Photodermatitis is an abnormal response to ultraviolet radiation (UVR) that can be acute or chronic. For clinical purposes, photodermatitis is categorized into four groups:

• Idiopathic photodermatoses (e.g., polymorphic light eruption, actinic prurigo, hydroa vacciniforme, chronic actinic dermatitis, solar urticaria), in which the mechanism of photosensitization is unknown;
• Exogenous chemical or drug reactions (e.g., phototoxic reactions, photoallergic reactions), in which photosensitizers (e.g., drugs, fragrances, sunscreens) are externally applied or ingested;
• Metabolic or genetic photodermatoses (e.g., xeroderma pigmentosum, variegate porphyria, pellagra—from niacin deficiency, Hartnup's disease—a congenital disorder due to a defect in renal tubular absorption of amino acids and excretion of tryptophan derivatives), in which the photosensitizer is endogenously formed and deposited in the skin;
• Systemic and cutaneous diseases exacerbated by UVR (e.g., systemic lupus erythematosus, herpes simplex, acne, rosacea, eczema, pemphigus, dermatomyositis).

UVR is often classified by wavelength ranges; wavelengths ranging from 290 to 400 nm can adversely affect human skin. Categories are as follows:

• UVC is less than 290 nm and is mostly blocked by the ozone layer.
• UVB ranges from 290 to 320 nm and causes sunburn, tanning, aging, and carcinogenic changes to the skin.
• UVA (long wave UV light) ranges from 320 to 400 nm and can cause photoreactions through window glass.

UVR on earth is 90% UVA and 10% UVB. Photoreactions from UVR depend on the season or time of the year, the latitude, thickness of the ozone layer, amount of light reaching the earth, and the topography.

More than 115 chemical agents and drugs in the United States taken systemically or applied topically may cause photodermatitis. A certain wavelength of light, usually 320 to 400 nm (UVA), induces sunburn responses and eczematous and urticarial reactions. Phototoxic reactions (nonimmunologic) result from the absorption of UVB light. Phototoxic drugs or chemicals include:

• Coal tar derivatives
• Antipsychotics (e.g., phenothiazines)
• Antimicrobials (e.g., tetracyclines, sulfonamides)
• Antidepressants (e.g., desipramine)
• Anxiolytics (e.g., alprazolam, tetrazepam)
• Antifungals (e.g., griseofulvin)
• Antimalarials (e.g., quinine)
• Thiazide diuretics
• Sulfonylureas
• Dyes (e.g., eosins, methylene blue)
• Chemotherapeutic agents (e.g., 5-fluorouracil, vinblastine)
• Psoralens
• Retinoids
• Nonsteroidal anti-inflammatory drugs (e.g., piroxicam)
• Furocoumarins (i.e., plant derivatives found in limes and celery)

Photoallergic reactions (immunologic) result from absorption of UVA light, causing a delayed hypersensitivity response. Photoallergic drugs or chemicals include fragrances (e.g., methylcoumarin, musk ambrette), sunscreens with p-aminobenzoic acid (PABA) esters, and salicylanilide-containing industrial cleaners.

Immunologic diseases such as systemic lupus erythematosus (SLE), solar urticaria, porphyria cutanea tarda, erythropoietic protoporphyria, pellagra, pemphigus, or polymorphous light eruption may induce photodermatitis or be exacerbated by UVR.

• Exposure to UVR for 30 minutes to several hours; thus, outbreaks in spring and summer months are characteristic
• Exposure to UV light from 11:00 a.m. to 2:00 p.m., when 50% of the UVR is emitted
• Skin type may influence likelihood of reaction. Skin type I is fair, white; red or blond hair; green or blue eyes; most sensitive. Skin type II is white, blond or light brown hair; blue eyes; minimal tanning

• Pruritic papules, vesicles, bullae, or plaques
• Eczematous, lichenoid, and hyperpigmented lesions
• Localization of outbreaks to photoexposed areas
• Pain, erythema, and swelling
• Chills, headache, fever, and nausea
• Diminution of symptoms after repeated exposure (60%)

• Systemic lupus erythematosus (SLE)
• Benign lymphocytic infiltration of skin
• Atopic or seborrheic eczema
• Sunburn of patients with extremely fair skin or xeroderma pigmentosa
• Lymphocytoma cutis
• Sarcoidosis

The history and physical examination are the most important diagnostic tools for photodermatitis, particularly when focused on the time of year and duration of exposure leading to eruptions; duration, distribution, and morphology of eruptions; and age, sex, occupation, topical application, skin exposures, medication, recreational activities, and family history of the patient. A review of systems is instrumental in helping to detect an associated connective tissue disease.

