Intestinal tuberculosis is a form of extrapulmonary tuberculosis that falls within the broader category of gastrointestinal tuberculosis, which itself accounts for only roughly one to three percent of all tuberculosis cases worldwide. In most patients it follows a chronic, smoldering course marked by nonspecific complaints such as abdominal pain, weight loss, fever, diarrhea, constipation, or bloody stools. Acute presentations are the exception rather than the rule, and the clinical picture closely mimics Crohn’s disease and gastrointestinal malignancy, both of which share a predilection for the ileocecal region. That overlap makes definitive diagnosis difficult without tissue, and the median time from symptom onset to diagnosis has been reported at approximately thirteen weeks. In the Japanese patient, the interval between the first symptoms and perforation was measured in days.

The patient’s background offered subtle but important clues. He had lived in Japan for a year and a half after moving from Nepal, a country with a high tuberculosis burden, and he had lost about six kilograms over the preceding year despite maintaining a body mass index of 29.7 kilograms per square meter. He had no history of diabetes, malignancy, autoimmune disease, immunosuppressive therapy, or recent antibiotic use, and both his HIV antibody test and serum beta-D-glucan assay were negative. When he presented to the hospital, his temperature was 38.1 degrees Celsius, his abdomen was distended and soft, with tenderness in the lower abdomen but no rebound tenderness. His white blood cell count of 8,800 per microliter, with 7,234 neutrophils and 1,118 lymphocytes, and a C-reactive protein level of 1.03 milligrams per deciliter were only modestly abnormal, providing little to suggest the catastrophe unfolding within his small bowel.

Contrast-enhanced computed tomography of the abdomen supplied the first strong signal. The scan revealed continuous dilatation and symmetric thickening of the small intestinal wall, increased density of the surrounding fat, and enlarged mesenteric lymph nodes. Multiple para-aortic nodes measuring more than one centimeter were also visible. Chest radiography and chest computed tomography showed no active pulmonary lesions, meaning the intestinal disease was not accompanied by the classic lung findings that usually trigger suspicion of tuberculosis. The patient was admitted, managed with fasting, rehydration, and a nasogastric tube, and started on empiric cefmetazole, an antimicrobial choice consistent with the hospital’s protocol for presumed intra-abdominal infection in a patient without prior antibiotic exposure or recent hospitalization.

Over the next two days the clinical course deteriorated sharply. Abdominal pain worsened on the second hospital day and failed to improve by the third. Repeat laboratory testing showed a C-reactive protein concentration that had surged to 32.86 milligrams per deciliter, alongside a procalcitonin level of 1.46 nanograms per milliliter, a pattern consistent with bacterial peritonitis. A repeat contrast-enhanced computed tomography scan demonstrated free air within the abdominal cavity, the radiographic signature of gastrointestinal perforation, together with increased peri-intestinal fat density and fluid collections indicating an intra-abdominal abscess. The diagnosis of small intestinal perforation was made, and the patient was taken to the operating room for emergency surgery.

At laparotomy, the surgical team encountered feculent peritonitis with a fibrinous exudate that was most prominent in the pelvis. A two-millimeter perforation was identified in the distal ileum, surrounded by roughly thirty centimeters of edematous bowel. The affected segment was resected and intestinal continuity was restored with a stapled side-to-side anastomosis. The peritoneal cavity was irrigated with twenty liters of saline, three drains were placed, and the abdomen was closed in layers. The resected bowel then became the key to the diagnosis, because the differential diagnosis at this stage still included intestinal tuberculosis, Crohn’s disease, and malignant tumor.

The imaging features argued against some of these alternatives. The lesion was located in the ileocecal region, where intestinal tuberculosis most commonly localizes, typically involving a short segment of bowel. The symmetric wall thickening favored tuberculosis, whereas the asymmetric thickening highly specific for Crohn’s disease was absent, as were the skip lesions characteristic of that condition. Lymph nodes larger than one centimeter are more often seen in intestinal tuberculosis than in its mimics. Malignant tumors, meanwhile, are far more common in the large intestine than in the small bowel, and no mass lesion was identified on axial or coronal contrast-enhanced images, although the authors acknowledged that small-bowel tumors can occasionally escape detection on imaging. Definitive classification therefore awaited pathology.

