Pulmonary tuberculosis and nutritional vulnerability during anti-tumor necrosis factor therapy for inflammatory bowel disease: Two case reports

Abstract

BACKGROUND

Tumor necrosis factor (TNF) inhibitors are effective in the treatment of inflammatory bowel disease (IBD) but increase tuberculosis (TB) risk. Standard latent TB infection screening before biologic therapy does not fully eliminate this risk. We report two cases of active pulmonary TB developing despite negative baseline screening, highlighting nutritional vulnerability and crowded living environments as underrecognized contributing factors. This report uniquely combines nutritional assessment data with environmental context to provide a more comprehensive perspective on TB risk in patients receiving biologic therapy.

CASE SUMMARY

Two young female university students with IBD developed active pulmonary TB within six months of initiating anti-TNF therapy despite negative baseline screening using tuberculin skin test, interferon-gamma release assay, and chest radiography. Both patients resided in crowded university dormitories. Nutritional assessment by a registered dietitian using 24-hour dietary recall revealed inadequate dietary intake with low energy, protein, fiber, iron, calcium, and vitamin B12 levels in both cases. Anti-TNF therapy was discontinued, and anti-TB treatment was initiated, leading to clinical improvement in both patients. Both patients achieved clinical improvement; Case 1 completed treatment with confirmed mucosal remission, while Case 2 remains under follow-up.

CONCLUSION

TB prevention in biologic-treated inflammatory bowel disease should incorporate nutritional assessment and environmental risk evaluation alongside standard screening.

Key Words: Inflammatory bowel diseases; Tumor necrosis factor inhibitors; Tuberculosis; Pulmonary; Malnutrition; Immunosuppression; Case report

Core Tip: Standard latent tuberculosis (TB) infection screening before anti-tumor necrosis factor therapy does not fully protect against active TB in patients with inflammatory bowel disease (IBD). This report is the first to systematically document both nutritional deficiency and crowded dormitory exposure as concurrent, potentially modifiable risk factors in this setting. Clinicians managing IBD with biologic therapy should integrate routine nutritional assessment and environmental risk evaluation into their preventive approach, particularly for young patients in communal living settings. These findings support expanding TB prevention beyond serology to a multifactorial clinical framework.

INTRODUCTION

Tumor necrosis factor (TNF) inhibitors have substantially improved the management of inflammatory bowel disease (IBD), enabling effective induction and maintenance of remission in both Crohn’s disease (CD) and ulcerative colitis. However, by suppressing cellular immune responses, these biologic agents also increase susceptibility to opportunistic infections, particularly tuberculosis (TB). For this reason, screening for latent TB infection (LTBI) using tuberculin skin testing (TST), interferon-gamma release assays (IGRAs), and chest imaging is routinely recommended prior to initiating anti-TNF therapy. Despite these precautions, active TB continues to be reported in patients receiving biologic treatment, suggesting that current preventive strategies may not fully eliminate the risk[1-3].

Several studies have highlighted this concern. In a multicenter Korean cohort, Kang et al[2] found that the incidence of TB remained elevated among IBD patients treated with TNF inhibitors, with no significant difference between individuals with positive and negative LTBI screening results. Similarly, Giri et al[3] reported that 8.4% of Indian patients receiving anti-TNF therapy developed TB despite comprehensive baseline screening. These findings indicate that additional factors beyond baseline LTBI status may contribute to disease development. Environmental exposure may be particularly relevant in settings such as university dormitories, where large numbers of students live in close proximity and routine TB surveillance is uncommon.

Another factor that may increase vulnerability is nutritional status. Malnutrition is known to impair both innate and adaptive immune responses, especially cell-mediated immunity that is essential for controlling Mycobacterium tuberculosis infection[4]. Patients with IBD frequently experience nutritional deficiencies related to chronic inflammation, dietary restrictions, and reduced intake during disease flares. In this context, the interaction between immunosuppressive therapy, environmental exposure, and nutritional vulnerability may create conditions that favor TB reactivation or new infection.

