Eric B. Goosenberg, MD
Which infectious forms of esophagitis are most common in AIDS patients?
Candida albicans, Herpes simplex virus (HSV), and cytomegalovirus (CMV).
A 47-year-old man with chronic obstructive pulmonary disease (COPD) on inhaled steroids complains of a 3-week history of dysphagia without weight loss or other systems. An endoscopy is performed with the finding demonstrated in the figure. What is the most likely diagnosis?
Figure 9-1 See also color plate.
What are the most common risk factors for Candida albicans esophagitis?
Immunosuppression, most commonly due to corticosteroid use (particularly when inhaled), AIDS or cancer chemotherapy, or suppression of normal oropharyngeal flora by antibiotic use.
Which AIDS patients are at greatest risk of contracting Candida esophagitis?
Those with a CD4 cell count less than 100/mm3, those not taking antiretroviral therapy (ART, formerly referred to as HAART for highly active antiretroviral therapy), and those who have failed to restore immunocompetence while receiving treatment for HIV.
True/False: The most common cause of odynophagia in an AIDS patient is Candida esophagitis.
False. This symptom, particularly in the absence of dysphagia and oral thrush, is more often due to ulcerative esophagitis, such as that occurs in Herpes simplex or CMV infection, idiopathic ulcers of advanced HIV infection, pill-induced esophagitis, or severe reflux esophagitis.
What underlying medical conditions increase the risk of developing Candida esophagitis?
Gastric hypochlorhydria, diabetes mellitus, adrenal dysfunction, alcoholism, and conditions associated with impaired esophageal peristalsis/transit such as achalasia, benign strictures, esophageal cancer, and scleroderma.
True/False: Failure of an AIDS patient with dysphagia to respond to a course of fluconazole is strongly suggestive of a resistant strain of Candida.
False. It is more likely that the patient has some other form of esophagitis.
True/False: Infectious esophagitis in patients having undergone bone marrow or solid organ transplant is most commonly due to Candidiasis.
False. HSV and CMV are the most common pathogens in this setting, as well as during acute rejection after transplantation.
How should an immunocompetent patient who recently received a course of antibiotic therapy and now has Candida esophagitis be treated?
A nonabsorbable oral agent such as nystatin is usually adequate and less expensive than systemic alternatives.
How should an AIDS patient with Candida esophagitis be treated?
A systemically absorbable antifungal agent such as fluconazole should be given as a loading dose of 400 mg once, followed by 200–400 mg daily (orally or intravenously) for a total of 14 to 21 days. Voriconazole or posaconazole could be used alternatively but are usually reserved for cases refractory to fluconazole. Caspofungin (and related echinocandins, micafungin, and anidulafungin) are given intravenously but are also usually reserved for fluconazole failures in patients requiring hospitalization because of severe dysphagia. Amphotericin B is effective but can only be given intravenously and has the greatest toxicity. As a consequence, it is infrequently used for Candidaesophagitis.
True/False: It is reasonable to empirically treat an HIV-infected patient with dysphagia but without oropharyngeal Candidiasis with fluconazole.
True. Even in the absence of oral thrush, Candida esophagitis is the most common cause of dysphagia in HIV.
How should a cancer patient with granulocytopenia and clear evidence of Candida esophagitis be treated?
Intravenous amphotericin B can prevent and treat disseminated infection and it is also effective for systemic aspergillosis. Flucytosine may need to be added to amphotericin in life-threatening disease. Parenteral fluconazole is adequate for the treatment of Candidiasis but does not cover aspergillosis.
A 37-year-old woman, 4 months out from an allogeneic stem cell transplant, presents complaining of a 10-day history of severe odynophagia and 4 kg weight loss. Endoscopy demonstrates a single superficial ulceration near the esophagogastric junction. Biopsies are obtained. What is the most likely diagnosis?
Figure 9-2 See also color plate.
CMV esophagitis. Demonstrated in the figure is a cytomegalic cell characterized by the presence of a large eosinophilic intranuclear inclusion with basophilic intracytoplasmic inclusions (hematoxylin and eosin staining).
True/False: Non-Candida fungal infections (eg, Aspergillus, Blastomyces, Cryptococcus, and Histoplasma) of the esophagus occur only in severely immunocompromised individuals.