Histopathological examination of the resected small intestine settled the question. Microscopy revealed epithelioid granulomas with caseous necrosis and Langhans giant cells, the pathological hallmarks of tuberculosis, visible on hematoxylin and eosin staining at magnifications of 200 and 400 times. A tuberculosis polymerase chain reaction test performed on the ascitic fluid returned a positive result, confirming the microbiological diagnosis of intestinal tuberculosis causing perforation. The isolate proved sensitive to all major first-line drugs, allowing prompt initiation of standard anti-tuberculosis chemotherapy: a four-drug regimen of isoniazid, rifampicin, ethambutol, and pyrazinamide for the first two months, followed by a two-drug regimen of isoniazid and rifampicin for the subsequent four months.

The recovery was uncomplicated. No drug side effects were observed during treatment, the abdominal pain resolved, and the C-reactive protein level normalized. A contrast-enhanced computed tomography scan performed three months after the start of therapy showed that the intra-abdominal abscess had resolved and the enlarged lymph nodes had decreased in size. The patient completed the full six months of treatment and experienced no recurrence. This favorable trajectory is consistent with the broader literature, which indicates that anti-tuberculosis therapy generally proceeds smoothly once the diagnosis is made and appropriate drugs are administered, underscoring that the principal barrier in such cases is recognition rather than treatment.

The case carries a sobering epidemiological message. Japan became a low-burden tuberculosis country in 2021, and national case numbers continue to decline, which means clinicians there encounter intestinal tuberculosis ever less frequently and are correspondingly less likely to suspect it in patients presenting with abdominal symptoms. Yet global migration means that people from high-burden countries such as Nepal continue to live in low-burden settings, and they may carry forms of tuberculosis that clinicians rarely see. Intestinal perforation complicates four to 7.6 percent of intestinal tuberculosis cases and carries a mortality rate as high as thirty percent, making early recognition a matter of survival. The authors note that a previously reported patient who presented with obstruction from abdominal tuberculosis avoided perforation through diagnostic surgery, and they suggest that in their own patient the combination of characteristic computed tomography findings and a year of unexplained weight loss might likewise have allowed earlier diagnosis and prevention of the perforation. Their warning to colleagues is explicit: even subtle signs such as weight loss should not be overlooked, and in patients from high-burden countries presenting with abdominal symptoms and suggestive imaging, intestinal tuberculosis must remain on the differential list, because the disease can progress from obstruction to perforation within a matter of days.

Subject of Research: A case of intestinal tuberculosis causing small bowel perforation in a Nepalese migrant living in a low tuberculosis-burden country

Article Title: Intestinal Perforation Caused by Intestinal Tuberculosis of a Nepalese Man Living in a Low Tuberculosis‐Burden Country: A Case Report

Article References: Matsushita, S., Kanata, K., Matsushita, S., Ito, Y., Ichijo, K., & Uehara, M. (2026). Intestinal Perforation Caused by Intestinal Tuberculosis of a Nepalese Man Living in a Low Tuberculosis‐Burden Country: A Case Report. Clinical Case Reports, 14(9), Article e73521. https://doi.org/10.1002/ccr3.73521

Image Credits: AI Generated

DOI: 10.1002/ccr3.73521

Keywords: intestinal tuberculosis, bowel perforation, extrapulmonary tuberculosis, Nepal, Japan, case report, ileocecal region, computed tomography, granulomas, anti-tuberculosis therapy, low-burden country, differential diagnosis

Histoplasma capsulatum is a thermally dimorphic fungus that grows as a mold in soil enriched with bat or bird guano and converts to a yeast form at human body temperature. People acquire infection by inhaling microconidia—tiny airborne spores—released when contaminated soil is disturbed, whether in caves, poultry farms, or construction sites. In most immunologically healthy people, inhaled spores are contained by the lungs’ innate defenses and produce either no symptoms or a self-limited pulmonary illness. The fungus is endemic to the Mississippi and Ohio River valleys of North America, with additional foci across Central and South America, parts of Africa, and regions of Asia including the Indian subcontinent. In a subset of patients, however, the infection escapes pulmonary containment and spreads throughout the body as progressive disseminated histoplasmosis, a condition classically seen in people with defective cellular immunity such as those with HIV/AIDS, transplant recipients on immunosuppressive drugs, or patients receiving biologic agents.

