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Actinomycosis esophagitis in a patient with persistent dysphagia.

Abstract: Many causes of esophagitis exist in immunocompromised patients. Uncommon pathogens must be considered to facilitate timely and appropriate therapy. A limited number of cases of esophageal actinomycosis have been reported. This report describes an unusual case of esophageal actinomycosis in a patient with persistent dysphagia. The broad differential may have delayed definitive diagnosis in the case study patient. Biopsy and culture are essential for accurate diagnosis. Although actinomycosis is a rare disease, it should be included in the differential diagnosis of patients presenting with oral or esophageal complaints. It may also be considered as an opportunistic infection in immunocompromised patients. The treatment of choice is parenteral penicillin G, 18 to 24 million units for 2 to 6 weeks followed by oral therapy for 6-12 months. (1)

Key Words: actinomycosis, esophagitis, immunosuppression

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Immunocompromised patients are susceptible to a wide variety of opportunistic infections affecting different organs of the body. Increased morbidity and mortality occur as a result of their low threshold for infection for both typical and atypical pathogens. An impairment in the cellular and humoral immunity with decreased quantity and/or quality of the immunoglobulins protective of the mucosal barrier might explain why those patients are more susceptible to opportunistic infections. Immunocompromised patients may have an imbalance of the gastrointestinal bacterial flora with pathogenic bacteria overwhelming commensals. Possible pathogens include viruses, bacteria, and fungi. Uncommon pathogens must be considered in immunocompromised patients presenting with common disease-related complaints.

Case Report

A 61-year-old male diagnosed with non-small cell distal tracheal carcinoma presented with recurrent dysphagia. The patient had endotracheal excision and radiotherapy, with the last radiation occurring 4 months before presentation. At the same time, the patient was also receiving carboplatin, docetasel, and gemcitabine hydrochloride regimen once per week. The patient's other medical history was significant for chronic obstructive pulmonary disease and arthritis. Several weeks after radiotherapy, he had development of odynophagia with dysphagia to solids and liquids and a 15-pound weight loss over a period of 2 to 3 weeks. The patient denied fevers or chills. An esophagogastroduodenoscopy (EGD) done at that time indicated a stricture in the mid esophagus and one ulcer, as shown in Figure 1. The cause of the dysphagia was assumed to be radiation esophagitis. The patient continued to have dysphagia, mildly relieved with nystatin and lidocaine suspension. Two months after the dilation procedure, a computed tomography of the chest was completed that revealed fullness in the esophageal tissue from the level of the sternomanubrial joint to the carina. No obvious mediastinal air, adenopathy, or tracheal mass was identified. A repeat EGD again indicated esophageal stricture and ulcer. Biopsy specimens were taken from the ulcer base, and pathology results were positive for actinomycosis. No dysplasia, malignancy, or viral inclusions were present. Special stains were negative for cytomegalovirus, herpes simplex virus, and fungi. The patient was started on doxycycline. Two weeks after initiating doxycycline, the patient continued to have persistent dysphagia with retrosternal burning. Only liquids were tolerated. The patient was admitted to the hospital for further evaluation. He had lost an additional 10 pounds. He reported having no fever, chills, night sweats, nausea, vomiting, or diarrhea. No oral thrush or significant dental pathology was identified on physical examination. A complete blood count indicated leukocytosis at 12,400 m[m.sup.3], macrocytic anemia, and a platelet count of 71,000. The patient underwent another EGD that identified a 1.5-cm-deep ulcer at 30-cm length from the incisors (Fig. 2). Biopsy of the ulcer showed an acute erosive esophagitis with ulcer debris and reactive squamous mucosa. There was no evidence of viral inclusion, dysplasia, or malignancy. The throat culture revealed normal oral flora with no documented Actinomyces.

The patient was started on continuous intravenous drip of penicillin G 24,000 U per 24 hours for 6 weeks. Clinical improvement was achieved, and the patient was able to tolerate both solids and liquids. The elevated leukocytes normalized. Repeat EGD 4 weeks later showed improvement, with complete resolution of the ulcer at the 3-month EGD follow-up visit.

