Mucormycosis differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]

Differential diagnosis

Mucormycosis must be differentiated from other conditions with similar presentation. Invasive fungal disease should be considered in any immunocompromised patient presenting with a new cranial neuropathy or ocular motility abnormality for example:

• Invasive aspergillosis

Other differential diagnoses which may involve progressive facial swelling, ulceration and destruction and resemble mucormycosis include:

• Orbital cellulitis
• Extra nodal T cell lymphoma
• Cutaneous Anthrax

Histopathologically, mucormycosis may resemble:

• Pancreatic panniculitis
• Gouty panniculitis

Disease	General features	Signs and Symptoms			Radiological abnormalities	Histopathological abnormalities	Other differentiating characters
		Facial/Sinus swelling and ulceration	Cranial neuropathy	Disturbance in ocular motility
Mucormycosis	The agents of mucormycosis are ubiquitous in soil and decaying vegetation, and infection may be acquired by inhalation, ingestion, or contamination of wounds with sporangiospores from the environment. As with Aspergillus species, nosocomial spread of mucormycosis may occur by way of air-conditioning systems, particularly during construction Focal outbreaks of mucormycosis have also been associated with the use of contaminated adhesive bandages or tape in surgical wound dressings, resulting in primary cutaneous mucormycosis In addition to causing infection in immunocompromised patients, the Mucorales(agents causing mucormycosis) may also cause lethal infections in patients with diabetes, patients receiving deferoxamine therapy, injection drug users, and patients with no apparent immune impairment Invasive mucormycosis is clinically similar to aspergillosis and is marked by angioinvasion and tissue infarction	Present (Mucosal thickening on the paranasal sinuses is more common in Rhino-cerebral mucormycosis rhinocerebral mucormycosis(ROCM) than bacterial orbital cellulitis(BOC)	Present (Specially if there is invasion of the cavernous sinus)	Present (Limited eye movement is more common in patients with Rhino-cerebral mucormycosis (ROCM) than in those with bacterial orbital cellulitis)	The reverse halo sign on CT scan (characterized by central ground-glass opacity (GGO) which is surrounded by a partial or complete rim of consolidation) is more common in patients with pulmonary mucormycosis than in those with invasive pulmonary aspergillosis		Mucormycosis is generally more commonly observed in immunocompromised patients Patients with orbital fungal infections are more likely to be infected with mucormycosis compared with Aspergillus the prognosis of pulmonary mucormycosis has not improved significantly over the last ten years, mainly because of challenges in early diagnosis and the limited activity of current antifungal agents against Mucorales
Invasive aspergillosis	Aspergillosis is a heterogenous group of infectious diseases caused by Aspergillus (commonly A. fumigatus), a ubiquitous fungus. Apergillosis It may be classified according to the clinical syndrome it causes into allergic bronchopulmonary aspergillosis, allergic Aspergillus sinusitis, aspergilloma, chronic pulmonary aspergillosis, invasive aspergillosis, or cutaneous aspergillosis.  Aspergillus is primarily transmitted to the human host by either inhalation of airborne conidia (usually during dust exposure during building renovation or construction) or by contaminated biomedical devices, but not from one individual to another. Immunocompromised status (e.g. organ or stem cell transplant recipient) and history of prior lung disease are the most important risk factors in the development of aspergillosis.	Present	Present	Present (There may be painful ophthalmoplegia if there is invasion of the cavernous sinus)	CT scan of Allergic bronchpulmonary aspergillosis (ABPA) are not specific, the demonstration of bronchial dilatation, wall thickening, and centrilobular nodules in an asthmatic patient should suggest the diagnosis	Microscopic observation under ultraviolet light shows that the hyphae of aspergillus have characteristic dichotomous branching, parallel walls, and numerous septa. These septa structure is clearly different from those of the mucor Airway-invasive features, such as clusters of centrilobular nodules, peribronchial consolidations, and bronchial wall thickening, are more common in patients with invasive pulmonary aspergillosis
Orbital cellulitis	Orbital cellulitis is an inflammation of the soft tissues of the eye socket behind the orbital septum, a thin tissue which divides the eyelid from the eye socket Infection isolated anterior to the orbital septum is considered to be preseptal cellulitis Orbital cellulitis most commonly refers to an acute spread of infection into the eye socket from either the adjacent sinuses, skin or from spread through the blood The most common pathogens in orbital cellulitis are streptococcus and staphylococcus	Present	Present	Present (The ocular symptoms of bacterial orbital cellulitis (BOC) , such as facial edema, pain, and blepharoptosis, are similar to those of rhino-cerebral mucormycosis (ROCM) soon after infection onset, therefore it maybe difficult to distinguish the two during the initial phase of infection. Eye lid swelling is more common in BOC than ROCM)
Extra nodal T cell lymphoma	These tumors are more clearly classified as nasal-type extranodal T-cell/natural killer (T/NK) cell lymphoma and natural killer cell leukemia Epstein bar virus (EBV) has been found to be one of the major causes. They are characterized immunophenotypically by the expression of CD2, CD3ϵ (but not CD3 and the T-cell receptor), and CD56 The lesion produced are destructive and involve the nasal cavity, oropharynx, upper palate, and larynx Immunophenotyping shows these lesions to be lymphoid in nature	Present	Present (Primary CNS NK/Tcell lymphoma of the nasal type)	May be present
Cutaneous Anthrax	Cutaneous anthrax is extremely rare in developed countries Usually patient history points towards the diagnosis of cutaneous anthrax Patient develops a painless ulcer with vesicles, edema, and has a history of exposure to animals or animal products; whereas patients with cutaneous mucormycosis are mainly debilitated (diabetics, hematological malignancies, organ transplant recepients) and present as a black necrotic eschar	Present	Not present	Not present