Rhizopus nigricans

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Code: m11
Latin name: Rhizopus nigricans
Source material: Spores and mycelium
Family: Mucoraceae

Mould

A mould, which may result in allergy symptoms in sensitised individuals.

Allergen Exposure

Fungi can be found throughout the world. They may live or be found in indoor as well as outdoor environments.

Fungi are eukaryotic, non-chlorophyllous and heterotrophic organisms that depend on external nutrients and therefore live as saprophytes on non-living organic material, or as invasive pathogens in living tissue. (1, 2) They may live as parasites or symbionts of animals and plants under nearly all environmental conditions. Because they have the capability to grow under highly variable conditions, they are ubiquitous throughout most environments. (1, 3)

Fungi may have from a unicellular to a dimorphic or filamentous appearance. They are principally dispersed as sexual spores or asexual conidia, and are common components in the atmosphere. In addition, unidentifiable fungal hyphae fragments may be aerosolised in large numbers, which further increases the risk of human exposure through breathing. (1)

More than 80 genera of the major fungal groups have been associated with symptoms of allergy. Most of these fungi are classified under Ascomycetes and Deuteromycetes with a few in Basidiomycetes. Some of the most frequently occurring are Cladosporium, Penicillium, Aspergillus, Alternaria, and Aureobasidium.

The fungal spore counts in outdoor and indoor air vary considerably, depending on various environmental and other factors. (4) Fungi are highly variable, both in their morphology and in their antigenic makeup. (2) With some fungi it is almost impossible to grow two consecutive cultures with similar antigenic profiles, (2) although growing allergenic fungi in synthetically defined media has resulted in allergenic extracts which show less variability and demonstrate specific reactivity with patients. (2)

Unlike many other airborne allergens, fungi are associated with a variety of illnesses besides IgE-mediated allergy. (1) In contrast to pollen, fungi may cause adverse health effects in humans through other harmful immune response, by toxic or irritant effects, or by direct infection. The most prevalent immune disease caused by moulds is type I allergy (asthma and allergic rhinitis), but allergic bronchopulmonary mycoses, allergic sinusitis, hypersensitivity pneumonitis and atopic dermatitis may also occur. (5, 6) The prevalence of respiratory allergy to fungi is estimated at 20 to 30% among atopic individuals, and up to 6% in the general population. (Cited in  2, 7, 8, 9)

These diseases may result from exposure to spores, vegetative cells, or metabolites of the fungi. In addition, as the fungal spores are small (usually less than 10 µm) a majority of them are capable of penetrating the lower airways of the lung and mediate allergic reactions. (2) The conidia and fungal spores associated with immediate-type hypersensitivity are usually larger than 5 µm, while those associated with delayed-type hypersensitivity are considerably smaller, and can penetrate the smaller airways. (Cited in 2, 5, 6)

A feature of fungal allergies is the lack of clear evidence of disease, or of a well-defined pathology. (1, 10) There are various reasons for this diagnostic inadequacy, including heterogeneous disease symptoms and differences in routes and amount of exposure – but also the difficulties in characterisation and identification of the allergenic species. (1)

Rhizopus nigricans is the fungus commonly known as bread mould, and is the most common species of Rhizopus. It is found on old food and in soils, and even in children's sandboxes. The genus contains some 50 species, and bread mould is sometimes confused with species of Mucor or other species of Rhizopus such as Rhizopus oryzae. Rhizopus is closely related to Mucor and inhabits the same ecological niches. The spores are dispersed in hot, dry weather. (11)

Other typical microhabitats include fresh or decaying litter such as pine needles and leaves. Other known substrates are sweet potato, cold-stored strawberries, stewed fruits, and the nests, feathers and droppings of wild birds. The risk for occupational exposure is most likely to occur among food handlers during the storage, transfer and marketing of strawberries, peaches, cherries, corn and peanuts (Sneller, p252, cited in 51).

R. nigricans has been found to be prevalent in the atmosphere throughout the world, and is an important fungal allergen. (12) It is found abundantly on damp walls, basement areas and on kitchen leftovers, and clinically an important fungus. R. nigricans has also been found in library and archive storage facilities (13), in the bioaerosol formed during conservative dental treatment, (14) in silos storing imported wheat, (15, 16) in wheat mills, (17) in bakery dust, (18) in vegetables at the time of harvest, (19) from sweet potato, applesauce, and strawberries, (20) and from indoor and outdoor aerobiological studies. (21, 22)

Allergen Description

The spores contain allergenic proteins with 31 distinct allergens. (11)

No allergens have been characterised.

