Tuberculosis in pregnancy:a challenging differential diagnosisfor inflammatory bowel disease

Overview

Objective:
To describe a case of tuberculosis with intestinal variant in a pregnant woman in the 17th week of pregnancy.

Design:
Case report.

Setting:
Department of Obstetrics, Federal University of São Paulo (UNIFESP), São Paulo-SP, Brazil.

Conclusion:
Tuberculosis is a public health problem that concerns many countries in the world. It was declareda public emergency by the World Health Organization in 2005. Its presence during pregnancy brings maternal risk and fetal impairment if not treated quickly and properly. The intestinal variant is not the most common form of the disease and may be confused with inflammatory bowel diseases, especially Crohn‘s disease. Knowledge of the specific characteristics, combined with a detailed medical history and appropriate diagnostic methods can make all the difference in gestational prognosis. We report the case of a pregnant woman who wrongly underwent treatment for inflammatory bowel disease at another service. After admission to our university hospital, fruitful diagnostic clarification was achieved and the patient was diagnosed and treated for tuberculosis. We describe the details of the investigation and, in particular, review the main characteristics in the literature for differentiating the two diseases.

Keywords:
tuberculosis, pregnancy, X-ray, colonoscopy, microscopy

INTRODUCTION

Tuberculosis is one of the oldest diseases in human history. It was declared a public health problem in Africa in 2005 [8] and, in 2009; 1.7 million people were reported as dead, totaling 4,700 deaths per day [1]. About a third of the global population (1.75 billion) is infected with the bacillus of this disease, which kills 500,000 women annually [19]. Typically, it is diagnosed in immigrants and immunosuppressed individuals, especially those infected with HIV, in whom the risk of developing the disease is about 20 to 37 times higher than in uninfected individuals [9].

The site usually affected is the pulmonary system. However, tuberculosis is a systemic disease and its intestinal form is the sixth most common extrapulmonary presentation [7]. The symptoms of the intestinal form mimic other conditions, especially inflammatory bowel disease, which makes early diagnosis difficult, especially in places with inadequate health resources [6].

Tuberculosis, in its active form during pregnancy, is associated with increased risk of prematurity, fetal growth restriction, low birth weight and perinatal mortality.

We describe the approach used in a case of extrapulmonary tuberculosis during pregnancy, in order to review the characteristics relating to this disease, with special attention to the differential diagnosis of inflammatory bowel diseases.

CASE REPORT

A 24-year-old woman of African ancestry, in her second pregnancy (parity = 1), was admitted to the emergency service of Hospital São Paulo, Federal University of São Paulo (UNIFESP), in her 17th week of pregnancy. She had a history of fever for 10 days, associated with severe abdominal pain, vomiting and diarrhea. She reported that she had lost 20 kg of weight in 4 months and that, in the previous month, she had been attended at another hospital with the same complaints. At that time, a diagnosis of inflammatory bowel disease was suggested and, thus, treatment with prednisone (20 mg/day) and antibiotic therapy using a third-generation cephalosporin were instituted. During a second hospitalization, clinical support and subsidiary propaedeutics were implemented; chest radiography showed a cavity in the right hemithorax (Figure 1) and investigation of Koch’s bacillus in sputum was positive.

In view of the exuberant intestinal condition, it was decided that a colonoscopy should be performed. This revealed deep ulcers in the sigmoid and descending colon, while sparing the region of the rectum (Figure 2). A biopsy was also conducted (Figure 3), in which the presence of granuloma with numerous bacilli corroborated the proper diagnosis of tuberculosis. Therefore, regimen I treatment (rifampicin, isoniazid, pyrazinamide and ethambutol) was applied. After adequate treatment, the patient was discharged with significant clinical improvement, and the therapy was maintained with follow-up in the high-risk prenatal outpatient clinic.

The patient was readmitted at 38 weeks of pregnancy, in labor, and progressed to vaginal delivery 6 hours after admission, giving birth to a male weighing 3,250 g, with Apgar 9/10. The newborn was handed over to the neonatology team for the initial care to be performed.

DISCUSSION

Tuberculosis is a matter of public health concern and its appearance during pregnancy increases maternal and fetal risks. Therefore, it merits full attention from the obstetric team. Some authors have reported that disease progression is delayed when young women begin their reproductive life earlier [17]. However, others have stated that infected women who become pregnant would have to be counseled regarding the importance of therapeutic abortion [18]. In reality, what has been observed over the years is that the initial condition of the disease in the initial stage of pregnancy is what will dictate the evolution of the disease. Coinfection with HIV and an advanced stage of the disease reflect an unfavourable prognosis, such as prematurity, fetal growth restriction and increased neonatal mortality [14]. Low maternal weight gain during pregnancy and high rates of miscarriage have also been widely observed [10].

