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Background
The most common cause of esophagitis is gastroesophageal reflux disease (GERD). Other important, but less common, causes are infections, medications, radiation therapy, systemic disease, and trauma. Eosinophilic esophagitis has emerged as an important cause of esophagitis in both children and adults. The image below demonstrates where fungal and viral infections occur in esophagitis-associated ulcers. This article does not discuss GERD -induced esophagitis.1
Esophagitis. Location of fungal and viral infecti...
Esophagitis. Location of fungal and viral infections in ulcers.
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Esophagitis. Location of fungal and viral infecti...
Esophagitis. Location of fungal and viral infections in ulcers.
Pathophysiology
The pathophysiology of esophagitis depends on its etiology. Infective esophagitis is most commonly observed in immunosuppressed hosts but has also been reported in healthy adults and children. A wide range of abnormalities in host defense may predispose an individual to opportunistic infections, such as neutropenia, impaired chemotaxis and phagocytosis, alteration in humoral immunity, and impaired T-cell lymphocyte function. Steroids, cytotoxic agents, radiation, and immune modulators can also contribute to impaired host immune function. Disruption of mucosal protective barriers and antibiotics that suppress the normal bacterial flora may contribute to the invasive ability of commensal organisms.2
The prevalence of symptomatic infection is high in individuals with AIDS, leukemia, and lymphoma and is low (<5%) in the general medical population. In people with HIV, the most significant risk factor is a persistently low CD4 count, but reports exist of individuals who develop fungal esophagitis during the seroconversion phase. Patients with systemic diseases (eg, diabetes mellitus, adrenal dysfunction, alcoholism) and those of advanced age can be predisposed to infectious esophagitis because of altered immune function. Illnesses that interfere with esophageal peristalsis, such as achalasia, progressive systemic sclerosis, and esophageal neoplasias, may contribute to fungal esophagitis.
Steroid therapy and other immunosuppressive medications contribute to fungal infection by suppressing both lymphocyte function and granulocyte function. Other medications associated with pill esophagitis cause injury by local or topical injury. Other medications, usually medications associated with pill esophagitis, cause injury by local contact.
The mechanism of eosinophilic esophagitis remains to be elucidated. However, a corrugated esophagus characterized by fine concentric mucosal rings is commonly observed in patients and believed to be related to histamine released from sensitized mast cells in the esophageal wall. This activates a cascade of reactions culminating in acetylcholine release that contracts muscle fibers in the muscularis mucosae resulting in the formation of concentric esophageal rings. This hypothesis can be tested by performing endoscopic ultrasound, which will reveal contraction of the muscle layers of the muscularis mucosae and may be related to immunoglobulin E (IgE) activation.
Frequency
United States
Unknown3
International
Unknown
Mortality/Morbidity
Patients may experience dysphagia, pain, odynophagia, and malnutrition in severe esophagitis. Rarely, life-threatening bleeding occurs and may lead to death. Outcomes and survival in these patients are related to the severity of their underlying systemic illness.
Race
No racial predilection is observed.
Sex
No sexual predilection is observed.
Age
No age-related differences are reported. Esophagitis is commonly seen in adults and is uncommon in childhood.4
Clinical
History
A history of immunosuppression, steroid therapy, recent antibiotic use, or systemic illness supports the diagnosis. Although patients may be asymptomatic, typical symptoms include the following:
* Onset of difficult or painful swallowing (ie, dysphagia, odynophagia)
* Heartburn
* Retrosternal discomfort or pain
* Nausea, vomiting
* Fever, sepsis
* Abdominal pain
* Epigastric pain
* Hematemesis (occasionally)
* Anorexia, weight loss (depends on chronicity and severity of underlying illness)
* Cough
Physical
* Look for signs of immunosuppression and skin signs of systemic disease (eg, telangiectasias and sclerodactyly in scleroderma).
* Examine the oral cavity (for thrush or ulcers).
Causes
See Histologic Findings.
