Discussion

Mucormycosis refers to any fungal infection by members of the order Mucorales, which is in the class Zygomycetes. Most pathogenic species are members of the family Mucoraceae. In immunocompetent hosts, the killing and removal of mucorales species is mediated by both neutrophils and macrophages.Reference Shoham and Levitz² Therefore, deficiencies in circulating neutrophils (e.g. due to neutropenia) and impaired phagocyte function (e.g. in diabetes mellitus during steroid therapy) are risk factors for this infection.Reference Rogers³ Most diseased patients are immunologically or metabolically compromised, with diabetic patients constituting the largest group with the rhinocerebral form of the disease.Reference Ruoppi, Dietz, Nikanne, Seppa, Markkanen and Nuutinen⁴ In some immunocompetent patients, the disease is associated with local predisposing factors such as chronic rhinosinusitis or penetrating trauma.Reference Del Valle Zapico, Rubio Suarez, Mellado Encinas, Morales Angulo and Cabrera Pozuelo^5, Reference Prabhu and Patel⁶

Artis et al. reported that serum from diabetic ketoacidotic patients has the ability to stimulate fungal proliferation only while the patients are acidotic; the simple addition of glucose, up to 1000 mg/dl in nutrient broth, did not stimulate the growth of Rhizopus oryzae.Reference Artis, Fountain, Delchere and Jones⁷ Our fourth patient, who had well-controlled diabetes mellitus, showed no acidosis and had a chronic, non-invasive case of mucormycosis, in the form of a fungal ball in the operation field. Some authors have reported the successful treatment of paranasal mucormycosis in controlled diabetics using only the Caldwell–Luc procedure.Reference Pastore^8, Reference Henderson, Robbins, Weitzner, Dyer and Jahrsdoerfer⁹ Thus, hyperglycaemia per se might not play a major role in the pathogenesis of invasive mucormycosis.

Invasive mucormycosis in the nose and paranasal sinuses presents initially with the signs and symptoms of acute bacterial rhinosinusitis; these usually progress very rapidly in the invasive form of the disease.Reference Ruoppi, Dietz, Nikanne, Seppa, Markkanen and Nuutinen⁴ Patients with rhino-orbital-cerebral mucormycosis typically show other signs and symptoms within 72 hours of the first symptom. The leading symptom is fever (44 per cent), followed by nasal ulceration or black, necrotic tissue in the nose (38 per cent), periorbital or facial oedema (34 per cent), visual changes (30 per cent), headache (25 per cent), and facial pain (22 per cent). Ultimately, 80 per cent of patients develop a necrotic lesion of either the nasal or oral mucosa.Reference Yohia, Bullock, Aziz and Markert¹⁰ However, the presenting symptoms and physical findings are often subtle in indolent paranasal mucormycosis in immunocompetent patients.Reference Ketenci, Unlu, Senturk and Tuncer^11, Reference Ferguson¹² In our series, the symptoms and signs were similar to those of chronic rhinosinusitis or fungal sinusitis, and the mean duration of the clinical symptoms was four years. It is worth mentioning that in invasive mucormycosis, spread into the orbit or brain takes place within a few days of onset of the disease.

The treatment of invasive mucormycosis requires correction of the cause of immunocompromise, aggressive surgical debridement and systemic antifungal drugs.Reference Avet, Kline and Sillers¹³ However, amphotericin B treatment is limited by toxicity, which may be acute (with fever, rigors and anaphylaxis) or chronic (predominantly renal, with rising creatinine levels).

There is uncertainty regarding the most appropriate therapy for apparently immunocompetent patients with indolent sinonasal mucormycosis. Most reports suggest that a cure can be achieved with aggressive surgical debridement in combination with long-term antifungal drug therapy; both treatments are used because of concern over the risk of progression to fulminant disease.

There are only three previously reported cases which appear to have been cured by endoscopic sinus surgery without long-term antifungal drugs post-operatively; however, these outcomes seem to have been achieved without a reasonable basis.Reference Ketenci, Unlu, Senturk and Tuncer^11, Reference Uri, Cohen-Kerem, Elmalah, Doweck and Greenberg¹⁴ Because the clinical, radiological and operative findings did not suggest invasive fungal sinusitis in our patients, all were treated with endoscopic sinus surgery alone, with no long-term systemic or local antifungal drugs, despite the post-operative histopathological diagnosis of mucormycosis (obtained after discharge).

The underlying disease and presence of invasion are important determinants of survival; the overall mortality rate is approximately 62 per cent in rhinocerebral mucormycosis and 16 per cent in sinus infections without cerebral involvement; by way of comparison, the survival rate is 75 per cent in patients with no systemic disease, 60 per cent in diabetics and 20 per cent in those with other disorders.Reference Blitzer, Lawson, Meyeres and Biller¹⁵ However, our literature review did not identify any investigation of the relationship between prognosis, host immunity and disease localisation. In our series, the excellent prognosis indicated that host immunity may be as important as disease extent in determining the treatment and outcome of indolent paranasal mucormycosis.