Cladosporium herbarum

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Code: m2
Latin name: Cladosporium herbarum (obsolete name Hormodendrum)
Mold
A mold, which may result in allergy symptoms in sensitized individuals. Cladosporium is the most frequently encountered mold in the air (1).

Allergen Exposure

Spores of Cladosporium spp. probably occur more abundantly worldwide than any other spore type and are the dominant airborne spores in many areas, especially in temperate climates. (1, 2, 3, 4) Although C. cladosporioides may be the most prevalent airborne species, C. herbarum frequently dominates indoor and outdoor air and is a major source of fungal inhalant allergens. (3, 5)

There are about 500 species of Cladosporium. Many are saprophytic on plant litter.

C. herbarum is widely distributed in our environment and is a major source of fungal inhalant allergen. (4) C. herbarum is one of the most common environmental fungi to be isolated worldwide. It occurs abundantly on fading or dead leaves of herbaceous and woody plants, as a secondary invader on necrotic leaf spots, and has frequently been isolated from air, foodstuffs, paints, textiles, humans and numerous other substrates. It is also known to occur on old carpophores of mushrooms and other fungi and as a common endophyte, especially in temperate regions. Under favourable climatic conditions C. herbarum also germinates and grows as an epiphyte on the surface of green, healthy leaves. (6)

While Alternaria alternata is a major allergen in houses as well as in outdoor air in humid climates (such as the southern part of the United States), Cladosporium is the leading allergenic mould in cooler climates (such as Scandinavia). (7) The most common in temperate and arctic climates is C. herbarum, accounting for the largest number of spores recovered in outdoor sampling. (8)

Due to the nature of this allergen, nearly all exposure is unexpected.

Thread mould is a defect which occurs sporadically in maturing vacuum-packaged Cheddar cheese and is caused by the growth of fungi in the folds and wrinkles of the plastic film in which the cheese is packaged. In a study of 110 Cheddar cheese blocks exhibiting this thread mould defect, the major causative species were found to be C. cladosporioides, Penicillium commune, C. herbarum, P. glabrum and a Phoma species. Yeasts were also frequently isolated from the cheese, the majority belonging to the genus Candida. These species were also found in the cheese factory environment, on cheese-making equipment and in air, which suggests it may be a risk for occupational sensitisation. (9)

Allergen Description

About 60 antigens from C. herbarum have been identified, of which at least 36 react with IgE antibodies from patients' sera. (10)

Fungal allergens can be grouped into several categories: proteases; glycosidases; components of protein production; oxidative stress response proteins; and enzymes involved in gluconeogenesis or the pentose phosphate shunt. Proteases and glycosidases are secreted enzymes that have a direct effect on the host. The latter three are suggestive of metabolism in spores germinating in a hostile environment. (11)

The following allergens have been identified to date:

  • Cla h 1, a 13 kDa protein. (3, 7, 12, 13)
  • Cla h 2, a 23 kDa protein. (3, 12, 13, 14, 15, 16, 17, 18, 19, 20)
  • Cla h 3, an aldehyde dehydrogenase. (21)
  • Cla h 4 is now known as Cla h 5.
  • Cla h 5, a 11 kDa protein, an acid ribosomal protein P2. (7, 14, 22, 23)
  • Cla h 6, a 48 kDa protein, an enolase. (7, 24, 25, 26)
  • Cla h 7, a YCP4 protein. (1, 7, 14)
  • Cla h 8, a mannitol dehydrogenase (14, 27, 28)
  • Cla h 9, a vacuolar serine protease. (14, 29, 30)
  • Cla h 10, an aldehyde dehydrogenase. (3, 7, 14, 21)
  • Cla h 12, an acid ribosomal protein P1. (14, 21, 31)
  • Cla h 42kD, a 42 kDa protein. (7)
  • Cla h abH, an alpha/beta hydrolase. (32)
  • Cla h 8 CSP, a cold shock protein (CSP). (7, 33)
  • Cla h GST, a glutathione-S-transferase. (34)
  • Cla h HCh1, a hydrophobin. (35 )
  • Cla h HSP70, Heat Shock Protein 70. (21, 36, 37)
  • Cla h NTF2, Nuclear Transport Factor 2. (21, 24)
  • Cla h TCTP, Translationally Controlled Tumour Protein, also known as Histamine Releasing Factor, HRF, TCTP. (38, 39)

