Maxillary Sinusitis Caused by Mucormycosis

RECEIVED May 13, 2013, REVISED July 16, 2013, ACCEPTED November 26, 2013 Correspondence to Young-Wook Park

Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University 7 Jukheon-gil, Gangneung 210-702, Korea

Tel: 82-33-640-3139, Fax: 82-33-640-3113, E-mail: [email protected]

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Yong-Yun Ha, Suk Keun Lee , Young-Wook Park, Seong-Gon Kim, Min Keun Kim, Hyun-Young Kim

Departments of Oral and Maxillofacial Surgery,

Oral Pathology, College of Dentistry, Gangneung-Wonju National University

Abstract

A 60-year-old male complained of headache, nasal discharge, and diplopia for over one month with a history of left upper molar extraction, and he had recently experienced severe discharge of purulent exudate from his left antrum. Under the diagnosis of maxillary sinusitis, the Caldwell-Luc operation was performed, and several fragments of amorphous white mucoroid materials were removed. In the histological observation, sinus mucosa was relatively well preserved, but showed diffuse infiltration with eosinophilic polymorphonuclears. Huge molds of mucormycosis were associated with the surface of mucosa.

He was treated with amphotericin-B deoxycholate, resulting in the uneventful healing of the antral lesion. The current case of antral mucormycosis was very rare but effectively treated by surgical removal of antral mucosa and the following antibiotic therapy for the strong inhabitants of fungal molds. We also presumed that the patient was superinfected with commensal fungus of mucormycosis during broad spectrum antibiotic therapy for the previous dental infection.

Key words: Mucormycosis, Superinfection, Maxillary sinusitis, Debridement

Introduction

Mucormycosis infection in the head and neck region is rare, characterized by opportunistic, rapid, and ag- gressive invasion, which is often fatal. Pathogenic fungi are Zygomycetes, including Mucor, Rhizopus, Abisidia , and Rhizomucor , which are commonly found in the natu- ral environment. Normally, healthy people do not be- come infected, since these organisms characteristically cause opportunistic infection, mainly affecting diabetes or other immunocompromised patients. Clinical character- istics include nasal obstruction, bloody nasal discharge, facial pain, and facial swelling[1,2] and most of them are similar to symptoms of what is commonly known as max- illary sinusitis.

We report on this case of a patient who was cured of mucormycosis with no specific systemic disease, including conditions that could lead to immunosuppression.

Pathohistological findings will also be described.

Case Report

A 60-year-old male suffering with headache, nasal dis- charge, and diplopia for one month, with a recent history of left upper molar extraction due to severe periodontal disease, showed discharge of purulent exudate from the ipsilateral antrum. Intensive antibiotic therapy (augmentin) was implemented for two weeks, and he was referred to our dental hospital.

When he visited our department, he did not show signs

Fig. 1. Radiological observation. (A) Water’s view showing diffuse haziness (arrows) in the left maxillary sinus. (B, C) Computed tomography showing condensed haziness (arrows) filling the entire sinus space. (B) Coronal view; (C) axial view.

of fatigue or chill but was rather calm and stable. However, he felt pain when finger pressure was applied on the left cheek area. The patient did not have swelling of the face or discoloration of the intraoral mucosa, and no fistula was observed on the extraction socket area. In addition, he had no history of diabetes mellitus or other systemic disease, including autoimmune disease.

Hematological examination did not reveal any abnormal conditions. Water’s view and computerized tomographic imaging showed entire haziness in the left maxillary sinus.

The radiological observation of Water’s view and com- puted tomography showed condensed haziness, which fil- led the whole left maxillary sinus (Fig. 1), however, the surrounding bony wall of the sinus was not affected.

Although the extraction socket had healed completely with- out development of an antral fistula, the coronal image of computed tomography showed a small defect in the sinus floor near the extraction socket (Fig. 1B).