* Infectious causes include the following:
o Candida species
o Noncandidal fungi (eg, Aspergillus, Histoplasma, Cryptococcus, Blastomyces)
o Herpes simplex virus (HSV)
o Cytomegalovirus (CMV)
o Varicella-zoster virus (VZV)
o Epstein-Barr virus (EBV)
o In HIV -infected hosts - CMV, HSV, Mycobacterium avium-intracellulare, idiopathic
o Human papillomavirus (HPV)
o Poliovirus
o Bacterial species (eg, normal flora, Mycobacterium tuberculosis, Mycobacterium avium-intracellulare)
o Parasitic infections (eg, Chagas disease, Trypanosoma cruzi, Cryptosporidium, Pneumocystis, Leishmania donovani)
* Systemic illnesses include the following:
o Skin disorders
+ Epidermolysis bullosa
+ Pemphigus vulgaris
+ Bullous pemphigoid
+ Cicatricial pemphigoid
+ Drug-induced skin disorders (eg, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis)
+ Other skin disorders (eg, lichen planus, psoriasis, acanthosis nigricans, leukoplakia)
o Eosinophilic esophagitis
o Behçet disease
o Graft versus host disease (GVHD)
o Inflammatory bowel disease (Crohn disease)
o Sarcoidosis
o Chronic granulomatous disease
o Metastatic cancer
o Collagen vascular disease
o Medications
+ Pill esophagitis (eg, Fosamax)
+ Antibiotics (eg, tetracycline)
+ Potassium
+ Nonsteroidal anti-inflammatory drugs (NSAIDs)
+ Quinidine
+ Chemotherapy (eg, dactinomycin, bleomycin, cytarabine, daunorubicin, 5-fluorouracil, methotrexate, vincristine)
o Radiation therapy.Differential Diagnoses
Angina Pectoris
Gastroesophageal Reflux Disease
Peptic Ulcer Disease
Pulmonary Embolism
Other Problems to Be Considered
Coronary artery disease
Pericarditis
Aortic aneurysm
Nonulcer reflux disease
Functional dyspepsia
Stricture
Workup
Laboratory Studies
* CBC count in patients with neutropenia or who are immunosuppressed
* CD4 count and HIV test in patients with risk factors for HIV
Imaging Studies
* Barium studies are recommended as the initial imaging study in patients presenting with dysphagia.
o A case can be made for initial upper endoscopy because this approach would reveal more diagnostic information (eg, inflammatory characteristics, ability to obtain samples for pathological examination, cytological examination, viral and bacterial cultures). Barium studies are less accurate for mucosal detail and can also reduce the capability of obtaining positive cultures.
o The authors do not recommend barium studies for patients with absolute dysphagia or odynophagia. Upper endoscopy would be recommended under these circumstances. The authors view barium studies and upper endoscopy as complementary rather than competing tests in the evaluation of patients with dysphagia.
Other Tests
* No specific other tests are recommended; other tests are performed based on underlying disease (eg, CD4 count in HIV, CBC count in neutropenia) and collagen workup (eg, antinuclear antibody [ANA], anti-dsDNA).
Procedures
* Esophagogastroduodenoscopy (EGD) is preferred in patients with odynophagia because this is a specific symptom of esophagitis. EGD is the main diagnostic tool used for esophagitis.
o Allows mucosal visualization
o Can obtain mucosal biopsies and brushings
o Wide variety of findings based on the underlying cause
* Blind brush cytology has been used in the past; however, with the availability of EGD, its use has diminished. It is performed by passing a cytology brush in a sheath similar to a nasogastric or orogastric tube. Once the end of the catheter is in the mid esophagus, the brush is extended and brushings are taken. Finally, the brush is withdrawn back into the sheath. This is performed without any direct visualization, as occurs when brushings are performed during an EGD.
Histologic Findings
Candida
Oral thrush is a frequent finding and is often an indicator of esophageal involvement. Oral thrush can be absent in 25% of cases of Candida esophagitis. Candida infection is frequently asymptomatic.
The grading scale for candidal esophagitis is as follows:
* Grade 1 - Few raised white plaques up to 2 mm in size, no ulceration
* Grade 2 - Multiple raised white plaques more than 2 mm in size, no ulceration
* Grade 3 - Confluent, linear, nodular, elevated plaques with ulceration
* Grade 4 - Grade 3 with narrowed lumen
Candida plaques are typically creamy white or pale yellow, with underlying raw mucosa. Brushings should be obtained with a sheathed cytology brush, spread onto slides, and stained with periodic acid-Schiff, silver, or Gram stains. The presence of mycelial forms and masses of budding yeast is consistent with candidal infection. Cultures are seldom indicated because Candida species are commensal organisms, and differentiating normal flora from infection is difficult. Cultures are useful for resistant Candida or Aspergillus.
