Introducing a real-life case which has turned out to be a major public health problem taking over the lives of young women. We will start with a Clinical case of Female Genital Tuberculosis (FGTB) & discuss the symptoms, diagnosis, complications, & treatments.
Table of Contents
Clinical case scenario:
Imagine a 31-year-old female patient presents to you with a chief complaint of fever, cough and chest tightness for 2 weeks that was aggravated for 10 days. This patient describes that two weeks ago, she developed fever after catching a cold, which was severe at night. She further mentions that there was no obvious chills and shivers during the fever and the cough was mainly a dry cough. She complains of symptoms such as chest tightness at rest but is worsened after activity. She does not have symptoms such as hemoptysis, chest pain, dizziness, abdominal pain and diarrhea.
To make matters worse for this patient; Eight days ago, she complains the symptoms mentioned above worsened and went to emergency department, with a high body temperature of 39.6 ℃. Her chest CT showed “diffuse mass shadows in both lungs and a little consolidation in both lower lobes and a small amount of pleural effusion on both sides were also noted. The emergency diagnosis considered “pulmonary infection; type I respiratory failure”, and was given treatment such as “moxifloxacin” and “methylprednisolone”. Then this patient’s cough, shortness of breath, fever and other symptoms were relieved.
Since her illness, she has had poor sleep and appetite, normal urination, unresolved stool for 4 days, and lost about 1kg of weight.
When looking into her past medical history it was discovered that Three months ago, the patient underwent an IVF “embryo implantation”
After undergoing a series of examinations, it was concluded that her diagnosis was Female genital tuberculosis (FGTB). Now it begs the question as to how in fact such a diagnosis was made but before we get into the how’s and whys, let me explain to you a little bit about this particular diagnosis.
What is Female genital tuberculosis (FGTB)?
Genital tuberculosis (TB) in females is by no means uncommon, particularly in communities where pulmonary or other forms of extragenital TB are common. TB can affect any organ in the body, can exist without any clinical manifestation, and can recur. In more than half of the cases, both urinary and genital organs are involved. Despite the fact that involvement of genitourinary organs is almost always secondary to Tb elsewhere in the body and is rarely contagious, GUTB can result in a significant morbidity and even mortality due to renal failure. Female genital TB (FGTB) is an important cause of significant morbidity, short- and long-term sequelae especially infertility. Timely diagnosis and prompt appropriate treatment may prevent infertility and other sequelae of the disease. Very rarely, Tb can infect genital organs primarily, without prior pulmonary involvement. Female genital TB is typically understood as a disease of young women, with 80% to 90% of cases diagnosed in patients 20–40 years old, often during workup for subfertility but Up to 11 % of women with genital TB may be asymptomatic. Although in many developing countries, genital TB is more common among younger women, in developed countries most patients are older than 40 years.
What is the clinical presentation?
The clinical diagnosis of genital TB requires a high index of suspicion. About 20% of patients with genital TB give a history of TB in their immediate family. As a rule, they were exposed to an adult with TB during childhood. Approximately 50% of patients might have had tuberculous pleurisy, peritonitis, erythema nodosum, or renal, osseous, or pulmonary TB. A history of primary infertility in a woman in whom examination reveals no apparent cause and who gives a family history or personal history of TB should arouse suspicion of genital TB. It is reported that infertility is the common presenting symptom as well as a complaint in women with genital TB due to the involvement of fallopian tubes (blocked and damaged tubes), endometrium (non-reception and damaged endometrium with Asherman’s syndrome) and ovarian damage with poor ovarian reserve and volume. A history of poor general health persisting over months or years and associated with weight loss, fatigue, low-grade fever, menstrual disturbances such as amenorrhea, menorrhagia, metrorrhagia and oligomenorrhea or vague lower abdominal discomfort, abdominal swelling, postcoital bleeding, vaginal discharge and dyspareunia is often elicited in patients with genital TB.