• UV-induced cell damage, caused by energy absorption leading to generation of singlet oxygen, superoxide anion radical, and other free radicals
• Perivascular infiltrate in upper dermis and middle dermis; dominated by T cells with some neutrophils
• Dermal and perivascular edema as well as endothelial swelling
• Spongiosis (intracellular edema), dyskeratosis (abnormal keratinization of keratinocytes), exocytosis (aggregation of leukocytes in epidermis), and basal cell vacuolization (formation of small spaces or vacuoles)

Laboratory tests are used to rule out systemic illness:

• Measurement of antinuclear factor—to rule out SLE
• Anti-SSA (Ro) and anti-SSB (La) antibody titers—to rule out SLE
• Measurement of porphyrin concentrations of blood, urine, and stool—to determine comorbid conditions such as porphyria cutanea tarda or variegate porphyria
• Histologic assessment of skin lesions

• Immunofluorescence—to rule out SLE
• Phototesting and photopatch testing—to identify allergens that may exacerbate or induce photosensitivity; to test cross-reactivity of drugs and chemicals

• Identification and avoidance of the offending agent
• Measures to protect skin from sun exposure
• Cool, wet dressings for vesicular or weepy eruptions
• Desensitization with narrow band 312 nm phototherapy
• Phototherapy—UV exposure of prophylactic low-dose psoralen plus UVA light (PUVA) or UVB therapy—to control symptoms of polymorphous light eruption

• Immunosuppressive therapy with azathioprine (50 to 150 mg/day)—for extremely photosensitive patients
• Glucocorticoids (for <1 week)—to control eruptions
• Hydroxychloroquine, thalidomide, beta-carotene, and nicotinamide—for patients unable to be treated with PUVA

Given the immunologic, inflammatory, and often recurrent nature of photodermatitis, it seems logical that certain CAM approaches or modalities would be helpful adjuncts to conventional care, particularly in reducing the frequency and severity of reactions. In fact, some promising results have been published regarding the following antioxidants and other micronutrients:

• Beta-carotene and other carotenoids (see section on Drug Therapies above)
• Fish oil and other forms of omega-3 fatty acids
• Glutathione
• Vitamin B₃
• Vitamin B₆
• Vitamin C
• Vitamin D
• Vitamin E

See the subsections that follow for details about each of these topics.

In addition, pellagra, one cause of photodermatoses, reflects a niacin deficiency; raising questions about the possibility of other nutrient deficiencies also contributing to photosensitivity as is seen in the case of actinic prurigo associated with protein deficiency.

Similar to some of the nutrients mentioned, green tea contains antioxidants that may also confer photoprotection. Finally, similar to medication that can predispose an individual to photoreactivity, certain herbs can have the same sensitizing effect (see section entitled Herbs).

Beta-carotene and Other Carotenoids

In a trial of 20 healthy subjects randomly assigned to carotenoids, primarily from beta-carotene, or carotenoids plus vitamin E, MED improved when on either carotenoids alone or in combination with vitamin E. Each group served as its own control, comparing MED before and after supplementation. Each group improved significantly from its own baseline, but the two groups did not differ significantly from one another in terms of level of MED at the end of the trial. The implication is that vitamin E did not confer benefit over and above the carotenoid supplement alone (Stahl et al. 2000).

Although beta-carotene is used standardly for treatment of certain types of photodermatitis, results of studies have not all been positive. Following baseline MED determinations, subjects were given either a single oral supplement of 120 mg beta-carotene or placebo and exposed to UV irradiation equivalent to 3xMED. The formation of sunburn cells was not significantly different between the treatment group and placebo. The authors remark that although beta-carotene has been used clinically in treating erythropoietic protoporphyria and other photosensitivity conditions, it may not protect against cutaneous photodamage in normal individuals (Garmyn et al. 1995).

