Summary

A 69 years old man presented to the accident and emergency department complaining of dysphagia and repeated vomiting for four days. He had long history of chronic obstructive pulmonary disease and was on regular nebulised budesonide (Pulmicort) for several months. Oesophago-gastro-duodenoscopy revealed multiple white and yellow plaques over the right tonsillar region and lower oesophagus, compatible with candidiasis. This complication has to be borne in mind in patients on inhaled steroids. As effective treatment is available, accurate and timely diagnosis of Candida oesophagitis is essential to minimise morbidity.

摘要

一名69歲男病者因連續嘔吐四天及吞嚥困難到急症室求診。他患有慢性阻塞性肺病多年，數月來定期使用類固醇激素(budesonide)噴霧治療(pulmicort)。上消化道內窺鏡檢查發現右扁桃腺及下食道有大量黃白斑，診斷為念珠菌感染。念珠菌食道炎是使用吸入類固醇激素引起的併發症，提高警覺就可以及早診斷和及時有效地治療。

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Introduction

Inhaled corticosteroids are common prophylactic therapy for bronchial asthma in adults and children and in some adults with chronic obstructive pulmonary disease (COPD). Oropharyngeal candidiasis is a well-known common side effect associated with prolonged use of inhaled steroids and appears to be dose-related.¹ However, oesophageal candidiasis has only been encountered rarely.^2-4 This is a report of a case of oesophageal candidiasis presenting with severe dysphagia and vomiting after prolonged use of nebulised glucocorticoid.

Case report

Figure 1: Candida oesophagitis with multiple white and yellow plaques

A 69 years old man presented to the accident and emergency department complaining of dysphagia and repeated vomiting for four days. He was unable to tolerate even fluids. He had history of chronic obstructive pulmonary disease for twenty years. He had self-administered nebulised budesonide (Pulmicort, a non-halogenated glucocorticoid) and salbutamol (Ventolin) four times daily for the past seven to eight months, apparently with good symptom control. He had no history of diabetes mellitus or conditions of impaired immunity. He had no history of recent use of antibiotics. Physical examination and vital signs were essentially normal. Oesophago-gastro-duodenoscopy revealed multiple white and yellow plaques over the right tonsillar region and lower oesophagus (Figure 1). There was an acute erosion at the posterior incisura of the stomach. Rapid urease test was positive, suggesting the presence of Helicobacter pylori. Oesophageal biopsy confirmed acute oesophagitis with abundant fungal hyphae compatible with candidiasis. Gastric biopsy revealed Helicobacter-associated chronic gastritis with ulceration. White cell count was 14.7 x 10⁹/L (normal range 3.9-10.7 x 10⁹/L). Spot sugar was 5.0mmol/L. Liver and renal function tests were essentially normal. He was treated with nystatin suspension for the candidiasis and omeprazole, clarithromycin and amoxycillin for the Helicobacter-associated gastritis. Budesonide inhalation was stopped. His symptoms rapidly improved. Test result of antibodies to Human Immunodeficiency Viruses 1 and 2 returned later as negative. At a follow up oesophago-gastro-duodenoscopy examination one month later, there was no evidence of candidiasis. However, there was still evidence of gastritis. The rapid urease test was still positive. Gastric biopsy revealed chronic gastritis but no Helicobacter. His pulmonary symptoms seemed to be under good control with bronchodilators alone, without acute exacerbation in the intervening month.

Discussion

Candida albicans, a yeast found in normal human oral flora, is the most common cause of fungal oesophagitis. Other Candida species, such as C. tropicalis, C. glabrata, C. parapsilosis, and C. krusei, are occasional pathogens.⁵

Oropharyngeal candidiasis is a well-known and the most common side effect associated with prolonged use of inhaled steroids.¹ They seldom cause serious problems. They may be avoided or minimised by mouth rinsing with warm water after each administration, using a spacer, reducing the dose of steroid and/or reducing the dosing frequency.^2,6 Candida laryngitis,⁷ laryngotracheitis⁸ and oesophagitis,² though uncommon, have also been reported.

Candida oesophagitis⁵ occurs in patients with impaired immunity caused by human immunodeficiency virus infection, aggressive radiation therapy or immunosuppressive chemotherapy, malignancy (especially haematological), organ transplantation and bone marrow transplantation. Other contributing causes include alcoholism, diabetes mellitus, advanced age, congenital immunodeficiency syndrome such as chronic mucocutaneous candidiasis, steroids,⁹ altered microbial flora as a result of antibiotic therapy, and hypochlorhydria secondary to H₂ receptor antagonists, proton-pump inhibitors or gastric surgery. Abnormal oesophageal structure or motility such as scleroderma, achalasia, strictures, oesophageal diverticulum, obstructing tumours and oesophageal burns from caustic ingestion can also predispose to candidal infection.

