Contact Dermatitis Part One

1. Contact Dermatitis Part One Boris Ioffe, D.O., Pharm.D. 08-14-06

2. Irritant contact dermatitis (ICD) • Accounts for approximately 80% of all contact dermatitis • ICD is the result of a local toxic effect when the skin comes in contact with irritant chemicals such as soaps, solvents, acids, or alkalis • This 37-year-old woman developed a contact irritant dermatitis from obsessive-compulsive hand washing 20-30 times a day. www.drmatlas.org

3. Introduction to Irritant Contact Dermatitis • ICD is a cutaneous inflammation resulting from a direct cytotoxic effect of a chemical or physical agent • Constitutes nearly 80% of occupational contact dermatitis (OCD) • OCD is a matter of public health importance, contributing to combined direct and indirect annual costs (in the USA) of up to $1 billion when accounting for medical costs, workers compensation, and lost time from work

4. Epidemiology of ICD • The US Bureau of Labor Statistics data show that occupational skin diseases accounted for 10% to 15% of all occupational illnesses • High-risk occupations with frequent irritant exposure in caterers, furniture industry workers, hospital workers, hairdressers, chemical industry workers, dry cleaners, metal workers, florists, and warehouse workers

5. Epidemiology of ICD • Clinical manifestations of ICD are determined by: • Properties of the irritating substance • Host factors • Environmental factors including concentration, mechanical pressure, temperature, humidity, pH, and duration of contact • Cold alone may also reduce the plasticity of the horny layer, with consequent cracking of the stratum corneum • Occlusion, excessive humidity, and maceration increase percutaneous absorption of water-soluble substances

6. Bilateral shoe irritant dermatitis resulting from chronic occlusive footwear

7. Epidemiology of ICD • Important predisposing characteristics of the individual include: • Age, race, sex, pre-existing skin disease, anatomic region exposed, and sebaceous activity • Both infants and elderly are affected more by ICD because of their less robust epidermal layer • Patients with darkly pigmented skin seem to be more resistant to irritant reactions • Other skin disease such as active atopic dermatitis may predispose an individual to develop ICD • The most commonly affected sites are exposed areas such as the hands and the face, with hand involvement in approximately 80% of patients and face involvement in 10%

8. Pathogenesis of ICD • Denaturation of epidermal keratins • Disruption of the permeability barrier • Damage to cell membranes • Direct cytotoxic effects

10. Acute Irritant Contact Dermatitis • Commonly seen in occupational accidents • Irritant reaction reaches its peak quickly, within minutes to hours after exposure • Symptoms include stinging, burning, and soreness • Physical signs include erythema, edema, bullae, and possibly necrosis • Lesions restricted to the area where the irritant or toxicant damaged the tissue • Sharply demarcated borders and asymmetry pointing to an exogenous cause • Most frequent irritants are acids and alkaline solutions

12. Acute Delayed Irritant Contact Dermatitis • Delayed inflammatory response characteristic of certain irritants such as anthralin, benzalkonium chloride, and ethylene oxide • Visible inflammation is not seen until 8 to 24 hours after exposure • Symptoms are more frequently burning rather than pruritus • Sensitivity to touch and water are elicited • This form of ICD is commonly seen during diagnostic patch testing

13. Irritant Reaction Irritant Contact Dermatitis • Type of subclinical irritant dermatitis in individuals exposed to wet chemical environments such as hairdressers, caters, or metalworkers • Characterized by scaling, redness, vesicles, pustules, and erosions • Often begins under occlusive jewelry and then spreads over the fingers to the hands and forearms • May simulate dyshidrotic dermatitis

14. Cumulative Irritant Contact Dermatitis • Consequence of multiple sub-threshold skin insults, without sufficient time between them for complete barrier function repair • In contrast to acute ICD, the lesions of chronic ICD are less sharply demarcated • Itching and pain due to fissures of hyperkeratotic skin are symptoms of chronic ICD • Skin findings include lichenification, hyperkeratosis, xerosis, erythema, and vesicles

15. Asteatotic Dermatitis • Exsiccation eczematid ICD • Seen mainly during the winter months in elderly individuals who frequently bath without remoisturizing • Skin appears dry with ichthyosiform scale and patches of eczema craquele

16. Traumatic Irritant Contact Dermatitis • May develop after acute skin trauma, such as burns, lacerations, or acute ICD • Patients should be asked if they have cleansed with strong soaps or detergents • Characterized by eczematous lesions most commonly on the hands, that persist • Healing is delayed with redness, infiltration, scale, and fissuring in the affected areas