A physical examination is important in establishing a diagnosis of genital TB. There is little correlation between presenting complaints and physical findings in genital TB. Most patients have an entirely normal examination. Most of the presents with a palpable adnexal mass on examination. Adnexal masses vary in size and in consistency and may result from thickened, edematous tubes, pyosalpinges, a conglomeration of pelvis organs matted together by adhesions, or a tubo-ovarian abscess. A temperature greater than 38°C was seen and the abdominal examination may reveal a “doughy” sensation, which has been ascribed to tubercle formation on the intestines and peritoneum. Ascites, either general or sacculated, may produce distention of the abdomen. Tuberculous ascites with increased intraabdominal pressure has been blamed for an occasional primary presentation such as uterine prolapse in an otherwise asymptomatic patient. Irregular masses caused by the matting together of intestines, omentum, and pelvic organs may be palpated. In an adolescent female presenting with ascites, pain, and low-grade fever, the cause is frequently TB.
In menopausal women, genital TB may cause an enlarged uterus that is tense and tender on examination, the result of pyometra formation. Physical examination may suggest ovarian malignancy. A fistulous tract between the genital tract and the bowel, bladder, or cutaneous area may be identified. These are usually caused by rupture of a tuberculous pyosalpinx into adjacent organs. Less common findings include lesions of the cervix and external genitalia.
What’s the differential diagnosis of this patient?
As genital TB may manifest in different ways with no characteristic symptoms and signs, the differential diagnosis depends upon the clinical presentation. For women who presents with abdominal pain and adnexal mass, the differential diagnosis that may come to mind are acute and chronic pelvic infections, ectopic pregnancy, endometriosis, ovarian cancer and, appendicitis. Abdomino-pelvic TB and FGTB are great mimickers and may be confused with other genital diseases like ovarian cyst, vulval or vaginal cyst, ectopic pregnancy, endometriosis genital malignancies and other intestinal diseases (appendicitis, Crohn’s disease) actinomycosis and various miscellaneous conditions (Schistosomiasis, filariasis, silicosis, leprosy, granuloma inguinale). Other conditions that produce a similar clinical picture, such as hepatitis, cholecystitis, appendicitis, ovarian cancer, and renal and cardiac diseases, should be excluded. Hence, history taking, meticulous clinical examination and judicious investigations are required to make the appropriate diagnosis of FGTB and to rule out other diseases.
Now coming back to our case;
What were the initial laboratory and imaging results of the patient?
An accurate and efficient laboratory examinations and diagnostic tests are crucial for doctors to create effective treatment plans that allow patients to recover as quickly as possible with the least amount of complications. Therefore, for this particular patient her lab results are as follows; The diagnosis of TB is based on the identification of M. tuberculosis and the following investigations were performed to confirm the diagnosis of genital TB of this patient ;
- WBC 2.86×10^9/L↓，N% 83.6%↑，RBC 3.86×10^12/L, Hb 111g/L↓，PLT 86×10^9/L↓
- ALT 105 IU/L↑，AST 163 IU/L↑，Alb 26.5 g/L↓
- PCT 0.50 ng/ml ↑，CRP 46.30 mg/L↑ ，ESR 56 mm/h ↑
- ABG: Nasal catheter oxygen inhalation 5L/min
- pH 7.426，PaO2 58.2mmHg↓，PaCO2 37.6mmHg，HCO3- 24.2mmol/L
- β-HCG＞1364 mIU/ml
The patient’s sputum culture was negative as well as her blood culture was negative. A nucleic acid test of the virus was done which also gave a negative result. This patient underwent a computerized tomography (CT) scan and the images are as follows;
Let’s discuss!
What do you think is the diagnosis basis? From the above CT images, we can see that this patient has lesions in both lungs from top to bottom. According to the laboratory examinations the patient’s presentation looks like its infectious, especially due to the increased ESR and CRP.But we must remember that CRP and ESR are non-specific inflammatory index factors, then therefore even though these two indicators have increased it does not confirm whether it be infectious or non-infectious. However, PCT is a relatively specific indicator, which is generally significantly increased in bacterial infection, especially gram-negative bacterial infection and we can see an increase in PCT in this patient but then again, the increase was not obvious. Moreover, the white blood cell count did not increase.