That is precisely why this case is so unsettling. The young man had no history of corticosteroid use, diabetes, substance abuse, or high-risk sexual behavior. He denied fever, night sweats, and cough. When HIV serology came back negative, and when his morning cortisol and adrenocorticotropic hormone levels proved normal—ruling out the adrenal insufficiency that clinicians had considered given his persistent hyponatremia—he was, by all standard measures, immunocompetent. Disseminated histoplasmosis in such individuals is recognized but rare, generally attributed to overwhelming inoculum exposure or subtle, often undocumented, defects in innate immune signaling. The one telling detail in his history was a recent exploration of caves in hilly terrain. Bat guano accumulated in cave environments serves as the primary ecological niche for the fungus’s mycelial growth, and heavy exposure to cave aerosols can flood the lungs with organisms in quantities sufficient to overwhelm even intact immune defenses, seeding systemic dissemination.

The diagnostic odyssey began long before his hospital admission. An outside colonoscopy had already suggested either intestinal tuberculosis or inflammatory bowel disease, and given the region’s high tuberculosis burden and a strong family history of TB, his physicians had reasonably started empirical four-drug anti-tubercular therapy. He complied fully for 60 days and improved not at all. On admission, he was cachectic, pale, and profoundly ill, with bilateral digital clubbing, pitting pedal edema, a solitary ulcer on the hard palate, and firm, non-tender cervical lymph nodes. Laboratory work revealed microcytic hypochromic anemia with hemoglobin of 8.6 grams per deciliter, a C-reactive protein of 143.35 milligrams per liter, albumin of just 2 grams per deciliter, and serum sodium of 127 millimoles per liter. A chest radiograph showed mild bilateral pleural effusions.

Imaging then painted a deceptively clear picture. Magnetic resonance enterography demonstrated multi-segmental bowel wall thickening involving the distal jejunum and ileum without stricture formation, along with small reactive-appearing mesenteric lymph nodes, and the radiological impression favored Crohn’s disease. Fecal calprotectin—a protein released from neutrophils in inflamed intestinal mucosa—was markedly elevated at 1849.47 micrograms per gram, a level widely associated with active inflammatory bowel disease. Stool microscopy showed 8 to 12 pus cells per high-power field with mucus. Everything pointed toward a chronic inflammatory process of the gut. Yet as the case authors emphasize, fecal calprotectin is a marker of mucosal neutrophilic infiltration, not of any specific disease. It can be substantially elevated in infectious enteritis, including histoplasmosis, salmonellosis, and intestinal tuberculosis, and its dramatic rise should prompt a search for etiology rather than a reflexive diagnosis of IBD.

Endoscopic findings reinforced the mimicry. Upper endoscopy revealed a small benign-appearing duodenal ulcer, while colonoscopy demonstrated an ulcero-nodular lesion in the caecum studded with pseudopolyps distributed across the ascending, transverse, and descending colon. A repeat colonoscopy days later confirmed ulcero-nodular lesions with skip-pattern involvement of the distal ileum, ileocecal valve, and caecum—an appearance that overlaps almost perfectly with the colonoscopic spectrum of tuberculosis and Crohn’s disease. The ileocecal region is preferentially affected in all of these conditions, partly because the high density of Peyer’s patches in the terminal ileum facilitates reticuloendothelial seeding by pathogens, whether mycobacteria or fungi. GeneXpert MTB/RIF testing of tissue was negative for Mycobacterium tuberculosis, and a QuantiFERON-TB Gold Plus assay was non-reactive, a combination that carries a high negative predictive value for active mycobacterial disease.