Cla h 5, a ribosomal P2 protein, previously known as Cla h 4, shares 60% sequence homology with other ribosomal P2 proteins. (23)

Until recently, no dominant major allergen of this species had been found, until the identification of NADP-dependent mannitol dehydrogenase (Cla h 8), which has been demonstrated to be a major allergen recognised by the IgE antibodies of 57% of all Cladosporium-allergic patients. (48)

Potential Cross-Reactivity

Extensive cross-reactivity between the different individual species of the genus may be expected. (1)

Cross-reactivity is seen between Alternaria and Cladosporium as a result of homologous allergens (Alt a 10 and Cla h 3), aldehyde dehydrogenase (Alt a 6 and Cla h 4), acidic ribosomal protein P2 (Alt a 7 and Cla h 5), Saccharomyces cerevisiae protein (YCP4); and Alt a 11 and Cla h 6 (enolase, a major allergen). (7, 16, 40)

Fifty percent of Cladosporium and Alternaria-sensitive patients have been shown to react to recombinant enolase (rCla h 6). Inhibition studies show essential identity between Alt a 11 and Cla h 6. (16) Cla h 6, an enolase, is recognised by approximately 22% of sera of Alternaria-allergic patients tested. (15) Saccharomyces cerevisiae (Baker's yeast) enolase was shown to exhibit high cross-reactivity to other fungal enolases, including Cladosporium herbarum, alternaria alternata, Candida albicans and Aspergillus fumigatus. (26) Hev b 9, an enolase present in Natural rubber latex, is cross-reactive with enolases from C. herbarum and Alternaria alternata. (25)

Enolase is a common allergen found in many species of mould, and has been shown to exhibit high cross-reactivity to other fungal enolases. In particular, enolase from Alternaria alternata and Cladosporium herbarum are major allergens, and about 50% of the sera from patients have been reported to be reactive to each Cladosporium and Alternaria. (16) IgE cross-reactivity has also been reported to occur between enolases from A. fumigatus, P. citrinum and A. alternata. (16) Extensive cross-reactivity has been reported to occur between the enolases of C. herbarum, A. alternata, S. cerevisiae, C. albicans and A. fumigatus. (16) The enolase from R. mucilaginosa shares high sequence identity with enolase allergens from Candida albicans (85%), Saccharomyces cerevisiae (76%), Penicillium citrinum (76%), Aspergillus fumigatus (76%), Cladosporium herbarum (76.5%), and Alternaria alternata (74%). Although enolases are highly conserved allergens among different fungal species, most of the allergic patients examined in this study differed in their IgE reactivity to the 5 different fungal enolases tested. (16) The Latex allergen Hev b 9 is an enolase and has been shown to be cross-reactive with enolases from Cladosporium herbarum and Alternaria alternata. (16, 41)

The nuclear transport factor 2 (NTF2) allergen from A. alternata has sequence homology with allergens from Cladosporium herbarum and Aspergillus fumigatus. (16)

Epi p 1 allergen from Epicoccum purpurascens has been reported to exhibit dose-dependent inhibition with Aspergillus fumigatus, Alternaria alternata, Curvularia lunata, Cladosporium herbarum and Fusarium solani, confirming cross-reactivity of this allergen. Other laboratory methods confirmed that Epi p 1 shares common epitopes with the fungi tested. (42)

A 45 kDa protein isolated from Fusarium solani demonstrated cross-reactivity with Epicoccum nigrum, Curvularia lunata, Cladosporium herbarum and Alternaria alternata. The allergen involved did not show homology to enolase or other known fungal proteins. (43) Marked cross-reactivity has also been reported between Epicoccum nigrum and A. alternata, with less reported for C. lunata, C. herbarum, and P. citrinum. (44)

Clinical Experience

IgE-mediated reactions

In the allergic population, sensitisation to moulds may vary from 5 to 30%. (45, 46) The wide range of allergenic proteins in C. herbarum may result in sensitisation and subsequent expression of a range of immune-related diseases. Cladosporium sensitisation is particularly associated with severe or life-threatening asthma. Upper respiratory symptoms occur with exposure to Cladosporium, but asthma symptoms are more prevalent. Cladosporium may also result in allergic bronchopulmonary cladosporiosis, having even been described in a child. (8) Other genus members have also been associated with a range of diseases, e.g. C. carrioni causes chromoblastomycosis, a verrucous dermatitis of the legs seen in the tropics. C. herhamm is the source of the mycotoxin epicladosporic acid, which has been implicated in toxic leukopenia from ingestion of contaminated grain. (8)