A heat shock protein, Hsp70, has been isolated. (23, 24, 25)

Potential Cross-Reactivity

No studies have evaluated the cross-reactive potential of R. nigricans.

Cross-reactivity has been suggested between the Curvularia lunata allergen Cur l 3, and the closely related genus member R. oryzae, as well as with Alternaria alternata, Cladosporium herbarum, Fusarium solani, Epicoccum purpurascens, Curvulana lunata, Aspergillus fumigatus, Mucor hiemalis, Penicillium citrinum, and Candida albicans. (26)

Clinical Experience

IgE-mediated reactions

Rhizopus nigricans is responsible for opportunistic infections and hypersensitivity reactions such as symptoms of asthma and hypersensitivity pneumonitis in sensitised individuals, and is an important occupational allergen. (51, 27, 28, 29)

It has been postulated that fungi may contribute to increased severity of asthma. A study evaluating skin-prick tests and the prevalence of allergy to 15 mould allergens in 105 hospitalised patients with exacerbation of asthma found that sensitivity to Aureobasidium pullulans was significantly associated with more severe asthma. Sensitisation to Helminthosporium was associated with an increased number of asthma exacerbations that required hospitalisation. Of this group, 21 (20%) were sensitised to R. nigricans. (30)

A number of studies have evaluated the prevalence of sensitisation to moulds in various population groups and geographical regions.

Almost 11% of patients with sensitivity to fungal allergens attending a clinic in India were sensitive to crude R. nigricans extract as demonstrated by skin test response. (31) These patients were shown to have serum-specific IgE directed at R. nigricans. In a more recent Indian study, 2 880 skin-prick tests with 60 allergens were performed on 48 patients with nasobronchial allergy, and found that 1.3% were sensitised to fungi. Only one patient was skin-prick test-positive for Rhizopus nigricans. (32)

Rhizopus is often included in the list of moulds which are thought to have clinical relevance for skin-testing mould-sensitive patients. (33) About half of the 21 suspected mould-allergy patients in a US population tested in vitro for IgE antibodies to Rhizopus were positive. (34)

In a study in Sao Paulo, Brazil, evaluating sensitisation in 201 patients with asthma and/or allergic rhinitis to 42 airborne fungi using skin-specific IgE tests, 15 were shown to be sensitised to Alternaria, 15 to Aspergillus, 23 to Aureobasidium, 37 to Candida, 15 to Chaetomium, 19 to Epicoccum, 17 to Mucor, 20 to Phoma, and 14 to Rhizopus. (35)

The aim of a Turkish study was to determine whether or not first-degree relatives with respiratory allergies were more likely to be skin test-positive to the same allergen extracts than unrelated patients were. Skin test results for 35 common aeroallergens were compared in 264 pairs of genetically related subjects, and 264 pairs of age- and sex-matched but unrelated subjects. Positive skin tests for Rhizopus nigricans were found in 0.8% of the test group. (36)

In Thessaloniki, Greece, in 1 311 asthmatics with atopy, positive skin reaction to fungal spores was observed in 421 (32%). Positive skin reaction to Alternaria species was observed in 177 patients (13.5%), in 98 (7.4%) to Cladosporium, 65 (5%) to Aspergillus, 45 (3.4%) to Fusarium and 36 (2.7%) to Rhizopus. (37)

A retrospective review of 247 patients conducted in Monclova, Coahuila, Mexico, showed that sensitisation to moulds was as follows: Candida (3.2%), Alternaria (2.7%), Rhizopus (3.6%), Penicillium (2.1%), Fusarium (2.1%), and others (8.7%). (38, 39)

From a large Phadia (Sweden) repository of human blood serum, an assessment of a subset of 668 unique serum samples of individuals found to have at least 1 positive serum-specific IgE test (>0.35 kUA/l) for a selection of 17 moulds found that 353 were positive for Rhizopus nigricans. (1)

In particular, R. nigricans has been reported to be an important allergen in a number of occupational settings, and to be responsible for occupational respiratory disease, (40) hypersensitivity pneumonitis such as malt worker's lung, (41) and wood trimmer's disease. (42)

