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Introduction
Drug-induced esophagitis is an uncommon esophageal disorder in children. Most cases of drug-induced esophagitis are related to the use of nonsteroidal anti-inflammatory drugs (aspirin), antibiotics (tetracycline, doxycycline, and clindamycin), ferrous sulfate, alendronate, ascorbic acid, quinidine gluconate, and potassium1,2. Some cases of L-arginine-induced esophagitis have been reported in the literature. The presumptive diagnosis is based mostly on the clinical presentation and the history of ingestion of some known drugs that potentially cause esophageal injury. Barium esophagogram can detect superficial ulcers and subtle changes in the esophageal mucosa. However, the definitive diagnosis is established endoscopically2-5.
Several associated risk factors with this disease are known:
This report aimed to determine the endoscopic findings related to L-arginine esophagitis and the suggested treatment in a pediatric population.
Case reports
The clinical presentation, endoscopy findings, histopathology, and clinical course of six adolescent patients who experienced pill esophagitis on treatment with L-arginine as a treatment for short stature are described (Table 1). The main symptoms were odynophagia, retrosternal pain, and dysphagia, which led them to the emergency room. Endoscopies were performed due to acute severe pain. The findings were erosions and ulcers in the mid esophageal mucosa (Fig. 1-3). Patients were hospitalized and managed with liquid diet, proton-pump inhibitors, sucralfate, and suspending the use of L-arginine. No recurrence was reported.
Table 1 Age, gender, clinical presentation, doses, time of treatment with L-arginine, and histopathological findings of the cases reported
| Case | 1 | 2 | 3 | 4 | 5 | 6 |
|---|---|---|---|---|---|---|
| Gender | M | M | F | M | F | F |
| Age (years) | 15 | 13 | 12 | 12 | 14 | 12 |
| Doses (mg/day) | 500 | 1000 | 500 | 500 | 500 | 500 |
| Time of treatment with L-arginine | 1 m | 3 m | 3 m | 1 m | 1 m | 1 w |
| Histopathology | Acute ulcerations with regenerative atypia. No fungi, no viral scytopathic changes, no metaplasia | Acute esophagitis, chronic ulcerates granulation tissue, epithelial regeneration, no metaplasia, no dysplasia | Acute esophagitis, chronic ulcerates, with multifocal thrombi and fibroblast proliferation | No biopsies | Acute inflammatory and plasma cell infiltration. Superficial ulceration with neutrophilic reaction | GE reflux changes with acanthosis spongiosis, papillary congestion eosinophilic, PMN infiltrates |
M, male; F, female; m, month; w, week; GE, gastroesophageal; PMN, polymorphonuclear leukocytes.
Discussion
The injuries caused by drugs in the esophagus are manifested as esophagitis. The main symptoms reported are dysphagia, odynophagia, and retrosternal pain. Due to the esophageal anatomy, the most common site of injuries is the mid esophagus. However, pill esophagitis can be located at any narrowing area of the esophagus, such as the upper sphincter, the aortic arch, or compression of the left main bronchus, and the lower esophageal sphincter that could delay the passage of the pill4. Other risk factors that have been described are decreased esophageal motility, small amounts of fluid ingested with the medication, supine position, as well the size and coating of the pill5,6. Although the mechanism of injury is not precise, the direct contact of neutral or acid pH drugs, such as L-arginine, might produce a corrosive effect on the esophageal mucosa. None of the cases studied reported a predisposing factor such as cardiomegaly, esophageal motility disorders, stenosis, gastroesophageal reflux, achalasia, or infectious esophagitis4. The lesions, characterized by different size ulcers, were found in the mid esophagus similar to the sites of the previous reports2-4,7.
L-arginine is used for the treatment of short stature without clear scientific bases. Although it has been shown to have a direct effect on increasing muscle volume by improving blood supply and the amount of nitric oxide in the blood, in addition to stimulating the release of growth hormone, no clinical trials support its use in this particular condition8-11.
In the presence of acute severe odynophagia, dysphagia, and retrosternal pain, and drug-induced esophagitis should be considered as a possible diagnosis. Several oral medications may cause tissue damage such as L-arginine.
Patient and family information about possible medication side effects, appropriate fluid intake with the pill, and avoiding lying down 30 min after taking the pill, should help to reduce this type of injury to the esophageal mucosa6,7.
The physician should always perform a careful balance of risk and benefits of a medication. There are no clinical trials that support the use of L-arginine for the treatment of short stature.
Ethical disclosures
Protection of human and animal subjects. The authors declare that no experiments were performed on humans or animals for this study.
Confidentiality of data. The authors declare that they have followed the protocols of their work center on the publication of patient data.
Right to privacy and informed consent. The authors have obtained the written informed consent of the patients or subjects mentioned in the article. The corresponding author is in possession of this document.
