Enteric fever masquerading as Crohn’s disease in a child with abdominal tuberculosis

Abstract

In tropical countries, like India, various types of infectious diseases like tuberculosis, enteric fever, malaria and dengue are prevalent. Disease trend over time has been gradually shifting from infective to inflammatory frame because of increasing awareness regarding hygiene and increasing immunisation coverage. This case report describes an adolescent boy having a long history of abdominal pain, bleeding per rectum and documented weight loss, presented with an acute episode of fever. But the coexisting infections and/or inflammatory conditions presented challenges to the treating physician in diagnosis and management despite of good clinical experience. In this case, a chronic gastrointestinal infection caused by Mycobacterium tuberculosis with a superadded Salmonella typhi infection was masquerading as inflammatory bowel disease (Crohn’s disease). Utmost caution should be exercised to reach the correct diagnosis and take the necessary steps to manage this type of situation in tropical countries like India.

Background

In a tropical country, like India, various infectious diseases like tuberculosis (TB), enteric fever and malaria are more prevalent in comparison to inflammatory conditions. TB remains one of the most common chronic infective conditions worldwide irrespective of salutary advancements in medical science and technology. Abdominal TB comprises 11% of all TB cases worldwide.¹ It can affect any part of the bowel starting from the oral cavity to the rectum, the ileocecal junction being the most common site of gastrointestinal (GI) involvement as seen in 75% of cases of abdominal TB. It can also involve the peritoneum, hepatobiliary tree, pancreas, perianal area and lymph nodes (LNs). Clinically abdominal TB mostly presents with low-grade fever, weight loss, abdominal pain.² But abdominal distension, diarrhoea, ascites, organomegaly, bowel obstruction and abdominal mass can be the presenting features. The burden of enteric fever among children is highest in South Asian countries. Common clinical features include fever with coated tongue, anaemia and abdominal pain, vomiting, loose stools with or without blood in stool or constipation, abdominal distension and hepatosplenomegaly. As far as the clinical features of enteric fever are concerned, they are non-specific and clinically difficult to distinguish from other febrile illnesses (malaria, dengue, TB, etc) commonly encountered in tropical areas. That leads to inappropriate diagnosis and delay in the proper treatment of the condition. On the contrary, inflammatory bowel disease (IBD) is one of the emerging diseases in children in low-income and middle-income countries. The most common presentation consists of abdominal pain, blood in stool and/or weight loss. As per the literature, nearly 25% of the affected children can be symptomatic before the age of 17 years.³

Differentiating IBD from intestinal TB is a diagnostic challenge to the treating physician despite extensive experience. This case report aims to address the approach to diagnosis and emphasises all aspects to be considered before giving a diagnosis of lifelong IBD.

Case presentation

A boy in his early 20s presented with abdominal pain and intermittent blood in stool for 1 year. Involuntary weight loss was noted over the last few months of illness but he presented to us with fever for 15 days. Abdominal pain was insidious, progressive, dull aching type involving epigastric and periumbilical area, leading to reduced activity. He had 2–3 episodes of semiformed, non-mucoid stools per day, intermittently mixed (3–4 episodes per week) with a small quantity of fresh blood. There were episodes of urgency, nocturnal awakening and tenesmus. Weight loss of 10 kg was documented in serial out patient department (OPD) visits to other hospitals, in the last 6 months prior to presenting to us. It was associated with poor appetite and apathy but no vomiting. He had abrupt-onset fever episodes (38.3°C - 38.8°C), intermittent type, not associated with chills, rigours or rash. There was no family history of IBD or TB contact in the recent past. He had received multiple courses of oral antibiotics (including cefixime, a combination of ofloxacin and ornidazole, and later ciprofloxacin for the duration of 5 –7 days for each) causing temporary symptomatic relief. His nutritional intake was poor with a calorie deficit of 40% and protein deficit of 30% during the period of illness. On examination, he had pallor but the skin, oral cavity and perianal area were found to be normal. There was mild tenderness over the periumbilical region, liver and spleen were palpable at 3 cm and 2 cm below the right and left costal margins, respectively. The rest of the systemic examination was normal.

Investigations

His investigation showed complete blood count (CBC) with mild neutrophilia (74%) and mild thrombocytopaenia (130×10³/mm³⁾ raised erythrocyte sedimentation rate (ESR) (98 mm in first hour) and CRP (171 mg/L); Mantoux was positive (15×10 mm); liver transaminases were high (AST (aspartate transaminase)-175 U/L, ALT (alanine transaminase)-137 U/L, ALP (alkaline phosphatase)-980 U/L, GGT (gamma glutamyl transpeptidase)-524 U/L) with normal total bilirubin of 0.4 mg/dL and albumin (3.4 gm/dL). Ferritin (3245 mg/dL) and LDH (lactate dehydrogenase) (1018U) were high, ANA was negative, faecal calprotectin was high (540 μg/gm) and HIV was non-reactive.

