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ALLERGIC HYPERSENSITIVITY to FUNGI by J Postgrad Med J: first published as 10.1136/pgmj.35.406.436 on 1 August 1959. Downloaded from 436 ALLERGIC HYPERSENSITIVITY TO FUNGI By J. PEPYS, M.B., M.R.C.P., M.R.C.P.E. Senior Lecturer in Allergy, Institute of Diseases of the Chest, Brompton Hospital, London Allergic reactions to the ubiquitous pathogenic experimental animals. Arthus reactions in man and non-pathogenic fungi are models for the study have been suspected because of the similarity of of hypersensitivity. Emphasis will be placed the histological changes in Arthus reactions in wherever possible in this paper on findings in animals to those found in vascular reactions in man, in whom fungal hypersensitivity is widely man which are regarded as being possibly of prevalent. These findings throw light upon fungal allergic origin. The Arthus skin test reaction antigens in relation to clinical manifestations and develops after several hours, that is, later than the upon the nature and mechanism of allergic re- immediate type weal reaction, and is maximal actions. It is hoped that this outline will serve as within 24 hours, that is, earlier than the delayed a guide to some of the many problems requiring type reaction. Arthus hypersensitivity is de- further study. pendent upon precipitating antibody and can beProtected by copyright. A description of certain of the features of the transferred passively by the injection of serum three clearly defined types of allergic hyper- containing precipitins into a non-sensitive re- sensitivity will be given as a source of reference cipient. for the subsequent discussion. The induction of hypersensitivity is influenced by antigenic configurations which can be modified Delayed, Tuberculin Type of Hypersensitivity so as to favour one or other form of hypersensi- This is characteristic of the allergy of infection. tivity (Benacerraf and Gell, I959; Gell and Bena- The reaction to skin tests develops slowly and is cerraf, 1959). The various types of hyper- maximal at 48 to 72 hours. The antibody respon- sensitivity may co-exist and the reaction elicited sible for the reaction appears to be linked to cells on testing depends upon the antigenic component of the reticulo-endothelial system and is trans- employed. In addition, it seems that immediate ported by circulating lymphoid cells to the site or Arthus reactions or both may interfere with of the test reaction. Passive transfer of the the development of delayed reactions. There are http://pmj.bmj.com/ delayed type of hypersensitivity can be effected a number of examples where it would be most by the injection of these cells, but not the serum, instructive to make a clear distinction of the of a sensitive donor into a non-sensitive recipient. various types of hypersensitivity which may be present at the same time. Immediate, Anaphylactic Type, Hyper- sensitivity Fungal Hypersensitivity This is characteristic of the clinical allergic Fungal hypersensitivity may be classified under disorders such as asthma, hay fever, conjunc- two main headings: (i) delayed type hyper- on September 25, 2021 by guest. tivitis and urticaria. The reaction to skin tests is sensitivity associated with pathogenic fungi, and of the urticarial weal and flare type, developing (2) immediate type hypersensitivity associated within a few minutes, becoming maximal within with non-pathogenic fungi. Whilst these groups 20 to 30 minutes and resolving within II to 2 are well defined other forms of hypersensitivity hours. The non-precipitating antibody present may co-exist. in the serum is capable of sensitizing the skin and smooth muscle and is known as reaginic anti- Hypersensitivity to Pathogenic Fungi body. Passive transfer of the hypersensitivity is Infections with these fungi provide classical effected by the injection of serum from a sensitive examples of the allergy of infection. For example, donor into a non-sensitive recipient. Bloch (I928) described the accelerated response, rapid course and early resolution which appeared Arthus Type Hypersensitivity on re-infection with a fungus of subjects who had Arthus reactions are customarily studied in previously been infected. This phenomenon is Postgrad Med J: first published as 10.1136/pgmj.35.406.436 on 1 August 1959. Downloaded from August 1959 PEPYS: Allergic Hypersensitivity to Fungi 437 analogous to that described by Koch in tuber- as trichophytin in skin tests may also excite ' id' culous re-infection. The appearance of delayed eruptions (Sulzberger, I940). type hypersensitivity is closely associated with Erythema nodosum may occur in fungal infec- this accelerated response to infection. tions, for example in 5 per cent. of patients with coccidioidomycosis (Kligman and DeLamater, Delayed Type Hypersensitivity 1950), and these subjects