[FIGURE 1 OMITTED]

[FIGURE 2 OMITTED]

Discussion

A broad differential diagnosis for dysphagia and esophagitis exists in immunocompromised patients. Candida is the most common cause of infectious esophagitis. Herpes simplex virus type 1 esophagitis is the second most common cause. Cytomegalovirus, HIV, tuberculosis, and varicella virus have all been identified as a cause of esophagitis. (1) Actinomycosis is an uncommon disease found in humans and cattle. It was first described by Von Langenbeck in 1845 and again in the late 1870s. (2-11) In 1891, Wolff and Israel reported isolation of the human Actinomyces, later named Actinomycosis israelii. (2-11) Originally, Actinomyces was believed to be a fungus. After the advent of cell wall studies in the 1950s, Actinomyces was characterized as a true bacteria. (5-11) Actinomyces are Gram-positive, non-spore-forming, branching filamentous obligate or facultative anaerobes. Most strains are microaerophilic, and their growth is often enhanced by an atmosphere containing 10% carbon dioxide. (11) Although the species A. israelii is the most common Actinomyces found in humans, four other species--Actinomycosis naeslundii, Actinomycosis viscosus, Actinomycosis odontolyticus, and Actinomycosis bovis--are capable of causing infection. (5-11)

A. israelii is a common commensal of gastrointestinal flora. It is found in gastric aspirates, bronchial secretions, and the female genital tract. (2,3,5,11) Actinomyces infections involve the cervicofacial region in 55% of cases. Only 20 and 15% occur in the abdominopelvic and pulmonothoracic areas, respectively. (5) Less than 4% of Actinomycosis involves the central nervous system. Central nervous system infection is rarely primary and is usually due to metastatic spread from the pelvis. (3,11) Actinomyces infection begins by invasion of normal mucosal barriers, either by trauma or by ulcers formed by other invasive pathogenic organisms. The break in mucosal barrier facilitates the entry of Actinomyces. Initially, Actinomyces is of low pathogenicity, being a commensal of the gastrointestinal flora. A chronic, localized suppurative infection characterized by indurated infiltration can occur. An abscess may form when a favorable anaerobic milieu for growth is present. The abscess may slowly proliferate and spread to contiguous structures disregarding tissue planes. (4) A draining fistula may result. The exudate is yellow/brown and contains sulfur granules. Sulfur granules are tiny, lobulated, grainy microcolonies of the organism with associated cellular debris and may be detected by hematoxylin and eosin stains. The infection can spread to lymph nodes when they lie in the path of bacteria, but enlargement of regional lymph nodes is not a clinical feature. Hematogenous spread can occur and result in metastatic dissemination, typically to the liver and to the brain. (5-11) A definitive diagnosis is made by culture of the organism in brain-heart agar or blood agar in an anaerobic media with 5% carbon dioxide atmosphere for 4 to 6 days at 37[degrees] C. (5) Cultures are positive in only 50% of the cases. The growth is usually slow, but in high-quality culture media, colonies are usually obtained in 5 days. (5-11) Sulfur granules are not specific for actinomycosis. Similar structures can be seen with Monosporium, Cephalosporium, Nocardia, Aspergillus, coccidioidomycosis, and some staphylococcal infections. (2) However, when present, (2) it indicates an active infiltrative disease. (12) No serologic tests or skin tests are available for detecting actinomycosis because of antibody cross-reactivity with tuberculosis. (5) In addition, the presence of branching does not suggest active disease. Actinomycosis can be found as a commensal of the esophageal mucosa. Branching could also suggest Candida, which can be found as a superinfection. A limited number of cases of esophageal actinomycosis have been reported with malignancy, such as reported in a patient with pancreatic adenocarcinoma. (3-10) It may also be considered an HIV-related opportunistic infection. The treatment of choice is parenteral penicillin G, 18 to 24 million units for 2 to 6 weeks followed by oral therapy with either penicillin VK or amoxicillin for a total duration of 6 to 12 months. Alternative treatment includes minocycline, tetracycline, erythromycin, clindamycin, ceftriaxone, and imipenem. Our patient did not improve with doxycycline treatment but did have a clinical and endoscopic response to penicillin. Surgical debridement may be a choice in extensive complicated infections. (3,8,9)