Fish Oil/Omega 3

As indicated in the Overview, polymorphic light eruption (PLE) is a common form of photodermatitis. Thirteen patients with PLE received dietary supplements of fish oil for three months. Photoprovocation testing with UVB and UVA was performed and skin prostaglandin levels were measured in all 13 patients before and after completion of 3 months of supplementation. Following fish oil supplementation, the MED of UVB significantly increased and the median score for provocation of PLE by UVA significantly decreased. Recent evidence suggests an immunologic basis for PLE; modulation of skin prostaglandins with omega-3 oils may be the cause of the photoprotection seen in this trial (Rhodes et al. 1995).

Similarly, two out of three case reports of children with hydroa vacciniforme, a rare scarring photosensitivity disorder also mentioned in the Overview, suggest possible benefits of supplementation with omega-3 oils. Fish oil supplementation in the first child demonstrated clinically pronounced improvements despite sun exposure. Fewer lesions than normal appeared in summer and no new scarring occurred. A challenge with UVA radiation provoked no response following fish oil supplementation. In the second child, mild clinical improvement was observed. Vesicles still appeared, although they were of shorter duration and less prone to scarring. Provocation test was positive but fewer lesions were provoked compared to baseline. No clinical improvement was seen in the third patient (Rhodes and White 1998).

Glutathione

In an animal study, glutathione demonstrated some protection against light induced oxidation (Kamat and Devasagayam 1996). How this translates to humans is not known at this time.

Protein 

Primarily seen in malnourished populations, actinic prurigo (see section entitled Overview) is hypothesized to be related to a diet deficient in protein or a specific amino acid. Patients treated with a high-protein diet have reportedly had good response for treatment of actinic prurigo, although patients tend to relapse a few weeks after returning to their standard diet (Magaña-Garcia and Magaña 1993).

Vitamin B₃

In a pilot study, 42 patients with polymorphous light eruption were treated with oral nicotinamide (the biologically active form of niacin), 3 g/day for 2 weeks. Despite extensive sun exposure, 25 subjects remained lesion-free (Neumann et al. 1986). Another more recent study of rats illustrated how nicotinamide may be conferring protection. Nicotinamide, acting as an antioxidant and free radical scavenger, showed inhibition of singlet oxygen in the animal study (Kamat and Devasagayam 1996).

Vitamin B₆

Two case reports describe marked reduction in erythropoietic protoporphyria associated phototoxicity by pyridoxine (vitamin B₆). Two children with erythropoietic protoporphyria and significant photosensitivity were administered high doses of pyridoxine with marked reduction of symptoms. Because pyridoxal phosphate promotes the enzymatic conversion of tryptophan to nicotinic acid, the authors speculate that the effects of high-dose pyridoxine are due to enhanced nicotinamide synthesis (Ross and Moss 1990). However, pyridoxine hydrochloride has also been implicated in photoallergic drug eruptions, although such cases seem very rare. Three case reports describe discrete episodes of photoallergic dermatitis following injection or oral administration of pyridoxine hydrochloride, which resolved upon withdrawal of the substance (Murata et al. 1998; Tanaka et al. 1996).

Vitamin D

Mice pretreated either systemically or topically with 1,25-dihydroxyvitamin D₃ showed significant dose-dependent protection against UVB-induced damage. Rat keratinocytes treated with 1,25-dihydroxyvitamin D₃ showed increased survival rates compared to controls. The authors suggest that the efficacy of low-dose vitamin D₃ against UVB-induced cytotoxicity is indicative of a natural defense system whereby derivatives of photochemically produced vitamin D₃ promote the synthesis of endogenous metallothionein (MT, a cysteine-rich antioxidant protein found in epidermal cells) (Hanada et al. 1995). It is not clear if this information will translate to humans and how it will do so. Future research should be conducted regarding photoprotection of vitamin D supplementation in humans.

Vitamins C and E

Given the connection between formation of free radicals and damage to the skin (see section entitled Pathology/Pathophysiology), reactive oxygen scavengers (such as the antioxidant vitamins C and E) may be employed to reduce UV-induced skin reactions. In a double-blind, placebo-controlled study, 20 subjects were randomized to take either 2 g ascorbic acid and 1,000 IU of d-alpha-tocopherol or placebo for 8 days. The treatment and control groups had equivalent minimal erythema dose (MED) at baseline. At the end of 8 days of supplementation, the vitamin group showed an increased MED (indicating less photosensitivity) in 80% of the subjects compared to no change in the placebo group (Eberlein-König et al. 1998).