Two cases of active pulmonary TB occurring shortly after initiation of anti-TNF therapy in young university students with IBD was presented, highlighting the potential contribution of nutritional and environmental factors to TB risk. This report uniquely combines nutritional assessment data with environmental context to provide a more comprehensive perspective on TB risk in patients receiving biologic therapy.

CASE PRESENTATION

Chief complaints

Case 1: This case was initially documented as a brief letter in the European Journal of Gastroenterology & Hepatology in 2020 and is now presented with additional nutritional and clinical context[5]. A 22-year-old female university student presented with fatigue, productive cough, night sweats, and unintentional weight loss approximately six months after initiation of anti-tumor necrosis factor (anti-TNF) therapy.

Case 2: A 24-year-old female university student presented with persistent cough, fatigue, fever, and recent unintentional weight loss approximately three months after starting biologic therapy.

History of present illness

Case 1: The patient had been diagnosed with moderately active CD (ileocolitis). Initial treatment included oral mesalazine and azathioprine (2.5 mg/kg). Due to persistent disease activity, adalimumab therapy was initiated approximately eight months after the initial diagnosis. Baseline screening for LTBI, including TST, IGRA, and chest radiography, was negative. There was no history of TB or chronic pulmonary disease. Six months after initiating biologic therapy, the patient developed fatigue, productive cough, and night sweats, accompanied by progressive weight loss.

Case 2: The patient was diagnosed with ulcerative colitis (Mayo 3 pancolitis) in June 2023 after presenting with 15-30 episodes of bloody diarrhea daily. Endoscopic examination showed extensive mucosal ulceration. Initial therapy included intravenous prednisolone (40 mg) and oral mesalazine. Due to inadequate response, adalimumab therapy was initiated in January 2024. Baseline LTBI screening with TST, IGRA, and chest radiography was negative. No previous history of TB or other chronic respiratory illness was reported. Approximately three months after starting biologic therapy, the patient developed a persistent cough, fatigue, and fever, followed by unintentional weight loss over two to three weeks.

Both patients were managed in the Department of Gastroenterology at Bezmialem Vakif University Faculty of Medicine, Istanbul, Türkiye.

Personal and family history

Case 1: The patient was a university student living in a shared dormitory room with two other students. She denied smoking or alcohol consumption. No family history of TB or inflammatory bowel disease was reported.

Case 2: The patient lived in an overcrowded state university dormitory shared with four students in a building housing more than 1500 residents. No known TB exposure was reported among dormitory residents. There was no reported family history of TB or inflammatory bowel disease.

Physical examination

Case 1: The patient appeared underweight. Her body weight had decreased from 53 kg to 46 kg, corresponding to a body mass index (BMI) of 17.3 kg/m².

Case 2: The patient presented with recent weight loss. Her body weight decreased from 54 kg to 51 kg, with BMI declining from 18.7 kg/m² to 17.6 kg/m².

Laboratory examinations

Case 1: Baseline TB screening prior to biologic therapy using QuantiFERON-TB Gold assay and TST was negative. Dietary assessment revealed low energy intake of approximately 1620.7 kcal/day, with insufficient protein intake (62.1 g/day) and fiber intake (15.6 g/day). Micronutrient intake was also suboptimal, including vitamin B12 (4.7 μg/day), iron (8.5 mg/day), and calcium (573.1 mg/day).

Case 2: Baseline LTBI screening using TST and IGRA was negative. Dietary evaluation demonstrated markedly reduced energy intake (1241 kcal/day) and inadequate protein consumption (19.7 g/day). Fiber intake was 10.9 g/day. Micronutrient intake was insufficient, including vitamin B12 (1 μg/day), iron (4.6 mg/day), and calcium (410.5 mg/day). Despite these findings indicating nutritional vulnerability, no formal nutritional assessment or dietitian consultation was performed during clinical management.

Dietary assessment was performed by a registered dietitian using the 24-hour dietary recall method in both cases. A comprehensive summary of anthropometric measurements, Mini Nutritional Assessment-Short Form scores, dietary intake, and clinical timeline for both cases is presented in Table 1.

Table 1 Comprehensive nutritional assessment and clinical summary of cases.