17. Pustular and Acneform Irritant Contact Dermatitis • Result to certain irritants such as metals, croton oil, mineral oils, tars, greases, cutting and metal working fluids, and naphthalenes • Should be considered in conditions in which folliculitis or acneform lesions develop in setting outside of typical acne • Pustules are sterile and transient • Milia may develop in response to occlusive clothing, adhesive tape, ultraviolet and infrared radiation Chloracne. Note heavy involvement of retroauricular skin with comedones and cysts

18. Subjective or Sensory Irritant Contact Dermatitis • Reports of stinging or burning in the absence of visible cutaneous signs of irritation • Response to irritants such as lactic or sorbic acid

19. Airborne Irritant Contact Dermatitis • Develops on irritant-exposed skin of the face and periorbital regions • Often simulates photoallergic reactions • Involvement of the upper eyelids, philtrum, and submental regions help to differentiate from photoallergic reaction

20. Frictional Irritant Contact Dermatitis • Results from repeated low-grade frictional trauma • Plays adjuvant role in ACD and ICD • Characterized by hyperkeratosis, acanthosis, and lichenification, often progressing to hardening, thickening, and increased toughness 9 year old girl demonstrates a lichenified hyperpigmented round plaque on the top of her thumb produced by chronic thumbsucking. www.dermatlas.org

21. Pathology of ICD • Variable mix of inflammation, necrosis of epidermal keratinocytes, and mild spongiosis • Combination of an upper dermal perivascular infiltrate of lymphocytes with minimal extension of inflammatory cells into the overlying epidermis, and widely scattered necrotic keratinocytes is most typical picture • True features of interface dermatitis are absent, and spongiosis should be focal or absent • Over time additional histologic findings include acanthosis with mild hypergranulosis and hyperkeratosis

22. Acids • Inorganic and organic acids can be corrosive to the skin • Cause epidermal damage via protein denaturation and cytotoxicity • Symptoms include erythema, vesication, and necrosis • Hydrofluoric and sulfuric acid can cause the most severe burns • Hydrofluoric acid, used in the semiconductor industry, is able to penetrate intact skin with subsequent dissociation in deeper tissues and resultant liquefactive necrosis

23. Chromic acid causes ulcerations known as ‘chrome holes’ and often perforates the nasal septum Chemical burns and irritant dermatitis from nitric acid can cause a distinctive yellow discoloration In general, organic acids are less irritating than inorganic acids Formic acid has the greatest corrosive potential of the organic acids Acids Examples of chrome holes www.cdc.gov/niosh/ocderm

24. Alkalis • Strong Alkalis include sodium, ammonium, potassium hydroxide, sodium and potassium carbonate, and calcium oxide • Found in soaps, detergents, bleaches, ammonia preparations, lye, drain pipe cleaner, toilet bowl cleansers, and oven cleaner • Often more painful and damaging than acids • No vesicles, necrotic skin that appears dark brown then black, ultimately becomes hard, dry, and cracked • Alkalis disrupt barrier lips and denature proteins with subsequent fatty acid saponification

25. Cement mixed with water can cause ulcerative damage due to alkalinity Changes appear 8 to 12 hours after exposure Chronic irritant cement dermatitis may also develop over months to years Can accompany allergic contact dermatitis Alkalis Hand dermatitis due to contact with cementdermnetnz.org/dermatitis/chrome

26. Metal Salts • Include arsenic trioxide, beryllium compounds, calcium oxide, copper salts, inorganic mercury, thimerosal, and selenium • Signs ranging from ulceration to folliculitis

27. Solvents • Act mainly by dissolving the intercellular lipid barrier of the epidermis • Prolonged skin contact can result in severe burns and well as systemic toxicity • Examples include turpentine, benzene, toluene, xylene, carbon tetrachloride, gasoline, and kerosene

28. Professional paint and crayon illustrator with bilateral palmar dermatitis secondary to repeated contact with paint solvents. Extensive patch testing excluded allergic contact dermatitis

29. Detergents and Cleansers • Include any surface active agent (surfactant) that concentrates at the oil-water interfaces and has both emulsifying and cleansing properties • Found in skin cleansers, cosmetics, and household cleaning products • Surfactants cause protein denaturation of the stratum corneum, impairing barrier function • Anionic detergents such as alkyl sulfates and alkyl carboxylate salts are the most irritating

30. Disinfectants • Include, alcohols, aldehydes, phenolic compounds, halogenated compounds, surfactants, dyes, oxidizing agents, and mercury compounds • Weak toxic agents that can cause chronic ICD Practicing dentist with moderately severe irritant hand dermatitis from chronic exposure to disinfecting solutions and antiseptics. The results of patch testing, latex challenge testing, and RAST testing were negative.