The possible synergistic effects of vitamins C and E were examined further in a randomized, placebo-controlled study of 40 subjects with skin type II (see section entitled Risk Factors for definition) taking either 2 g (3,000 IU) per day of d-alpha-tocopherol (group 1), 3 g per day of ascorbic acid (group 2), 2 g (3,000) per day of d-alpha-tocopherol combined with 3 g per day of ascorbic acid (group 3), or placebo (group 4) for 50 days. Only group 3 showed statistically significant increases in MEDs after supplementation. These results suggest that vitamins C and E may have synergistic protective effects, although supplementation only achieved a sun protection factor (SPF) of approximately 2 (Fuchs and Kern 1998).

Treatment with vitamin E may also be beneficial in cases of actinic prurigo (see section entitled Overview). A comparison study of patients treated for six months with either 100 IU daily of vitamin E or 500 mg tid of tetracycline showed similar results; tetracycline is thought to be beneficial in this condition because of its suppression of oxygen radical activity. Two groups of eight patients were observed under treatment. Efficacy was analyzed for cheilitis, papules, infiltrates, plaques, lichenification, and pruritus, the primary signs and symptoms of actinic prurigo. Although cheilitis, infiltrates, and plaques did not show significant changes throughout the study, lichenification and pruritus demonstrated remarkable improvement in both the vitamin E and tetracycline groups (Durán et al. 1996).

• Green Tea—Antioxidant properties in green tea may provide protection against UV-light–induced erythema. Epigallocatechin-3-gallate (EGCG), the major polyphenolic constituent of green tea (Camellia sinensis), has demonstrated photoprotection in previous animal models. In a human study, volunteers were subjected to UVB radiation equal to a 4 MED dose, delivered to buttock skin with or without topical EGCG applied 30 minutes before exposure. Skin punch biopsies were obtained from the treated areas and nontreated control areas and evaluated for myeloperoxidase and cyclooxygenase activities. While EGCG does not block UVB absorption, it appears to act indirectly. In this study, EGCG significantly inhibited erythema formation and myeloperoxidase and cyclooxygenase activities; it also protected against leukocyte infiltration, prostaglandin metabolite formation, and cellular oxidative damage (Katiyar et al. 1999).
• St. John's wort (Hypericum perforatum) is known to exhibit phototoxic properties when large amounts are ingested or when combined with photosensitizing drugs.

In addition to St. John's wort, other possible photosensitizing herbs include:

• Angelica seed and root (Angelica archangelica) (Blumenthal et al. 1998)
• Celery stems (Apium graveolens) (Newall et al. 1996)
• Rue (Rutae folium) (Blumenthal et al. 1998)
• Lime oil/peel ( Citrus aurantifolia) (Leung and Foster 1996)

Anecdotal reports suggest that individualized homeopathic remedies may be a useful adjunct to the prevention and treatment of photodermatitis; however, potential benefits in this area have not yet been subjected to scientific inquiry.

Patients who require steroids for photosensitivity reactions must be monitored closely. In addition, anyone with a history of photodermatitis or photoreactivity should monitor frequency and duration of eruptions. This information can help determine etiology and treatment.

• Limit skin exposure especially at peak ultraviolet intensity.
• Use broad-spectrum sunscreens, especially against UVA, with a sun protection factor (SPF) of 30 to 50.
• Cover up with long-sleeved shirts, long pants, and wide-brimmed hats.
• Discontinue use of the photosensitizing drug or agent.

• Persistence of photosensitivity, resulting in chronic actinic dermatitis
• Postinflammatory hyperpigmentation
• Premature aging of the skin
• Squamous cell and basal cell carcinomas
• Increased UV exposure after PUVA and UVB phototherapy
• Melanoma

Most photosensitivity reactions are benign and self-limited; however, symptoms can be severe when associated with a systemic disorder or when the exposure has been severe. Some photosensitivity reactions can continue for years after exposure has discontinued.

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