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Garlic-induced Esophagitis and : A Review of Four Cases

Gurinder S. Grewala,°*, Adam Amlania* Citation info: UBCMJ. 2015: 7.1 (48-51) ° Corresponding author: [email protected] a MD Candidate 2016, Faculty of Medicine, University of British Columbia, Vancouver, BC * Co-first authorship

abstract

Garlic, or Allium sativum, is a common culinary ingredient used as a natural medicine for hypertension, hyperlipidemia, cancer prevention, treatment of fungal infection, and atherosclerosis prevention. We reviewed all cases of garlic–induced esophagitis and gastroenteritis available in academic literature. A literature search using combinations of the MeSH headings “garlic”, “Allium sativum”, “esophagitis”, and “deglutition disorders” was conducted in the Embase and PubMed computer databases. References involving reports of esophagitis and gastroenteritis were retrieved. Additional relevant articles were found by analyzing the references provided within the retrieved articles. Our review uncovered four published case reports of garlic–induced esophagitis, and one possible garlic–induced gastroenteritis. In three cases, the was caused by direct injury, both by mechanical and possibly caustic effects. Garlic was thought to have caused eosinophilic inflammation in the remaining two cases, both of which involved a significant atopic medical history. Given the prevalence of garlic in both culinary and therapeutic settings, we believe clinicians should be aware of its potential for gastrointestinal symptoms. Esophagitis and gastroenteritis should be on the differential as a cause of upper gastrointestinal symptoms in garlic users, especially in atopic patients. In suspect patients, thorough medical histories, , , and cutaneous testing may all be useful and should be utilized when appropriate. Management should include avoidance of the offending agent, and supportive care. Oral corticosteroids may be useful in certain patients. Follow–up endoscopy can be considered, especially in patients who have experienced direct injury.

atopic, IgE–mediated condition, usually and atherosclerosis prevention.11 Aside introduction occurring in response to food allergens. from causing a mild blood pressure sophagitis refers to inflammation It is an important consideration for decrease in hypertensive patients, Eof the . Typical symptoms patients presenting with complaints of quality evidence for the remainder of include retrosternal pain or discomfort, retrosternal discomfort and , the indications is currently insufficient , and dysphagia.1,2 Rarely, especially when unresponsive to and limited.11 Side effects of garlic use , , and weight treatments for gastroesophageal reflux are usually mild and include malodorous loss can occur.1,2 Etiologies include disease. The most common food culprits breath and dyspepsia.11 Rarely, garlic infection, gastroesophageal reflux, in adults include legumes, nuts, fruits, can cause significant gastrointestinal trauma, caustic ingestion, medications, wheat, milk, eggs, and soy.5-7 In children, problems, including gastroenteritis and and .3 the common triggers include milk, esophagitis.12-16 Medication–induced esophagitis eggs, wheat, beef, soy, and chicken.8 Herein, we review all cases of garlic– can occur via both systemic and direct Diagnosis typically requires eosinophilia related esophagitis and gastroenteritis causes.4 Direct mucosal injury of the of the esophageal epithelium on .9 available in the academic literature, esophagus may occur with prolonged Management usually involves treatment including both direct and allergic causes. contact between oral medications with oral corticosteroids and initiation and the esophageal lining, causing pill– of an elimination diet avoiding the six methods induced esophagitis. Several medications common allergic food triggers.6,9,10 A literature search using combinations may cause pill–induced esophagitis, Gradual stepwise reintroduction is used of the MeSH headings “garlic”, “Allium including NSAIDs, antibiotics, potassium to identify the offending foods.6,9,10 sativum”, “esophagitis”, and “deglutition chloride, and .4 It is Garlic (Allium sativum) is a disorders” was conducted in the Embase more frequently seen in females and common culinary ingredient often used and PubMed computer databases. patients with advanced age, diabetes, therapeutically as a natural medicine References involving reports of esophagitis and/or ischemic heart disease.4 for hypertension, hyperlipidemia, cancer and gastroenteritis were retrieved. is an prevention, treatment of fungal infection, 48 ubcmj.com reviews