Herpes simplex virus
HSV esophagitis diagnosis is made at endoscopy. The earliest esophageal lesions are rounded 1- to 3-mm vesicles in the middle to distal esophagus. Centers slough to form discrete circumscribed ulcers with raised edges.
Advanced HSV esophagitis may be indistinguishable from candidal esophagitis. Plaques, cobblestoning, or a shaggy ulcerative appearance is observed.
HSV preferentially infects epithelial cells, as seen in the image below. Biopsy should be performed on ulcer margins of islands of squamous mucosa for histology and culture.
Esophagitis. Location of fungal and viral infecti...
Esophagitis. Location of fungal and viral infections in ulcers.
[ CLOSE WINDOW ]
Esophagitis. Location of fungal and viral infecti...
Esophagitis. Location of fungal and viral infections in ulcers.
The ulcer base is devoid of epithelial cells and is inadequate to diagnose HSV esophagitis.
Immunologic staining of centrifugation cultures is more sensitive than routine histology.
* Multinucleated giant cells
* Ballooning degeneration
* Ground glass intranuclear Cowdry type A inclusion bodies
* Margination of chromatin
Immunohistologic stains using monoclonal antibodies to HSV antigens or in situ hybridization techniques may improve the yield in difficult cases.
Cytomegalovirus
The virus infects submucosal fibroblasts and endothelial cells (as shown in the above image, under Herpes simplex virus), not the squamous epithelium. Diagnosis depends on biopsies from the EGD. Superficial erosions with serpiginous nonraised borders in the middle to distal esophagus are observed. With infection progression, shallow ulcerations may deepen and expand for 5-10 cm. Tissue is needed for confirmation; obtain multiple biopsies from the ulcer base. (See Cytomegalovirus Esophagitis.)
Varicella-zoster virus
This organism can cause severe esophagitis. The key to diagnosis is finding concurrent dermatologic VZV lesions. The appearance on EGD ranges from occasional vesicles to discrete ulcerative lesions to a confluence of ulcerations with necrosis. On histologic examination, epithelial cells with VZV show edema, ballooning degeneration, and multinucleated giant cells with intranuclear eosinophilic inclusion bodies. Immunohistochemical staining using monoclonal antibodies is helpful to differentiate VZV from HSV.
Epstein-Barr virus
Histologic features of esophageal lesions are similar to those of oral hairy leukoplakia.
Human immunodeficiency virus
Multiple, small, aphthoid lesions are observed during the period of transient fever, chills, malaise, and rash of early HIV infection. Later, giant deep ulcers extending up several centimeters are observed. Fistula formation, perforation, hemorrhage, or superinfection may complicate large ulcers.
Human papillomavirus
HPV esophagitis is asymptomatic. Lesions are typically found in the middle to distal esophagus. They may appear as erythematous macules, white plaques, nodules, or exuberant frondlike lesions. The diagnosis is made based on histology. Koilocytosis, giant cells, and cytologic atypia are visible on immunohistochemical stains.
Mycobacterium tuberculosis
Esophageal symptoms result from direct extension from adjacent mediastinal structures. EGD reveals shallow ulcers, heaped-up lesions mimicking neoplasia, and extrinsic compression of the esophagus. Specimens should be sent for acid-fast stains and mycobacterial culture.
Drug-induced skin disease
Drug-induced skin diseases, which rarely occur, affect the esophagus with a blistering process and desquamation of large areas of epithelium. Both focal and long strictures and webs may form.
Behçet disease
Esophageal involvement is rare. Esophageal lesions include ulcerations that can tunnel the mucosa, strictures, fistulous tracts, and perforations.
Graft versus host disease
Histologic changes in acute GVHD are observed in the squamous epithelium, including the esophagus. Chronic GVHD damages the esophagus more extensively. Generalized desquamation is visible on EGD. Barium contrast radiographs may reveal webs, rings, and tight strictures in the upper and mid esophagus.
Inflammatory bowel disease
The esophagus can be involved in Crohn disease. Aphthous ulcers are observed in the esophagus. Inflammatory strictures, sinus tracts, filiform polyps, and fistulas to adjacent structures may be observed. Histology shows diffuse and nodular lymphoid aggregates; 50% of EGD biopsy specimens show noncaseating granulomas.
Metastatic cancer
Diagnosis is best made by barium contrast radiography and CT scan. EGD is used to exclude primary esophageal cancer.
Collagen vascular diseases
Motility disorders of the esophagus lead to poor acid clearing, with resulting epithelial damage (ie, GERD in scleroderma).
