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Esophageal Candidiasis

Esophageal Candidosis

Esophagitis is one of many infections caused by Candida albicans and is mainly seen in immunocompromised individuals. Clinical presentation is comprised of dysphagia, food passage obstruction, as well as nausea and vomiting. Some patients may have concomitant oral candidiasis, which can be helpful in making the initial diagnosis, while endoscopy is used to confirm the presence of Candida in the esophagus. Use of antifungals is the mainstay of treatment.


Presentation

One of the main clinical features of Candida esophagitis is the presence of odynophagia and dysphagia that may be quite severe. Passage of food and saliva may be significantly impaired, which can be accompanied with nausea, vomiting and substernal pain. Concomitant presence of oral candidiasis may not be observed as frequently as expected [10]. A prolonged course of disease is characterized by weight loss, weakness and poor general condition.

Hoarseness
  • Symptoms included hoarseness (8/12), dysphagia (6/12), and hemoptysis (1/12). There was poor correlation between oral lesions and esophageal or laryngeal involvement.[pediatrics.aappublications.org]
  • Symptoms of esophagitis include: difficulty swallowing (dysphagia) pain when you swallow ( odynophagia ) sore throat hoarse voice heartburn acid reflux chest pain (worse with eating) nausea vomiting epigastric abdominal pain decrease in appetite cough[healthline.com]
Odynophagia
  • None of the upper GI symptoms predict candida esophagitis in HIV-infected patients, but dysphagia and odynophagia predict candida esophagitis in non-HIV-infected patients.[ncbi.nlm.nih.gov]
  • Steroids Chemotherapy Radiotherapy Diseases which cause delayed esophageal emptying Scleroderma Strictures Achalasia S/P fundoplication Rarely may occur in otherwise healthy individuals Produces whitish slightly raised plaques Clinical Findings Dysphagia Odynophagia[learningradiology.com]
  • Appropriate diagnostic tests must be performed promptly when symptoms of odynophagia or dysphagia develop in these patients.[ncbi.nlm.nih.gov]
  • Dysphagia, odynophagia, and retrosternal chest discomfort were all absent. Oral thrush was present only at the outset. Standard therapy for massive bleeding with blood products alone was not successful.[ncbi.nlm.nih.gov]
  • […] evaluated the diagnostic value of blind brushing of the esophagus via nasogastric tube in 66 patients with human immunodeficiency virus (HIV) infection [acquired immune deficiency syndrome (AIDS) (N 59), or AIDS-related complex (ARC), (N 7)] complaining of odynophagia[ncbi.nlm.nih.gov]
Gagging
  • However, since she was introduced to textured foods at age 7 months, she had been gagging, coughing, and choking with them each time.[journals.lww.com]
  • Predominant symptoms in school-aged children and adolescents include dysphagia (difficulty swallowing), food impactions, and choking/gagging with meals, particularly when comprised of foods with coarse textures.[aacijournal.biomedcentral.com]
Progressive Dysphagia
Chest Pain
  • Patients typically present with acute odynophagia with severe substernal chest pain during swallowing. Dysphagia, chest pain, and upper gastrointestinal bleeding are less often observed.[med-ed.virginia.edu]
  • He tried to relieve the impaction with self-induced vomiting without relief followed by multiple episodes of hematemesis associated with dysphagia, odynophagia and severe chest pain.[omicsonline.org]
  • pain Experience pain in your mouth or throat when you eat Have shortness of breath or chest pain that occurs shortly after eating Vomit large amounts, often have forceful vomiting, have trouble breathing after vomiting or have vomit that is yellow or[mayoclinic.org]
  • Its most frequent symptoms are: diarrhea vomiting heartburn chest pain food sticking difficulty swallowing Many who suffer from eosinophili esophagitis also have seasonal allergies , rhinitis , asthma or eczema .[healthblurbs.com]
  • […] your ability to eat properly headache, muscle aches, or fever Seek immediate medical attention if: You have chest pain lasting more than a few minutes, especially if you have a history of heart problems, elevated blood pressure, or diabetes.[healthline.com]
Retrosternal Chest Pain
  • Dysphagia and odynophagia are the two main complaints, while accompanying symptoms may include obstruction, nausea, vomiting and retrosternal chest pain.[symptoma.com]
  • chest pain; vomiting and fever are the usual manifestations of candida esophagitis.[ispub.com]
Cutaneous Manifestation
  • manifestations of Candidiasis Mycetoma resembling large intraluminal tumor is rare Diagnosis Endoscopy most sensitive method of making diagnosis for mild cases Double-contrast esophagography should pick up 90% of cases Treatment Mycostatin Findings usually[learningradiology.com]

