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Scientific Problems of Photosensitivity

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Scientific Problems of Photosensitivity Medicina (Kaunas) 2006; 42(8) 619 Scientific problems of photosensitivity Rūta Dubakienė, Miglė Kuprienė Republican Center of Allergology, Vilnius University, Lithuania Keywords: photosensitivity, photosensitizers, phototoxic reaction, photoallergic reaction. Summary. Photosensitive skin reactions occur when human skin reacts to ultraviolet radiation or visible light abnormally. The forms of photosensitivity are phototoxicity and photoallergy. Phototoxic disorders have a high incidence, whereas photoallergic reactions are much less frequent in human population. Several hundred substances, chemicals, or drugs may invoke phototoxic and photoallergic reactions. In order to avoid photosensitive reactions it is essential to determine the photosensitizing properties of such substances before drugs are introduced in therapy or products made available on the market. The article reviews the mechanisms of photosensitization, explains the most important differences between phototoxic and photoallergic reactions, summarizes the most common photosensitizers, and presents the clinical features and diagnostic procedures of phototoxic and photoallergic reactions. History of the problem photoreactive agents could be found in products and Photosensitive reactions have been recognized for how to prevent or control photosensitivity disorders. thousands of years. In ancient Egypt, India, and Greece psoralen-containing plants extracts were combined Photosensitivity reactions with exposure to sunlight to treat skin diseases. Photosensitivity is an adverse cutaneous reaction In 1897, reports of dermatitis following contact that results when a certain chemical or drug is applied with parsnips and/or angelica came from both the topically or taken systemically at the same time when United States and England, and in 1916, E. Freund a person is exposed to UVR or visible light (2). Pho- observed characteristic hyperpigmented lesions that tosensitivity reactions may be more specifically cate- he attributed to eau de cologne containing bergamot gorized as phototoxic or photoallergic in nature (2– oil (1). Unfortunately, none of the authors recognized 5). Phototoxicity is much more common than pho- the necessity of ultraviolet radiation (UVR) for the toallergy (2–7). reaction. Photosensitivity reactions are hardly predictable. In 1938, H. Kuske showed that plant furocoumarins They can occur in persons of any age (4) but are more caused photosensitization, and shortly thereafter, T. common in adults than children, possibly because Jensen and K. G. Hansen reported that UVR between adults are usually exposed to more medications and 320 and 380 nm caused the reaction maximum (1). In topical agents (5). The degree of photosensitivity 1967, British researchers discovered that sandalwood varies among individuals; having the same impacts oil in sunscreens and cosmetics caused photoallergies not everyone will have a photoreaction. A person who (2). Shortly thereafter, French scientists demonstrated has a photoreaction after a single exposure to an agent that bergamot oil in sunscreens caused photosensitivity may not react to the same agent after repeated expo- disorders, and German researchers isolated photoreac- sures; on the other hand, person who is allergic to one tive agents from colognes, perfumes, and oral contra- chemical may develop photosensitivity to related che- ceptives (2). mical (2). Researchers published lists of photoreactive agents Several factors, such as quantity and location of found in several hundred of substances, chemicals, the chemical or drug on/in the skin; quantity, spectrum, and drugs. In order to avoid photosensitive reactions, and penetration of the activating radiation; thickness scientists try to determine the photosensitizing pro- of the horny layer; degree of melanin pigmentation; perties of such substances before drugs are introduced immunological status of the affected person (6), may in therapy or products made available on the market. influence the features of photosensitivity reactions. In recent years research focuses on identifying what Person’s immunological status is very important be- Correspondence to R. Dubakienė, Republican Center of Allergology, Vilnius University, Antakalnio 124, Vilnius 10200, Lithuania. E-mail: [email protected] 620 Rūta Dubakienė, Miglė Kuprienė cause photosensitivity reactions are found frequently 10). Some of the common drugs and their mechanisms in immunocompromised human immunodeficiency of photodamage are listed in Table. virus (HIV)-infected patients (2, 6). If patient exhibits Topically applied photosensitizers, halogenated sa- photodistributed skin problems of unknown origin, licylanilides, benzocaine in soaps