Medications (pill esophagitis)
Antibiotics, potassium chloride, NSAIDs, quinidine, emperonium bromide, and Fosamax account for 90% of the reported cases. The following are important pill and patient factors:
* Chemical nature of drug
* Solubility
* Contact time with mucosa
* Size, shape, and pill coating
* Amount of water (ie, too little) taken to swallow pill (eg, Fosamax)
* Preexisting esophageal pathology (eg, stricture, achalasia)
EGD findings range from reddened edematous mucosa to small superficial ulcers to large ulcers with heaped up inflamed margins, often with exudate.
Chemotherapy esophagitis
Dactinomycin, bleomycin, cytarabine, daunorubicin, 5-fluorouracil, methotrexate, and vincristine may cause severe dysphagia because of oropharyngeal mucositis.
Radiation and chemoradiation esophagitis
Radiation therapy over 30 Gy to the mediastinum typically causes retrosternal burning and painful swallowing, which is usually mild and limited to the duration of therapy.
* A dose of 40 Gy causes mucosal redness and edema.
* A dose of 50 Gy causes a higher incidence and severity of esophageal damage.
* A dose of 60-70 Gy causes moderate-to-severe esophagitis with strictures, perforations, and fistulas.
Sclerosant and band ligation therapy for varices
This can cause necrosis of esophageal tissues and mucosal ulcers. Incidence and severity are higher with sclerosant therapy. Later, strictures can develop.Treatment
Medical Care
Treatment is directed at the underlying cause. The goal of medical care is to treat the underlying cause and minimize morbidity. Treatment options are as follows:
* Candida esophagitis
o Topical nonabsorbable agents include nystatin, clotrimazole, and oral amphotericin B.
o Oral agents include fluconazole and itraconazole.5
o Parenteral agents include amphotericin B, fluconazole, and flucytosine.
o Choice of agent depends on the severity of infection and degree of host defense impairment.
* HSV esophagitis diagnosis made at endoscopy
o Acyclovir
o Foscarnet for acyclovir-resistant cases
o Famciclovir (acyclovir analog)
* CMV esophagitis
o Ganciclovir (acyclovir analog)
o Foscarnet
* Varicella-zoster virus esophagitis
o Acyclovir
o Famciclovir
o Foscarnet for acyclovir-resistant cases
* EBV esophagitis: Acyclovir (may require long-term maintenance to suppress oral hairy leukoplakia)
* Human immunodeficiency virus esophagitis
o Corticosteroid therapy, usually for longer than 1 month
o Antiretroviral therapy for HIV
* Human papillomavirus esophagitis
o Often asymptomatic (No treatment is usually needed.)
o Systemic interferon-alfa, bleomycin, and etoposide used with variable results
* M tuberculosis esophagitis: Standard antituberculous therapy is used for immunocompetent hosts.
* Bacterial esophagitis: Normal flora, usually observed in immunocompromised patients, is extremely rare in healthy hosts.
o Infections are often polymicrobial and include Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus viridans, and Bacillus species.
o Broad-spectrum beta-lactam antibiotics are used, usually in combination with an aminoglycoside. Adjustments are based on response and culture results.
* Behçet disease esophagitis
o Corticosteroids for serious inflammation
o Chlorambucil or azathioprine for long-term therapy
* Graft versus host disease esophagitis
o Dilation and antireflux measures
o Prednisone, cyclosporine, azathioprine, and thalidomide
* Inflammatory bowel disease esophagitis
o Corticosteroid therapy for inflammatory lesions
o Dilation for strictures
o Surgery - May be needed for fistulas and strictures
* Metastatic cancer esophagitis
o Radiation therapy
o Palliation with stents
* Collagen vascular diseases esophagitis
* Medication-related esophagitis (pill esophagitis)
o Stop medication.
o Control of acid reflux may accelerate healing.
o Patients should take medication with plenty of water while sitting in the upright position.
* Chemotherapy esophagitis
* Radiation and chemoradiation esophagitis
Surgical Care
Surgical care may be necessary for perforation and fistulas.
Consultations
* Consult a gastroenterologist to facilitate diagnosis and treatment.
* Consulting an infectious disease specialist may be necessary in difficult cases.
* A surgical consultation may be necessary for perforation and fistulas.
* Other consultations may be sought, as indicated.