Intestinal tuberculosis is highly associated with low socioeconomic status, malnutrition, overcrowding and HIV infection. It can usually be a primary or secondary infection in relation to the pulmonary site. The result from exposure to Mycobacterium tuberculosis is dependent on the bacterial and human genotyping. Studies have shown that in the Asian population, polymorphism of the T597C nucleotide in the TLR2 receptor was more often found in patients infected by the bacterium [4].

The diagnostic challenge lies in the fact that both intestinal tuberculosis and inflammatory bowel diseases include clinical conditions such as anorexia, fever, weight loss, abdominal pain and abdominal distension, along with vomiting, which represents an intestinal obstruction. Mucosal lesions caused by ulceration are reflected in malabsorption and diarrhea. A family history of the disease speaks in favor of inflammatory bowel diseases, but lung alterations and disease location outside of the digestive tract, such as lymph node involvement, direct the diagnosis towards intestinal tuberculosis [3].

Crohn‘s disease is the main inflammatory bowel disease to be differentiated from intestinal tuberculosis. From a serological point of view, the leukocyte count, decline on hemoglobin and elevation of C-reactive protein are similar in both cases. Assaying of anti-Saccharomyces cerevisiae antibodies (ASCA), given that tuberculosis presents chronic inflammatory lesions, is also similar [3].

Mycobacterium tuberculosis takes a long time to grow in culturing media (4 to 6 weeks) which may delay effective propaedeutics. Use of immuno-fluorescence may increase the sensitivity and specificity for cases of intestinal tuberculosis [3]. The polymerase chain reaction (PCR) can bring faster results (48 h) for tuberculosis patients but, in addition to high cost, it may occasionally be positive in patients with Crohn‘s disease [2]. The in vitro ELISA test Quantiferon-TB Gold (QFT-G) seems to be a useful tool, with a sensitivity of 80%, but it is subject to cross-reaction with the BCG vaccine. Its advantage in cases of intestinal tuberculosis is still not very clear, and it is more suitable for monitoring the antibiotic therapy [11].

Colonoscopy is mandatory for differentiating between intestinal tuberculosis and inflammatory bowel disease, especially when biopsies are performed on multiple segments of the intestine. The tuberculoid ulcers are generally transverse and hypertrophic lesions and nodularity can be observed. On the other hand, in Crohn‘s disease, the ulcers are longitudinal, aphthous and deep [12].

Observation of the biopsied intestinal mucosa under a microscope shows that, in 50-80% of the cases, granulomas are found in patients with tuberculosis that has already been confirmed, and in 15-65% of the patients with Crohn‘s disease. Tuberculoid granulomas are confluent, have peripheral lymphocytes and are large, with a diameter greater than 400 um. Each biopsied segment has five or more granulomas, in addition to often being located in the submucosa. In Crohn‘s disease, these granulomas are small, unorganized and, in most cases, isolated [15].

The benefit of contrast-enhanced computed tomography is also evident in cases of extra-intestinal tuberculosis. Short ileocecal lesions are more common in intestinal tuberculosis with intestinal tapering and pre-stenotic dilatation. In inflammatory bowel diseases, these lesions are long, with sacculations and without pre-stenotic dilatation. Fistulas and perforations are very frequent in Crohn‘s disease, while enteroliths are observed in intestinal tuberculosis [13].

Treatment with an antibiotic regimen is essential for pregnant women. A regimen consisting of isoniazid, rifampicin, ethambutol and pyrazinamide for at least six months is recommended. These drugs are considered safe for use during pregnancy [5]. For multidrug-resistant pregnant women, second-line drugs such as cycloserine, ofloxacin, amikacin, kanamycin, capreomycin and ethionamide are recommended as treatments, even though insufficient studies have been conducted to assess the risk during pregnancy. Ethionamide has been associated with defects in the fetal nervous system if used in the first trimester [16].

CONCLUSION

In summary, the diagnosis of tuberculosis should be a matter of concern for public health programs, especially in countries where its incidence is still worrisome. The approach towards intestinal tuberculosis needs to be multiprofessional, and all the available resources, such as colonoscopy with biopsy, contrast-enhanced computed tomography, culturing and PCR should be used to differentiate the diagnosis from inflammatory bowel diseases, especially Crohn‘s disease, which is the most similar variant. Considering that most of these resources are expensive for the public health system, obstetricians should always use these propaedeutics in association with detailed investigation of the patient’s clinical history, in order to assure maternal and fetal wellbeing.

Prof. Edward Araujo Júnior, PhD

Department of Obstetrics

Federal University of São Paulo (UNIFESP)

Rua Carlos Weber, 956, apto. 113 Visage

Vila Leopoldina

São Paulo – SP

Brazil

CEP 05303-000

e-mail: araujojred@terra.com.br