PHOTOSENSITIVITY

A number of substances known as photosensitizers may induce an abnormal reaction in skin exposed to sunlight or its equivalent. Contact of the skin with these substances may be external, or internal by enteral or parenteral administration, or by host synthesis of photosensitizers in response to an administered drug. The result may be either a markedly increased sunburn response without prior allergic sensitization (phototoxicity) or actual allergic sensitization triggered by sunlight, produced either internally (photoallergic dermatitis, photodrug reaction) or by external contact (photocontact dermatitis). Drugs associated with photosensitivity (photosensitizers), according to Baer and Harber, are usually resonating compounds with a ram-molecular weight of less than 500. Absorption of radiant energy (sunlight) by the photosensitizer produces an excited state, which then reacts to dissipate itself through fluorescence, phosphorescence, charge transfer, heat, or free radical formation. Each photosensitizing substance absorbs only a specific wavelength of light. Depending upon the cellular localization of the photosensitizer, primary damage may occur in the nucleus, cytoplasmic organelles, or cell membrane. A representative list of photosensitizers in man is shown in Table 3-2. Action Spectrum. The specific wavelengths of light required to evoke a photosensitive drug reaction are known as the action spectrum. This action spectrum is approximately the same as the absorption spectrum of the photosensitizing substance. The action spectrum for photoallergy is mostly in the long ultraviolet (UVA) (320 to 423 nm) region and may extend into the visible light region. Apparatus. Various types of apparatus are avail-able to produce these specific wavelength radiation ranges. The fluorescent sunlamp tube (Westinghouse) has a range 'between 285 and 350 nm. The fluorescent black light tube (Westinghouse tube, GE, Sylvania) has 'a 320 to 450 rim range. Other light sources that may also be of use in eliciting photosensitivity reactions include the high-pressure mercury-vapor lamp (hot-quartz), carbon arc, and an intense Wood light (Black-Ray 13-100 A). Types of Photosensitivity. In order that a photosensitivity reaction may occur, several factors must be present. The photosensitizing substance must be in or on the skin and exposed to specific wavelengths of light characteristic of the absorption spectrum of the photosensitizer. The prime factors determining the magnitude of a cutaneous photosensitivity response are the concentration of the photosensitizer and the intensity of the light absorbed. Adverse photosensitivity may occur through diverse mechanisms. Three major pathways are phototoxic, photoallergic, and enzyme-induced photosensitization.

Phototoxic Reaction. A phototoxic reaction is a non immunologic reaction that develops within two to six hours after the skin has been exposed to a photosensitizing substance and light of the proper wavelength and intensity. There is a sunburn-type of reaction, with erythema occurring only on the sunexposed parts. This type of reaction can be elicited in many persons who have no previous history of sensitivity to that particular substance: individual susceptibility varies widely. To elicit a phototoxic reaction a considerably greater amount of the photosensitizing substance is necessary than in the case of the photoallergic reaction. The erythema begins (like any sunburn) within a few hours, but worsens for 48 to 96 hours before beginning to subside. In severe cases, nails may be involved (photo-onycholysis). Photoallergic Reaction. After exposure of the photosensitizing substance on the skin to a suitable light source, a clinical response is elicited in 24 to 48 hours. There is a papulovesicular, eczematous, or exudative dermatitis that occurs chiefly on the light-exposed areas; in addition, the eruption may extend onto other parts of the body. This type of reaction occurs only in the previously sensitized person. The reaction may be produced with only small amounts of the photosensitizing substance. However, there is evidence to suggest that a sufficiently high concentration of the particular substance will also show phototoxic attributes. Enzyme-Induced Photosensitivity. Some drugs taken internally may act upon the metabolism systemically to induce changes in enzyme activity. In response to these enzymes the host manufactures the photosensitizer, such as tetrapyrroles, which figure prominently in the porphyrias. The drugs producing exacerbations in acute porphyria increase the delta aminolevulinic acid synthetase in hepatic cells and increase tetrapyrrole (porphyrin) synthesis. This type of photosensitivity may be induced by estrogens, Sedormid ([2isopropyl-4 pentenoyl] urea), barbiturates, and griseofulvin. Similar abnormalities have been noted in thousands of people who developed porphyria from the ingestion of cereals sprayed with hexachlorobenzene. In addition, alcohol (chlorinated phenols) may alter enzyme activity. This photosensitivity is an expression of a phototoxic reaction to a porphyrin produced by the host as a result of an ingested drug or chemical.

PHOTOTOXICITY

Phototoxic dermatitis usually occurs with the first exposure to the photosensitizing substance, when it is in a high cutaneous cellular concentration and is followed by exposure to sunlight. Prior sensitization is not required. As already noted, the dermatitis occurs upon the sun-exposed areas within a few hours after exposure. Clinically the most common finding is the sunburned appearance of the skin, followed later by hyper pigmentation. Sometimes bullae develop. The action spectrum is usually in the 285 to 450 nm range. The phototoxic substances causing this type of dermatitis usually absorb radiation in the ultraviolet or visible light range and have a gram-molecular weight of 500 or less. Phototoxic Tar Dermatitis. Coal tar, creosote, crude coal tar, or pitch, in conjunction with sunlight exposure, may induce a sunburn reaction with episodes of severe burning sensation. This is followed by hyper pigmentation, which may persist for years, especially in those whose occupations involve constant exposure to sunlight. Coal tar or its derivatives may be found in cosmetics, drugs, dyes, insecticides, and disinfectants. In the Goeckerman therapy of psoriasis, the phototoxic effect is utilized to advantage by making the skin more susceptible to ultraviolet light. Phytophotodermatitis. The phototoxicity-inducing furocoumarins in many plants may bring about phytophotodermatitis when these plants come in contact with moist skin which is then exposed to sunlight. Several hours after exposure to the plant at burning erythema occurs, followed by edema and the development of small vesicles. The following day the small blisters coalesce into large bullae. This is followed by involution and then by an intense residual hyper pigmentation that may persist for weeks or months. The hyper pigmentation is the post inflammatory type. It is epidermal as well as dermal, i.e., increased melanin within keratinocytes and also in dermal histiocytes, and is only very slowly reversible with time. Phytophotodermatitis is believed to be caused mostly by plants containing furocoumarin (psoralen, 8-methoxypsoralen and 5-methoxypsoralen), which are

