Aspergillosis of the orbit

Lspergillosis of the orbit is a rare entity, only 35 cases have been reported in the literature since 1913.l ~ ' Interestingly, three of the 35 cases have been from the New Orleans area.1- 8 We are reporting an additional case of orbital aspergillosis to illustrate the difficulties that may be encountered in making such a diagnosis.
Case Report

A 57-year-old man presented in November 1980 to the Veterans Administration Hospital of New Orleans with a two-year history of proptosis of the right eye. The patient s past medical history included pulmonary tuberculosis diagnosed in 1945 by examination of gastric specimens and radiologic findings. Treatment consisted of bed rest for one year. A 1962 follow-up chest film revealed significant changes and he received treatment with INH and pyridoxine for one year. There was no further evidence of tuberculosis. Additional medical history included a hemorrhoidectomy in 1971 and resection for benign prostatic hyperplasia in 1979. The patient was a non-smoker and a school bus driver for most of his life. There was no history of agricultural work. Initial physical examination including x-rays and CT scan revealed a soft tissue mass of the right frontal, ethmoid and maxillary sinuses and the inferior orbit. A Caldwell-Luc exploration was performed. It was clinically felt to be a mucocele involving the maxillary sinus; however, a biopsy revealed chronic inflammation and foreign body giant cell reaction of nasal mucosa. The patient did well until September 1981 when his proptosis began to increase. A repeat Caldwell-Luc procedure was performed. Biopsy tissue revealed marked chronic inflammation, fibrosis and diffuse granulomatous inflammation with focal caseous-like necrosis. There was no vasculitis. Special stains for organisms were negative. Cultures of this tissue failed to grow fungi or tuberculous organisms. Histology was, however, compatible with tuberculosis despite the absence of organisms and the
From the Departments of Pathology and Otolaryngology, LSI 1 Medical Center and Veterans Administration Medical Center, New Orleans, La.

Fig. 1. Biopsy tissue showing necrotic and granulomatous process containing septate hyphae with dichotomous branching of Aspergillus species (PAS x 200).

patient was again placed on anti-tuberculosis medications. Worsening proptosis necessitated readmittance in April 1982 for reevaluation. A repeat CT scan showed a mass invading the right orbit and cribriform plate. Clinically it was then felt that because of previous histology7, failure to respond to antituberculous therapy and location of the process the patient had lethal midline granuloma. He was then placed on prednisone. One month later in May 1982 worsening proptosis necessitated a third Caldwell-Luc exploration. Biopsy tissue showed chronic inflammation, fibrosis. and granulomatous inflammation. Special stains revealed septate fungal hyphae with uniform diameter and dichotomous branching consistent with Aspergillus species (Fig 1). Culture of the tissue specimen grew Aspergillus fumigatus sensitive to Amphotericin B. The patient was put on intravenous Amphotericin B therapy. In November 1982 a CT scan revealed invasion of the roof of the right orbit, which on biopsy showed granulomatous inflammation with focal necrosis containing Aspergillus hyphae. After excluding an involvement of the central nervous system by clinical examination,

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radiologic evidence, and examination of spinal fluid, he underwent a right orbital exenteration. Post-operatively the patient was placed on Rifampin and Amphotericin B and was discharged in satisfactory condition one month later. Discussion Aspergillus is a saphrophytic fungus grouped with the ascomycetes. It is virtually ubiquitous and is tound as an infectious agent in agricultural workers and those exposed to pigeons. It is a normal flora of the mucous membranes. In man, Aspergillus infections are usually those involving the lower respiratory tract and show a predilection for the immunosuppressed host. It frequently is implicated in "swimmer's ear" • caused by Aspergillus nisfr}. Infections of the paranasal sinuses and orbit are considered rare. The diagnostic work-up of Aspergillus intection includes the clinical and radiologic examination, culture and the microscopic examination of exudates or tissue with the use of special stains, serologic methods, and less commonly skin testing and injection of infected material into pigeons. Infection of the orbit is usually the result ot direct extension from paranasal sinuses. The eveball can become infected as well bv this process. There are no pre-

disposing factors and most of the cases have been tound in warm, humid climate such as that of the southeastern United States. The disease is ot slow, insidious onset. The patient usually presents with proptosis and impaired ocular movement. There may be destruction of bony orbital walls on x-ray and CT scan. Physical examination usually reveals a sinusitis. Histologic studies of biopsied material show granulomatous inflammation and fibrosis with uniform, septate hyphae with dichotomous branching that stain better on periodic acid-Schiff i PAS) stain than hematoxylin and eosin (H&E) stain. Most cases ot orbital Aspergillosis are caused by Aspergillus fumigatus or Aspergillus niger. A. orijzae and A. flavus have also been implicated. l Treatment is primarily surgical including exenteration of the orbit. Systemic antitungal drugs, such as Amphotericin B. 5-Flurocytosin and Rifampin have been used as well as local washings by pimaricin. Antifungal susceptibility testing is of utmost importance. Outcome is often fatal. This case demonstrates problems in the diagnosis ot orbital aspergillosis. First, growth of the organism may be difficult. Repeated attempts at growth were unsuccessful. The reason tor this is probably inadequate sampling. Secondly, serologic testing was non-reactive on both serum and cerebrospinal fluid for Aspergillus antibodies. Thirdly, the spectrum of granulomatous disease is quite broad, especially in the paranasal area, therefore an aggressive attempt at diagnosis should be made. A differential should include fungal disease as well as tuberculosis, sarcoidosis. secondary lues and gummas. earlv leprosy, lethal midline granuloma. polymorphic "reticulosis." Wegener s granulomatosis and relapsing polvchondritis. In addition to Aspergillosis. histoplasmosis. leishmaniasis. actinomycosis and coccidioidomvcosis should be included in the differential diagnosis. References
1. Green \VR. Font RL. Zimmerman LE. Aspergillosis of the orbit. Report or' ten cases and review of the literature. Arch Ophthalmol 1969:82:302-313 2. Zinneman HH: Sinus-orbital aspergillosis. Minn Med 1972-55:661664 5. Lacaz CD. De Azevedo ML. Varuas AA. et al: Orbital aspereillosis caused bv Aspergillus tlavus. Rfc Paul Med 1978.91:64-67 4. Dhir SP. Banerjee AK. Chopra [S. et al: Orbitocramal aspergillo sis. Indian ] Ophthalmol 1978:26:34-38 5. Harmsch IP. Oberwinder D. Staib F. et al: Orbital asperaiilosis. Win Monatsbl Ausenheilkd 1979:175:65-71 6. SekulaJ. Popeilski L. Betkowski A: A case 01 aspergillosis involving the frontal sinus and orbit. Otolanmsol Pol 19SI.J.V365-369 7. Yu V'L. \VagnerGE. Shadomv S: Sino-orbital asperaiilosis treated with combination of antifunaal therapy. JAMA 1»80:244:814-815 S. Seaburv JH. Samuels M: The pathoeenetic <pectrum of asperaillosis. Am J Ctin Pathol 1963.40:21-33

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Sarma DP, Rohr W, Haindel C(1984): Aspergillosis of the orbit. J La State Med Soc 136:19-20. PMID: 6376706 [PubMed - indexed for MEDLINE]