and other household the possibility of HIV infection should be suspected. products, or musk ambrette in aftershave lotions; and Phototoxicity is a form of photosensitivity that is stilbenes in whiteners are the most frequent cause of not depended on an immunologic response (3–8). photoallergic eruptions (10). Phototoxic reactions are dose dependent and will oc- A common adverse effect of several anti-infective cur in almost any one who takes or applies an adequate agents and their derivatives is photosensitivity reac- amount of the offending agent and UVR, but the dose tions. Most of them are cyclic and tricyclic hydrocar- necessary to induce such a reaction varies among indi- bons, frequently containing an alternative double-bond viduals (5). Phototoxic reactions can appear on first isoprene or naphthyridine nucleus (6). Fluoroquino- exposure to the agent and demonstrate no cross-sensi- lones, antibacterial agents, are well known to cause tivity to chemically related agents (5). photosensitivity as an adverse effect, and their cross- Photoallergy is a form of photosensitivity that is reactivity has been clinically documented (11). Empi- immunologically mediated (3–8). Photoallergic reac- rical studies suggest pefloxacin and fleroxacin as the tions develop only in sensitized persons (6–9) and are most potent photosensitizers while enoxacin, norflo- not dose dependent, although a sensitized person is xacin, and ofloxacin are less potent (6). Tetracyclines likely to get a stronger reaction at a much higher dose are example of the phototoxic hazards of antibiotics. (6). Chemically related agents via cross-sensitivity or Among them, chlorine derivatives most frequently cross-allergenicity may cause eruptions (5). In such cause phototoxicity (6). cross-reaction, photosensitivity to one chemical in- Sulfa-derived drugs (sulfonamide antibacterials, creases a person’s tendency for photosensitivity to the hypoglycemics, diuretics) have been well-known cau- next chemical agent (2). ses of photosensitivity reactions since 1939 when S. Epstein first reported photoallergic contact dermatitis Photosensitizers following intradermal injection of sulfanilamide (6). Photoreactive agents or photosensitizers are che- Sunscreens help to reduce the effects of UVR, but micals that induce a photoreaction. The chemicals may some sunscreens contain ingredients that cause pho- be therapeutic, cosmetic, industrial, or agricultural tosensitivity themselves. Among them, para-amino- (10). Photosensitivity reactions can be caused by in- benzoic acid (PABA) most frequently causes photo- jected, oral, or topically applied chemical photosen- sensitivity reactions; benzophenones are second in sitizers (2). In most cases, the mechanism is photo- causing skin reactions (5). toxicity, but some agents cause photoallergy, and for Usage of products containing photoreactive agents some agents the mechanism is either uncertain, or both can aggravate existing skin diseases (eczema, herpes, mechanisms may be involved (2, 6). Most phototoxic etc.) and also precipitate or worsen autoimmune di- reactions result from the systemic administration of seases (lupus erythematosus, rheumatoid arthritis) (2). the agent; photoallergic reactions may be caused by either topical or systemic administration of the agent Mechanisms of phototoxicity and photoallergy (4). The sunlight plays an important role in photobio- Everyday used items such as perfumes, soaps, deo- logical processes. However, the sunlight that has given dorants, lotions, hair sprays and styling creams, arti- us life can also cause significant morbidity in the form ficial sweeteners, petroleum products, tattoos, and cer- of sunburns, drug reactions, photosensitive diseases, tain foods may contain photoreactive agents. and photoaging. Recurrent episodes of phototrauma Many widely used medications are associated with over a lifetime can lead to the development of skin photosensitivity reactions, but the frequency with cancers. which individual medication evokes this response is Transformation of H to He in sun’s interior libera- quite variable in the human population. The more tes vast amounts of energy which reach the earth’s commonly used medications containing photoreactive surface in the form of electromagnetic radiation agents include antibiotics (tetracyclines, fluoroquino- (EMR): x-rays, cosmic rays, electric waves, radio lones, sulfonamides, etc.), nonsteroidal anti-inflam- waves, infrared, visible light, and UVR (12). Photo- matory drugs (NSAIDs), cardiovascular drugs, diure- sensitivity reactions could be induced by a delimited tics, antidiabetic drugs, antidepressants, antipsy- range of the EMR spectrum that includes UVR (200– chotics, antihistamines, skin agents, and others (3, 4, 400 nm) and visible light (400–800 nm) (6). UVR Medicina (Kaunas) 2006; 42(8)
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