Subsequently, upper GI endoscopy and colonoscopy were done for tissue diagnosis in view of the chronic history of abdominal pain and bleeding per rectum with high faecal calprotectin value, which revealed multiple aphthous ulcers in the stomach (antrum) and in transverse and descending colon. He also had erythema and ulceration in the caecum and terminal ileum (figure 1A, B). histopathological examination (HPE) showed lamina propria oedema and chronic inflammatory infiltrate in the GI tract starting from stomach to rectum along with focal denudation of epithelial surface in the gastric and duodenal mucosa, focal crypt loss and a few ill-defined clusters of epitheloid cells in the ileal mucosa. Ziehl-Neelsen stain was negative. Multiple crypt abscesses were present with maintained architecture along with a few ill-defined clusters of epithelioid histiocytes in lamina propria and submucosa of the colon, and focal crypt loss were seen in rectal mucosa. There was no crypt distortion or crypt branching (figure 1C, D).

Figure 1.

Colonoscopic and histopathology findings. (A) Apthous ulcer in the descending colon. (B) Erythema and ulceration in the caecum. (C) Low power field image showing a section of rectum with the epithelial lining—regularly arranged crypts, inflammatory cell infiltrates. (D) High power field image of the section (C) showing evidence of cryptitis, no crypt distortion.

Among the radiological investigations, chest X-ray was normal. Ultrasound abdomen showed hepatosplenomegaly (liver-14 cm, spleen-15.8 cm) with multiple enlarged peripancreatic LNs (2.9×1.4 cm) and mesenteric LNs (2.7×2 cm). Intrahepatic biliary radicals, gall bladder and common bile duct were normal with no evidence of ascites. For further evaluation of lymphadenopathy and endoscopy findings, CT-enterography was done. It revealed segmental mural thickening involving terminal ileum and caecum, mild diffuse peritoneal thickening, mild free fluid, hepatosplenomegaly (liver-18 cm, spleen-17 cm), multiple mesenteric LNs (3.2×3.4 cm) (figure 2A, B).

Figure 2.

CT enterography and lymphnode cytology. (A) Coronal section of CT-enterography showing evidence of thickened terminal ileal wall and caecum with multiple mesenteric lymphnodes. (B) Multiple ileocaecal and mesenteric lymph node. (C) FNAC of ileocaecal LN (low power field) showing epitheloid granulomas. (D) High power field image of (C) showing a large epitheloid granulomas. FNAC, fine-needle aspiration cytology.

Inconclusive biopsy and radiological findings prompted us to re-evaluate the cause of the fever. His Widal test was positive in 1:240 (for both somatic antigen O and flagellar antigen H). Fine-needle aspiration cytology (FNAC) of ileocaecal LN was carried out, for possible lymphoma and TB, which showed granulomatous inflammation but no evidence of necrosis or malignant cells, and acid fast bacillus (AFB) was negative (figure 2C, D). By considering all the findings including history, physical examination, haematological, microbiological, radiological and histopathological evidence, the present case was diagnosed to be abdominal TB and Crohn’s disease (CD) was excluded.

Differential diagnosis

IBD most likely CD was our first differential diagnosis because of our long history of abdominal pain, weight loss. Bleeding per rectum is not common in CD but may be seen in Crohn’s colitis. Fever may be a presenting feature of IBD.

Abdominal TB was our second differential as it is a common diagnosis in India and chronicity also favoured TB. However, acute-onset high-grade fever is not a common observation in TB.

HIV cholangiopathy and lymphoreticular malignancy like lymphoma were our other diagnostic considerations given because of clinical features and multisystemic presentation.

Treatment

Initially, the child was started on intravenous cefotaxime empirically, at a dose of 150 mg/kg /day in three divided doses. Meanwhile, the delayed blood culture showed Salmonella typhi growth sensitive to both ceftriaxone and erythromycin. Oral azithromycin was also added at the dose of 20 mg/kg/day and given for 7 days because of persistent fever. Cefotaxime was continued for 14 days. The repeat LFT showed improvement with the transaminase levels decreasing to <2 times of upper normal limit, antitubercular treatment (ATT) was thereby started. Six months of ATT regimen was planned as per the latest guidelines, comprising 2 months intensive phase with four drugs—isoniazid, rifampicin, pyrazinamide and ethambutol. It was followed by 4 months continuation phase with three drugs—isoniazide, rifampicin and ethambutol. He responded well to the treatment with a gradual decrease in febrile episodes and control of abdominal pain and bleeding per rectum.