Diet
No particular restrictions are necessary. If the patient has odynophagia or is unable to consume calories orally, then gastric feeding or parenteral feeding may be needed.
Activity
No limitations on patient activity are necessary.
Medication
Therapy is directed at the underlying condition, with the goal of minimizing symptoms and preventing complications. The choice of the therapeutic agent depends on the severity of infection and the degree of host defense impairment. Medical therapy for fungal conditions falls into 3 categories, as follows: (1) topically active agents (eg, nystatin, clotrimazole, oral amphotericin B), (2) orally administered absorbable agents (eg, fluconazole, itraconazole), and (3) parenterally administered agents (eg, amphotericin B, fluconazole, flucytosine). Most patients with fungal esophagitis who are immunocompetent can be treated with a topical antifungal agent. They are virtually devoid of adverse effects and have few, if any, drug-drug interactions because they are not absorbed.
In a study at the digestive endoscopy unit of a Brazilian hospital, Wilheim et al investigated the frequency of esophageal candidiasis among patients, which Candida species were causing the disease, the distribution of these species in association with predisposing factors, and the susceptibility of these organisms to fluconazole.5 The authors found the incidence of esophageal candidiasis to be low, determining that 40 out of 2,672 patients (1.5%) who underwent esophagogastroduodenoscopy had endoscopic findings compatible with the disorder. Just over half of these 40 patients were male, and 65% of them were inpatients. Of the 90% of patients in whom associated diseases were identified, 21 (52.5%) were infected with the human immunodeficiency virus (HIV). Among the 21 patients under age 50 years, 82.6% were HIV positive.
Endoscopy revealed severe forms of esophagitis in 50% of patients in the Wilheim study with a CD4 count below 200 cells/mm3. Candida species other than C albicans were isolated in 22.7% and 45% of HIV-positive and HIV-negative patients, respectively. Six patient Candida samples were found to be fluconazole-resistant, while 2 samples had dose-dependent susceptibility to this agent.
The treatment of eosinophilic esophagitis continues to evolve. Various interventions, such as complete avoidance of precipitating food allergens, esophageal dilatation, corticosteroids, cromolyn sodium, and leukotriene inhibitors, have been performed. Until the natural history of this disease is understood more fully and appropriate trials are performed, the treatment of this condition will continue to be empirical.
Antifungal agents
Topical or systemic treatment of fungal infections.
Clotrimazole (Mycelex)
Nonabsorbable imidazole. Broad-spectrum synthetic antifungal agent that inhibits growth of yeasts by altering cell membrane permeability.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
Immunocompetent patients: 10 mg buccal troches dissolved 5 times/d for 1 wk
Immunocompromised patients: 100 mg vaginal tab dissolved in mouth tid
Pediatric
<3 years: Not recommended
>3 years: Administer as in adults
* Dosing
* Interactions
* Contraindications
* Precautions
None reported
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Not for treatment of systemic fungal infections; avoid contact with the eyes; if irritation or sensitivity develops, discontinue use and institute appropriate therapy; abnormal findings on LFTs and SGOT have occurred; periodically monitor LFTs in hepatic disease
Nystatin (Mycostatin)
Nonabsorbable polyene antifungal agent obtained from Streptomyces noursei. Binds to sterols in cell membrane of susceptible fungi, with resulting change in membrane permeability allowing leakage of intracellular components. Indicated for treatment of PO candidiasis.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
Troche: 200,000-400,000 U dissolved PO 4-5 times/d
Susp: 400,000-600,000 U swish and swallow 4-5 times/d for 1 wk
Pediatric
Troche: Not established
Susp: Administer as in adults
* Dosing
* Interactions
* Contraindications
* Precautions
None reported
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Do not use to treat systemic mycoses; PO irritation or sensitization may occur; GI distress may occur with large doses
Fluconazole (Diflucan)