Parameter	Case 1	Case 2	Reference/threshold
Anthropometric and clinical characteristics
Height (cm)	163	170	-
Pre-illness body weight (kg)	53	54	-
Body weight at presentation (kg)	46	51	-
BMI at presentation (kg/m²)	17.3	17.6	18.5-24.9
Unintentional weight loss (%)	13.20	5.60	≥ 5% clinically significant
MNA-SF
A: Food intake decline in past 3 months (0-2)	1	0
B: Weight loss in past 3 months (0-3)	0	2
C: Mobility (0-2)	2	2
D: Psychological stress/acute disease (0-2)	0	0
E: Neuropsychological problems (0-2)	2	2
F: BMI	0	0
MNA-SF total score	5	6	12-14 = normal
MNA-SF nutritional status	Malnourished	Malnourished	0-7 = malnourished
Nutrient intake (24-hour dietary recall)
Energy (kcal/day)	1620.7	1241	2000-2200
Protein (g/day)	62.1	19.7	46-50 g/day
Protein (g/kg body weight/day)	1.35	0.39	≥ 1.2 (IBD guideline)
Dietary fiber (g/day)	15.6	10.9	25-28 g/day
Iron (mg/day)	8.5	4.6	18 mg/day
Calcium (mg/day)	573.1	410.5	1000 mg/day
Vitamin B12 (μg/day)	4.7	1	2.4 μg/day

MNA-SF: Mini Nutritional Assessment-Short Form; IBD: Inflammatory bowel disease; BMI: Body mass index.

Imaging examinations

Case 1: Chest computed tomography (CT) revealed cavitary lesions and infiltrates in the upper lung lobes. Sputum culture confirmed pulmonary TB.

Case 2: Contrast-enhanced thoracic CT demonstrated radiological findings consistent with active pulmonary TB.

FINAL DIAGNOSIS

Both patients were diagnosed with active pulmonary TB occurring during anti-tumor necrosis factor (anti-TNF) therapy for inflammatory bowel disease. Case 1 involved a patient with CD, while Case 2 involved a patient with ulcerative colitis.

TREATMENT

In both cases, adalimumab therapy was discontinued immediately after the diagnosis of pulmonary TB. Standard anti-TB therapy was initiated according to national TB treatment guidelines, consisting of a multidrug regimen including rifampicin, isoniazid, pyrazinamide, and ethambutol during the intensive phase, followed by continuation therapy as clinically indicated.

OUTCOME AND FOLLOW-UP

Both patients showed clinical improvement after initiation of anti-TB therapy. In Case 1, the symptoms resolved, and the patient completed anti-TB treatment. Follow-up colonoscopy demonstrated mucosal healing and remission of CD. In Case 2, the patient experienced gradual symptom resolution and gained approximately 3 kg, with BMI improving from 17.6 kg/m² to 19.0 kg/m². Her ulcerative colitis remains under clinical follow-up.

DISCUSSION

These two cases illustrate the ongoing challenges in preventing TB among patients with IBD receiving anti-TNF therapy, particularly in regions with a higher TB burden. Both patients developed active pulmonary TB within six months of initiating biologic therapy despite negative baseline LTBI screening, including IGRA, TST, and chest radiography. The temporal relationship between the initiation of anti-TNF therapy and the onset of TB symptoms suggests a possible association between biologic-induced immunosuppression and disease development. Similar observations have been reported in previous studies demonstrating that TB may occur despite negative LTBI screening in patients receiving TNF inhibitors[1-3].

Evidence from the literature supports the persistence of TB risk in patients with IBD treated with TNF inhibitors. Kang et al[2] reported that the incidence of TB remained significantly higher among IBD patients treated with TNF inhibitors compared with the general population, regardless of LTBI screening status. Likewise, Giri et al[3] observed that a proportion of patients receiving anti-TNF therapy developed TB despite comprehensive baseline evaluation. Our cases are consistent with these findings but additionally highlight the potential contribution of environmental and nutritional factors that are less frequently emphasized in previous reports.

