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Table of Contents
CASE REPORT
Year : 2022  |  Volume : 13  |  Issue : 1  |  Page : 47-50

Unforeseen gastrointestinal events following antituberculous therapy


Department of Gastroenterology, Medical Trust Hospital, Kochi, Kerala, India

Date of Submission05-Jul-2021
Date of Acceptance25-Dec-2021
Date of Web Publication3-Aug-2022

Correspondence Address:
Dr. Sandheep Janardhanan
Department of Gastroenterology, Medical Trust Hospital, Kochi - 682 016, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/atp.atp_13_21

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  Abstract 

Eosinophilic enteritis is a rare entity affecting human gastrointestinal tract. The exact etiology is unknown, and some drugs are implicated in causing this condition. We report a case of drug-induced eosinophilic enteritis, caused by antituberculous therapy (ATT). The cessation of ATT-induced clinical remission and symptoms were reproduced on drug re-challenge, which corroborated our diagnosis.

Keywords: Antituberculous therapy, ascites, eosinophilic gastroenteritis


How to cite this article:
Janardhanan S, Varghese SJ, Sebastian B, Mathai S. Unforeseen gastrointestinal events following antituberculous therapy. Ann Trop Pathol 2022;13:47-50

How to cite this URL:
Janardhanan S, Varghese SJ, Sebastian B, Mathai S. Unforeseen gastrointestinal events following antituberculous therapy. Ann Trop Pathol [serial online] 2022 [cited 2022 Aug 15];13:47-50. Available from: https://www.atpjournal.org/text.asp?2022/13/1/47/353198


  Introduction Top


Eosinophilic enteritis is a rare and benign inflammatory disorder, affecting small intestine, characterized by tissue infiltration of the intestinal wall with eosinophils, with or without peripheral eosinophilia.[1]

Several causes have been attributed to eosinophilia-induced gastrointestinal (GI) tract involvement including diseases such as inflammatory bowel disease, connective tissue disorder, parasitosis, malignancy, and drugs. Last but not the least, certain drugs have been implicated in causing eosinophilia. Here, we report an interesting case of drug-induced eosinophilic enteritis, offending agent being antituberculous therapy (ATT).


  Case Report Top


A 55-year-old female presented to our emergency department with a history of diffuse abdominal pain and occasional nonbilious vomiting associated with loss of weight and appetite of 20 days duration. She had been recently diagnosed as having tuberculosis-related cervical lymphadenopathy and was started on standard quadruple ATT directly observed treatment regimen (rifampin 600 mg/isoniazid [INH] 300 mg/day, pyrazinamide 1 g/day, and ethambutol 800 mg/day). Two weeks after commencement, her symptoms started and gradually progressed. She consulted her family physician who advised her to stop ATT 5 days back and was referred to our department.

On examination, she was emaciated (body mass index = 18.4), there was no generalized/local lymphadenopathy, and systemic examination including respiratory and abdominal examination was within normal limits.

Her baseline blood, urine, and stool examination was normal, except for the fact that she had significant eosinophilia in hemogram and peripheral smear (eosinophils - 40%, absolute eosinophil count - 6000) [Figure 1]. Chest X-ray was normal, and abdominal ultrasonogram showed moderate ascites without any organomegaly. Peripheral smear did not show any parasites or abnormal cells. Kidney, liver, and thyroid function tests were normal, and cardiac evaluation was unremarkable.
Figure 1: Peripheral smear showing eosinophilia

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Ascitic fluid analysis was suggestive of low serum ascites albumin gradient (3.6 mg/dl − 3.2 mg/dl = 0.4) and high protein (4.6 mg/dl) ascites. Ascitic fluid eosinophil count was 30%, and malignant cytology was negative. Hence, in view of exudative ascites, to localize the lesion, we proceeded with contrast-enhanced computed tomography of the abdomen which showed proximal jejunal and ileal wall thickening with multiple small mesenteric nodes and mild ascites [Figure 2]. We did panendoscopy (upper and lower GI scopy) and took segmental biopsies which were within normal limits. Hence, to evaluate small bowel, we proceeded with push enteroscopy, in the absence of double bowel enteroscopy, and took multiple jejunal biopsies. Even though endoscopy appeared normal, histology revealed eosinophilic infiltration of the jejunum (25–30/hpf) and there was no evidence of granuloma, parasite, or malignancy [Figure 3], [Figure 4], [Figure 5]. Emerging agents include mepolizumab–anti-IL-5 agent, omalizumab (anti-IgE antibody), and antieotaxin antibodies.[10] [Figure 6].
Figure 2: Contrast-enhanced computed tomography abdomen showing jejunal and ileal wall thickening with small mesenteric nodes and ascites

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Figure 3: Low- and high-power views of jeunal and ileal biopsy specimen showing marked tissue eosinophilia

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Figure 4: Low- and high-power views of jeunal and ileal biopsy specimen showing marked tissue eosinophilia

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Figure 5: Low- and High-power views of jeunal and ileal biopsy specimen showing marked tissue eosinophilia

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Figure 6: Flowchart showing mediators and mechanisms of eosinophil activation

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To rule out hematopoietic cause, hematologist opinion was obtained, and as per their advice, bone marrow examination and biopsy done showed eosinophilic precursors without any malignant shift [Figure 7].
Figure 7: Bone marrow examination showing eosinophillic precursors without any malignant cells

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With a final diagnosis of eosinophilic enteritis associated with peripheral and marrow eosinophilia, we strived to find the etiological cause. There was no history of atopy, food allergy, family history, respiratory tract infections, parasitosis, and connective tissue disorders/malignancies/vasculitis. We suspected drug-induced cause and hence reviewed the existing literature about drugs causing eosinophilic gastroenteritis [Table 1].
Table 1: Drugs causing eosinophilic gastroenteritis

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A recent hemogram taken before commencing ATT and repeated outside was normal (2% eosinophil count and a normal peripheral smear). With this history and no other drug/past history available, we reasonably concluded ATT as the offending agent.