True/False: Acyclovir is the preferred drug for treatment of Herpes simplex esophagitis in both immunocompetent and immunosuppressed patients.
True. Acyclovir (400 mg po five times a day or 5 mg/kg body weight IV) should be given for 7–10 days for immunocompetent patients and for 2–3 weeks in immunosuppressed patients. The intravenous dosage is used when a patient is unable to tolerate oral medication or if disseminated Herpes infection is demonstrated or suspected.
True/False: Biopsies of esophageal ulcers looking for Herpes simplex infection should be targeted toward the center of the ulcer, as the heaped-up margins are typically composed of normal epithelial cells.
False. The opposite is true. Herpes simplex preferentially infects the epithelial cells, which are present at the ulcer margins.
True/False: The endoscopic appearance and location of the ulceration seen in the figure would be consistent with CMV esophagitis.
Figure 9-3 See also color plate.
True. CMV esophagitis usually causes one or more large but relatively superficial ulcers at the level of the distal esophagus and may have associated smaller surrounding ulcers. It less often appears as a diffuse esophagitis.
True/False: In the absence of immunosuppression, an individual with nasolabial herpetic lesions and concurrent esophageal symptoms should have endoscopic biopsies and cultures done before a diagnosis of Herpesesophagitis is made.
False. In this situation, a clinical diagnosis of Herpes esophagitis is likely enough to justify empiric treatment.
Describe the typical endoscopic appearance and location of Herpes esophagitis.
Herpes esophagitis usually presents as multiple erosions or shallow ulcers, usually in the proximal or mid-portion of the esophagus.
True/False: A patient with known CMV infection who presents with new symptoms of dysphagia and odynophagia should be treated empirically for a diagnosis of CMV esophagitis without further diagnostic evaluation.
False. Nausea, vomiting, epigastric pain, fever, and weight loss are usually the more prominent symptoms rather than classic symptoms of esophageal infection. Endoscopy should be done to rule out a separate explanation for esophageal symptoms.
True/False: Biopsies and culture specimens of esophageal ulcers, looking for CMV infection, should be targeted toward the center of the ulcer, as the heaped-up edges are typically normal epithelial cells.
True/False: ART, while of clear benefit in preventing opportunistic infections such as CMV, also substantially reduces mortality when initiated after the onset of CMV esophagitis.
True. Mortality is reduced by 35%–40%.
What are the main oral and intravenous medications used to treat CMV esophagitis?
Oral valganciclovir or intravenous foscarnet is used for induction therapy for 3–6 weeks, usually starting with valganciclovir because of lower cost and toxicity, with the duration being based on clinical response and tolerance of the medication. Treatment failures are switched to the other of these agents or a combination of both. Once symptoms have responded, some practitioners will switch to oral valganciclovir combined with ART in HIV-infected patients. Recurrent CMV infection is treated with reinduction then maintenance with oral ganciclovir in conjunction with ART in HIV-infected patients. Cidofovir is only used if a patient has failed therapy with the combination of ganciclovir and foscarnet, or if these medications are not tolerated.
True/False: Patients with reactivation of Herpes zoster infection on the chest wall who also have esophageal symptoms should be suspected of having zoster-associated esophagitis.
True. Zoster-associated esophageal ulcers that endoscopically resemble those of Herpes simplex infection have been reported in this setting. These ulcers generally resolve with resolution of the skin eruptions.
What is the most common pathophysiology of esophageal involvement in tuberculosis?
Esophageal tuberculosis is most often the result of contiguous spread from an infected mediastinal lymph node. Infection reaches the esophagus by way of a fistula or due to lymphatic obstruction. This infection has become more common as a complication of AIDS.
• • • SUGGESTED READINGS • • •
Pappas PG, Kauffman CA, Andes D, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious
Diseases Society of America. Clin Infect Dis. 2009;48:503.
Chen LI, Chang JM, Kuo MC, Hwang SJ, Chen HC. Combined herpes viral and candidal esophagitis in a CAPD patient: case report and review of literature. Am J Med Sci. 2007 Mar;333(3):191-193.
Amaro R, Poniecka AW, Goldberg RI. Herpes esophagitis. Gastrointest Endosc. 2000 Jan;51(1):68.