In both patients, nutritional intake appeared clearly inadequate, characterized by low caloric intake, insufficient protein consumption, and deficiencies in micronutrients such as iron, calcium, and vitamin B12. Malnutrition is known to impair both innate and adaptive immune responses, particularly T-cell-mediated immunity, which plays a central role in controlling Mycobacterium TB infection[4]. In this context, nutritional vulnerability may have further weakened host immune defenses, potentially amplifying the susceptibility created by anti-TNF-mediated immunosuppression[6]. These observations are hypothesis-generating rather than conclusive, given the small number of cases and the absence of objective biochemical nutritional markers; however, they highlight nutritional status as a potentially underrecognized modifier of TB risk in patients receiving biologic therapy.

Environmental conditions may also have contributed to disease development. Both patients were university students living in crowded dormitory settings, environments where airborne pathogens such as Mycobacterium tuberculosis can spread more easily. Routine TB screening is not universally implemented in many student housing systems, and early symptoms may go unrecognized. Public health strategies including mandatory screening at dormitory admission, improved ventilation, periodic symptom surveillance, and health education programs could reduce transmission risk in such high-density environments. Notably, no formal public health contact tracing was conducted among dormitory residents following these diagnoses, which limits conclusions regarding community transmission and the extent of potential exposure.

The precise origin of TB in our patients whether representing reactivation of previously undetected latent infection or new primary acquisition could not be determined. Both mechanisms are plausible. The crowded dormitory environment raises the possibility of new airborne exposure, while anti-TNF-mediated immunosuppression may have enabled rapid progression of latent infection that escaped baseline screening. This distinction has clinical implications: New primary acquisition would reinforce the role of ongoing environmental surveillance, whereas reactivation would support more frequent LTBI re-screening during therapy. In the absence of molecular epidemiological data, both pathways should be considered.

Regarding IBD management after anti-TNF discontinuation: In Case 1, follow-up colonoscopy demonstrated mucosal healing and sustained remission of CD without reinitiation of biologic therapy during the observed follow-up period. In Case 2, ulcerative colitis remained clinically quiescent during anti-TB treatment; decisions regarding reinitiation of biologic therapy will be guided by disease activity once TB treatment is completed. These outcomes highlight the importance of close multidisciplinary monitoring of IBD activity after treatment withdrawal.

Several limitations should be acknowledged. First, this report includes only two cases and therefore cannot establish causality or quantify risk. Accordingly, all associations described should be interpreted as hypothesis-generating observations. Second, complete biochemical markers of nutritional status (including serum albumin, prealbumin, ferritin, and vitamin D) were not available for both patients, limiting objective confirmation of malnutrition. Third, dietary intake was assessed by 24-hour dietary recall, a method subject to recall bias; the markedly low protein intake reported in Case 2 (19.7 g/day) may reflect underreporting or short-term dietary disruption during acute illness and should be interpreted with caution. Fourth, no formal public health contact tracing was performed among dormitory residents, precluding conclusions about community transmission. Finally, the precise source of TB exposure could not be definitively identified. Nevertheless, the consistent temporal relationship between the initiation of anti-TNF therapy and TB onset, combined with similar environmental and nutritional risk factors in both patients, strengthens the plausibility of the observed associations.

Taken together, these cases emphasize that TB risk in patients receiving anti-TNF therapy may be influenced by multiple interacting factors beyond LTBI screening results. Recognition of nutritional vulnerability and environmental exposure may help clinicians identify individuals at higher risk and guide more comprehensive preventive strategies.

CONCLUSION

In TB-endemic settings, patients with inflammatory bowel disease receiving biologic therapy may remain vulnerable to active TB despite negative baseline screening. The present cases highlight that this risk is likely multifactorial, reflecting not only therapy-related immunosuppression but also nutritional vulnerability and environmental exposure in crowded living environments. These observations suggest that TB prevention strategies in patients treated with anti-TNF agents should extend beyond baseline LTBI screening to include continued clinical surveillance, routine evaluation of nutritional status, and attention to environmental risk factors. In clinical practice, integrating nutritional assessment and targeted public health measures particularly in communal living settings such as university dormitories may help identify patients at increased risk. Future studies should further explore the role of nutritional status and environmental exposure in modifying TB risk among individuals receiving biologic therapy.