emDOCs Podcast – Episode 38: Mucormycosis

Today on the emDOCs cast with Brit Long, MD (@long_brit), we cover mucormycosis.

Mucormycosis

Introduction:

Mucormycosis can present in a variety of ways, primarily in immunocompromised patients. Rhino-orbital-cerebral and pulmonary infections are most common.  These fungi are found naturally on decaying vegetation and soil. They grow rapidly and release large numbers of airborne spores. All humans have frequent exposure to the fungal species in the environment, but a normal immune system is quickly able to destroy the fungi. Genera include Rhizopus and Mucor most commonly. For those of you who love the study of fungi, the hyphae are broad with irregular branching and rare septations.

These fungi contain ketone reductase, with allows the organisms to grow rapidly in environments with high sugar and low pH. The fungi also contain a siderophore that increases iron uptake, stimulating growth. Once an individual inhales the spores, cilia transport them to the pharynx, lungs, and gastrointestinal tract. Most individuals clear the organisms. Susceptible patients suffer infections that begin in the nasal turbinates and alveoli. The organism can then spread. The fungi invade blood vessels, allowing rapid spread but can cause infarction of infected tissues.

Epidemiology:

By far the most common risk factor is diabetes, especially with ketoacidosis. Chronic steroid use, hematologic malignancies, stem cell/solid organ transplant patients, deferoxamine treatment (other iron chelating agents do not increase risk), iron overload, injection drug use, and trauma all predispose to infection.  The fungi grow well in acidotic, hyperglycemic, and iron-containing environments.

Presentation:

Mucormycosis results from vascular invasion by hyphae, causing infarction and necrosis of tissues. For the rhino-orbital-cerebral form, which is most common, inhalation of spores allows bacteria to invade. Sinusitis (26%), fever (44%), congestion, nasal discharge, and headache (25%) are all initial symptoms. Unfortunately, most cases will progress rapidly. The classic case is palatal necrosis with eschar formation (38% of cases), turbinate destruction, nasal swelling (34%), and erythema of the face. If the orbits are involved, edema, proptosis, and decreased vision (30%) or blindness can result.   If intracranial spread occurs, mental status changes are prevalent. Cranial nerve palsies are also common. The most common underlying comorbidity is diabetes in this form (up to 70% of this form is correlated with diabetics).

The pulmonary form is rapidly progressive and occurs after spores reach alveoli and bronchioles. Pneumonia and infarction set in, often resulting in hemoptysis. From the lungs the organisms can spread to the mediastinum and heart. In this form, iron supplementation, glucocorticoid treatment, and malignancies are the most common underlying conditions (diabetes is less common).

The gastrointestinal tract can also be involved, though much rarer, with the stomach most commonly affected, followed by the colon. Hematemesis and pain are presenting symptoms. Perforation, peritonitis, and bleeding can result from ulcer formation.

Cutaneous mucormycosis usually is due to wound inoculation. The lesion starts as a small bite-like lesion that develops into cellulitis.

Renal, isolated CNS (IV drug use, HIV patients), and disseminated forms are also present.

Diagnosis: 

One important key is that if a patient is high risk and has symptoms/signs of this disease (diabetic with sinusitis, fever, infarcted palatal/nasal tissue), then treat first!  The ultimate diagnosis requires culture confirmation with slide preparation to identify the organism, which shows nonseptate hyphae. In patients with rhino-orbital-cerebral infection, endoscopic imaging is needed. CT head/orbits is also useful. For pulmonary infection, chest Xray and/or CT often demonstrates focal consolidation, mass, pleural effusion, or nodules.  Both the pulmonary and GI forms require tissue sampling.  PCR is currently being investigated for use as definitive diagnosis. Ultimately, it comes down to your exam and history. If the patient is immunocompromised/has risk factors and your exam findings support the diagnosis, begin treatment.

Treatment:

Like in severe sepsis, treatment revolves around source control with surgical debridement and antifungal therapy. Predisposing factors such as acidosis, hyperglycemia, deferoxamine, and immunosuppression should be addressed. For example, patients in the setting of DKA with mucormycosis do show improved outcomes with better hydration and blood glucose control.

The antifungal most widely used is IV amphotericin B (lipid) at 5mg/kg daily. Posaconazole is used as step-down therapy or as salvage therapy. One study demonstrated that patients with delayed antifungal treatment (greater than six days) had double the mortality! Debridement is also required as soon as possible to remove the source of infection.

Prognosis:

Outcomes vary based on time to treatment. Mortality rate for the pulmonary form is up to 87%, with the rhino-orbital-cerebral form possessing a mortality of 25-62%.

Summary:

Mucormycosis has a variety of forms: rhino-orbital-cerebral, pulmonary, and GI. Immunosuppressed patients, particularly diabetics and patients with hematologic malignancies, make up the majority of patients.  The organisms are found all over, and normal hosts are able to fight off infection. If infection occurs, fungi invade tissue, causing infarction and necrosis with vascular invasion. Diagnosis requires organism identification by histopathology, but if suspected, begin treatment with lipid formulation of amphotericin B. Surgical debridement is the second necessary arm of treatment.