Disseminated Tuberculosis With Placental Involvement in a Crohn’s Disease Patient Treated With Combination Therapy

Abstract

In the current therapeutic landscape of inflammatory bowel disease, safety considerations regarding immunosuppressive agents are essential. Combination therapy with antitumor necrosis factor agents and thiopurines increases the risk of opportunistic infections, including tuberculosis. We report the case of a 39-year-old pregnant woman with ileal Crohn’s disease who developed severe, life-threatening disseminated tuberculosis during treatment with infliximab and azathioprine. The case highlights the possibility of involvement of atypical sites, such as the placenta. In endemic areas, a high index of suspicion is required for uncommon manifestations of the disease.

Introduction

Crohn’s disease is a chronic, immune-mediated inflammatory disorder, often difficult to control, which may require the continuous use of advanced therapies, such as biologics, to achieve sustained remission.¹ Among these, antitumor necrosis factor (anti-TNF) agents remain widely used, with high efficacy in controlling disease activity and contributing to improved prognosis and quality of life. However, due to their immunogenic potential, combination with immunosuppressants such as azathioprine is often necessary to optimize the therapeutic response.²

The use of these therapies has been associated with an increased risk of opportunistic infections, particularly tuberculosis (TB). Although anti-TNF agents alone already increase this risk, combination therapy appears to potentiate it significantly.^3,4 In this context, we report a severe and uncommon presentation of TB in a patient with Crohn’s disease receiving combination therapy.

Case Report

A 39-year-old pregnant woman with recently diagnosed ileal Crohn’s disease presented to a quaternary referral center with septic shock and acute respiratory failure requiring mechanical ventilation. She reported a 2-month history of fever, cough, and night sweats, and had previously received empirical treatment for community-acquired pneumonia without clinical improvement.

Combination therapy with infliximab and azathioprine had been administered for 6 months, with no other relevant past medical history. On physical examination, pulmonary auscultation revealed diffuse crackles, and the abdomen was distended due to ascites.

A chest computed tomography demonstrated diffuse bilateral micronodules with random distribution, suggestive of miliary TB, with associated pleural effusion (Figure 1). Abdominal computed tomography revealed ascites, peritoneal thickening, and omental irregularity consistent with tuberculous peritonitis (Figure 2). Bronchoalveolar lavage confirmed the presence of Mycobacterium tuberculosis. Immunosuppressive agents were promptly discontinued, and antituberculosis therapy was initiated.

Figure 1.

Chest computed tomography (axial view) demonstrating diffuse bilateral micronodules with random distribution, consistent with miliary tuberculosis, and associated pleural effusion.

Figure 2.

Abdominal computed tomography showing ascites, peritoneal thickening, and omental irregularity, consistent with tuberculous peritonitis.

Despite treatment, the patient experienced progressive clinical deterioration. Acute fsletal distress prompted emergency cesarean delivery at the 30th week of pregnancy. She subsequently developed new-onset seizures and intracerebral hemorrhage secondary to tuberculous vasculitis (Figure 3). Cerebrospinal fluid analysis was positive for M tuberculosis, confirming central nervous system involvement. Placental histopathology revealed acute villositis with abscess formation, caseating granulomas, and numerous acid-fast bacilli, establishing the diagnosis of placental TB (Figure 4).

Figure 3.

Brain computed tomography demonstrating tuberculous central nervous system involvement. (A) Noncontrast image showing a hyperdense lesion in the left occipital region, consistent with intraparenchymal hemorrhage. (B) Contrast-enhanced image revealing intense and irregular vascular enhancement adjacent to the hemorrhagic lesion, consistent with tuberculous vasculitis.

Figure 4.

Placental histopathology (Ziehl-Neelsen stain) demonstrating numerous acid-fast bacilli (arrows, dashed boxes), confirming the diagnosis of placental tuberculosis.

She required prolonged intensive care, including renal replacement therapy, and multiple antituberculosis regimens due to nephrotoxicity and hepatotoxicity. She gradually improved and was discharged for outpatient follow-up.

Discussion

TB remains a highly prevalent infectious disease in Latin America, representing a major public health concern and an important cause of morbidity and mortality.⁴

In patients with inflammatory bowel disease, the risk of TB is significantly increased with the use of biologic and immunosuppressive therapies. TNF is essential for the formation and maintenance of granulomas and for the cellular immune response against M tuberculosis.⁵ Previous studies have demonstrated that the risk of active TB in patients receiving anti-TNF therapy is 2–8 times higher than in the general population.⁶ Observational data further indicate that this risk is even greater in individuals receiving combination therapy compared with anti-TNF monotherapy (hazard ratio, 5.67; 95% confidence interval, 2.42–10.21 vs hazard ratio, 3.26; 95% confidence interval, 1.18–9.05).³ Moreover, systematic reviews have shown a higher frequency of extrapulmonary and disseminated forms of TB in patients exposed to anti-TNF agents, a pattern consistent with the present case.⁷

This report reinforces the risk of disseminated TB in patients with inflammatory bowel disease receiving immunosuppressive therapy and highlights the potential for placental involvement during pregnancy, with possible implications for fetal outcomes. It also underscores the need for rigorous TB screening before and during therapy, as well as the maintenance of a high index of suspicion for atypical and extrapulmonary presentations, particularly in patients from endemic areas.