Antifungal and Surgical Management of a Case of Maxillary Sinus Aspergilloma

1. Antifungal and Surgical Management of a Case of Maxillary Sinus Aspergilloma Riina Rautemaa DDS, PhD, Consultant of Oral Microbiology Helsinki University Central Hospital Maxillofacial Clinic and Laboratory Diagnostics; and Haartman Institute, University of Helsinki, Finland riina.rautemaa@helsinki.fi

2. Maxillary sinuses can be a focus of a fungal infection and a source of serious cranial and disseminated infections in immunocompromised patients. • We here describe a case of maxillary sinusitis in a 45-year-old female with a history of recurrent sinusitis and epileptic seizures.

3. The patient is a 45 year old female Finn with a history of recurrent sinusitis over most of her adulthood. • As a child she experienced multiple streptococcal tonsillitis, but otherwise has not been found to be especially prone to infections. • She has recently been diagnosed a slightly elevated blood pressure which is under control as treated with an angiotensin II antagonist (Micardis®).

4. During the past two years the patient has experienced some epileptic petit mal seizures and one grand mal in September 2003. • She was examined at the Neurological Clinic but the cause of her seizures could not be determined and she was not receiving prophylactic medication. • Otherwise, she was generally healthy.

5. In June 2003 she experienced another radiograph-verified maxillary sinusitis. • The bacterial findings of the maxillary lavage were suggestive of a dental origin and the patient was referred to her dentist for dental infection-focus examination.

6. In the orthropantomogram (OPG) a small (2-3mm) radio opaque finding was seen in the right maxillary sinus adjacent to a root treated first molar with a apical root filling excess. Otherwise the teeth and periodontium were in very good condition. • The patient was referred to Helsinki University Central Hospital Maxillofacial Clinic for removal of the foreign material.

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8. At the Surgical Hospital CT scans were taken and the size of the opaque dense material was estimated to be 6mm. • In the radiology report the possibility of a fungal infection was brought up. 9/03

9. A dense mass in the maxillary sinus was removed. The gross pathology of the soft material was suggestive of a fungal mycetoma.

10. Due to concern regarding infiltration of the causative organisms outside the maxillary sinus aliposomal formulation of amphotericin B(AmBisome®,1 mg/kg) and Cefuroxim (1.5 g)were administered during and immediately after the operation.

11. Per oral solution of itraconazole (Sporanox®) was prescribed (200mg b.d) post operatively combined with Cefuroxim (Zinnat®) (250mg b.d). • To ensure ventilation of the sinus these were combined with antihistamine containing epinephrine (Duact®) and vasoconstictive nasal spray (Otrivin®).

12. Direct microscopy revealed densely packed fungal filaments. • Aspergillus galactomannan antigen testing of an extract of the fungal mass was positive. Culture revealed heavy bacterial contamination but was negative for filamentous fungi.

13. The bacterial culture finding reported 2 days after the operation was a heavy growth of Enterobacter cloacae resistant to ampicillin, cefuroxim and the combination of amoxicillin clavuronic acid. • It was sensitive to siprofloxacin and the antibiotic was changed to Ciproxin® (750mg b.d).

14. Invasive fungal rhinosinusitis is a true invasive infection where fungal hyphae invade the sinus mucosa, blood vessels, or bone. • In non-invasive fungal rhinosinusitis, the fungi play a pathogenic role in the rhinosinusitis disorder but reside within the sinus cavity without penetration of the mucosal barrier.

15. Non-invasive fungal rhinosinusitis can present as a fungal ball (mycetoma), a mass of numerous hyphae compressed into a mat or ball. • Initially a non-invasive fungal ball sometimes forms an expansive mass that causes bone necrosis of the thin walls of the sinus. If the ethnoid bone becomes traversed, mucin may enter the orbit and cause proptosis. • Aspergillus species produce fungal spores that may occasionally become disseminated into blood stream.

16. The pathological diagnosis of the removed mass and neighbouring sinus mucosa confirmed a filamentous fungus infection which was found to be restricted to the sinus cavity. • The mucosa was reported to have a chronic inflammation without fungal infiltration or allergy cells.

17. After receiving all data a revision of the sinus combined with a sinus fenestration (FESS) operation was scheduled in two weeks of time.

18. Before the second operation MRI of the head area was performed. No sign of fungal infiltration outside the maxillary sinuses e.g. eyes or brain could be detected.

19. More mucosa was cleared and the sinus was rinsed with conventional amphotericin B (Fungizone®). Amphotericin B was also administrated i.v. at the induction of the antesthesia combined with meronem (Meronem®).

20. The ventilation of the sinus was ensured by performing a sinus fenestration (FESS) operation.

21. Per oral solution of itraconazole (Sporanox®) was again prescribed post operatively (200mg b.d. for the first two weeks and then 100mg b.d. for the following two weeks. • It was combined with Doxicyclin (Doximycin®) (150mg per day) for three weeks • and Prednisolon 50mg x1 for 2 weeks and 25mg x1 for the following week. • These were further combined with epinephrine containing antihistamine (Duact®) and vasoconstictive nasal spray (Otrivin®).

22. leuc: CRP: crea: examin.: 7,9 <5 60 preop.1: 9,7* 71 postop.1: 11 preop.2: 7,8 postop.2: 12,5* 10 189* 8,7 71 The single infusion of the conventional amphotericin B during the second operation caused a significant elevation of serum creatinine (189 mmol/l). This returned to normal during the 2 week follow up.

23. Four weeks post operatively • The patient is clinically asymptomatic • No nasal congestion • No further epileptic seizures • The serum liver and kidney function parameters returned to normal • Serum levels of Aspergillus antigen became negative.

24. Discussion • In immunocompetent patients fungal spores are rapidly eliminated by the immune system. The induced inflammatory reaction may, however, result in instability to the surrounding tissues. • The patient described here had a history of epileptic seizures which could be explained by occasional fungaemia caused by spore release. • Due to the history of the patient it was decided to prevent the possible dissemination of the filamentous fungus during the surgical removal of the fungal mass by giving optimium antifungal cover.

25. In conclusion, the case presented here demonstrates the efficacy of appropriate antifungal therapy following surgical removal of a paranasal sinus fungal ball to minimise the risk of invasion and dissemination, and the combined use of histopathology and the Aspergillus galactomannan antigen test in diagnosing the aetiological agent.