Therefore, we diagnosed the lesion as primarily maxillary sinusitis or mucocele. The lesion was explored and debride- ment was performed via Caldwell-Luc surgery under gen- eral anesthesia. A vestibular incision and flap were made on the canine fossa region, followed by opening of the window on the left maxillary sinus using a round bur and chisel. Instant window opening was performed, purulent

and cheese-like material filling almost the entire sinus space was spontaneously discharged. The lesion was sufficiently irrigate and radical debridement was performed.

The specimen obtained from the operation consisted of many fragments of grayish yellow homogeneous material and granulomatous sinus mucosa (Fig. 2A). In histological observation, the sinus mucosa showed signs of in- flammation, which was limited only to the superficial layer (Fig. 2B, 2C). The sinus mucosa epithelium was relatively well preserved considering the acute inflammatory reaction closely associated with the fungal infection. Some tightly attached hyphae were observed on the surface of sinus mucosa, however, no invasion was found in the underlying connective tissue (Fig. 2D, 2E). The sinus mucosa showed heavy infiltration with polymorphonuclears (PMNs), espe- cially with an increase in the number of eosinophil PMNs (Fig. 2F, 2G). There are several factors for differential diag- nosis of mucormyces. Fungal mold, non-pigmented hy- phae similar to that of Aspergillus spp., and typical little septation are characteristics of mucormyces[3]. Observation revealed fungal hyphae branched almost in a right angle showing no septation with clear cytoplasmic spaces (Fig.

2H). However, the entire sinus mucosa showed severe eosinophilia.

After the operation, the patient complained of mild swel-

Fig. 2. Photomicrographs of mucormycosis-induced maxillary sinusitis. All specimens were stained with H&E. (A) Low power view (original

×12.5) of a microsection showing several fragments of fungal molds (arrows) with small pieces of sinus mucosa in the center. (B) The sinus mucosa was inflamed, but it was localized at the superficial layer. (C) The surface mucosal epithelium was relatively well preserved and the underlying connective tissue was heavily infiltrated with inflammatory cells. (D) Some attached fungal hyphae were observed on the surface mucosal epithelium (arrowhead). (E) High magnification (original ×400) of (D) arrowhead. Severe eosinophilia is shown near the fungal hyphae infection site. (F, G) Severe eosinophilia (arrows) was distributed throughout the whole sinus mucosa.

(H) Typical features of mucormyces, exhibiting a right angled branch and no septation.

ling and tenderness on the paranasal area, which was re- solved by the fifth day after the operation. Based on the biopsy result, we prescribed amphotericin B deoxycholate for the mucormycosis, which is the drug of first choice[4].

One week after surgery, we consulted with the division of infectious diseases for further evaluation. It was agreed that the patient did not require additional treatment.

Thereafter, the lesion was closed uneventfully five months after surgery and medication. The patient was satisfied with

the treatment outcome (Fig. 3).

This case was diagnosed as maxillary sinusitis with mu-

cormycosis (zygomycosis) demonstrating symptoms of

acute onset (of mucormycosis-induced maxillary sinusitis),

which is very rare and should be treated adequately by

both surgical removal and antibiotic therapy.

Fig. 3. Radiographic observation on follow-up. Five months after treatment, left maxillary sinus haziness was significantly resolved.

Discussion

Mucormycosis is a rare opportunistic fungal infection.

In the United States, incidence of mucormycosis is 10∼

50-fold lower than that of aspergillosis or candidiasis[2,5].

In Korea, only a few studies considering mucomycosis of the head and neck region have been conducted.

Mucormycosis is caused by families of mucoraceae , which include Mucor , Absidia , Rhizopus , Rhizomucor , and Cokeromyces as genera and are members of the order mucorales .