Dysphagia and/or odynophagia are the most frequent presenting symptoms of Candida oesophagitis, occurring in 59-79% of cases. Oral thrush accompanies Candida oesophagitis in about 75%. Hence, the lack of dysphagia or oral thrush cannot exclude Candida oesophagitis.⁵ Nausea and vomiting are rare. Despite extensive oesophageal involvement, 20-25% of Candida oesophagitis is asymptomatic, especially when the patient is immunocompetent.

Endoscopic classification⁵ is based on the severity of involvement: grade 1, few raised white plaques up to 2mm in size but no ulceration; grade 2, multiple raised white plaques >2mm in size but no ulceration; grade 3, confluent, linear, and nodular elevated plaques with ulceration; and grade 4, findings of grade 3 with narrowing of the lumen. Our patient seemed to have grade 2 lesions.

Treatment depends on the severity of the infection and the immune status of the patient. Patients on chronic steroid therapy, diabetics and the elderly have minimal impairment of immunity. They can be treated with topical antifungal agents alone such as nystatin, clotrimazole, miconazole and amphotericin B. Oral nystatin is inexpensive and effective, but unpalatable. Systemically absorbed imidazoles, e.g. fluconazole, itraconazole and ketoconazole, are effective but have risks of adverse systemic effects. Intravenous fluconazole and amphotericin B are reserved for the severely immunocompromised with life-threatening disseminated infections. Duration of therapy is usually 10-14 days, or up to 1-2 weeks after resolution of symptoms. Correction of reversible predisposing factors may require discontinuation of the inhaled steroid therapy, as prolonged antifungal therapy increases the risk for development of drug-resistant Candida albicans as well as colonisation by non-albicans Candida and other opportunistic micro-organisms.⁵

The mainstay of management of COPD is smoking cessation, vaccination, inhaled bronchodilators (beta₂ agonists or/and anticholinergics) and supplemental oxygen in hypoxaemic patients.¹⁰ Theophyllin is an effective second line option for maintenance therapy because of its side effects. The efficacy of inhaled steroids in the treatment of stable COPD patients remains controversial.^10-20 Because inhaled corticosteroids can prevent airway inflammation and permanent lung damage in patients with asthma, they are commonly prescribed for patients with COPD despite a lack of clinical data supporting similar benefit in COPD. The results of recent randomised, double-blind, placebo-controlled clinical trials have been disappointing, with little to suggest any long-term benefit from inhaled steroids in most patients with COPD.^15-20 In contrast to asthma, only a minority of COPD patients (approximately 10% who have concomitant asthmatic component) respond substantially to inhaled steroids.²¹ Therapeutic trials documenting spirometric response, in those with moderate to severe disease manifesting repeated exacerbations, are recommended before committing to long-term treatment. Side effects with inhaled steroids are usually confined to the oropharynx, causing local irritation, sore throat, cough, hoarseness, dysphonia and candidiasis. Systemic abnormalities involving soft tissue, bone, adrenal, carbohydrate and lipid profiles have been noted with high doses of inhaled steroids, although without significant clinical effects.^{11,13,17,18,20} Drug cost is also a consideration.¹⁶ Although systemic corticosteroids have been demonstrated to be useful in acute exacerbations, chronic treatment should be avoided because of the unfavourable benefit-to-risk ratio.²¹ Our patient administered potent nebulised steroid without a doctor's prescription or supervision. This has to be discouraged.

In conclusion, Candida oesophagitis should be borne in mind in patients taking inhaled steroids. Accurate and timely diagnosis is essential as effective treatment is available. However, other possible diagnoses such as pill-induced oesophagitis, gastro-esophageal reflux, or structural and functional oesophageal abnormality should not be overlooked.

Key messages

1. Oropharyngeal candidiasis is a well-known common side effect associated with prolonged use of inhaled steroids. Candida oesophagitis occurs rarely.
2. These complications may be minimised by mouth rinsing with warm water after each administration, using a spacer, reducing the dose of steroid and/or reducing the dosing frequency.
3. Dysphagia and/or odynophagia are the most frequent presenting symptoms of Candida oesophagitis.
4. Candida oesophagitis can be treated with topical antifungal agents for 10-14 days or up to 1-2 weeks after resolution of symptoms, in addition to correction of reversible predisposing factors.
5. The efficacy of inhaled steroids in the treatment of stable chronic obstructive pulmonary disease (COPD) patients remains controversial. The results of recent randomised, double-blind, placebo-controlled clinical trials have been disappointing with little to suggest any long-term benefit from inhaled steroids in most patients with COPD.

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References