Outcome and follow-up

The child was discharged after 15 days of hospitalisation. He was followed up in OPD weekly for the first two visits and fortnightly for next two visits. Then subsequent visits were done monthly for 2 months and quarterly thereafter till the completion of ATT. After discharge, he remained afebrile, his abdominal pain improved and bleeding per rectum subsided. On further follow-up visits, his liver enzymes remained normal with improvement in appetite and weight gain. A repeat ultrasound abdomen was done once after a month of discharge which showed normal findings except for the mesenteric LNs.

Discussion

In the present case, an adolescent boy presented with a long history of abdominal pain and bleeding per rectum for 1 year along with an acute episode of fever for 2 weeks with documented weight loss. Physical examination revealed an average nutritional status with relatively stable vitals, some pallor and hepatosplenomegaly without a family history of IBD or a history of TB contact. Initial differential diagnoses were intestinal TB and IBD.

Though at the beginning it seemed more to be a case of IBD, that is, CD where the child may have weight loss, abdominal pain, bloody diarrhoea, raised faecal calprotectin and presence of aphthous ulcers in the stomach and colon which were all seen in this case. But there was no other extraintestinal manifestations like perianal disease (fistula/fissure/abscess/skin tag) and dermatological manifestation (pyoderma gangrenosum/erythema nodosum) of CD.⁴ The HPE also did not reveal the classical findings of crypt distortion, crypt branching, an irregular mucosal surface and skip lesions except for the crypt abscess which is not specific for CD. CT-enterography revealed only segmental mural thickening involving terminal ileum and caecum which again is a non-specific finding. Whereas the definitive CT-enterography findings of small bowel involvement in CD like narrowing or obstruction, or enteric fistulae were absent.⁵ There was no evidence of non-caseating granulomas in colonic mucosal biopsy, which is a characteristic finding of CD. So, all the above findings were not suggestive of CD except for the history and some of the physical findings which were not conclusive of it. In view of long clinical history and the presence of large abdominal LNs, the high chance of TB and lymphoma were thought.

In patients of intestinal TB constitutional symptoms such as fever, malaise, night sweats, anorexia and weight loss are common. The signs and symptoms also depend on the site of involvement and the type of lesion in the GI tract. Abdominal pain being the most common manifestation followed by diarrhoea (11%–37%) and lower GI bleeding (5%–15%). Abdominal pain can occur because of a stricture in the intestinal lumen, mesenteric inflammation and/or peritoneal involvement. Similarly, in this case, the child had long-standing abdominal pain, weight loss and GI bleeding along with hepatosplenomegaly and lymphadenopathy. The corroborative evidence of TB abdomen like segmental mural thickening of terminal ileum and caecum, diffuse peritoneal thickening, ascites, hepatosplenomegaly and multiple mesenteric LNs in CT-enterography were seen. There was also the presence of characteristic granulomatous inflammation in the ileocaecal LN in FNAC. All of the above findings strongly suggested abdominal TB in this child.

He had recent onset moderate grade of fever with Widal positivity and blood culture showing Salmonella typhi growth, considered the gold standard for diagnosis, explained the associated fever at the time of presentation. This might be a part of the diagnosis but could not explain the entire long-term symptoms in this case. But it was helpful for right antibiotic decision and aided to the treatment. As per the present case bleeding per rectum in the presence of enteric fever was also documented in a review of 552 patients of culture-proven typhoid fever in Bangladesh, which showed that rectal bleeding was seen in 9% of cases across all the age groups.⁶ In another study, the CT scan findings of patients with enteric fever those who had a longer clinical course, with less specific symptoms favouring the diagnosis of enteric and those having complications like rectal bleeding were found to have mesenteric lymphadenopathy and splenomegaly (75%), circumferential small bowel wall thickening (58.3%) and ascites (50%).⁷ The authors also explained that these radiological features may overlap with other abdominal infections. The similar findings were also noted in the present case report where abdominal TB was the coexisting infection with enteric fever which was proven by biopsy.

Concomitant infection caused by Salmonella typhi and M. tuberculosis affecting only the GI tract may masquerade many other chronic inflammatory states, most commonly IBD. Diagnosis and management should be based on local epidemiology and a stepwise diagnostic algorithm should be adopted. Common conditions should always be ruled out before proceeding to a relatively uncommon condition.

Learning points.

• In a tropical country like India, every clinician should consider common infective conditions like tuberculosis, enteric fever, shigellosis, giardiasis, etc as their first differentials diagnosis while evaluating a child with predominant gastrointestinal manifestations.

• Infective conditions may coexist in several situations and need to be addressed simultaneously.

• Common conditions should always be ruled out before proceeding to a relatively uncommon condition.

Ethics statements

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Consent obtained from parent(s)/guardian(s).