of female genital TB.21
It is a rapid and sensitive molecular biologic method for detecting DNA
of Mycobacterium tuberculosis. In a study reported from New Delhi,22
endometrial aspirates as well as biopsies and fluid from pouch of douglas
were investigated for mpt64 gene by PCR in 25 women with infertility and
it was observed that 14 out of 25 patients were positive, correlated well with
laparascopic findings. Multiple sampling from several sites increases the
diagnostic yield.

TREATMENT
Standard anti-TB drug regimens are used to treat genital TB. It has been
recommended that an initial 2 months intensive phase of treatment in which,
usually, four drugs—rifampicin, isoniazid, pyrazinamide and ethambutol
(or streptomycin)—are given followed by a 4-month continuation phase
in which only rifampicin and isoniazid are given. Excellent cure rates have
been reported with the standardized regimen. In India, patients with female
genital TB receive DOTS category I under Revised National Tuberculosis
Control Program (RNTCP).
Surgical intervention is required when there is persistence or increase
of pelvic masses despite of adequate anti-TB treatment (ATT), recurrence of
positive endometrial culture or histology, persistence of clinical symptoms
such as pain or bleeding after conservative treatment and recurrence
of pyometra due to TB in a postmenopausal patient.2 Minimal disease
is managed by conservative treatment including monthly examination.
Dilatation and curettage is done after 6 months of ATT for histological and
bacteriological examination. Advanced disease such as palpable tubo-ovarian
masses are treated with total abdominal hysterectomy and bilateral salpingo-
oophorectomy after 6 months of conservative therapy.2 In vitro fertilization and
embryo transfer (IVF-ET) can be an alternative option for successful pregnancies
in young female patients with genital TB.23 Tuboplasty can be performed
after adequate medical treatment as infertility is the most common symptom.
However, results are disappointing and very few successful pregnancies have
been reported as most of pregnancies are likely to result in ectopic pregnancy
or abortion.

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572 Clinical Tuberculosis: Diagnosis and Treatment

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