It was mentioned that she was treated with “moxifloxacin” and “methylprednisolone” which caused the patient’s cough, shortness of breath, fever and other symptoms to relieve. This shows that these anti-bacterial treatment had some effects.
Now you may be wondering, if the patient has a gram-negative infection, how did their blood and sputum cultures become negative? This maybe because, sometimes sputum culture and blood culture may not catch the pathogen in time. In clinical scenarios we must remember that just because something isn’t found, does not necessarily mean that it doesn’t exist. Therefore, in clinical practice, sputum culture and blood culture may be done several times to help confirm a diagnosis.
For this patient, due to the presentation of fever, rapidly progressive lung lesions, elevated inflammatory indicators, and improvement after the use of antibiotics, priority must be given to the idea that it could be of infectious origin.
If we consider that it is in fact infectious; we usually need to find evidence, whether it is bacterial or fungal or viral or tuberculosis and so on till we exclude each one and reach a possible conclusion.
Bacterial and viral origin can be excluded as WBC levels did not increase and the CT does not support viral origins. I would also like to point out that in the likely occurrence of a tuberculosis infection leukocytes can be reduced and inflammatory indicators are increased, as is the case here therefore there is a high suspicion of tuberculosis.
Another important detail that needs to be pointed out is that this patient β-HCG value which is ＞1364 mIU/ml which indicates that she is pregnant BUT it was also mentioned that three months ago, the patient underwent IVF “embryo implantation”. Due to her history of an IVF surgery, it may suggest that she may have problems with infertility. Therefore, when looking at the above information we have gathered, one of the most important causes of infertility, in relation to the rest of the clinical presentation is pathological causes like genital TB. Therefore, a diagnosis of female genital tuberculosis can be suspected.
How was this diagnosis confirmed?
The patient underwent further diagnostic examinations and the results are as follows;
- PPD（+）
- TB-IGRA（+）
- Bronchoalveolar lavage fluid (BALF): TB-DNA（+）
What was the treatment plan for this patient?
Once the diagnosis of genital tract TB is confirmed, it is important to rule out TB in other parts of the body. A chest radiograph and three early-morning sputum or gastric aspirate samples, or early morning urine samples for AFB stain and culture and intravenous urogram, are recommended.
To plan effective treatment, the gynecologist must consider if active TB is present elsewhere and the extent of the genital tract lesion. The doctor must also determine if medical management is enough, whether surgical management needed and if pregnancy is possible after treatment.
Pharmacological treatment;
A 6-month regimen consisting of isoniazid (INH), rifampin (RIF) and pyrazinamide (PZA) for 2 months, followed by INH and RIF for 4 months, is the preferred treatment for patients with a fully susceptible organism who adhere to treatment. Ethambutol (EMB) or streptomycin (SM) should be included in the initial regimen until the results of drug sensitivity studies are available, unless there is little possibility of drug resistance. This four-drug, 6-month regimen is effective even when the infecting organism is resistant to INH. This recommendation applies to both HIV-infected patients and those who are noninfected with HIV. However, in the presence of HIV infection, the clinical course should be closely monitored, and treatment should be prolonged if the course is determined to be slow or suboptimal.
A 9-month regimen of INH and RIF is acceptable in patients who cannot tolerate PZA. EMB or SM should be included until the drug susceptibility studies are available, unless there is little possibility for drug resistance. Consideration should be given to treating all patients with directly observed therapy (DOT).
The women however should be counseled about the importance of taking ATT(Anti-tuberculosis therapy) regularly and consumption of good and nutritious diet and should report in case of any side effects of the drugs. Liver function test is no longer done regularly unless there are symptoms of hepatic toxicity. Similarly, pyridoxine is not routinely prescribed with ATT unless there are symptoms of peripheral neuropathy with isoniazid.