Synthetic triazole fungistatic agent. Highly selective inhibitor of fungal cytochrome P-450 sterol C-14 alpha demethylation.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
200 mg PO on day 1, then 100 mg PO qd for 2-3 wk after symptoms resolve
Alternatively, 400 mg PO on day 1, then 200 mg PO qd
Can use up to 400 mg/d
Pediatric
6 mg/kg PO on day 1, then 3 mg/kg PO qd for 3 wk; can use up to 12 mg/kg/d
* Dosing
* Interactions
* Contraindications
* Precautions
Levels may increase with hydrochlorothiazide; fluconazole levels may decrease with long-term coadministration of rifampin; coadministration of fluconazole may decrease phenytoin concentrations; may increase concentrations of rifabutin, theophylline, tolbutamide, glyburide, and glipizide; effects of anticoagulants may increase with fluconazole coadministration; increases in cyclosporine and tacrolimus concentrations may occur when administered concurrently
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; administration with terfenadine or cisapride
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Adjust dose for renal insufficiency; monitor closely if rashes develop and discontinue drug if lesions progress; may cause clinical hepatitis, cholestasis, and fulminant hepatic failure (including death) with underlying medical conditions such as AIDS or a malignancy while taking multiple concomitant medications; not recommended for nursing mothers; convenience and efficacy of single-dose regimen for treatment of vaginal yeast infections should be weighed against difficulties resulting from higher incidence of adverse reactions reported with PO fluconazole versus intravaginal agents; caution in patients taking OCPs containing ethinyl estradiol and levonorgestrel
Amphotericin B, conventional (Amphocil, Fungizone)
Binds to sterols in the cell membrane and alters permeability. Used in patients with granulocytopenia. PO route infrequently used and has no advantage over PO clotrimazole or nystatin.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
0.5 mg/kg/d IV in febrile patients or patients with disseminated disease for a total dose of 1.5-2 g over 6-12 wk
Alternatively, 0.3 mg/kg/d IV for 7-10 d
Pediatric
Infants: Not established
Children: Administer as in adults
* Dosing
* Interactions
* Contraindications
* Precautions
Antineoplastic agents may enhance the potential of amphotericin B for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; the risk of renal toxicity is increased with cyclosporine use
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Monitor renal function, serum electrolytes such as magnesium and potassium, liver function, CBC count, and hemoglobin concentrations; resume the therapy at the lowest level (eg, 0.25 mg/kg) when the therapy is interrupted for more than 7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in patients who are neutropenic receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion); fever and chills are not uncommon after first few administrations of drug; rare acute reactions may include hypotension, bronchospasm, arrhythmias, and shock
Anidulafungin (Eraxis)
Antifungal agent of the echinocandin class. Inhibits synthesis of 1,3-beta-D-glucan, an essential component of fungal cell walls. Indicated to treat esophageal candidiasis, candidemia, and other forms of candidal infections (eg, intra-abdominal abscesses, peritonitis).
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
Candidemia or other candidal infections: 200 mg IV on day 1, decrease dose on day 2 and thereafter to 100 mg/d IV
Esophageal candidiasis: 100 mg IV on day 1, decrease dose on day 2 and thereafter to 50 mg/d IV
Do not exceed infusion rate of 1.1 mg/min
Pediatric
Not established
* Dosing
* Interactions
* Contraindications
* Precautions
None reported
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Common adverse effects include hypokalemia, diarrhea, elevated hepatic enzyme levels, and headache; rare reports of serious hepatotoxicity; infusion-related reactions (eg, rash, urticaria, flushing, pruritus, dyspnea, hypotension) may occur, particularly with rapid infusion; following reconstitution, dilute further with D5W or NS before administration
Antiviral agents
Treat HSV or CMV viral infections. In addition to the drugs listed below, famciclovir (Famvir), a prodrug of the antiviral agent penciclovir, which is not currently recommended for treatment, may replace acyclovir in prophylaxis and treatment.
