Mucor racemosus
Summary
Mucor is a saprotrophic, ubiquitous microorganism found in the dung, plants or animal dead tissue/material, and employed as a food additive in some traditional cultures. Mucor genus has worldwide distribution. Mucor racemosus (M. racemosus) is an outdoor as well as an indoor mold. Its presence has been reported in homes, schools, hospitals, and water damaged buildings. M. racemosus thrives in environments with limited ventilation or sheltered from wind, high humidity, and poor light. Mucor species is characterized by columellate multi-spored sporangia. Inhalation of fungal spores is the primary route of exposure to the allergens, while ingestion of Mucor contaminated food may be the secondary route of exposure. M. racemosus induces mostly respiratory allergic reactions, such as asthma, allergic rhinitis, and sinusitis. Moreover, oral allergy symptoms and occasional anaphylaxis are reported. Occupational exposure to Mucor species may result in hypersensitivity pneumonitis and asthma among workers. The allergens of Mucor species have not yet been characterized. However, a detailed investigation of the cross-reactivity of Mucor with other mold species showed the presence of multiple common bands. Mucor hiemalis, a species related to M. racemosus, contains multiple IgE-binding proteins likely involved in cross-reactivity, but direct studies are lacking.
Epidemiology
Worldwide distribution
Mucor sensitization was an early finding in European allergic asthmatic patients, albeit with differences in prevalence across various regions and as a function of the diagnostic material employed, with figures varying from 3 to 40%.
In a cross-sectional study in Egypt, 19.4% of 62 (n=12) allergic bronchial asthma and allergic rhinitis (AR) patients showed a positive skin prick test (SPT) to M. racemosus allergen.
A Chinese study of adult and pediatric asthmatic patients with IgE sensitization to Aspergillus fumigatus (n = 54) or allergic broncho-pulmonary aspergillosis (n = 18) showed frequent co-sensitization to other molds, including M. racemosus in 25% and 50% of these patients respectively.
The prevalence of IgE sensitization to Mucor spp. may be significant as early as preschool age. Indeed, a 12-year survey in Mexico City found a prevalence of 10.3% and 11.8% respectively of M. mucedo positive SPT among 7565 mold-sensitized children. Of note, among the 8794 children aged 2-18, addressed for asthma, AR, or atopic dermatitis (AD), and receiving SPT investigation, 86% demonstrated SPT sensitization to at least one mold, with A. fumigatus (17%) being the most prevalent.
The relative contribution of genuine co-sensitization and cross-reactivity was not addressed in these studies, leaving open the question of the pathophysiological role of Mucor spp. in allergic diseases.
Route Of Exposure
Main
The primary route of exposure to Mucor spp. allergen is the inhalation of fungal spores.
Secondary
Another route of exposure is oral i.e. ingestion of Mucor contaminated food. Penetration of the fungus, belonging to the order Mucorales, across damaged epithelium or a wound (surgical site, trauma) is also reported.
Clinical Relevance
Allergic rhinitis (AR) and and rhinosinusitis
M. racemosus may induce immunoglobulin E (IgE)-mediated sensitization and allergic reactions in asthmatic, allergic sinusitis, and AR patients. Exposure and sensitization to Mucor spp. may lead to AR or worsen the condition. Mucor was found to be a common fungal genus associated with AR.
A study in Egypt found 6.4% of 94 patients with AR showing positive SPT to M. racemosus.
Hypersensitivity to mold is involved in chronic rhinosinusitis, with Mucor hypersensitivity known to cause allergic fungal rhinosinusitis. Lin et al. (2005) presented a case of 39-year-old Chinese male patient having a 10-year history of nasal congestion, a foul smell and occasional yellowish discharge. Histopathology showed fungal elements. Extensive investigation of fungal-induced sensitization evidenced high-level of monosensitization to M. racemosus, with no IgE binding to other mold species. The final diagnosis was Mucor induced sinus mycetoma in relation to immediate hypersensitivity to Mucor.
The association of fungi with the occurrence of nasal polyposis was studied in 190 patients with polyposis compared to 190 healthy individuals without chronic rhinosinusitis or nasal polyposis. M. racemosus positive SPT were found in 5.8% patients and 0.5% control individuals. IgE to M. racemosus was found in 1.8% of 170 patients but in no controls. Further, polyp samples from 138 patients and nasal secretions of 30 controls were cultured. Mucorales was found to be one of the common fungal species (9.8%) in the nasal cultures of 81 fungal positive patients; however, not detected in 18 positive controls.