Mould may damage airways by production of toxins, proteases and enzymes, as well as by production of volatile organic compounds (VOCs). It actively produces a wide range of allergenic proteins. (11)

Therefore, mould may cause illness from growth and toxin production in individuals and immune-compromised hosts. Although VOCs may be detectable in (for example) compost heaps, exposure in other environments (such as a bedroom) and its effects are mostly unclear: VOCs may be an irritant of the respiratory mucosa. (11)

C. herbarum is an important allergenic fungal species that has been reported to cause allergic diseases in nearly all climatic zones, with 5 to 30% of the allergic population demonstrating IgE sensitisation against moulds. Sensitisation to Cladosporium may often be associated with severe or life-threatening asthma, and less frequently with chronic urticaria and atopic eczema. (8, 11, 47, 48, 56) Upper respiratory symptoms occur with exposure to Cladosporium, but asthma symptoms are more prevalent. (49,)  (50)

A cross-sectional study of 1 132 adults with asthma found that sensitisation to Alternaria alternata or C. herbarum is a significant risk factor for severe asthma in several European countries, and also in Australia, New Zealand, and Portland in the USA. (48) Studies from California and Pennsylvania have reported that asthma symptoms are increased on days when spore counts are high. (51, 52)

In the six regions of the European Community respiratory health survey (ECRHS), the prevalence of sensitisation to C. herbarum was documented (see Table 1).

Table 1: Proportions (%) of participants with asthma with sensitisation to allergens tested in the six regions of the European Community respiratory health survey (ECRHS) (48)

Allergen

All (n=1132)

UK and Republic of Ireland (n=205)

Northern Europe (n=264)

Central Europe (n=139)

Southern Europe (n=150)

Australia/New Zealand (n=335)

Portland (US) (n=39)

Alternaria alternata

11.9

17.6

10.2

13.7

4.7

10.5

28.2

Cladosporium herbarum

5.8

6.8

9.9

4.3

0.7

4.5

10.3

 

In children with asthma, sensitisation to common allergic fungi (A. fumigatus, Penicillium spp., Alternaria spp. and Cladosporium spp.) were found to be relatively uncommon in the UK and in Finnish schoolchildren  (53) compared with Arizona  (54) and Australia, where up to 31% of asthmatic children and up to 23% of non-asthmatic controls were found to be sensitised to at least one fungal allergen. (50, 55, 56) (Cited in (11))

Adults whose domestic exposure to Cladosporium had doubled over a 2-year period had 52% greater odds of reporting an attack of asthma in the previous 12 months. (57)

Sensitisation to C. herbarum has also been reported to occur in hot and humid climates, (58) as well as in desert climates such as Saudi Arabia and Kuwait. (59, 60, 61) As an indoor allergen source, seasonal peaks may occur in late summer and autumn. (15) An allergological study conducted for 12 months in three regions of Saudi Arabia to evaluate allergenicity to Cladosporium was conducted, including skin-prick tests on 605 allergic individuals using commercial extracts of C. herbarum. Overall, 19.67% of this group were shown to be sensitised, with the majority showing mild reactions. Cladosporium was the most prevalent genus in the outdoor environment, constituting up to 25% of all fungal spores in the dry region and 37.1 and 41.2% in two coastal cities. A number of species of Cladosporium were documented. (59)

Cladosporium has also been cultured from the nasal cavities of 135 subjects aged 18-35 years. All lived in the metropolitan area of Barcelona, Spain. Fungi were isolated from 41.5% of healthy people and 14.8% of allergy patients. 50.4% of the isolates were located within 4 genera: Cladosporium, Penicillium, Aspergillus and Alternaria, the fungi that are considered the most allergenic. Of the Cladosporium genus, the most prevalent species were C. herbarum and C. cladosporioides. (62)

Other reactions

A case of allergic broncho-pulmonary cladosporiosis has been reported in a child. (63)

Two hypersensitivity pneumonitis (HP) cases which developed in an office area and in a home in Japan have been described: a 47-year-old woman with acute-onset HP and a 72-year-old woman with chronic HP. Cladosporium cladosporioides and Cladosporium herbarum were isolated, respectively. (64)

Compiled by Dr Harris Steinman, harris@zingsolutions.com

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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.