Mucormycosis differential diagnosis

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

Overview

Mucormycosis can be difficult to diagnose and a high degree of clinical suspicion is required. Mucormycosis should be differentiated from diseases like invasive aspergillosis, orbital cellulitis, extra nodal T cell lymphoma and cutaneous anthrax. Patient history is an important part of the diagnosis and aids in ruling out other differentials. Other features which help differentiate conditions with similar presentations are radiological and histopathological appearance.

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 and cutaneous anthrax. Histopathologically mucormycosis may resemble pancreatic and 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	Agents found in: decaying vegetation Soil Acquired by: Inhalation Ingestion contamination of wounds with sporangiospores from the environment. Air-conditioning systems, particularly during construction Use of contaminated adhesive bandages or tape in surgical wound dressings Susceptible individuals: Immunocompromised patients Diabetics Patients receiving deferoxamine therapy Injection drug users Patients with no apparent immune impairment Invasive mucormycosis is clinically similar to aspergillosis and is marked by angioinvasion and tissue infarction	+ (Mucosal thickening on the paranasal sinuses is more common in rhinocerebral mucormycosis(ROCM) than bacterial orbital cellulitis(BOC)	+ (Specially if there is invasion of the cavernous sinus)	+ (Limited eye movement is more common in patients with rhino-cerebral mucormycosis (ROCM) than in those with bacterial orbital cellulitis)	CT scan: Reverse halo sign (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	Nonpigmented, wide (5- to 20-μm), thin-walled, ribbon-like hyphae with few septations (pauciseptate) and right-angle branching In lesions exposed to air, thick-walled spherical structures can form at the ends of the hyphae Fungal elements invading the blood vessel wall or inside their lumen	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
Invasive aspergillosis	Aspergillosis is a heterogenous group of infectious diseases caused by Aspergillus(commonly A. fumigatus) Classified into: Allergic bronchopulmonary aspergillosis (ABPA)  Aspergilloma  Chronic pulmonary aspergillosis   Invasive aspergillosis  Cutaneous aspergillosis  Trasmitted by: Inhalation of airborne conidia (usually during dust exposure during building renovation or construction) Contaminated biomedical devices, but not from one individual to another. Susceptible individuals: Immunocompromised status (e.g. organ or stem cell transplant recipient) History of prior lung disease	+	+	+ (There may be painful ophthalmoplegia if there is invasion of the cavernous sinus)	CT scan: Reverse halo sign Allergic bronchopulmonary 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 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	+	+	+ (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)	CT scan: Cross-sectional imaging demonstrates diffuse soft-tissue thickening anterior to the orbital septum and obliteration of the adjacent fat planes in pre-septal cellulitis	Biopsy may show a neutrophilic infiltration of the tissues due to acute inflammation
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	+	+ (Primary CNS NK/Tcell lymphoma of the nasal type)	+/-	CT scan: The CT and MR imaging appearances are nonspecific and do not allow reliable distinction of this disease from other nasal cavity tumors such as squamous cell carcinoma or from minor salivary gland tumor.	“Angiocentric” invasion of lymphoid cells is Angiocentricity is seen in about half of all cases but is also found in other lymphoma subtypes. Invasion of vascular walls by lymphoid cells causes occlusion of the lumen. The vascular occlusion is usually associated with prominent ischemic necrosis of both tumor cells and normal tissue.
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	+			Imaging modalities are not indicated in cutaneous anthrax	Epithelium is edematous with loss of continuity. Sub-epidermal, chronic and acute infiltrates involving adipose tissue and capillaries, with areas of necrosis. Gram stain shows large solid and beaded gram-positive rods, particularly beneath the epithelium. The bacilli are not visible on the hematoxylin and eosin stain.