TOXIC RESPONSES OF THE SKIN

SKIN
Two major components of the skin:
2 Epidermis
2 Dermis (makes up approximately 90% of the skin, in terms of thickness)
Functions of the Skin
1. Protection
2. Sensation
3. Temperature regulation
4. Excretion
5. Water resistance
SKIN as a Barrier
2 Skin protects the body against external insults in order to maintain homeostasis.
2 If an insult is severe or intense enough to overwhelm the protective function of the skin,
acute or chronic injury becomes readily manifest.
Percutaneous absorption
2 Is the process of absorption through the skin from topical application.
2 Stratum corneum is the primary barrier to percutaneous absorption.
2 Disease (e.g., Psoriasis) or other conditions (e.g., wounds and abrasion) that compromise this
barrier can permit greatly increased uptake of poorly permeable substances.
Transdermal Drug Delivery
2 Specially designed patches are currently in use to deliver drugs such as clonidine, estradiol,
testosterone, nitroglycerin, scopolamine, fentanyl and nicotine for therapeutic purposes.
Biotransformation
2 The ability of the skin to metabolize agents that diffuse through it contributes to its barrier
function.
2 The epidermis and pilosebaceous units are the major sites of metabolism in the skin.
CONTACT DERMATITIS
2 Contact dermatitis is a type of skin inflammation that results from exposure to allergens or
irritants.
2 Occupational skin diseases
2 Clinical characteristics:
| Erythema (redness)
| Induration ( thickening and firmness)
| Scaling (flaking)
| Vesiculation (blistering)
Two major categories of Contact dermatitis
1. Irritant dermatitis
| A non-immune-related response caused by the direct action of an agent on the skin.
| Strong acids, bases, solvents, and unstable or reactive chemicals are possible irritants.
MOTA:
| Agents causing irritant dermatitis acts by disrupting the keratin ultrastructure or directly
injuring critical cellular macromolecules or organelles.
| Examples : Direct corrosives, solvents, oxidizing, and reducing agents, and dehydrating agents

2. Allergic Contact Dermatitis
| A delayed type IV hypersensitivity reaction
| an allergic response caused by contact with a substance or allergen.
| A minute quantity of material elicits overt reactions.
| 20% of all contact dermatitis is allergic in nature
| Examples: Nickel, Chromium, Cobalt, Formaldehyde etc.

MOTA:
2 Agents causing sensitivity reaction that are systemically administered (orally) results in a
generalized skin eruption with associated symptoms such as headache, malaise and arthralgia.

Chemical Burns
2 Caused by extremely corrosive and
reactive chemicals that produce
immediate coagulative necrosis that
results in tissue damage, with
ulceration and sloughing.

PHOTOTOXICOLOGY
Phototoxicology
2 It deals with the injurious effects of
ultraviolet and visible radiation.
2 The principal phototoxic effect is
the erythema, edema, and pain
(sunburn) produced in skin by
exposure to solar radiation.
2 Is the study of adverse events
resulting from the interaction
between light and a test material or
substance
2 Phototoxic dermatitis occurs when
the allergen or irritant is activated by sunlight.
Photosensitivity
2 An abnormal sensitivity to UV and visible light
2 may result from endogenous or exogenous factors
2 May lead to photoxicity or photoallergy.
COMPARISON OF PHOTOTOXICITY AND PHOTOALLERGY
PHOTOTOXICITY PHOTOALLERGY
Photo irritation Type IV delayed
hypersensitivity reaction
MOTA occurs when a
phototoxic substance or
drugs was activated by
exposure to sunlight
and cause damage to
the skin.
ultraviolet exposure
changes the structure
of the drug so that it
is seen by the body's
immune system as an
invader (antigen).
Onset Immediate (min-hours) Delayed (1-3 days)
characteristics Resembles sunburn Lead to eczema
Recurrence clears up once the drug
is discontinued.
may recur after sun
exposure even after the
drug has been cleared
from the system.
Immune
relation
Not related Immune related
Examples Bergamot oil, psoralen,
tetracycline
Chlorpromazine,
Chlorothiazide,
sulfonamides
Selected Phototoxic chemicals
Flurocoumarins
2 8-Methoxypsoralen
2 5-Methoxypsoralen
2 Trimethoxypsoralen
Polycyclic aromatic hydrocarbons
2 Anthracene
2 Fluoranthene
2 Acridine
2 Phenanthrene
Porphyrin derivatives
2 Hematoporphyrin
Drugs
2 Tetracycline
2 Sulfonamides
2 Sulfonylurea
2 Nalidixic acid
2 Thiazides
2 Phenothiazines
2 NSAID
Dyes
2 Disperse blue 35
2 Eosin
2 Acridine orange


ACNE
2 A pleomorphic disease with a multifactorial etiology.
2 May be influenced by of sebum, hormones, bacteria, genetics, and environmental factors.
Chloracne
2 is an acne-like eruption of blackheads, cysts, and pustules associated with over-exposure to
certain halogenated aromatic compounds like dioxins which are most often found in
fungicides, insecticides, herbicides and wood preservatives.
2 It develops a few months after swallowing, inhaling or touching the responsible agent.
2 the most consistent manifestation and hallmark of dioxin intoxication.
Pigmentary disturbunces
2 will be confined only to those disturbances of pigmentation which involve melanin. Generally
speaking such disturbances may be based on either
| an increase in amount,
| a decrease in amount or absence, or
| an abnormal location or distribution of melanin pigment in the skin or hair
Granulomatous- seen in a wide variety of diseases, both infectious and non-infectious.
Urticaria
2 (from the Latin urtica, nettle,)
2 commonly referred to as hives, is a kind of skin rash notable for pale red, raised, itchy
bumps. Hives might also cause a burning or stinging sensation.
2 Hives are frequently caused by allergic reactions; however, there are many nonallergic causes.
Most cases of hives lasting less than six weeks (acute urticaria) are the result of an allergic
trigger.




Toxic epidermal necrolysis (TEN)
2 Toxic epidermal necrolysis (TEN) is a potentially life-threatening dermatologic disorder
characterized by widespread erythema, necrosis, and bullous detachment of the epidermis and
mucous membranes, resulting in exfoliation and possible sepsis and/or death (see the image
below).
2 Mucous membrane involvement can result in gastrointestinal hemorrhage, respiratory failure,
ocular abnormalities, and genitourinary complications.
2 The pathophysiology of TEN has not been fully elucidated; however, various theories have
received wide acceptance. TEN is believed to be an immune-related cytotoxic reaction aimed at
destroying keratinocytes that express a foreign antigen
Skin cancers
2 Skin cancers (skin neoplasms) are named after the type of skin cell from which they
arise. Basal cell cancer originates from the lowest layer of the epidermis, and is the most
common but least dangerous skin cancer. Squamous cell cancer originates from the middle
layer, and is less common but more likely to spread and, if untreated, become fatal. Melanoma,
which originates in the pigment-producing cells (melanocytes), is the least common, but most
aggressive, most likely to spread and, if untreated, become fatal.
Basal cell carcinoma
Note the pearly translucency to fleshy color, tiny blood vessels on the surface, and sometime
ulceration which can be characteristics. The key term is translucency.
Squamous cell carcinoma
Commonly presents as a red, crusted, or scaly patch or bump. Often a very rapid growing tumor.
Malignant melanoma
The common appearance is an asymmetrical area, with an irregular border, color variation, and often
greater than 6 mm diameter.

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