Acyclovir (Zovirax)
Synthetic purine nucleoside analog that stops replication of viral DNA. Used for HSV esophagitis.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
250 mg/m2 IV q8h for 7-10 d
Pediatric
Administer as in adults
* Dosing
* Interactions
* Contraindications
* Precautions
Concomitant use of probenecid or zidovudine prolongs half-life and increases CNS toxicity of acyclovir
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in renal failure or when using other nephrotoxic drugs
Foscarnet (Foscavir)
Organic analog of inorganic pyrophosphate that inhibits replication of HSV and CMV. Used for acyclovir-resistant cases.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
Induction: 90 mg/kg IV q12h for 3-6 wk
Maintenance: 90-120 mg/kg/d IV single infusion
Pediatric
Not established
* Dosing
* Interactions
* Contraindications
* Precautions
Coadministration with potentially nephrotoxic drugs (eg, aminoglycosides, amphotericin B, IV pentamidine) may increase nephrotoxicity (do not administer unless potential benefits outweigh risks); coadministration with IV pentamidine may cause hypocalcemia
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause decline in renal function; for correct dosing, obtain 24-h serum creatinine at baseline and continue to monitor (discontinue if serum creatinine <0.4 mL/min/kg); hydration may reduce nephrotoxicity; carefully monitor electrolytes (eg, calcium, magnesium); assess for electrolyte and mineral level abnormalities if mild perioral numbness, paresthesias symptoms, or seizures occur; granulocytopenia and anemia may occur (regularly monitor CBC count); infuse foscarnet solutions into veins with adequate blood flow to avoid local irritation; to avoid toxicity, do not administer by rapid or bolus IV injection
Ganciclovir (Cytovene)
Acyclic nucleoside analog that inhibits replication of herpes viruses. Active against CMV and HSV.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
Induction: 5 mg/kg IV q12h for 2-3 wk
Maintenance: 6 mg/kg IV 5 times per wk
Pediatric
Administer as in adults
* Dosing
* Interactions
* Contraindications
* Precautions
Concomitant administration with cytotoxic drugs such as dapsone, vinblastine, Adriamycin, pentamidine, flucytosine, vincristine, amphotericin B, trimethoprim/sulfamethoxazole combinations, or other nucleoside analogs may result in additive toxicity in bone marrow, spermatogonia, and the germinal layers of skin and GI mucosa (coadminister only if potential benefits outweigh risks); coadministration with imipenem-cilastatin may cause generalized seizures (use only if potential benefits outweigh risks); serum creatinine may increase following concurrent use of ganciclovir with either cyclosporine or amphotericin B; in the presence of probenecid, ganciclovir renal clearance is reduced; bioavailability may increase when didanosine is administered either 2 h prior to or simultaneously with ganciclovir; bioavailability of ganciclovir may decrease in the presence of zidovudine, while bioavailability of zidovudine is increased in the presence of ganciclovir
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Clinical toxicity of ganciclovir includes granulocytopenia, anemia, and thrombocytopenia; because PO ganciclovir is associated with a higher rate of CMV retinitis progression compared to the IV formulation, use only when benefits outweigh risks (advanced HIV disease); half-life and plasma/serum concentrations of ganciclovir may be increased as a result of reduced renal clearance; dosages > 6 mg/kg IV may result in increased toxicity; rapid infusions may result in increased toxicity; initially, reconstituted solutions of IV ganciclovir have a high pH (11); phlebitis or pain may occur at site of IV infusion despite further dilution in IV fluids; administration of ganciclovir should be accompanied by adequate hydration; photosensitization (ie, photoallergy, phototoxicity) may occur
Corticosteroids
Have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.
Prednisone (Deltasone, Sterapred, Orasone)
Administered in immunosuppressive doses, which may vary based on the underlying disease process. Dose is usually slowly tapered over wk to mo. Equivalent dose of methylprednisolone (Solu-Medrol) may be used instead of prednisone.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
30-60 mg PO qd or divided bid/qid; taper over few wk to mo, as symptoms resolve
Literature reports a large variability in dose; generally use lowest dose that produces a clinical response
Pediatric
Not established.Follow-up
Further Inpatient Care
* The goals of treatment are disease-specific; however, relief of symptoms and maintenance of nutritional status are common outcomes. Goals of treatment are the same for inpatient and outpatient care.
Inpatient & Outpatient Medications
* See Medication.
Complications
* Stricture formation, malnutrition, and, rarely, perforation or bleeding may occur.
Prognosis
* The prognosis is good with rapid diagnosis and proper treatment. Ultimately, prognosis depends on the underlying disease process.
Patient Education
* Educate patients on the disease process and the importance of early medical evaluation at the onset of symptoms.
* To prevent pill esophagitis, instruct patients to take medications with plenty of water while sitting upright. Avoid certain medications (eg, Fosamax) in patients with known esophageal varices.
* For excellent patient education resources, visit eMedicine's Heartburn/GERD/Reflux Center and Esophagus, Stomach, and Intestine Center. Also, see eMedicine's patient education articles Reflux Disease (GERD), Heartburn, and Understanding Heartburn/GERD Medications.
Miscellaneous
Medicolegal Pitfalls
* Fosamax in patients who are cirrhotic could precipitate GI bleeding from erosions over an esophageal varix.
* Always consider the possibility of systemic illness causing the esophageal manifestations (eg, AIDS, scleroderma, SLE, pemphigus).
Special Concerns
* Concerns are specific to the underlying disease process.