A 30-year-old coal miner complaining of rhinorrhoea, sneezing, cough, and wheezing, which only presented in the mine where he worked, was shown to be sensitised to R. nigricans. Rhizopus spp. were found inside the mine and cultured. Total serum IgE level was 191 kU/l, and serum-specific IgE for R. nigricans was 3.50 PRU/ml. An intradermal test was positive for R. nigricans only. (43)

Workers in certain occupations are at greater risk of exposure to R. nigricans. In a study of 130 tobacco-processing workers and 112 control workers, the prevalence of chronic respiratory or nasal symptoms in exposed workers was significantly higher than that in control workers. Sensitisation as determined by serum-specific IgE for A. fumigatus was found in 26.9% of the workers, with a figure of 51.5% for R. nigricans in exposed workers; whereas by skin-prick test, these figures were 18.4% and 23.9% respectively. (44)

Rhizopus has been particularly associated with occupations involving wood. It has also been shown to grow on cut surfaces of wood, and is aerosolised by trimming of the wood into pieces, which may result in acute hypersensitivity pneumonitis as described in Scandinavian sawmill workers (Wood trimmer's disease). (45, 46, 47, 48)

Short-lasting alveolitis-like symptoms were described in Swedish sawmill workers responsible for trimming and sorting mouldy planks. Precipitating antibodies to Rhizopus antigen were demonstrated in more than 50% of these workers. Febrile reactions with muscular pain and malaise occurred in 10-20% at peak exposure levels. Sawmill workers with repeated acute symptoms had high levels of precipitating antibodies. The prevalence of this disease in the total Swedish wood-trimmer population was estimated at 5-10%. Less typical symptoms from upper and lower airways, and a mild, reversible decrement in forced vital capacity over one week's work shift was also suspected to be caused by this airborne mould. (48)

Pulmonary function was studied in 66 wood trimmers exposed to organic dust (moulds) after a month of no exposure (their summer vacation) and then three and 27 months later, and also during a working week. The forced vital capacity (FVC) and forced expired volume in one second (FEV1) were reduced by an average of 0.4 and 0.31 respectively after one month of no exposure. Measurements three months later, after two days of no exposure, showed a further reduction in FVC and FEV1 by an average of 0.21 in a sawmill with high exposure to moulds, but not in another sawmill with ten times lower exposure. Further recordings 27 months later displayed no further worsening in lung functions. Impairments were more obvious at a sawmill with higher air concentrations of organic dust. (49)

Importantly, other species of Rhizopus may be involved, as demonstrated by a study of Norwegian sawmills during the 1980s, which demonstrated antibody responses to Rhizopus microsporus. (50)

The risk for occupational exposure to mould allergens (and R. nigricans) has been reported to be most likely to occur among food handlers during the storage, transfer and marketing of strawberries, peaches, cherries, maize (corn) and peanuts. (51)

Rhizopus-induced hypersensitivity pneumonitis occurred in a 49-year-old male farmer with a 5-month history of progressive dyspnoea, fatigue, and a non-productive cough. He did not experience fever, chills, or acute episodes of dyspnoea. A presumptive diagnosis of chronic farmer's lung was made. However, the patient's serum did not reveal precipitins to common thermophilic actinomycetes. Cultures obtained from gross contamination of an enclosed-cab farm tractor air-conditioning system resulted in luxuriant growth of Rhizopus species, and immunodiffusion confirmed precipitin bands for a Rhizopus extract made from the culture plate colonies. (45)

Other reactions

Various species of Rhizopus have been implicated in non-IgE mediated reactions.

Pulmonary infection with Rhizopus microsporus var. rhizopodiformis has been reported. (52)

Rhizopus has also been implicated as a cause of fungal sinusitis, in particular in diabetic or immunocompromised patients, although it has also been reported in immunocompetent individuals. A study of the mycological and clinical aspects of fungal sinusitis in a tertiary referral centre in India found that of 211 culture-positive fungal sinusitis samples, Aspergillus flavus was the most common causative agent of allergic fungal sinusitis, and Rhizopus arrhizus was the most common causative agent of acute invasive sinusitis. (53)

‘Toxic mould syndrome’ is a controversial diagnosis associated with exposure to mould-contaminated environments. Mould metabolites may be irritants and may be involved in ‘sick building syndrome.’ (54)

Compiled by Dr Harris Steinman.

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As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.