Multiple simultaneous complications of acute otitis media in a child diagnosed with chronic granulomatous disease: a case report.

Abstract

While the prevalence of acute otitis media complications in pediatric patients has decreased over the past 30 years because of effective antibiotic therapy, the incidence has begun to rise again recently, possibly because of increased antibiotic resistance. Patients who simultaneously manifest multiple complications may require a more thorough evaluation, including an immunologic work-up. The presented case should encourage physicians to investigate the possibility of an underlying immunodeficiency when treating patients with multiple simultaneous complications of acute otitis media.

Introduction

Several factors might explain why acute otitis media (AOM) is more common in children than in adults. One such factor is the horizontal position and small lumen size of children's eustachian tubes; these allow bacteria within the nasopharynx to pass more readily through the eustachian tube into the middle ear cavity and cause inflammation, obstruction, and infection. This process may be associated with complications, defined here as infections that extend to areas outside the middle ear. Examples of otitis media complications include mastoiditis, meningitis, periauricular subperiosteal abscess, epidural or subdural abscess, brain abscess, lateral sinus thrombophlebitis, cavernous sinus thrombosis, and facial paralysis.

Although the prevalence of these complications has decreased over the past 30 years, in part because of the effectiveness of antibiotic therapy, the incidence has recently begun to increase again, possibly because of increased antibiotic resistance of the microorganisms that cause AOM. (1)

Some patients develop more than one serious complication. Patients who manifest multiple intracranial and extracranial complications mayrequire a more thorough evaluation, including an immunologic work-up. The case report that follows should encourage physicians who are treating patients with AOM associated with multiple complications to investigate the possibility of an underlying immunodeficiency, such as chronic granulomatous disease (CGD).

Case report

A 14-year-old boy was admitted to the Department of Otolaryngology at West Virginia University's Ruby Memorial Hospital with acute mastoiditis and left postauricular abscess. Prior to admission, he had been unsuccessfully treated as an outpatient for otitis externa and otitis media with both topical and oral antibiotics for 1 week. He then began to experience postauricular swelling with a high fever (102.9[degrees]F), headache, neck stiffness, and lethargy.

At the patient's admission, computed tomography (CT) of his head and neck revealed a left postauricular/ suboccipital multiloculated abscess measuring 15.0 x 9.0 cm and extending into the retropharynx. The CT scan also demonstrated opacification of the mastoid air cells with cortical bone thinning (figure, A), as well as partial occlusion of the left internal jugular vein caused by thrombus formation (figure, B). The patient's white blood cell (WBC) count was 28,800 (89% neutrophils, 1% bands, 4% lymphocytes, and 6% monocytes).

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Because he also exhibited signs of meningitis, the patient underwent lumbar puncture, which revealed a 2,680 WBC count (90% neutrophils, 120 mg/100 ml total protein, and 38 mg/100 ml glucose); no microorganisms were identified on Gram's stain. Intravenous antibiotics (vancomycin 60 mg/kg/day at 6-hour intervals and ceftriaxone 2 g q12h) were started empirically.

The patient was taken to the operating room, where incision and drainage of the abscess and a complete mastoidectomy were performed. The postoperative course was favorable; the patient was afebrile within 24 hours of the surgery and had no signs of meningitis by 48 hours. The culture from the abscess was positive for ceftriaxone-sensitive Streptococcus viridans; therefore, the vancomycin was discontinued on postoperative day 3. The patient progressed well and was discharged to home on postoperative day 6, where he received ceftriaxone 2 g IV daily over the following 34 days.

Because of the multiple complications of AOM in this patient, an immunologic evaluation was performed. A dihydrorhodamine assay was positive, confirming a diagnosis of autosomal-recessive CGD. The patient was treated with prophylactic trimethoprim-sulfamethoxazole (TMP-SMX) and sent to the CGD Clinic at the National Institutes of Health for further genetic analysis.