The first biopsies were inconclusive, yielding only granulation tissue with acute and chronic inflammatory infiltration—no definitive granulomas, no malignancy, and no organisms. This pattern is well documented in gastrointestinal histoplasmosis, where superficial sampling frequently misses the intracellular yeasts lurking within lamina propria histiocytes. The breakthrough came from two directions. A repeat deep biopsy targeting the caecum and ileocecal valve revealed dense inflammatory infiltration rich in eosinophils and, crucially, multiple encapsulated, uniform, small oval yeast forms exhibiting narrow-based budding and eccentric nuclei, both within and outside histiocytes—morphological features diagnostic of Histoplasma capsulatum. The following day, fine-needle aspiration cytology of a cervical lymph node showed granulomatous inflammation teeming with intracellular and extracellular Histoplasma organisms, confirming that the infection was disseminated. Periodic acid-Schiff and Gomori methenamine silver stains are widely advocated to enhance fungal detection in tissue sections, particularly when organism burden is low, and the case authors argue that clinicians should maintain a low threshold for requesting such stains in unresolved ileocecal pathology, especially after anti-tubercular therapy fails.

Treatment began immediately. Oral itraconazole at 200 milligrams twice daily was started on the day of diagnosis, and systemic therapy was escalated to liposomal amphotericin B at 3 milligrams per kilogram per day the following day. It was too late. After just two doses of amphotericin, the patient suffered a massive lower gastrointestinal hemorrhage with acute hemodynamic collapse—his blood pressure became unrecordable and his oxygen saturation fell to 85 percent on 15 liters per minute of supplemental oxygen. Despite transfusion, intravenous fluid resuscitation, and vasopressor support, he was transferred to the intensive care unit and died roughly six hours later of refractory cardiorespiratory failure. Extensive mucosal ulceration, vascular erosion by the fungal inflammatory process, and consumptive coagulopathy from disseminated infection all predispose to this most feared complication, and antifungal therapy initiated a mere 72 hours earlier could not reverse tissue destruction that had already progressed past the threshold of reversibility.

The broader lessons are sobering. Published mortality rates for disseminated gastrointestinal histoplasmosis range from 20 to 50 percent, rising substantially when diagnosis is delayed beyond four weeks; this patient’s diagnosis lagged more than three months after symptom onset. In high-tuberculosis-burden settings, anchoring bias favors mycobacterial explanations for ileocecal pathology, weight loss, and lymphadenopathy, and failure of empirical anti-tubercular therapy is often the first signal that a different diagnosis deserves consideration. Equally hazardous is the temptation to treat a compelling Crohn’s-like phenotype—bowel wall thickening on enterography, skip lesions, pseudopolyps, and sky-high fecal calprotectin—with immunosuppressive therapy before infection has been histopathologically excluded, a step that could accelerate fungal dissemination with catastrophic consequences. In this case, the decision to defer immunosuppression pending tissue confirmation likely bought valuable time. The authors note that fungal culture and urine or serum Histoplasma antigen testing, which might have accelerated diagnosis, were unavailable, and formal immunological evaluation for rare innate immune defects such as STAT3 or IL-12 pathway mutations was not feasible in the acute setting. Their conclusion is unambiguous: when anti-tubercular therapy fails in ileocecal disease, fungi belong on the differential, deep colonoscopic biopsies with fungal stains are essential and may need repeating, and no patient should receive empirical immunosuppression for presumed inflammatory bowel disease until infection has been ruled out under the microscope.

Subject of Research: Disseminated gastrointestinal histoplasmosis mimicking intestinal tuberculosis and Crohn's disease in an immunocompetent host

Article Title: Gastrointestinal Histoplasmosis Mimicking Intestinal Tuberculosis and Crohn's Disease: Ileocecal Involvement in an Immunocompetent Host

Article References: Sazal, R. S., Esha, S. S., Faisal, A. A., Azad, M. A. K., Murshed, K. M., & Aftab, K. A. (2026). Gastrointestinal Histoplasmosis Mimicking Intestinal Tuberculosis and Crohn's Disease: Ileocecal Involvement in an Immunocompetent Host. Clinical Case Reports, 14(9), Article e73555. https://doi.org/10.1002/ccr3.73555

Image Credits: AI Generated

DOI: 10.1002/ccr3.73555

Keywords: histoplasmosis, Histoplasma capsulatum, gastrointestinal histoplasmosis, intestinal tuberculosis, Crohn's disease, ileocecal disease, fecal calprotectin, immunocompetent host, liposomal amphotericin B, diagnostic delay, colonoscopy biopsy, fungal infection