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Skin
Disorders, Photodermatitis |
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Overview |
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Definition |
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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. |
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Etiology |
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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. |
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Risk Factors |
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- 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
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Signs and Symptoms |
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- 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%)
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Differential
Diagnosis |
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- 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
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Diagnosis |
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Physical Examination |
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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. |
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Pathology/Pathophysiology |
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- 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)
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Laboratory Tests |
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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
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Other Diagnostic
Procedures |
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- 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
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Treatment Options |
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Treatment Strategy |
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- 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
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Drug Therapies |
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- 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
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Complementary and Alternative
Therapies |
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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). |
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Nutrition |
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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). |
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Herbs |
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- 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)
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Homeopathy |
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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. |
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Patient Monitoring |
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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.
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Other
Considerations |
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Prevention |
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- 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.
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Complications/Sequelae |
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- 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
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Prognosis |
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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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References |
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Abramowitz AI, Resnik KS, Cohen KR. Margarita photodermatitis [letter]. N
Engl J Med. 1993;328(12):891.
Adamski H, Benkalfate L, Delaval Y, et al. Photodermatitis from non-steroidal
anti-inflammatory drugs. Contact Dermatitis. 1998;38(3):171-174.
American Academy of Pediatrics. Ultraviolet light: a hazard to children.
Pediatrics. 1999;104(2):328-333.
Blumenthal M, ed. The Complete German Commission E Monographs: Therapeutic
Guide to Herbal Medicines.Boston, Mass: Integrative Medicine Communications;
1998:35-36; 214-215; 245-249.
Callen JP. Photodermatitis in a 6-year-old child. Arthritis Rheum.
1993;36(10):1483-1485.
Darr D, Dunston S, Faust H, Pinnell S. Effectiveness of antioxidants (vitamin
C and E) with and without sunscreens as topical photoprotectants. Acta Derm
Venereol (Stockh). 1996;76(4):264-268.
Durán MM, Ordoñez CP, Prieto JC, Bernal J. Treatment of actinic prurigo in
Chimila Indians. Int J Dermatol. 1996;35(6):413-416.
Eberlein-König B, Placzek M, Przybilla B. Protective effect against sunburn
of combined systemic ascorbic acid (vitamin C) and d-alpha-tocopherol (vitamin
E). J Am Acad Dermatol. 1998;38(1):45-48.
Enta T. Dermacase. Contact photodermatitis. Can Fam Physician.
1995;41:577, 586-587.
Enta T. Dermacase. Photodermatitis reaction to chlorothiazide. Can Fam
Physician. 1994;40:1269, 1276.
Fernandez de Corres L, Diez JM, Audicana M. Photodermatitis from plant
derivatives in topical and oral medicaments. Contact Dermatitis.
1996;35(3):184-185.
Freedberg IM, Eisen AZ, Wolff K. Fitzpatrick's Dermatology in General
Medicine. Vol. 1. 5th ed. New York, NY: McGraw-Hill; 1996:1573-1586.
Fuchs J, Kern H. Modulation of UV-light-induced skin inflammation by
D-alpha-tocopherol and L-ascorbic acid: a clinical study using solar simulated
radiation. Free Radic Biol Med. 1998;25(9):1006-1012.
Garmyn M, Ribaya-Mercado JD, Russell RM, Bhawan J, Gilchrest BA. Effect of
beta-carotene supplementation on the human sunburn reaction. Exp
Dermatol. 1995;4(2):104-111.
Goldman L, Bennett JC. Cecil Textbook of Medicine. 21st ed.
Philadelphia, Pa: W.B. Saunders; 2000:2295-2296.
Hadshiew I, Stäb F, Untiedt S, Bohnsack K, Rippke F, Hölzle E. Effects of
topically applied antioxidants in experimentally provoked polymorphous light
eruption. Dermatology. 1997;195(4):362-368.
Hanada K, Sawamura D, Nakano H, Hashimoto I. Possible role of
1,25-dihydroxyvitamin D3-induced metallothionein in photoprotection against UVB
injury in mouse skin and cultured rat keratinocytes. J Dermatol Sci.