In particular, of these, Rhizopus is commonly associated with fungal infection of the head and neck region. These eugonic fungi show rapid growth, and can easily be found in spoiled food, compost, and soil. Most of these fungi cannot infect healthy humans and animals, but can infect humans with underlying systemic disease on rare occasions. Some risk factors known to be related to this infection include certain malignant tumors, hematopoietic diseases, organ transplantation, acute renal failure, pro- longed administration of antibiotics and steroids, burn, trauma, etc.[6,7]. However, our patient did not have an association with these factors. A few rare articles have re- ported infection of healthy patients[5,8-10]. Even so, it is possible to raise the question, “Why was our patient af- fected?”

Mortality of mucormycosis differs according to the au- thors, but is consistently quite high, and could be agreed

on as approximately 50%, which could go higher in cases of patients with underlying systemic disease[4,11]. The treatment of choice is known as a combination of medi- cations (amphotericin B) and surgery (debridement)[6,12].

Also, in general, penicillin is the drug of choice after oral surgery, and penicillin and trimethoprim are the drugs rec- ommended for maxillary sinusitis[13]. Regarding acute si- nusitis, two weeks of medical therapy before surgical inter- vention is the principle, if orbital and brain complications, including diplopia are absent. Therefore, primary medi- cation prescribed in a local clinic cannot be considered a big mistake, although the patient had diplopia.

However, improper use of antibiotics can increase in- cidence of opportunistic fungal infection[14]. There are sev- eral causes of induction of superinfection, including strains of human immunodeficiency virus, Haemophilus influenza , antibiotic agents, and so on. Of these, clindamycin, an antibiotic agent, is well known as a predisposing factor of colitis caused by Clostridium difficile . Broad spectrum antibacterial agents can establish a noncompeting environ- ment for fungi colonies, and some antibiotics can depress the human immune system. One study reported on admin- istration of penicillin in relation to increase of candida colonization. Penicillin can reduce the bacterial population of the gastrointestinal normal flora, especially Lactobacillus, which inhibits growth of candida leading to aggravation of candida colonization[15]. In addition, augmentin can aggravate growth of candida in the oro-gastrointenstinal tract[16]. Although no study considering augmentin in- duced aggravation of candia or mucromycosis on maxillary sinus has been reported, augmentin is known to act as an antibiotic for streptococci, which consists of normal si- nus flora[17], and could inhibit growth of fungi[18].

Therefore, it could be concluded that augmentin can de- stroy the ecosystem of the sinus, providing a good environ- ment for mucormycosis colonization.

Meanwhile, in this case, the sinus membrane was rela-

tively intact, indicating that there had been insufficient time

for the entire sinus to be severely affected and that outbreak

of sinusitis was recent, or, in the first place, sinusitis itself

could have been a non-aggressive type. On the other hand,

computed tomographic imaging revealed a mass-like lesion

on the entire unilateral sinus. In addition, these fungi are

known to be aggressive and show rapid growth[4,6].

minant environments owing to antibacterial agent, leading to set off of an allergenic reaction, subsequently causing peripheral eosinophilia. However, there is no way to prove this assumption of the superinfection.

Throughout this article, the doubt that the generally ac- cepted antibiotic protocol for acute sinusitis might cause a problem of superinfection is raised. And, again, nasal endoscopy is the most important tool in the diagnostic process of sinusitis, due to the specific cheesy like appear- ance of the fungus cluster, which is clearly distinguishable, compared to other sinusitis. Afterward, appropriate medi- cation and surgical procedure is applied, depending on the cause and diagnosis. Thus, the necessity of common sense should be emphasized once more, in that the drugs should always be administered under proper diagnosis and should not be abused.

The current case of maxillary sinusitis caused by mu- cormycosis was unusual and was treated by surgical de- bridement of fungal molds and subsequent antibiotic ther- apy, resulting in uneventful healing of the involved antrum.

We experienced a favorable outcome by surgical de- bridement and systemic administration of amphotericin B to the patient, who had no systemic disease and develop- ment of mucormycosis on the contralateral maxillary sinus.

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