Additional relevant articles were found by after consuming sliced raw fish and garlic.14 analyzing the references provided within results Esophagogastroduodenoscopy (EGD) the retrieved articles. Articles were then Our literature search revealed a total was performed and a 2.7 x 1.5 cm piece reviewed by two independent evaluators of four published case reports of garlic– of garlic was retrieved via forceps. Bullous to compare and contrast each of the induced esophagitis, and one possible necrotic changes were seen at the site cases with respect to the characteristics garlic–induced gastroenteritis. Results are of impaction. The patient was admitted of the patients, the identification and summarized in Table 1. for supportive care and was put on management strategies employed, and the Kim et al. (2008) reported a case NPO (nothing by mouth) protocol. Her eventual outcome of the case. The findings of a 60–year–old female presenting with symptoms resolved shortly afterwards. A are summarized in the Results section. severe and sustained 12 hours follow–up EGD three days after admission Table 1: Cases of garlic-induced esophagitis and gastroenteritis Study Age Gender Past medical History of presenting illness Primary Identifica- Manage- Outcome and history presenting tion ment Follow-up symptoms Kim et 60 F None men- Symptoms started 12 hours Severe sus- EGD 2.7x1.5 cm Cest pain improved al. 2008 tioned after eating sliced raw fish and tained chest piece of gar- when garlic removed. garlic pain lic removed Follow-up EGD after 3 by forceps. days revealed dramatic Admitted improvement, tiny whit- for support- ish scarring, and grey ive care. mucosal changes at the NPO. site of impaction. Adachi 42 F Pollinosis, None relevant , EGD, biopsy, Avoidance Symptoms resolved. 2010 asthma urticaria, patch test- of causative , ing, trial of agents peripheral removal of eosinophilia causative agents Ergül 46 M Hypertension History of swallowing garlic Acute onset Immediate Liquid diet, Resolved in 3 days. and without water one day before odynophagia upper en- lansoprazole Repeat endoscopy 4 Çakal symptoms occured. and retroster- doscopy 30 mg BID weeks later showed no 2012 nal pain x 12 and sucral- lesion. hours fate QID. Dogan 54 M Hypertension History of swallowing garlic Acute onset Upper Therapeutic Resolved in 5 days. et al. with little water odynophagia endoscopy push of Repeat endoscopy 4 2013 and retroster- garlic into weeks later showed no nal pain x 12 , lesion. hours liquid diet, lansoprazole 30 mg BID and sucral- fate QID. Mane et 58 M 1. Allergic >15 year history of upper Dysphagia, EGD, biopsy, Avoidance Marked improvement al. 2013 Rhinitis gastrointestinal symptoms re- , dys- history, skin of garlic and within a few weeks. 2. Asthma fractory to GERD treatment. pepsia prick testing cottonseed, After 3 months, 3. Auto- Subsequent 6 years worsening regular budesonide frequency immune dysphagia. EGD and biopsy intake of was reduced to once alopecia confirmed eosinophilic esoph- viscouse daily. Patient became 4. Auto- agitis. Patient was treated with budesonide largely . immune swallowed viscous budesonide, 0.5 mg BID thrombo- but this was taken irregularly. in sucralose cytopenia Next 2 years had increased powder 5. Splenecto- nausea, dyspepsia, dysphagia. A between my second EGD showed normal meals. mucosa but repeat biopsies showed . Referred to allergy/immunology, under- went skin prick testing. ubcmj.com 49 reviews