| Regimen | INH (isoniazid) | RIF (rifampin) | PZA (pyrazinamide) | EMB (ethambutol) | SM (streptomycin) |
|---|---|---|---|---|---|
| Daily | 5 (300) | 10 (600) | 15–30 (2000) | 15–25 | 15 (1000) |
| 2x/wk. (DOT; directly observed therapy) | 15 (900) | 10 (600) | 50–70 (4000) | 50 | 25–30 (1500) |
| 3x/wk. (DOT) | 15 (900) | 10 (600) | 50–70 (4000) | 25–30 | 25–30 (1500) |
Surgical Treatment;
The role of surgery in the treatment of genital TB in modern times is clearly as adjunctive therapy. Currently, clinical application of surgical treatment is limited and is advocated only if there is no other choice of treatment except in patients with a persistent pelvic mass, recurrent pelvic pain, or excessive bleeding. In patients with multidrug-resistant TB and pyosalpinx, tubercles, or a tubo-ovarian mass, surgery is suggested, including removal of the ovaries, uterus, and/or fallopian tubes. However, the consequent complications make surgical treatment of TB patients risky and difficult. An example of these problems is that patients with FGTB show severe complications, including increased excessive bleeding, bladder injury, and peritonitis during a laparoscopic operation. Patients with FGTB who receive vaginal hysterectomy show excessive bleeding, bowel injury, and a high fever post-operation.
Pregnancy?
What exactly is the outcome for this particular patient?
All four first-line medications used to treat TB (i.e., isoniazid, rifampin, ethambutol, and pyrazinamide) were classified by the Federal Drug Administration’s prior letter-based system of medications in pregnancy as category C. However, the use of pyrazinamide during pregnancy is controversial given the lack of evidence about its safety. If drug-susceptible active TB disease is diagnosed, a minimum of 9 months of therapy with isoniazid, rifampin, and ethambutol should be given. All treatment for active TB disease should be with directly observed therapy, in which a health care worker watches as a person takes each medication, which can be facilitated by the health department. Active TB disease treatment in pregnancy should occur with the support of an infectious disease specialist, especially in the context of antibiotic resistance, allergic reactions, extensive disease, or medication compliance concerns.
Despite the advances in chemotherapeutic treatment, pregnancy after a diagnosis of genital tract TB is rare, and when it does occur, it is more likely to be an ectopic pregnancy or to result in spontaneous abortion. If an early diagnosis is made and adequate therapy is given immediately, a more favorable outcome may be expected.
In conclusion:
Female genital tuberculosis is an important cause of infertility in patients. The operation and medication of IVF can also lead to the recurrence and spread of tuberculosis which is likely the cause for this patient. Not only is it considered a common health problem in developing countries with a poor conception rate, the atypical presentation, paucibacillary nature, arduousness in procuring appropriate clinical sample and poor sensitivity of conventional microbiological methods are rising challenges in forming a fast diagnosis. Therefore, it is vital that an early diagnosis must be made to improve the prognosis of those that are affected
Quiz
The most common site for female genital tuberculosis is :
a. Cervix
b. Uterus
c. Fallopian tube
d. Ovary
References:
1. Genital tuberculosis is common among females with tubal factor infertility: Observational study Abdulhakim Ali Al eryani, Ahmed Saleh Abdelrub & Abdelrahman H. Al Harazi
https://www.tandfonline.com/doi/full/10.1016/j.ajme.2014.11.004
2. Emerging progress on diagnosis and treatment of female genital tuberculosis
Ying Wang*, Ruifeng Shao*, Chihua He, Ligang Chen
https://journals.sagepub.com/doi/10.1177/03000605211014999
3. Female genital tuberculosis cases with distinct clinical symptoms: Four case reports
Gonul Aslan, Ph.D., Mahmut Ulger, Ph.D., Seda Tezcan Ulger, Ph.D., Huseyin Durukan, M.D., Faik Gurkan Yazici, M.D., and Gurol Emekdas, Ph.D.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899771/
4. Recent Advances in Diagnosis and Management of Female Genital Tuberculosis
J. B. Sharma, Eshani Sharma, Sangeeta Sharma & Sona Dharmendra
https://link.springer.com/article/10.1007/s13224-021-01523-9
Answer
The most common site for female genital tuberculosis is :
a. Cervix
b. Uterus
c. Fallopian tube
d. Ovary