Asthma
M. racemosus has been reported to induce sensitization in some individuals, as shown by skin-prick and provocation tests. It can also trigger allergen-induced exacerbation of asthma and rhinitis.
A study in Egypt found 7.5% of 80 patients with allergic bronchial asthma showing positive SPT to M. racemosus.
Mucor species contaminated esparto grass (Poaceae family) fibers found in the Mediterranean region may induce occupational asthma or hypersensitivity pneumonitis in exposed workers. A case of a 30-year old man developing occupational asthma on exposure to esparto fibers contaminated with Mucor species had been reported, confirmed by positive Mucor SPT, detectable specific serum IgE against M. racemosus and a positive challenge test
Oral allergy symptoms and Anaphylaxis
In Central and Southern Europe, flavor-enhancing molds are commonly added to traditional foods such as dry sausage, salami, Spanish ham, and French cheese. A case was reported of a 24-year-old man diagnosed with rhino-conjunctivitis and asthma due to allergy to pollen, mites, and mold. He had experienced 2 episodes of facial angioedema immediately after eating a few slices of dry sausage, which he had tolerated previously on many occasions. SPTs were positive for grass pollen, house dust mites, and molds (such as Alternaria alternata, Penicillium chrysogenum, M. racemosus, and Pullularia, Stemphylium, Helminthosporum, and Fusarium spp.), and negative for all the food allergens tested. Specific (s)IgE was positive for Alternaria alternata (58 kU/L), M. racemosus (2.67 kU/L), and Penicillium chrysogenum (3.03 kU/L). Penicillium and Mucor spp. were isolated from the sausage skin. The labial challenge test yielded a positive result, with the onset of angioedema of the lips, tongue, and uvula within 5 minutes. The diagnosis was facial angioedema after dry sausage ingestion due to IgE-mediated food allergy to Penicillium and Mucor spp. The patient was advised to avoid all products commonly contaminated with molds, such as dry, fermented sausages, Spanish ham, foie gras, and French cheeses such as Roquefort and Camembert.
Bennett et al. (2001) reported a case of fatal anaphylaxis and death of a 19-year-old male (with a history of multiple allergies to pets, molds, and penicillin) on ingestion of mold-contaminated pancake. He did not develop any cutaneous symptoms, but experienced bronchospasm immediately after eating several pancakes and died within an hour. Autopsy showed laryngeal edema, hyperinflated lungs, mucous plugging, and chronic asthma. The pancake mix was found to be contaminated with Mucor, Penicillium, Aspergillus, and Fusarium molds, which were considered as the probable cause of anaphylaxis.
Other diseases
Hypersensitivity pneumonia
There are several reports of hypersensitivity pneumonia due to M. racemosus. In a 44-year-old male cork worker, suberosis due to Mucor spp. was reported. The patient complained of bronchial obstruction, which is a rare presentation of hypersensitivity pneumonitis. Also, a study in Shanghai showed 20 cases of hypersensitivity pneumonitis among school teachers who were exposed to sugarcane contaminated with Mucor.
Sensitive skin syndrome
A study by Keum et al. (2020) evaluated microbiome and mycobiome of sensitive skin syndrome (SS) in 42 Korean women of age 22-52 years. The study found that M. racemosus was the most abundant fungus in SS patients, and suggested a link between M. racemosus and skin sensitivity.
Mucor spp. infections
Thermotolerant Mucor spp., which do not include M. racemosus, can cause local and invasive infections, especially in immunocompromised hosts. Mucor spp., together with Aspergillus spp., are prominent causes of invasive fungal rhinosinusitis in such patients. Mucormycosis is an emerging invasive fungal infection caused by the members of Mucorales in immunosuppressed individuals. It is the 3rd most common fungal infection that can invade blood vessels and result in death. Mucormycosis has diverse clinical manifestations; the most prominent features include infections in rhino-orbito-cerebral, pulmonary, cutaneous, disseminated and gastrointestinal regions. Its incidence is increasing.
Cross-Reactivity
Recent studies on Mucor cross-reactivity are scarce. Unsurprisingly, a detailed investigation of the cross-reactivity of Mucor with other mold species showed the presence of multiple bands. Some of these bands were later identified and characterized as fungal allergens in Fusarium spp., with potentially broad cross-reactivity among fungi including Mucor. Among Mucor spp., Mucor hiemalis, a species related to M. racemosus, containing multiple IgE-binding proteins is likely to be involved in cross-reactivity, but direct studies are lacking.
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