Lugol’s solution, named after the French Physician JGA Lugol (1786–1851), has a high affinity for glycogen in non-keratinised squamous epithelium.1 Since the 1960s when Lugol’s iodine was first used to investigate oesophageal diseases,2 advances in the field of diagnostic endoscopy have resulted in its increasing use to detect early mucosal abnormalities and to target biopsies from unstained areas.3,4 We have been performing chromoendoscopy using Lugol’s solution for the last 10 years, carrying out 10–15 procedures every year. Here we report the first case of an acute toxic reaction affecting the gastric mucosa.
At gastroscopy of a 67 year old woman with reflux symptoms, a small nodule was noted at the gastro-oesophageal junction together with reflux oesophagitis (LA grade B). Biopsies from the nodule raised the possibility of dysplasia within the squamous epithelium. One month later a repeat examination was performed to reassess the squamous epithelium and target biopsies using Lugol’s chromoendoscopy; 10 ml of 5% Lugol’s iodine was sprayed using an Olympus PL spraying catheter. Multiple biopsies were targeted to the unstained areas together with random biopsies from the distal oesophagus. At the end of the examination, the stomach was again entered to remove any stagnant iodine. The gastric mucosa underlying the pool of iodine was intensely oedematous and haemorrhagic (fig 1A ▶, 1B ▶) The patient did not complain of any symptoms either during or after the procedure. Gastric biopsies confirmed acute oedema of the lamina propria with loss of the superficial epithelium consistent with an acute toxic gastric mucosal injury induced by Lugol’s iodine solution (fig 1C ▶) The oesophageal biopsies showed no dysplasia.
Figure 1.
(A, B) Oedematous and haemorrhagic mucosa with loss of superficial gastric mucosal layer in the greater curve. (C) Mucosal oedema, loss of superficial gastric epithelium, and sparse inflammatory infiltrate in the lamina propria
During a follow up examination performed three months later to reassess the lower oesophagus, the gastric mucosa appeared endoscopically and histologically unremarkable.
Chromoendoscopy using Lugol’s solution is not without hazards. Local irritation of the oesophageal mucosa may cause retrosternal pain.5 General allergic reactions include laryngospasm, bronchospasm, and even cardiac arrest.6 The concentration of the solution used in studies ranges from 0.5% to 5%, and higher concentrations (3–5%) may be associated with a higher risk of complications.6 A Japanese study reported that washing the mucosa with sodium thiosulphate may neutralise the iodine solution and reduce retrosternal discomfort.7 Only two cases of gastric mucosal erosions have been reported after the application of iodine.8
In this case, the histological features of localised oedema and loss of superficial gastric epithelium in the absence of significant inflammatory cell infiltrate supported an acute toxic injury to the gastric mucosa. The toxic reaction was confined to the columnar epithelium in the greater curve of the stomach that was in direct contact with the pooled 5% Lugol’s iodine while the squamous oesophageal mucosa remained unremarkable both endoscopically and histologically. Gastric columnar epithelium may be more susceptible to the toxic effect of Lugol’s iodine and mucosal injury may go unrecognised unless the stomach is re-examined after application of the dye. To reduce the risks, we now use 10–20 ml of 1.5% Lugol’s solution and routinely aspirate the gastric pool before assessing the oesophageal mucosa.
Previous studies have shown that Lugol’s staining is useful in screening for early oesophageal cancer in high risk populations such as patients with previous or current non-oesophageal malignancy and those with a high alcohol intake.9,10 However, none of these studies commented on the adverse reactions to Lugol’s staining during endoscopy. We suggest that the adverse reactions and safety profile of iodine staining need to be addressed, in particular before recommending its routine use for screening purposes. Also, where it has to be used, a lower concentration of 1.5% may be less toxic to the gastric mucosa and is thus recommended.
Conflict of interest: None declared.
References
- 1.Fennerty MB. Tissue staining. Gastrointest Endosc Clin N Am 1994;4:297–311. [PubMed] [Google Scholar]
- 2.Brodmerkel GJ. Schiller’s test: An aid in esophagoscopic diagnosis. Gastroenterology 1971;60:813–18. [Google Scholar]
- 3.Sugimachi K, Kitamura K, Baba K, et al. Endoscopic diagnosis of early carcinoma of the esophagus using Lugol’s solution. Gastrointest Endosc 1992;38:657–61. [DOI] [PubMed] [Google Scholar]
- 4.Inoue H, Rey JF, Lightdale CJ. Lugol chromoendoscopy for oesophageal squamous cell cancer. Endoscopy 2001;33:75–9. [PubMed] [Google Scholar]
- 5.Aoyama N, Akaike S, Yoshizumi Y. Investigations of questionnaire about side effects of lugol staining. Jpn J Gastroenterol Surg 1983;16:939–44. [Google Scholar]
- 6.Stevens PD, Lightdale CJ, Green PHR, et al. Combined magnification endoscopy with chromoendoscopy for the evaluation of Barretts esophagus. Gastrointest Endosc 1994;40:747–9. [PubMed] [Google Scholar]
- 7.Kondo H, Fukuda H, Ono H, et al. Sodium thiosulphate solution spray for relief of irritation caused by Lugol’s stain in chromoendoscopy. Gastrointest Endosc 2001;53:199–202. [DOI] [PubMed] [Google Scholar]
- 8.Fumito K . Acute esophageal erosions and gastric ulcerations induced by Lugol’s solution spray at dye scattering esophagoscopy. Report of two cases. Gastroenterol Endosc 1984;26:2408–15. [Google Scholar]
- 9.Shimizu Y, Tukagoshi H, Fujita M, et al. Iodine staining in patients with other current or prior primary cancers. Gastrointest Endosc 2001;53:1–5. [DOI] [PubMed] [Google Scholar]
- 10.Yokoyama A, Ohmori T, Makuuchi H, et al. Successful screening for early esophageal cancer in alcoholics using endoscopy and mucosal iodine staining. Cancer 1995;76:928–34. [DOI] [PubMed] [Google Scholar]