Workup

The initial diagnosis of Candida esophagitis can be made by a thorough physical examination and patient history. Presence of Candida in the oropharynx, characteristic symptoms and discovery of risk factors that prone patients to this infection may narrow the differential diagnosis significantly. To make a definite diagnosis, laboratory and diagnostic studies can be performed. Blood workup should include a complete blood count (CBC), with an emphasis on leukocyte count. If there is credible suspicion toward HIV infection as a risk factor, CD4+ cell count should be performed as well. In fact, this condition is termed to be an AIDS-defining illness [10], which is why all individuals with Candida esophagitis should undergo HIV testing. Further laboratory studies depend on the accompanying symptoms and risk factors, which are used to determine the underlying disease, if there is any. Endoscopy is the method of choice for obtaining a direct view into the esophagus [11], and can confirm macroscopic identification of white plaques lining the esophagus. A microbial confirmation can be obtained through cultivation of observed material. Candida readily grows on standard antifungal media but results may take up to several days.

Esophageal Motility Disorder
  • Nevertheless, a primary esophageal motility disorder such as achalasia was unlikely because the patient responded well to medical therapy and had no recurrence of symptoms after the treatment was discontinued.[journals.lww.com]
  • Other possible predisposing risk factors were acid suppressive therapy (14 patients), prior gastric surgery (five), mucosal barrier injury (four), inhaled steroid use (four), oral steroid use (three), esophageal motility disorders (three), rheumatologic[ncbi.nlm.nih.gov]
  • motility disorders, gastric surgery, HIV, rheumatic disease, elderly and debilitated patients ( Dis Esophagus 2003;16:66 ) Associated with CMV or HSV esophagitis in immunocompromised (see case reports below); also esophageal stricture Clinical features[pathologyoutlines.com]
  • Thus, at-risk patients include those with AIDS, organ transplants, alcoholism, diabetes, undernutrition, cancer, and esophageal motility disorders. Candida infection may occur in any of these patients.[msdmanuals.com]

Treatment

Once the diagnosis of Candida esophagitis is made, antifungal treatment is used. Various antifungal regimens exist [4] [12]. First-line therapy includes administration of fluconazole, belonging to the group of azole agents, for 200-400 mg either PO or IV q24h. Echinocandins, such as caspofungin in doses of 50 mg IV q24h, micafungin 150 mg IV q24h or anidulafungin 200 mg IV q24h as a loading dose followed by 100 mg IV q24h, are all effective alternative drugs and are used in the setting of Candida esophagitis not responding well to fluconazole. Additionally, itraconazole 200 mg PO q24h or posaconazole 400 mg q12h for three days, followed by 400 mg q24h can be highly effective as well. Although considered as a third-line drug, Amphotericin B is also used in managing Candida esophagitis and is given in doses of 0.5 mg/kg IV q24h. Regardless of the regimen, the duration of therapy ranges between 14-21 days [4] [12]. For patients with recurrent esophagitis, chronic administration of fluconazole in doses of 100-200 mg 3x per week as long as necessary is recommended [12].

In addition to managing esophagitis through appropriate antifungal therapy, management of the underlying condition will significantly reduce the chance of recurrence and development of other opportunistic infections.

Prognosis

The prognosis of Candida esophagitis is generally good, as the condition is usually self-limiting and responds well to antifungal treatment. Co-infection by cytomegalovirus (CMV) and herpes simplex virus (HSV) may occur, while in very rare cases, complications such as bleeding, ulceration, esophageal perforation and dissemination of the infection may take place [2]. The prognosis may significantly depend on the overall condition of the patient and the severity of the underlying disease which predisposed the individual to this infection, especially if not managed adequately.

Etiology

Candida albicans is a unicellular fungal pathogen ranging from 4-6 µm in diameter and is responsible for various types of infections. Pathogenesis invariably includes immunosuppression, together with various virulence factors exhibited by this fungal pathogen. C. albicans is often mentioned to be a part of the normal oral flora, which makes immunosuppressed patients significantly vulnerable. For these reasons, esophagitis, but also other infections of internal organs caused by Candida are classified as endogenous. This yeast readily grows on standard media and is characterized by formation of white colonies made of hyphae and pseudohyphae [3]. One of the main distinguishing features of C. albicans is the ability to form germ tubes, which are small cellular projections that progress into hyphae.