may show a high degree The passive transfer of delayed hypersensitivity of sensitivity to coccidioidin (Wilson, 1957). in man to tuberculin and other delayed type There is some evidence to suggest that erythema antigens by the injection of circulating white blood nodosum may be an Arthus type reaction, but cells from sensitive subjects has been reported by decisive evidence in favour of delayed or Arthus Lawrence (1956). Similar passive transfer of hypersensitivity is lacking. delayed hypersensitivity in animals had been reported earlier by Chase (I945) and has been Immediate Type Hypersensitivity repeated by many other workers. More recently Immediate weal reactions in skin testing have Rappoport and others (I959) have reported the been reported in some of the systemic mycoses, passive transfer in man (by the same methods) of for example in coccidioidomycosis and blasto- delayed type hypersensitivity to a fungal antigen, mycosis. In coccidioidomycosis, Hirsch and coccidioidin, thus illustrating a common mechan- Benson (1927) and Smith and others (1948) ism in delayed type hypersensitivity to a variety obtained immediate reactions on skin testing. of antigens. The latter workers elicited immediate reactions Delayed type hypersensitivity is present in the to coccidioidin in persons who failed to give systemic mycotic infections, and in infections delayed reactions, and generalized urticaria ap- confined to the skin. Skin tests with the appro- peared in two subjects within 8 and i8 hours Protected by copyright. priate antigens give delayed reactions in histo- respectively after skin testing. A similar case is plasmosis, blastomycosis, sporotrichosis, coccidio- reported by Krudy and Hoff (1959), their patient idomycosis, moniliasis (candidiasis), and ringworm also failing to give a delayed reaction. Some infections. confusion exists in these reports since Smith and In some instances cross-sensitivity has been others (I948) found, as would be expected, that a found, for example in histoplasmosis and blasto- control test injection with sterile water also pro- mycosis, and in coccidioidomycosis and blasto- duced wealing. The use of prick tests with suit- mycosis. Although this cross-sensitivity may not able antigens and of appropriate non-irritant be of a high order, it may be important. A vehicles for the test materials would overcome pertinent example is provided by Peck (1950), any doubts as to the reactions. Prick tests with a who found that delayed skin test reactions to carbol saline extract of Candida albicans cells gave trichophytin were elicited in 6o per cent. of immediate weal reactions in about one-quarter of subjects who gave similar reactions to penicillin asthmatic patients tested by the author. It is http://pmj.bmj.com/ and in 33.3 per cent. of those who did not react to not unlikely that similar reactions may occur in penicillin. Delayed skin test reactions to both the other mycoses, requiring improved antigens penicillin and trichophytin were elicited in 9.7 per or more careful methods of testing for their cent. of treated subjects, and to penicillin alone in demonstration. 3.2 per cent. This cross-sensitivity is relevant-to Immediate weal reactions to trichophytin in the allergic reactions which may appear within the superficial fungus infections of the skin are 24 hours after the administration of penicillin for not uncommon. Marcussen (I937) has described the first time. Caution is necessary at the present the successful passive transfer of this hypersensi- on September 25, 2021 by guest. time, however, before attributing this to tinea tivity in man by the injection of serum, indicating infection, since penicillin may be ingested un- that reaginic antibody is involved. Sulzberger wittingly in foodstuffs. (1932) has also reported that the injection of trichophytin into sensitive subjects may provoke ' Id' Eruptions allergic reactions such as asthma and rhinitis, These are naturally occurring manifestations in these manifestations also being associated with fungal infections, and are regarded as expressions the presence of reaginic antibody. Anaphylactic of delayed type reactions in distant tissues to the and smooth-muscle sensitization to trichophytin fungi or their allergenic products. The ' id' in infected animals was reported by Jadassohn eruptions of tinea infections, and possibly of and others (I932, 1937). moniliasis, are attributed to haematogenous dis- In a study of trichophytin skin test reactions in tribution of antigen to the skin, and include patients infected with Trichophyton rubrum and vesicular, morbilliform, lichenoid, urticarial and Trichophyton mentagrophytes, Lewis and Hopper other manifestations. Injection of antigens such (1948) found that in patients infected with Postgrad Med J: first published
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