Conclusion

Many causes of dysphagia and esophagitis exist in immunocompromised patients. Infectious causes, including uncommon pathogens, must be considered to facilitate timely and appropriate therapy. The broad differential may have delayed definitive diagnosis in the case study patient. Biopsy and culture are essential for accurate diagnosis. Some infectious organisms, such as Actinomyces, have specific growth requirements. Although actinomycosis is a rare disease, it should be included in the differential diagnosis of patients presenting with oral or esophageal complaints.
Words are, of course, the most powerful drug used by mankind.
--Rudyard Kipling


Accepted November 4, 2004.

References

1. Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases, 4th ed, New York, Churchill Livingston Inc., 1995, p 2286.

2. Vossough A. Esophagitis, infectious. Emedicine 2003 May.

3. Weese WC, Smith IM. A study of 57 cases of actinomycosis over a 36-year period: a diagnostic 'failure' with good prognosis after treatment. Arch Intern Med 1975; 135:1562-1568.

4. Lee SA, Palmer GW, Cooney EL. Esophageal actinomycosis in a patient with AIDS (review). Yale J Biol Med 2001; 74:383-389.

5. Manfredi R, Mazzoni A, Cavicchi O, et al. Invasive mycotic and actinomycotic oropharyngeal and craniofacial infection in two patients with AIDS. Mycoses 1994;37:209-215.

6. Bennhoff DF. Actinomycosis: diagnostic and therapeutic considerations and a review of 32 cases (review). Laryngoscope 1984;94:1198-1217.

7. Spencer GM, Roach D, Skucas J. Actinomycosis of the esophagus in a patient with AIDS: findings on barium esophagograms. AJR Am J Roentgenol 1993;161:795-796.

8. Poles MA, McMeeking AA, Scholes JV, et al. Actinomyces infection of a cytomegalovirus esophageal ulcer in two patients with acquired immunodeficiency syndrome. Am J Gastroenterol 1994;89:1569-1572.

9. Yew WW, Wong PC, Wong CF, et al. Use of imipenem in the treatment of thoracic actinomycosis. Clin Infect Dis 1994;19:983-984.

10. Skoutelis A, Petrochilos J, Bassaris H. Successful treatment of thoracic actinomycosis with ceftriaxone. Clin Infect Dis 1994; 19:161-162.

11. Ng FH, Wong SY, Chang CM, et al. Esophageal actinomycosis: a case report. Endoscopy 1997;29:133.

12. Burden P. Actinomycosis (review). J Infect 1989;19:95-99.

13. Nair S, Pitchumoni CS. Image of the month. Gastroenterology 1999;117:296.

RELATED ARTICLE: Key Points

* Actinomycosis esophagitis is an uncommon disease.

* A limited number of cases of esophageal actinomycosis have been reported.

* Biopsy and culture are essential for an early and accurate diagnosis.

* It may also be considered as an opportunistic infection in immunocompromised patients.

* The treatment of choice is parenteral penicillin G.

Semaan Georges Kosseifi, MD, Kim Dittus, MD, Dima N. Nassour, MD, Mohammad Axis Shaikh, MD, and Mark F. Young, MD

From the Department of Gastroenterology, East Tennessee State University, Johnson City, TN.

Reprint requests to Dr. Mark F. Young, 310 N. State of Franklin Road, Suite 202, Johnson City, TN 37604. Email: giaofnet@aol.com
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Title Annotation:Case Report
Author:Young, Mark F.
Publication:Southern Medical Journal
Geographic Code:1USA
Date:Jun 1, 2005
Words:1821
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