1995;9(3):203-208.
Kamat JP, Devasagayam TP. Methylene blue plus light-induced lipid
peroxidation in rat liver microsomes: inhibition by nicotinamide (vitamin
B3) and other antioxidants. Chem Biol Interact.
1996;99(1-3):1-16.
Katiyar SK, Matsui MS, Elmets CA, Mukhtar H. Polyphenolic antioxidant
(-)-epigallocatechin-3-gallate from green tea reduces UVB-induced inflammatory
responses and infiltration of leukocytes in human skin. Photochem
Photobiol. 1999;69(2):148-153.
Leroy D, Dompmartin A, Szczurko C, Michel M, Louvet S. Photodermatitis from
ketoprofen with cross-reactivity to fenofibrate and benzophenones.
Photodermatol Photoimmunol Photomed. 1997;13(3):93-97.
Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in
Food, Drugs and Cosmetics. 2nd ed. New York, NY: Wiley and Sons; 1996.
Magaña-Garcia M, Magaña M. Actinic prurigo. The possible etiologic role of an
amino acid in the diet. Med Hypotheses. 1993;41(1):52-54.
Moschella SL, Hurley HJ. Dermatology. 3rd ed. Philadelphia, Pa: W.B.
Saunders; 1992:507-530.
Murata Y, Kumano K, Ueda T, Araki N, Nakamura T, Tani M. Photosensitive
dermatitis caused by pyridoxine hydrochloride. J Am Acad Dermatol.
1998;39(2 pt 2):314-317.
Neumann R, Rappold E, Pohl-Markl H. Treatment of polymorphous light eruption
with nicotinamide: a pilot study. Br J Dermatol. 1986;115(1):77-80.
Newall CA, Anderson LA, Phillipson JD. Herbal Medicine: A Guide for
Health-care Professionals. London: The Pharmaceutical Press; 1996.
Pigatto PD, Legori A, Bigardi AS, et al. Multicenter study of allergic
contact photodermatitis: epidemiological aspects. Am J Contact Dermat.
1996;7(3):158-163.
Quinones D, Sanchez I, Alonso S, et al. Photodermatitis from tetrazepam.
Contact Dermatitis. 1998;39(2):84.
Rhodes LE, Durham BH, Fraser WD, Friedmann PS. Dietary fish oil reduces basal
and ultraviolet B-generated PGE2 levels in skin and increases the threshold to
provocation of polymorphic light eruption. J Invest Dermatol.
1995;105(4):532-535.
Rhodes LE, White SI. Dietary fish oil as a photoprotective agent in hydroa
vacciniforme. Br J Dermatol. 1998;138(1):173-178.
Ross JB, Moss MA. Relief of the photosensitivity of erythropoietic
protoporphyria by pyridoxine. J Am Acad Dermatol. 1990;22(2 pt
2):340-342.
Scholzen TE, Brzoska T, Kalden DH, et al. Effect of ultraviolet light on the
release of neuropeptides and neuroendocrine hormones in the skin: mediators of
photodermatitis and cutaneous inflammation. J Investig Dermatol Symp
Proc. 1999;4(1):55-60.
Stahl W, Heinrich U, Jungmann H, Sies H, Tronnier H. Carotenoids and
carotenoids plus vitamin E protect against ultraviolet light-induced erythema in
humans. Am J Clin Nutr. 2000;71(3):795-798.
Tanaka M, Niizeki H, Shimizu S, Miyakawa S. Photoallergic drug eruption due
to pyridoxine hydrochloride. J Dermatol. 1996;23(10):708-709.
Tierney LM, McPhee SJ, Papadakis MA. Current Medical Diagnosis and
Treatment 2000. New York, NY: Lange Medical Books/McGraw-Hill;
2000:177-178. |
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Copyright © 2000 Integrative Medicine
Communications This publication contains
information relating to general principles
of medical care that should not in any event be construed as specific
instructions for individual patients. The publisher does not accept any
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interactions, and contraindications before administering any drug, herb, or
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