primarily in the families of the Umbelliferae, Rutaceae (rue), Compositae, Papilionaceae, and Moraceae. Plants known to cause phytophotodermatitis include the fig, cowslip, garden and wild parsnip, fennel, dill, parsley, wild carrot, garden carrot, masterwort, atrillal, angelica, common rice, gas plant, lime bergamot, lime, Persian lime, buttercup, mustard, blind weed, agrimony, yarrow, goose foot, bavachi, and St. John's wort. In Hawaii the anise scented mokihana berry (Pelea anisata) was known to natives for its phototoxic properties (the "mokihana burn"). Like the lime, it is a member of the rue family. Occupational disability from exposure to the pink rot fungus (Sclerotizzia sclerotiorunz) present on celery roots, which occurs in celery farmers in upper Michigan and Florida, has been reported by Birmingham. However, diseaseresistant celery of high quality contains furanocoumarins and was the probable source of phytophotodermatitis in an epidemic studied by Berkley et al in 1984. Phytophotodermatitis must be differentiated from vesicles and bullae due to poison ivy dermatitis. The vesicles and bullae of poison ivy are not necessarily limited to the sun-exposed areas. Itching is the most prominent symptom in poison ivy dermatitis, whereas there is burning in phytophotodermatitis. Treatment of a severe, acute reaction is wet compresses (1:5000) for 20 to 30 minutes daily and topical applications of Sarna lotion, Acid Mantle Creme, bland or corticosteroid cream, lotion, or ointment. Calamine lotion is a popular layman's remedy. Berloque (Berlock, Perfume) Dermatitis. In 1916 Freund described a peculiar artificial discoloration of the skin that appeared with the use of eau de Cologne during sunbathing. Clinically this pigmentary disturbance is characterized by lavaliere (hanging drop)-shaped pigmented patches. The word for pendant in French is berloque, and in German it is Berlocke. Other patches may be quadrilateral or occur in streaks of erythema or pigmentation. This dermatitis is seen most frequently on the sides of the neck and in the retro auricular areas of women. In addition, the shoulders, breasts, face, and other areas may be involved. When men have this type of dermatitis, it is usually on the bearded area and is caused by bergamot oil or related substances in aftershave lotion. The chief cause, oil of bergamot, contains a furocoumarin (5-methoxypsoralen), a potent photosensitizer. However, such compounds hive been re-moved from most perfumes and lotions, and berlock dermatitis is rarely seen anymore. Treatment consists of stopping the use of furocoumarin preparations. Benoquin, though a fairly effective bleach, is a potential sensitizer and should seldom be used unless total depigmentation (in nearly universal vitiligo) is being attempted. Effective, safe bleach which may be used is a modification of Kligman's formula: 5 per cent hydroquinone, 0.1 per cent retinoic acid, and 0.1 per cent dexamethasone in hydrophilic ointment rubbed in daily.

Azelaic acid cream may also be effective. Dermatitis Bullosa Siriata Pratensis (Grass or Meadow Dermatitis). This is a phytophotodermatitis with an eruption consisting of streaks and bizarre configurations with vesicles and bullae that heal with residual hyper pigmentation. Sunbathing in the fields with exposure to furocoumarin-containing plants is the cause of this unusual dermatitis. Treatment is that recommended for any phytophotoderrnatitis. Photosensitivity in Tattoo. Yellow cadmium sulfide, a known photosensitizer, has been incorporated into red mercuric sulfide pigment to produce a brighter red color. Bjornberg has reported extensively on the photosensitivity in tattoos due to the yellow pigment of cadmium sulfide. Goldstein has reported swollen erythematous verrucose lesions in the red parts of tattoos, containing cadmium sulfide, after exposure to sunlight. The other colors do not produce this disorder. Either the tattooed person must avoid sunlight exposure or the red part of the tattoo must be removed. Dyes Acridine Eosin Calcium cyclamate Oral Antitnicrobials Demeclocycline (Declomycin) Tetracycline (rarely) Sulfonamides Nalidixic acid (NegGram) Griseofulvin (infrequently) Furocoumarins (psoralens) Methoxsalen (Oxsoralen) Trimethylpsoralen (Trisoralen) Oral ("Photodrug") Diuretics - Chlorothiazides (Diuril, Hydrodiuril) Quinethazine Hypoglycemics Chlorpropamide (Diabinese) Tolbutamide (Orinase) Phenothiazines Percttlorperazine (Stelazine) (Hydromox)

Chlorpromazine (Thorazine) Promazine (Sparine) (Compazine) Promethazine (Phenergan) Trifluoperazine

Coal Tar Derivatives Acridine Anthracene Phenanthrene Pyridine Crude coal tar Furocoumarins (psoralens) Methoxsalen (S-MOP) in lime, rue, orange, celery, dill, anise, or mokihana berry. Bergapten (3-methoxypsoralen) in oil of bergamot Topical ("Photocontact") Antimicrobials Bithionol Sulfathiazole Halogenated salicylanilides carbanilides Hexachlorophene (usually only secondary sensitizer) Antihistamines Diphenhydramine? (Benadryl) and