All four front-line drugs have been implicated in causing eosinophil-associated disorders. Lange et al. described case of rifampicin-associated eosinophilic colitis.[2] Rifampicin-induced drug reaction with severe eosinophilia and systemic symptoms (DRESS). Rifampicin-induced lichenoid eruptions have also been described.[3],[4] INH has been implicated in DRESS syndrome by Ditto et al.[5],[6] DRESS syndrome and GI eosinophilia have been described with pyrazinamide and ethambutol.[7],[8] Hence, we completely withheld ATT and started steroids (1 mg/kg) for 2 weeks followed by a 6-week taper, along with antihistaminics (levocetirizine 5 mg) and antihelminthic agents (diethylcarbamazine - 2 mg/kg).[1]

Six weeks into follow-up, we reassessed her, her hemogram was normal, symptoms resolved, and repeat enteroscopy and histology were normal. Hence, after few days, we reintroduced INH and ethambutol. Initially, she was asymptomatic for 10 days; however, she soon developed abdominal pain again. Baseline investigations revealed eosinophilia on hemogram (10%), repeat ultrasonogram showed free fluid, and she was advised further workup; however, she was not willing and was subsequently lost to follow-up.


  Discussion Top


First described by Kaisger et al. in 1937, eosinophilic enteritis is a rare disease (more in middle-aged people). The pathogenesis is incompletely understood but thought to a combination of genetic predisposition, family history, atopy, etc.[9]

Three types have been described: mucosal (60%), presenting as failure to thrive and malabsorbtion; muscular (30%), presenting with vomiting and obstructive symptoms; and serous (5%–10%), presenting with exudative ascites as in our patient.[1],[10]

Drug-induced eosinophilic enteritis is still a rarer phenomenon. As all the four drugs have been implicated in causing eosinophilia, in this scenario, we cannot pinpoint one exact drug that caused the presentation. Anyway, it is safe and reasonable to attribute this to the starting of ATT since its inception leads to the clinical picture, which was promptly reversed on withdrawing ATT, along with the reappearance of symptoms postre-challenge. Unfortunately, since the patient was lost to follow-up, we could not fully document the clinical course. Because of rarity of disease, no guidelines exist for the treatment of drug-induced eosinophilic GI enteritis, let alone eosinophilic gastroenteritis. Stopping offending agents and starting antihelminthic and antihistaminics are the common remedial measures taken. Steroids can also be given in severe cases, as we have done in our case and can be tapered over a period of 1 month. Emerging agents include mepolizumab–anti-IL-5 agent, omalizumab (anti-IgE antibody), and antieotaxin antibodies.[10]

To sum it up, considering all these facts and background into equation, this is a rare case of ATT-induced eosinophilic enteritis.

Acknowledgment

Department of Medical Gastroenterology and Hepatology, Medical Trust Hospital, Kochi - 682 016, Kerala, is acknowledged.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Baig MA, Qadir A, Rasheed J. A review of eosinophilic gastroenteritis. J Natl Med Assoc 2006;98:1616-9.  Back to cited text no. 1
    
2.
Lange P, Oun H, Fuller S, Turney JH. Eosinophilic colitis due to rifampicin. Lancet 1994;344:1296-7.  Back to cited text no. 2
    
3.
Fathallah N, Bellasfar N, Ammar H, Slim R, Ouni B, Sriha B, et al. DRESS syndrome induced by rifampicin. Therapie 2018;73:441-3.  Back to cited text no. 3
    
4.
Shahul HA, Manu MK, Mohapatra AK, Mathew M. Rifampicin-induced lichenoid eruptions. BMJ Case Rep 2014;2014:bcr2013202346.  Back to cited text no. 4
    
5.
Lee JY, Seol YJ, Shin DW, Kim DY, Chun HW, Kim BY, et al. A case of the drug reaction with eosinophilia and systemic symptom (DRESS) following isoniazid treatment. Tuberc Respir Dis (Seoul) 2015;78:27-30.  Back to cited text no. 5
    
6.
Ditto A. Drug rash with eosinophilia and systemic symptoms (DRESS) secondary to anti-tuberculosis therapy with features of isoniazid toxicity. J Allergy Clin Immunol 2004;113:S309.  Back to cited text no. 6
    
7.
Kombila UD, Ka W, Mbaye FB, Diouf NF, Fall L, Ouedraogo P, et al. DRESS syndrome secondary to pyrazinamide: An uncommon complication of tuberculosis treatment. Rev Mal Respir 2018;35:69-73.  Back to cited text no. 7
    
8.
Wong PC, Yew WW, Wong CF, Choi HY. Ethambutol-induced pulmonary infiltrates with eosinophilia and skin involvement. Eur Respir J 1995;8:866-8.  Back to cited text no. 8
    
9.
Kaijser R. To the knowledge of the allergic affections of the Digestive tract from the surgeon's point of view.Arch Klin Chir 1937;188:36-64.  Back to cited text no. 9
    
10.
Zhang M, Li Y. Eosinophilic gastroenteritis: A state-of-the-art review. J Gastroenterol Hepatol 2017;32:64-72.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
 
 
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