Epidemiology

C. albicans is found in all environments and is isolated from soil, animals and humans, as it often comprises normal flora of various parts of the human host, including the gastrointestinal tract [3]. When it comes to risk factors, immunosuppression of various origin is usually the single most important predisposing condition. HIV and AIDS [5], malignant diseases, particularly those of hematopoietic origin, intravenous use of corticosteroid therapy and organ transplant recipients are shown to be at a significantly increased risk [6]. However, the introduction of various drugs that alter normal gastrointestinal flora and pH has led to the fact that their use may also predispose individuals to this infection. Antibiotics, such as tetracyclines, sulfonamides and aminoglycosides significantly impair normal function of neutrophils, thus promoting growth of Candida species. Proton pump inhibitors [7], and histamine-receptor antagonists, such as cimetidine, have also proven to be involved in reducing the capability of immune defenses, presumably by interfering with pH levels. Various studies have indicated that immunocompetent individuals may develop Candida esophagitis, without an identifiable risk factor [8], which implies that some other processes may play a role in the pathogenesis of this infection, in addition to immunosuppression and iatrogenic factors.

Sex distribution
Age distribution

Pathophysiology

Under physiological conditions, the immune system of the human host is able to fight off numerous pathogens. Neutrophils, monocytes and eosinophils induce lytic damage to hyphae and disrupt fungal structure, aided by respective functions of dendritic cells and lymphocytes. In general, the role of the innate immune system is considered to be more important than adaptive immune mechanisms when it comes to C. albicans [3]. In order for Candida to establish an infection, some form of immune deficiency is considered a prerequisite. In the case of HIV, downregulation of CD4+ T-helper cells occurs, which are one of the most important mediators of immune response, and infection by Candida species is rather frequently seen in these individuals, especially if HIV is not treated [9]. In addition to various leukocytic lineages, numerous cytokines and other cell types, including platelets, endothelial cells and fibroblasts have shown to be a part of the immune response against Candida [3].

Prevention

The overall burden of Candida esophagitis and other types of infection caused by this fungal pathogen can be significantly reduced through appropriate preventive strategies that include:

  • Proper management of underlying diseases
  • Avoiding the use of drugs that are known to interfere with immune mechanisms that promote fungal growth as much as possible
  • Adequate treatment that reduces the rates of recurrence

Summary

Candida albicans is a ubiquitous opportunistic fungal organism that can cause infections in virtually any part of the body, including the esophagus. Candida esophagitis is an infection characterized by development of numerous Candida plaques on the esophageal mucosa. Through various virulence factors, such as the ability to change its morphology (known as phenotype switching), but also increased susceptibility of the host, C. albicans is able to establish an infection in various tissues. Several patients populations are established to be of increased risk for this infection - those receiving corticosteroids, patients with acquired immunodeficiency syndrome (AIDS), usually as a result of human immunodeficiency virus (HIV) infection, cancer patients and organ transplant recipients [1]. The use of proton pump inhibitors, histamine-receptor antagonists and certain antibiotics have also been linked to increased rates of Candida esophagitis [2]. Although Candida is usually seen in immunocompromised individuals, cases of this infection in immunocompetent patients has become more frequent in recent years, presumably because of increased use of drugs that alter normal gastrointestinal flora and impair immune functions. It is assumed that the pathogenesis of Candida esophagitis requires an initial infection of the oral cavity and subsequent dissemination into the esophagus. However, many patients have esophageal involvement without obvious signs of oral cavity infection and the presumptive diagnosis remains on the presence of other symptoms [3]. Dysphagia and odynophagia are the two main complaints, while accompanying symptoms may include obstruction, nausea, vomiting and retrosternal chest pain. To confirm Candida esophagitis, endoscopy is the recommended diagnostic procedure, which can clearly show white plaques on the esophageal mucosa. Subsequent microbiological confirmation through culturing can be performed. Administration of either oral or systemic antifungals is recommended. Azoles such as fluconazole or itraconazole, echinocandins (caspofungin, micafungin or anidulafungin are all indicated) and amphotericin B can be used. More importantly, treatment must focus on management of the underlying disease as well, which is usually HIV, in which case antiretroviral therapy should be initiated or corrected appropriately [4]. This condition has a good prognosis if treated appropriately, but concomitant infections with cytomegalovirus and herpes simplex virus, as well as severity of the underlying disease, may significantly impact patient outcomes.