showed dramatic improvement, and the disease who had been treated for Endoscopic patient was discharged with no further gastroesophageal reflux disease for complications. over 15 years for upper gastrointestinal investigation was Adachi (2010) shared a case of symptoms, but only experienced partial a 42–year–old woman with a history improvement.15 In the subsequent six crucial in the of pollinosis and asthma presenting years, symptoms worsened and he began with urticaria, heartburn, diarrhea, and to experience significant dysphagia. EGD diagnostic evaluation of peripheral eosinophilia.16 She was found and biopsies confirmed eosinophilic all cases. In addition to to have marked eosinophils in the esophagitis, and the patient was given mucosa of her alimentary tract and was swallowed viscous budesonide as allowing visualization therefore diagnosed with eosinophilic treatment, which was taken irregularly. gastroenteritis, and subsequently The patient experienced two more and an opportunity underwent cutaneous patch testing. years of worsening nausea, dysphagia, to obtain biopsies, Patch testing was positive for garlic and and dyspepsia. A second EGD showed sesame, and given that improvement was normal-appearing mucosa, although endoscopy can play a seen with removal of these two allergens, biopsies showed the presence of it was thought that one or both of garlic eosinophils. The patient was seen in an key role in treatment... and sesame were the causative agents. allergy and immunology clinic for food Ergül and Çakal (2012) detailed a hypersensitivity testing. Skin prick testing pump inhibitor, and sucralfate. Follow–up case of a 46–year–old male with a history with 44 food extracts was positive only to EGD in the case reported by Kim et al. of hypertension presenting with 12 garlic and cottonseed. Medical history did (2008) was performed three days after hours of odynophagia and retrosternal not reveal consumption of cottonseed discharge, whereas follow–up pain.12 History revealed that the patient or any of the typical suspect foods, but in the cases reported by Ergül and Çakal had swallowed garlic as treatment for was positive for frequent consumption (2012) and Dogan et al. (2013) were hypertensive attack on the previous of garlic. Thus, the diagnosis of garlic– performed four weeks following discharge. day without water. Immediate upper induced eosinophilic esophagitis was As suggested by Ergül and Çakal endoscopy was performed and revealed made. The patient was recommended (2012), garlic may have had a caustic effect an edematous, fragile mucosal area with garlic and cottonseed avoidance and in the cases due to its acidic pH. Direct superficial ulcers in the upper esophagus. treated with regular budesonide. esophageal injury from mechanical trauma The patient was managed with a liquid Marked improvement was seen within is another possible mechanism. Lifestyle diet, lansoprazole, and sucralfate. a few weeks, and the frequency of his measures, including adequate water Esophageal symptoms resolved in three budesonide was decreased after three intake and avoidance of lying supine after days, and repeat endoscopy four weeks months. The patient became largely meals, are likely to reduce the incidence post–discharge showed no persisting asymptomatic with the exception of all types of “pill–induced esophagitis”, lesion. of occasional symptoms following including those caused by foods such as Dogan et al. (2013) reported a consumption of garlic–containing foods. garlic. strikingly similar case of a 54–year–old When comparing the two cases of man with hypertension, also presenting eosinophilic inflammation, both patients discussion 15,16 with 12 hours of odynophagia and had a positive atopic history. EGD, retrosternal pain and a history of In comparing the three cases of direct biopsy, and cutaneous testing were swallowing garlic with little water for injury caused by garlic, similarities can be diagnostically instrumental in both cases, 12-14 hypertensive attack.13 Endoscopy showed seen. In all three cases, symptoms and avoidance of garlic was a common garlic in the upper part of the esophagus started within 24 hours of garlic ingestion, strategy in management. Symptoms which was therapeutically pushed into and presenting symptoms included were different due to the different sites the stomach. A 2.5 cm long lesion was retrosternal chest pain consistent with an of inflammation. Elimination of typical seen in addition to edematous, fragile esophageal source. Endoscopy was a key agents via a thorough medical history mucosa. Management, as in the case diagnostic tool in all three cases. Symptom seemed to play a larger role in the case reported by Ergül and Çakal (2012), improvement was seen within three days reported by Mane et al. (2013), and unlike consisted of a liquid diet, lansoprazole, and follow–up visualization via endoscopy the patient reported by Adachi (2010), and sucralfate. Symptoms resolved in five showed significant improvement in all three management included viscous budesonide days, and follow–up endoscopy in four cases. However, there were differences and sucralfate. There was no mention of weeks showed no lesion. in management strategies and follow- follow–up endoscopies in either case. Mane (2013) published a case of up timelines. One case was managed Although standard elimination diets, a 50–year–old male with a history of with supportive care and NPO protocol, stepwise reintroduction of suspect foods, allergic rhinitis, asthma, and autoimmune whereas the others were managed with and oral corticosteroids are the typical the combination of a liquid diet, proton– management strategies of eosinophilic 50 ubcmj.com reviews

