Rhizopus nigricans (also known as R. stolonifer) is a mold of the Order Mucorales commonly found in humid environments, both indoors and outdoors. R. nigricans can contaminate most human environments, including crops and foodstuffs. The spores are the particles that induce sensitization.

People affected by mold sensitization are often already sensitized to other allergens, confounding the clinical picture. Allergic rhinitis and asthma appear to be the clinical presentations most commonly associated with mold allergy and sensitivity to R. nigricans; patients may also experience allergic dermatitis. Cross-reactivity with other molds and commons foods such as spinach and mushroom may occur.

Nature

Rhizopus nigricans (also known as R. stolonifer, agent of soft rot in crops) is characterized by complex rhizoids, sporangiophores, sporangium and sporangia. The main mycelium is conical/cylindrical in shape, up to 140 μm, with many branches conferring a tangled appearance. The mycelium produces erect hyphae, initially whitish and later forming black sporangiophores of 1-3 mm in length by 20-25 μm in diameter. Each sporangiophore produces a single spherical sporangium, containing sporangiospores. The spores vary in size, with the globose (spherical) type the most common shape (1).

The warmer months of spring and summer represent the peak of spores being present in the environment, although certain fungi are able to produce spores all year round. There is considerable overlap between peak spore season and other allergens such as grass and weed pollens, often masking the pathology caused by fungal spores in multi-sensitized people (2). R. nigricans showed no definite seasonal pattern (3).

R. nigricans is a common agent of crop and food spoilage (1). Alongside other members of the Order Mucorales, it is a permanent inhabitant of the human environment (4). Rhizopus spp. have been identified in spoiled pears (5), cereals (maize, wheat and barley; (6)) and sweet potatoes (7). It is also commonly found on bread surface (8). A Portuguese study found evidence of R. stolonifer in approximately 3% of tap water samples analyzed (9).

Spoiled crops and foods affected by R. stolonifer present moist/wet areas that become quickly covered by a gray, hairy mycelium presenting black-tipped sporangia. The initial infection of the crop occurs during harvest, handling and storage (6, 7, 10).

Taxonomy

Rhizopus nigricans (R. stolonifera) belongs to the Family Mucoraceae, Order Mucorales, Class Zygomycetes (1, 11).

Tissue

Spores and mycelium represent the tissues able to sensitize patients and cause allergic reactions (2).

Worldwide distribution 

Molds of the Genus Rhizopus are accountable for most cases of rhino-, orbital- and cerebral infections worldwide (4).

In a German study, R. nigricans was found to be one of the five most common fungal agents of sensitization (12).

Risk factors 

Relative humidity appeared to be a significant predictor for the airborne presence of a variety of fungal components (13), including R. stolonifer (8).

The risk of sensitization to molds was significantly increased by pre-existing atopy (14).

Certain workplaces may present an occupational health hazard in regards to fungal allergies; R. nigricans particles were commonly found in air samples from sawmills, especially those processing conifers (15). Museums, archives and libraries with old records may also pose a higher workplace risk (16). Exposure to damp and moldy workplaces (including healthcare settings, schools, offices, laboratories, children nurseries and production plants) is a risk factor for new-onset adult asthma (14).

Worldwide distribution 

Fungal allergies are a worldwide health issue (2). R. nigricans is most prevalent in temperate and subtropical regions, though also commonly found in the warmer tropics (7). Allergic disorders caused by molds are frequent across India, with allergy-related hospitalization a common occurrence (13).

Rhizopus may contribute only a small fraction of the total aerial catch, but was accountable for 15% of skin positive reactions in the patients studied (3).

Main 

Inhalation of spores and other parts of the mold (2).

Secondary 

Ingestion and skin contact (2).

Main methods 

An Andersen air sampler can be used to detect R. stolonifer in the air (8).

Measures

The concentration of airborne R. stolonifer can range between 4-47 CFU/m³ (8)

Molds cause new-onset adult asthma (14). Allergic rhinitis and asthma are the main conditions that can develop (and worsen in patients already affected) following exposure and sensitization to mold allergens. In particular, R. nigricans was responsible for 16.7% of positive skin tests and increased specific IgE in patients with allergic rhinitis (17).

In children, fever, dyspnea, wheezing and reduced lung capacity was observed in two siblings later diagnosed with allergic bronchopulmonary mycosis caused by R. nigricans (18).

A multi-mold extract containing R. nigricans antigens was used for skin-prick tests (SPTs) in children with allergic dermatitis; in this study, between 6-8% of children had a positive skin reaction to the mold extract (19).

Tests aimed at diagnosing fungal allergies are often in disagreement, as the antigenicity and therefore allergenicity of each extract can vary depending on strain variabilities, spontaneous mutations, different provenance of the raw materials, degrading enzymes (2). Usually, allergy to R. nigricans can be diagnosed with bioassays such as Skin Prick Test (SPT), or immunoassays in vitro (ELISA). SPT reactions to R. nigricans allergens in patients with respiratory allergies varied in positivity, with 41% of patients showing mild to moderately positive reactions, 15% showing moderately positive reactions and 9% showing highly positive skin reactions (3). In the same study, the serum of SPT+ (positive) patients was tested by ELISA for the presence of IgE specific for the fungal antigens that caused the positive skin reactions. This showed 66% concordance for R. nigricans antigens between the positives to the bioassay SPT and the in vitro immunoassay (3).

Allergen immunotherapy

Immunotherapy is currently not recommended for patients allergic to molds, due to complexities of the allergens and patient co-allergies (2).

Prevention strategies 

Avoidance is difficult in the case of aeroallergens encountered outdoors. Indoors, avoidance may be possible in certain circumstances, for example if visible mold is found (2).

Allergenic molecules

At least 31 different R. nigricans antigens were identified and characterized by crossed immunoelectrophoresis (CIE) and other assays (20).

Cross-reactivity

Cross-reactivity can occur when epitopes of protein and carbohydrate structures are shared between antigens from different fungi; these can be taxonomically related species, but also quite distantly related, or not at all related (2). A Spanish study demonstrated the existence of an allergen showing cross-reactivity between molds and common foods, such as spinach and mushroom (21).

Author: RubyDuke Communications

Reviewer: Dr. Christian  Fischer

Last reviewed: January  2022