Patient Information

Candida esophagitis is one of the forms of infection caused by the fungus known as Candida albicans. It is characterized by proliferation of this microorganism throughout the esophagus, which develops due to an underlying immunodeficiency in the vast majority of cases. Candida albicans is a ubiquitously found and is considered as a part of normal skin and gastrointestinal flora of the human host. Under physiological conditions, the immune system successfully fights this microorganism through several mechanisms, but when certain diseases lower the capacity of the immune system, such as human immunodeficiency virus (HIV), cancer, or use of potent immunosuppressive therapy like corticosteroids, Candida is able to proliferate and establish an infection. Other risk factors include the use of certain antibiotics, such as tetracyclines and sulfonamides, which directly inhibit the function of certain cells of the immune system. Additionally, the use of proton pump inhibitors such as omeprazole and histamine-receptor antagonists such as cimetidine have shown to alter normal gastric flora and pH, thus creating favorable conditions for Candida infection. Recent studies have shown that this type of infection may occur in apparently healthy individuals without obvious risk factors, which implies that other mechanisms may be involved. Because Candida is located in the gastrointestinal tract and is not acquired from the external environment, Candida esophagitis is usually classified as an endogenous infection. Usually, patients complain of bad breath and swallowing difficulties that may range from mild to severe enough to reduce normal passage of food and saliva. Some individuals report nausea, vomiting and pain in the chest, while weight loss and weakness are seen in infections that have a prolonged course. The initial diagnosis of Candida esophagitis can be made during the physical examination, which may reveal Candida in the oral cavity as well (known as oral thrush), but this may not always be the case. Laboratory studies should be performed, consisting of a complete blood count and mandatory testing for HIV infection, as Candida esophagitis is often seen in patients with this condition. To make a definite diagnosis, endoscopy is performed, which includes insertion of an endoscope into the esophagus to confirm the presence of white plaques on the esophageal mucosa. A sample may be obtained during this procedure for cultivation and subsequent microbial identification, but treatment is initiated as soon as macroscopic identification is achieved. Various antifungal drugs that pose different mechanisms are recommended. Fluconazole, itraconazole caspofungin, micafungin and amphotericin B are recommended against in managing this infection. Treatment usually lasts for 2-3 weeks and is given either orally or intravenously, depending on the general conditions of the patient. Overall, the prognosis for this infection is generally good and it resolves fully if adequately treated, but the underlying predisposing condition should be determined.

References

Article

  1. Murray PR, Rosenthal KS, Pfaller MA. Medical Microbiology. Seventh edition. Philadelphia: Elsevier/Saunders; 2013.
  2. Mandell GL, Bennett JE, Dolin R. Mandel, Douglas and Bennett's Principles and Practice of Infectious Diseases. Eight edition. Philadelphia, Pennsylvania: Churchill Livingstone; 2015.
  3. DN Gilbert, HF Chambers, GM Eliopoulos, MS Saag. The Sanford Guide to Antimicrobial Therapy 2015. 45th ed. Antimicrobial Therapy, Inc, Sperryville, VA; 2015.
  4. Vidal AP, Pannain VL, Bottino AM. Esophagitis in patients with acquired human immunodeficiency syndrome: an histological and immunohistochemistry study. Arq Gastroenterol. 2007;44(4):309-14.
  5. Underwood JA, Williams JW, Keate RF. Clinical findings and risk factors for Candida esophagitis in outpatients. Dis Esophagus. 2003;16:66–69.
  6. Karmeli Y, Stalnikowitz R, Eliakim R, Rahav G. Conventional dose of omeprazole alters gastric flora. Dig Dis Sci. 1995;40:2070–2073.
  7. Kliemann DA, Pasqualotto AC, Falavigna M, Giaretta T, Severo LC. Candida esophagitis: species distribution and risk factors for infection. Rev Inst Med Trop Sao Paulo. 2008;50(5):261-3.
  8. Choi JH, Lee CG, Lim YJ, Kang HW, Lim CY, Choi JS. Prevalence and risk factors of esophageal candidiasis in healthy individuals: a single center experience in Korea. Yonsei Med J. 2013;54(1):160-5.
  9. Mimidis K, Papadopoulos V, Margaritis V, et al. Predisposing factors and clinical symptoms in HIV-negative patients with Candida oesophagitis: are they always present? Int J Clin Pract. 2005;59(2):210-3.
  10. Bianchi Porro G, Parente F, Cernuschi M. The diagnosis of esophageal candidiasis in patients with acquired immune deficiency syndrome: is endoscopy always necessary?. Am J Gastroenterol. 1989;84(2):143-6.
  11. Nishimura S, Nagata N, Shimbo T, et al. Factors Associated with Esophageal Candidiasis and Its Endoscopic Severity in the Era of Antiretroviral Therapy. Chêne G, ed. PLoS ONE. 2013;8(3):e58217.
  12. Pappas PG, Kauffman CA, Andes DR, et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62(4):e1-50.

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Last updated: 2019-07-11 21:19