480 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS or generalised anaphylaxis, sometimes called "immediate" hypersensitivity. The most frequent allergens are pollens. The response of the body is to form circulating antibodies which are of the non-precipitating type (reaginic). Reagins have the property of adhering to tissue cells. The union of antigen and antibody in contact with the cell releases vasoactive sub- stances such as histamine and the clinical manifestation as far as the skin is concerned is urticaria. Tests for this type of allergy are based upon the introduction of minute amounts of the allergen into the skin either by pricking with a needle or by scratching, and in the presence of hyper- sensitivity, urticarial reactions develop at the site within a few minutes, reaching a maximum at 15-20 min, then fading gradually. Intradermal injections ire sometimes used but they are not without their dangers in that too much may be introduced, giving rise to severe generalised reactions and sometimes even death. TYPES 2 AND 3 HYPERSENSITIVITY From the point of view of allergy to cosmetics, types 2 and 3 allergic reactions are of little importance. Type 2 is the result of the development of excessive amounts of antibody directed against tissue cells and its clinical manifestations are exemplified by certain types of transfusion reactions, sometimes purpura and possibly agranulocytosis. Some cases of drug hyper- sensitivity are initiated in this way. In Type 3 reactions, large amounts of antigen react with precipitating antibody in the circulation to produce toxic complexes. These complexes are capable of destroying the small blood vessels and in addition, microprecipitation in the capillaries may occur. Clinically the reaction is usually one of allergic arteritis and it may be the cause of certain skin diseases such as erythema nodosa. In both types 2 and 3 reaction, the circulating antibodies can be easily detected by laboratory procedures since they will cause either cytotoxic effects in vitro, or pre- cipitation, or agglutination of red cells. TYPE 4 HYPERSENSITIVITY In allergy to cosmetics we are mainly concerned with type 4 reactions. This reaction pattern corresponds with "delayed hypersensitivity" or "tuberculin type hypersensitivity" and allergy to cosmetics is in most instances a specialised form of allergic contact dermatitis. In type 4 reactions no circulating antibodies can be detected but may be bound to

CONTACT ALLERGY 481 cells of the lymphoid-monocyte series. The allergy is confirmed by the intradermal injection of the suspected material into the skin and it gives rise to "a delayed skin reaction". This is an erythematous area of induration reaching a maximum some 24-48 h after the injection and subsequently fading within the next fe•v days. Occasionally the reaction is delayed for as long as a week. In the case of contact allergens the confirmation is made by applying a patch test and this is a procedure which must be executed and interpreted with considerable caution. The allergen is applied to the surface of the skin usually in the form of a lint soaked patch, covered with some impermeable dressing such as Cellophane. It is kept in contact with the skin for 48 h before removal unless the subject complains of severe irritation. A positive result is shown by the appearance of erythema and induration which con- forms to the outlines of the patch applied. If the subject is extremely sensitive, or if rather a high concentration is used, vesiculation at the site may also occur. In some instances light is necessary to mediate the allergic reaction- the photoallergic reaction. This can occur if photons catalyse the conversion of a non-allergic chemical into one which will combine with protein to form a true sensitiser, or when photons facilitate the union of substances with protein to form a sensitiser. This type of reaction must be distinguished from the phototoxic reaction. In this instance absorption of photons leads to electron excitation and the formation of free radicles which can react with the tissues causing liberation of inflammatory metabolites. A further type of allergic reaction which is considered to be a sub-group of Type 4 hypersensitivity is the allergic granulomatous reaction which has recently been shown to occur following the prolonged use of zirconium in deodorant sticks. It was noted that after several weeks of application to the axilla of deodorant sticks containing zirconium, subcutaneous nodules appeared in a proportion of the users, and in those subjects it was noted that minute amounts (as little as 0.2 •g) of sodium zirconium lactate injected into the upper dermis caused local granulomata to arise after about 6-8 weeks. This was shown to be clearly an allergic reaction, partly because of the histological nature of the lesion, and also because beryllium salts were without effect in these patients, and lastly the fact that con- tinuous exposure to zirconium reduced the time of development of the granuloma to as little as 2 weeks. I have mentioned that contact allergy to cosmetics is a special case of