Discussion

CGD is caused by genetic defects in the phox genes that make up the enzyme NADPH oxidase. (2) This enzyme, which is most abundant in phagocytic cells, generates superoxide and other oxidative compounds that are used by these cells to destroy microorganisms. The inability to manufacture oxygen radicals renders these cells incapable of undergoing the characteristic respiratory burst of phagocytosis and leads to recurrent infections.

Both X-linked and autosomal-recessive modes of inheritance have been described in the literature. (3) Patients with X-linked CGD generally have a more severe clinical course and increased mortality compared to patients with autosomal-recessive disease. (4) This tendency is due to different molecular defects of the NADPH oxidase enzyme that occur in the two forms of inheritance. (3) The microorganisms that cause the majority of infections are catalase-positive bacteria, such as Staphylococcus aureus, Burkholderia cepacia, and Klebsiella, Aerobacter, and Serratia spp. Fungal infections are also very prevalent, with Aspergillus being the most common species.

Patients with CGD typically present with recurrent infections of epithelial surfaces that have direct contact with the environment, such as skin, sinuses, lungs, and gut. (5) Cervical lymphadenitis, pneumonia, subcutaneous abscess, and sepsis are the most common infections and complications. Oral manifestations, such as aphthous ulcers and gingivitis, are also common.

The mainstay of treatment for patients with CGD is prophylactic antimicrobial or antifungal therapy; TMP-SMX, clotrimazole, and itraconazole are the most commonly used. Also, interferon-gamma has been used for prophylaxis because it is a macrophage-activating factor that has been shown to increase hydrogen peroxide generation in monocytes. (5) Other, newer methods of treatment currently being studied are bone marrow transplantation and gene therapy. (5) Surgical incision and drainage is often an essential adjuvant for complete management of infections.

Although our patient did have clinical features of CGD, there were aspects of the case that were inconsistent with the typical CGD presentation. For example, our patient was 14 years of age at the time of diagnosis, whereas most patients are diagnosed before 2 years of age. (5) However, CGD is a disorder that is likely underdiagnosed, with many patients remaining undiagnosed until adult life. (4) Another unusual feature was that catalase-negative S viridians, rather than the typical catalase-positive bacteria (S aureus, etc.) or fungus, was cultured from the abscess.

Conclusion

Patients who experience acute otitis media associated with multiple intracranial and extracranial complications should be considered for an immunologic evaluation because it is possible that these patients have an underlying immunodeficiency such as CGD, as did our patient.

References

(1.) Vera-Cruz P, Farinha RR, Calado V. Acute mastoiditis in children--our experience. Int J Pediatr Otorhinolaryngol 1999;50(2):113-17.

(2.) Sikora AG, Lee KC. Otolaryngologic manifestations of immunodeficiency. Otolaryng Clin North Am 2003;36(4):647-72.

(3.) Segal BH, Leto TL, Gallin JI, et al. Genetic, biochemical, and clinical features of chronic granulomatous disease. Medicine (Baltimore) 2000;79(3):170-200.

(4.) Goldblatt D, Thrasher AJ. Chronic granulomatous disease. Clin Exp Immunol 2000; 122(1): 1-9.

(5.) Curnutte JT. Chronic granulomatous disease: The solving of a clinical riddle at the molecular level. Clin Immunol Immunopathol 1993;67(3 Pt 2):S2-S15.

Robert Wilson, MD; Tarika Bhuta, MD; Richard Haydon, MD

From the Department of Surgery, Division of Otolaryngology, University of Kentucky College of Medicine, Lexington (Dr. Wilson and Dr. Haydon), and the Department of Otolaryngology, West Virginia University School of Medicine, Morgantown (Dr. Bhuta).

Corresponding author: Robert Wilson, MD, Department of Surgery, Division of Otolaryngology, University of Kentucky College of Medicine, 800 Rose St., Lexington, KY 40536-0298. Phone: [phone]; fax: [phone]; e-mail: robertwilson44@insightbb. com