esophagitis, sole use of these strategies gastroenteritis should be on the differential sis and management of esophageal eosino- would not have detected the true cause of diagnosis for gastrointestinal symptoms, philia and eosinophilic esophagitis (EoE). Am J Gastroenterol. 2013 May;108(5):679-92. the inflammation in the eosinophilic cases especially in the setting of an atopic patient. 10. Greenhawt M, Aceves SS, Spergel JM, Rothen- presented above. The six–food elimination Thorough medical histories, endoscopy, berg ME. The management of - diet, by design, is only diagnostically biopsies, and cutaneous testing may all be ic esophagitis. J Allergy Clin Immunol Pract. effective with respect to the six foods useful in the evaluation of these patients, 2013 Aug;1(4):332 40; quiz 341-2. 11. Li L, Sun T, Tian J, Yang K, Yi K, Zhang P. Garlic in in the diet. It can also be a challenging and should be utilized when appropriate. clinical practice: an evidence–based overview. treatment strategy for patients to follow. Management can include avoidance of Crit Rev Food Sci Nutr. 2013;53(7):670-81. Clinicians should consider cutaneous the offending agent, supportive care, and 12. Ergül B, Çakal B. Dysphagia caused by garlic testing in suspected cases of eosinophilic possibly oral corticosteroids. Follow–up induced esophagitis. Clin Res Hepatol Gastro- enterol. 2012;36(6):e134. esophagitis and gastroenteritis to rule endoscopy can be considered, especially 13. Dogan Z, Sarikaya M, Filik L, Ergül B. Garlic in- out atypical foods, such as garlic, as in patients who have experienced direct duced esophagitis. Acta Gastro-Enterol Belg. causes of inflammation. Cutaneous tests injury. 2013 Jun;76(2):262. were paramount in diagnosing the cases 14. Kim H-K, Kim J-S, Cho Y-S, Park Y-W, Son H-S, Kim S-S, et al. Endoscopic removal of an un- presented by Adachi (2010) and Mane et usual foreign body: a garlic–induced acute al. (2013). disclosures esophageal injury. Gastrointest Endosc. 2008 Endoscopic investigation was crucial Sep;68(3):565-6. The authors do not have any conflicts in the diagnostic evaluation of all cases. In 15. Mane SK, Jordan PA, Bahna SL. Eosinophilic of interest. esophagitis to unsuspected rare food al- addition to allowing visualization and an lergen. Ann Allergy Asthma Immunol. 2013 opportunity to obtain biopsies, endoscopy Jul;111(1):64-5. can play a key role in treatment, as 16. Adachi A. [Two cases of eosinophilic gastro- demonstrated in the case presented references whose causative allergens are use- fully diagnosed by patch test]. Arerugi Allergy. 1. Nurko S, Furuta GT. Eosinophilic esophagitis. by Dogan et al. (2013). Furthermore, 2010 May;59(5):545-51. GI Motil Online [Internet]. 2006 [cited 2015 endoscopy is important in follow–up, 17. Government of Canada PHA of C. Comple- Mar 2]; Available from: http://www.nature. mentary and Alternative Health — Canadian particularly in cases involving direct injury, com/gimo/contents/pt1/full/gimo49.html Health Network — Public Health Agency as it allows for evaluation of healing and 2. Patcharatrakul T, Gonlachanvit S. Gastro- Canada [Internet]. 2008 [cited 2015 Mar 9]. esophageal reflux symptoms in typical and treatment efficacy. We agree with the Available from: http://www.phac-aspc.gc.ca/ atypical GERD: roles of gastroesophageal acid suggestion made by Mane et al. (2013) chn-rcs/cah-acps-eng.php refluxes and esophageal motility. J Gastroen- regarding a low threshold for biopsy terol Hepatol. 2014 Feb;29(2):284-90. in symptomatic patients with normal 3. Noffsinger AE. Update on esophagitis: con- Garlic–induced appearing mucosa, due to the possibility troversial and underdiagnosed causes. Arch of an underlying eosinophilic process. This, Pathol Lab Med. 2009 Jul 1;133(7):1087-95. 4. Abid S, Mumtaz K, Jafri W, Hamid S, Abbas Z, esophagitis and however, should only be considered if an Shah HA, et al. Pill–induced esophageal inju- eosinophilic cause makes sense within the ry: endoscopic features and clinical outcomes. gastroenteritis have clinical context of the patient. Endoscopy. 2005 Aug;37(8):740-4. 5. Lucendo AJ, Arias Á, González–Cervera J, a small reported Yagüe–Compadre JL, Guagnozzi D, Angueira conclusion T, et al. Empiric 6–food elimination diet in- incidence in the duced and maintained prolonged remission Garlic is a common food ingredient in patients with adult eosinophilic esopha- academic literature. frequently used by individuals for therapeutic gitis: a prospective study on the food cause of the disease. J Allergy Clin Immunol. 2013 However, more than effects. It is important to be aware of its Mar;131(3):797-804. rare potential for harm. Thorough dietary 6. Lucendo AJ, Arias A. Treatment of adult eo- 70% of Canadians use and medication histories are important sinophilic esophagitis with diet. Dig Dis Basel for identification of adverse effects such Switz. 2014;32(1–2):120-5. 7. Gonsalves N, Yang G-Y, Doerfler B, Ritz S, Dit- complementary and as esophagitis or gastroenteritis. Garlic– to AM, Hirano I. Elimination diet effectively induced esophagitis and gastroenteritis treats eosinophilic esophagitis in adults; food alternative health care have a small reported incidence in the reintroduction identifies causative factors. academic literature. However, more than . 2012 Jun;142(7):1451-9. therapies regularly, and e1; quiz e14-5. 70% of Canadians use complementary 8. Spergel JM, Brown-Whitehorn TF, Cianfer- clinicians would benefit and alternative health care therapies oni A, Shuker M, Wang M-L, Verma R, et al. regularly, and clinicians would benefit from Identification of causative foods in children from broadening their broadening their differential diagnoses to with eosinophilic esophagitis treated with an 17 elimination diet. J Allergy Clin Immunol. 2012 differential diagnoses to include complications of these therapies. Aug;130(2):461-7.e5. Clinicians should be aware of both 9. Dellon ES, Gonsalves N, Hirano I, Furuta GT, include complications of direct and allergic causes of inflammation Liacouras CA, Katzka DA. ACG Clinical guide- in the . Esophagitis and line: evidence based approach to the diagno- these therapies. ubcmj.com 51