ABSTRACT

In this case report, we present the clinical findings and therapeutic outcomes of four rhino-orbital mucormycosis patients. The four patients (1 female, 3 male; age range, 55-77 years) all had diabetes mellitus and two also had chronic renal failure. All patients exhibited proptosis, sinusitis, and dark-colored lesions on the nasopharynx and/or hard palate; three patients had ipsilateral peripheral facial paralysis. Visual acuity was no light perception in the two patients with severe orbital involvement and 0.8 in two patients with limited orbital involvement. Histopathological examination of the hard palate, nasopharynx or sinus biopsy revealed typical Mucor hyphae. Systemic liposomal amphotericin B was initiated in all patients. The patients with limited ocular involvement received amphotericin B both intravenously and by local irrigation; both patients had complete recovery. The other two patients underwent orbital exenteration; one patient died after declining systemic treatment postoperatively. Rapid diagnosis and treatment are important for the survival of rhino-orbital mucormycosis patients. With orbital involvement, surgical debridement and systemic and local treatment with antifungal agents may help avoid mutilating surgery like exenteration.

Introduction

Mucormycosis is a rapidly progressing fungal infection caused by filamentous fungi in the Mucoraceae family and is frequently seen in diabetic and immunocompromised patients. Mucormycosis is categorized as rhinocerebral, pulmonary, cutaneous, gastrointestinal or disseminated, depending on organ involvement; the most common form is rhinocerebral (39%).¹ This form may be divided into subtypes based on which tissues are affected: rhinonasal, rhinoorbital or rhinoorbitocerebral.

Rhinoorbital infection begins when fungal spores are inhaled and invade the nasal mucosa, and sinusitis develops as the fungus spreads to the paranasal sinuses. Orbital involvement occurs when the infection invades the orbital wall from the paranasal sinuses. Symptoms may include pain, chemosis, vision loss, ophthalmoplegia and proptosis. Ophthalmoplegia arises from infection of the muscles and orbital space or when the third, fourth and sixth cranial nerves are affected. Peripheral seventh cranial nerve paresis or paralysis and hypoesthesia of the face are often observed.^1,2

This study presents the clinical findings and treatment outcomes of four patients with orbital mucormycosis following nasal involvement.

Discussion

Mucormycosis is a condition with a fulminant course and a high mortality risk. The most common predisposing factor is DM (60-80%), though hematologic diseases, neoplasias, chronic renal failure, antineoplastic agents, immunosuppressive therapy, corticosteroid use, protein-calorie malnutrition, organ and bone marrow transplantation, and other conditions resulting in immunosuppression such as AIDS also factor in its etiology.³ In a study by Yohai et al.² including 145 cases, the most common predisposing factor was DM (60%). Similarly, Ferry et al.⁴ found DM to be the greatest predisposing factor in their study population, with 83%. Gumral et al.⁵ reviewed reports in the Turkish literature between 2000 and 2010 and found that among 79 cases of mucormycosis, the predisposing factor was diabetes in 32 cases and hematologic pathologies in 32 other cases. Another risk factor for mucormycosis infection is renal failure. In these patients, acidosis as well as chronic desferoxamine use contributes to the progression of zygomycosis.^6,7 In our population, all patients had DM. Two patients also had chronic renal failure; the course of mucormycosis in these two patients was more severe and required exenteration due to extensive orbital invasion.

With orbital involvement, clinical symptoms and findings include periorbital edema, pain, proptosis, ophthalmoplegia and decreased vision. Yohai et al.² reported periorbital edema in 43% of their patients, periorbital pain in 11%, proptosis in 64%, ophthalmoplegia in 67% and vision impairment in 65%. In the same study, 22% of patients had facial paralysis and 20% had facial hypoesthesia. Among the 4 patients in our study, 2 had severe vision loss, proptosis and frozen orbit, and restricted eye movement was observed in another patient. Facial nerve involvement and facial hypoesthesia were found in 3 patients.

