Seminar on Dermatological Toxicities

Presented By: Surbhi sharma M.Pharm II sem Pharmacy Practice

Dermatological Toxicology
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Skin is the largest organ of the body. It protects the body from Environmental Insults, and maintains Body Homeostasis. Dermatological toxicity includes toxicities to skin, nails. Dermatotoxicological Investigations of Toxicities including Irritation, Skin Corrosion and Allergy necessitate Toxicological Skin Testing prior to Manufacture, Transport, or Marketing of Drugs, Cosmetics, and many other Products.

CONTACT DERMATITIS
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Contact dermatitis falls into the two major categories of irritant and allergic forms. Both involve inflammatory processes and have indistinguishable clinical characteristics of erythema (redness), induration (thickening and firmness), scaling (flaking), and vesiculation (blistering) in areas of direct contact with the chemical. High and long time exposure. Individuals vary greatly in sensitivity to irritant dermatitis. Lipid-rich moisturizers and barrier creams containing dimethicone or perfluoropolyethers may be useful in protecting skin from offending agents. Allergic contact dermatitis is a delayed (T-cell mediated) hypersensitive reaction.

Contact irritant dermatitis

Diagnosis and Testing When a patient exhibits allergic contact dermatitis, finding the responsible chemical is important to avoid continued exposure. Patch testing is commonly employed for this.

GRANULOMATOUS DISEASE

PHOTOTOXICITY
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Phototoxic reactions from exogenous chemicals may be produced by systemic or topical administration or exposure. Adequate doses of artificially produced UVC (<290 nm) or X-rays can produce profound physical and toxicological skin changes.. The protective skin pigment melanin, synthesized in melanocytes, absorbs a broad range of radiation from UVB (290320 nm) through the visible spectrum. Other chromophores in the skin include amino acids, primarily tryptophan and to a lesser extent tyrosine, and their breakdown products(e.g., urocanic acid), which absorb light in the UVB range. Biologically, the most significant chromophore is DNA, because damage from radiation can have lasting effects on the genetic information in target cells. The most evident acute feature of ultraviolet radiation exposure is erythema (redness or sunburn).

exposing the skin to coal tar and sunlight can quickly produce a stinging sensation and elicit damage resembling a bad sunburn with hyperpigmentation. Pigmentary changes such as freckling and hypomelanotic areas, wrinkling, telangiectasias (fine superficial blood vessels), actinic keratoses (precancerous lesions), and malignant skin lesions such as basal and squamous cell carcinomas and malignant melanomas are all consequences of chronic exposure to ultraviolet light exposure.

Phototoxicity from lime juice

PHOTOSENSITIVITY y Abnormal sensitivity to ultraviolet and visible light. y Results from a variety of genetic diseases, such as xeroderma pigmentosum, impair the cells ability to repair ultraviolet light induced damage. y A constitutional sensitivity to light (porphyria cutanea tarda) can be precipitated by alcohol, estrogens, or certain antibiotics in individuals with hereditary abnormalities in porphyrin synthesis, and an acquired sensitivity in general by hexachlorobenzene and mixtures of polyhalogenated aromatic hydrocarbons.

URTICARIA
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an immediate type I hypersensitivity reaction. subsequent contact can lead to development of hives. Food allergies and pharmaceuticals are major causes of acute urticaria.

PIGMENTARY DISTURBANCES
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Melanocytes protect the skin from harmful effects of ultraviolet light by producing the insoluble polymeric pigment melanin. hyperpigmentation is well knownto result from exposure to phototoxic agents including coal tar, coumarin derivatives found in perfumes and certain food such as limes (shown in Fig. 19-2G) and food plants (parsely, celery), dyes in cosmetics, and elements such as lead, bismuth, and arsenic

leukoderma from rubber antioxidants

hyperpigmentation from mercaptobenzothiazole

DERMATOLOGIC TOXICITY OF CHEMOTHERAPEUTIC AGENTS

There are anecdotal reports on the efficacy of pyridoxine at a dose of 50 mg three times daily for treatment of palmar-plantar erythrodysesthesia due to taxane therapy and one case of successful treatment with local hypothermia. Recently, a trial using a glycerin-containing Elasto-Gel thermal glove (APT, Akromed, France), which was cooled to 25C and worn on the hands just before, during, and after docetaxel infusion, was shown to significantly decrease the incidence of onycholysis, pigmentation, and acral erythrodysesthesia. There are anecdotal reports of successful treatment measures for liposomal doxorubicinassociated acral erythrodysesthesia, including topical 99% dimethylsulfoxide four times daily, regional cooling, and oral pyridoxine with methylprednisolone. Thalidomide was approved in 1998 for the cutaneous treatment of moderate to severe erythema nodosum leprosum. Hall et al summarized four historical and two new cases of exfoliative erythroderma and/or toxic epidermal necrolysis (TEN) associated with thalidomide therapy.

Tattoos in a dermatological perspective:

Tattoos are very popular used standard industrial pigments lacks basic knowledge concerning pigments, epidemiology and complications such as allergy, granulomas, skin cancer and foreign body reactions. risks associated with laser treatment are unknown.

References
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Curtis D. Klaassen, Casarett and Doulls Toxicology, Seventh Edition 2008, 741-761. Aimee S. Payne, William D. James, Raymond B. Weissb. Dermatologic toxicity of chemotherapeutic agents. Elsevier Inc. 2006; 86-97. Hgsberg T, O'Goshi K, Serup J. Tattoos in a dermatological perspective. Ugeskr Laeger. 2011 Jan 3;173(1):34-39.