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Editor,—Entomophthoramycosis is a rare granulomatous disease caused by the fungusConidiobolus (classZygomycetes), and usually manifests as chronic, indolent, and localised infection of the rhinofacial region.1 While immunodeficiency may predispose to dissemination of infection,2 the condition usually presents in immunocompetent individuals. Standard treatment includes single or combination antifungal therapy and surgical debridement.1
We report orbital entomophthoramycosis due toConidiobolus coronatus in an infant with congenital nasolacrimal duct obstruction, which resolved following excision of granulomatous tissue, administration of antifungal and immunomodulating drugs, and use of hyperbaric oxygen.
A 5 month old infant girl presented with a swelling near the left eye. From the age of 2 months, she had received various topical and oral antibiotics for suspected bacterial dacryocystitis.
Examination revealed a thriving infant weighing 7 kg, with redness and swelling over the left lacrimal sac and candidiasis of the nappy area and mouth. While the candidiasis responded to oral and topical nystatin, the orbital swelling continued to increase despite broad spectrum, topical and systemic antibiotic therapy. Computed tomography (CT) of the orbit demonstrated a solid mass in the region of the left lacrimal sac (Fig 1). Microscopic examination of a biopsy revealed fungal hyphae, and subsequent culture on Sabouraud's agar led to identification of the fungus Conidiobolus coronatus(Fig 2). There was no evidence of underlying immunodeficiency.
Intravenous fluconazole (6 mg/kg/day) and co-amoxiclav (100 mg/kg/day) were commenced, but due to lack of sustained improvement, they were replaced with intravenous amphotericin B (1 mg/kg/day) and cloxacillin (200 mg/kg/day). Despite this change, the child's condition deteriorated with extension of the granuloma into surrounding tissue (Fig 3). One month after admission, all visible tumour, including adhesions to overlying skin, was excised. A drain was left in situ to facilitate daily amphotericin irrigation.3 Within a week, however, new indurated areas appeared in the nasal part of the upper eyelid, and proptosis with downward and outward displacement of the eyeball was observed. Biopsy showed persistence of fungal elements and CT of the orbit demonstrated extension of the tumour towards the orbital apex. Chest x ray revealed a right upper lobe opacity, which was suspected to be metastatic fungal infection. Antibiotic was discontinued at this stage and oral itraconazole (loading dose 28 mg/kg/day; maintenance 10 mg/kg/day) was administered for 10 days, but without benefit.
Therapy with high dose intravenous fluconazole (12 mg/kg/day), liposomal amphotericin B (AmBisome) (7 mg/kg/day), and oral potassium iodide (20 mg/kg/day) was then initiated. Subcutaneous granulocyte-colony stimulating factor (5 μg/kg/day) was added to the treatment regimen. Hyperbaric oxygen therapy was commenced 10 days later and consisted of 90 minute sessions of exposure to 100% oxygen at 2.8 atm. There were two daily sessions in the first 2 weeks, and a total of 40 sessions were administered over 6 weeks. In the hyperbaric chamber, the child was sedated intravenously with a 4–8 ml solution of ketamine and midazolam,4 and a Bain circuit was used to administer the pure oxygen. Intense redness over affected areas was observed during treatment sessions.
The earliest signs of recovery, with reduction in proptosis and softening of the tissue mass appeared 5 days after starting combination antifungal therapy, and this trend was maintained during treatment with hyperbaric oxygen. CT of the orbit performed at the end of 6 weeks confirmed resolution of the fungal mass and chestx ray showed resolution of the pulmonary lesion. Intravenous antifungal therapy was continued for another 15 weeks, followed by oral fluconazole and potassium iodide for a further 10 weeks.
Three years later, there has been no evidence of recurrence of the fungal granuloma, the only sequela of the orbital infection being a small angle exotropia of the left eye and epiphora (Fig4).
Infection with Conidiobolus coronatuscharacteristically begins in the inferior nasal turbinates and extends to the perinasal tissues, producing nodular, subcutaneous masses and occasionally, severe disfigurement.1 Rarely, pulmonary and systemic infection may be encountered.2 Ours is the first report of orbital infection with C coronatus, and our patient appears to be the youngest case of entomophthoramycosis on record.56
C coronatus, is ubiquitous in nature and is commonly present as a saprophyte in soil and on decaying vegetation. The majority of reports of human infection come from the tropical rain forest areas of Africa7; however, this is the first report from Oman which experiences an arid climate. The pathogenesis of infection is unclear, but rarity of the disease indicates low intrinsic pathogenicity. The portal of entry of spores is believed to be by inhalation or direct inoculation. The child's home, with open roofed hall, was located close to a small area containing humid and rotting vegetation. We suspect that prolonged antibiotic treatment disturbed the normal immunity in our patient, allowing fungal spores which had been inhaled or had entered her conjunctiva, to germinate and become established.
Diagnosis is made by demonstrating distinctive non-septate hyphae with surrounding eosinophilic sleeve (Splendore-Hoeppli phenomenon) in tissue sections. Vascular invasion and thrombosis as well as tissue infarction are notably absent. Culture of the fungus allows identification of the species; however, as hyphal elements of zygomycetes are prone to physical damage, specimens must be directly inoculated onto culture media avoiding excessive grinding.7 Despite being recognised as a common laboratory contaminant, C coronatus is infrequently isolated in the clinical laboratory,7 and in human infections, reliable culture identification of the fungus is made in less that 50% of the cases.8
Although spontaneous resolution is known, the fungal granuloma is more likely to persist and extend without effective treatment.59 Surgery, which includes removal of infected tissue and reconstructive procedures, is seldom curative. A wide variety of antifungal drugs, singly or in combination, have been reported to be effective, including ketoconazole, itraconazole, fluconazole, sulphamethoxazole, potassium iodide, and amphotericin B.1569-12 Susceptibility testing for fungi responsible for entomophthoramycosis is not standardised and is an unreliable guide to choice of therapeutic agent.1 Several authors have reported a beneficial effect of hyperbaric oxygen in rhinocerebral mucormycosis,1314 and there has been one report of successful use in the therapy ofConidiobolus infection.15Hyperbaric oxygen is believed to accelerate the healing process by enhancing vasodilatation, thereby improving perfusion of compromised infected tissue and augmenting immune responses. Our patient was successfully managed by employing more than one form of treatment. Progressive development of the child's own immune system also, no doubt, contributed to resolution. It can only be conjectured whether one or more of these factors, acting independently or synergistically, was instrumental in her final recovery.
In conclusion, a healthy child with congenital lacrimal duct stenosis treated with prolonged courses of broad spectrum antibiotics, developed extensive mucocutaneous candidiasis and invasive orbital entomophthoramycosis by the fungus C coronatus. Addition of hyperbaric oxygen to standard therapy (combination antifungal therapy and surgery) aided recovery. Although rare, the possibility of fungal superinfection should dissuade clinicians from indiscriminate use of antibiotics in the management of congenital nasolacrimal duct obstruction.
We acknowledge the Public Health Laboratory (Mycology Reference Laboratory), Bristol, UK, for confirming the identity of the fungal isolate and Professor Des Gorman, Department of Occupational Medicine, Auckland University, New Zealand for advice on hyperbaric oxygen therapy.