The early diagnosis and treatment of mucormycosis is very important in terms of prognosis. Patients who begin treatment within 6 days have a survival rate of 76-81%, while a treatment delay of more than 12 days reduces this rate to 36-42%.^8,9 In our study, the time between symptom onset and hospital admission varied between 9 days and 1 month. Compared with the literature, these patients were late in seeking medical help and this delayed the initiation of treatment.

Amphotericin B has become the gold standard in the systemic treatment of mucormycosis. Before the use of amphotericin B, the survival rate of mucormycosis patients was just 6%, whereas after the introduction of amphotericin B this rate dramatically increased to the 60% range.^10,11,12 Liposomal amphotericin B is the first choice of treatment, as it crosses the blood-brain barrier more effectively.^11,13 Another drug that can be used in systemic treatment is posaconazole. In a large European study, fluconazole was ineffective, itraconazole was found to be partially effective, and posaconazole was effective.^{14,15,16,17,18} For our patients, oral posaconazole was chosen as maintenance antifungal therapy after the completion of amphotericin B treatment.

A critical stage in the treatment of mucormycosis is debridement of necrotic tissue. In our study, all cases underwent surgical debridement of necrotic areas; endoscopic maxillectomy and hard palate resection were added when deemed necessary. Two patients with extensive orbital mucormycosis invasion and total vision loss underwent exenteration. Exenteration was deemed necessary to reduce the fungal load and prevent cerebral involvement and the fatal progression of the disease. Despite extension to the orbit in the other two patients, close monitoring, medical therapy and local amphotericin B irrigation were preferred due to good visual potential and positive response to treatment.

As mucormycosis forms vascular obstruction, it may be difficult for drugs to reach the affected tissues. For this reason, local irrigation of infected areas with amphotericin B is used in conjunction with surgery and systemic therapy. Seiff et al.¹⁹ reported that among 7 cases of mucormycosis treated with local amphotericin B irrigation in addition to surgery and systemic therapy, the fungal progression stopped or regressed in 6 patients, and only 1 patient required exenteration. In a multi-center study, Kaya et al.²⁰ used local amphotericin B irrigation together with different standard treatments in 4 patients, but all of those patients died. Songu et al.²¹ reported that in 3 cases that underwent debridement and local amphotericin B irrigation in addition to systemic treatment, spread of the fungal infection was successfully halted and none of the cases required exenteration. Konuk et al.²² reported 2 fatal cases that did not receive amphotericin B irrigation, whereas in a report of 2 non-fatal cases by Özay et al.,²³ one patient received local irrigation and the other did not. In our study, 3 out of 4 patients underwent local amphotericin B irrigation. Local irrigation was effective in facilitating socket healing in one patient following exenteration, while in the other two patients, irrigation was used in the maxillary sinus pathways and contributed to the healing of their orbital infection.

Orbital involvement in a high-mortality infection like mucormycosis may necessitate the decision to perform exenteration. This difficult decision is made when the extent of the disease and the risk of mortality outweigh the desire to keep the patient’s globe in place. Local antifungal therapy in the form of irrigation can be used in addition to systemic treatment and debridement to save the globe. Local use of antifungal agents facilitates their delivery to affected tissues. Patients’ general condition, course of the disease and response to treatment should be closely monitored, and exenteration should be performed if there is life-threatening progression of the disease.

Concept: Şeyda Karadeniz Uğurlu, Sedat Selim, Aylin Kopar, Murat Songu Design: Şeyda Karadeniz Uğurlu, Sedat Selim, Aylin Kopar, Murat Songu Data Collection or Processing: Sedat Selim Analysis or Interpretation: Şeyda Karadeniz Uğurlu Literature Search: Sedat Selim Writing: Şeyda Karadeniz Uğurlu, Sedat Selim Peer-review: Externally peer-reviewed Conflict of Interest: No conflict of interest was declared by the authors Financial Disclosure: The authors declared that this study received no financial support