31. Plastics • Three categories: thermoplastics, thermosettings, elastomers • Skin damage is attributed to monomer ingredients, hardeners, and stabilizers • Final hardened plastic product is generally considered inert

32. Food • Agriculture, fishing, catering, and food processing • Often work without gloves, in damp working conditions with frequent hand washing • Mechanical, thermal, and climatic factors • Nearly 100% of exposed persons in food handling and fishing professions may be affected by chronic irritant hand dermatitis

33. Water • Ubiquitous skin irritant • Tropical immersion foot, seen during Vietnam War • Hairdressers, hospital cleaners, cannery workers, bartenders • Irritancy of water is exacerbated by occlusion 9 year old is an habitual hand washer who develops a contact irritant dermatitis every winter. At times she washes over 10 times a day. www.dermatlas.org

34. Fibers larger than 3.5 um in diameter cause the highly pruritic contact dermatitis caused by fiberglass Erythematous papules with superimposed excoriations on neck and dorsal hands Wool and rough clothing cause dermatitis in atopic individuals Fabric/man-made vitreous fibers Fiberglass dermatitis www.cdc.gov/niosh/ocderm

35. Differential Diagnosis • Allergic and ICD, especially in chronic stage appear similar by clinical appearance, histology, and immunohistology • Look identical with erythema, papules, xerosis, scaling, and lichenification with sharp borders • ICD has remained a diagnosis of exclusion when dermatitis is not explained by positive patch test to a known allergen • More frequent complaint of burning and stinging with ICD in contrast to pruritus in ACD

37. Treatment • Avoidance of causative irritants at home or in the workplace is the primary TX • Engineering controls to reduce exposure in the workplace • Shielding and personal protection such as gloves and special clothing • Pre-exposure protection by protective creams, removal of irritants by mild cleaning agents, and enhancement of barrier function generation by emollients and moisturizers • Emphasizing personal and occupational hygiene • Establishing educational programs to increase awareness in the workplace

38. TX Chemical Burns • Initial tx irrigation with large volumes of water, if chemical is insoluble in water a soap solution may be used • High pressure water to be avoided to prevent splashing • 2.5% calcium gluconate gel used to tx hydroflouric acid burns, immediate application of a weak acid such as vinegar, lemon juice, or 0.5% hydrochloric acid will lessen the effect of alkali burns • Ulcerated areas should be managed with antibacterial creams or ointments to prevent secondary infection • Frequent evaluation is required because ulcers may progress over several days • Excision, debridement and/or grafting may speed healing • Monitoring of blood, liver, and kidney function may be needed when exposed to chemicals with potential for systemic toxicity such as hydrofluoric acid, phenolic compounds, chromic acid, and gasoline

39. Chronic ICD Treatment • Tx goal is to restore normal epidermal barrier function • Topical corticosteroids frequently used • Systemic corticosteroids although helpful in reducing inflammation, are not useful in treatment of chronic ICD unless offending contactants are avoided • PUVA and Grenz ray considered for chronic dermatitis that does not respond to other tx • Hyperkeratotic palmoplantar dermatitis from frictional or chronic ICD may benefit from the adjunctive use of systemic retinoids such as acitretin

40. Allergic contact dermatitis (ACD) • ACD accounts for approximately 20% of all contact dermatitis • ACD is a type IV, delayed or cell-mediated immune reaction that is elicited when the skin comes in contact with a chemical to which an individual has been previously sensitized • Synonyms include contact dermatitis and contact eczema • Allergic contact dermatitis. Linear streaks seen with ACD to poison ivy.

41. Key Features ACD is a pruritic, eczematous reaction Acute ACD and many cases of chronic ACD are well demarcated and located to the site of contact with the allergen Prototypic reactions are ACD due to poison ivy and nickel Patch testing remains the gold standard for accurate and consistent diagnosis ACD This healthy adolescent developed an intensely pruritic vesiculobullous allergic contact dermatitis from hair dye. Dermatlas.org

42. Classic picture of ACD is a well-demarcated erythematous vesicular and/or scaly patch or plaque with well defined margins corresponding to the area of contact • Chronic allergic contact dermatitis leading to hand dermatitis. This golfer wore one leather glove and had positive patch tests to potassium dichromate and a piece of his glove. Courtesy of Kalman Watsky, M.D.

43. Allergic contact dermatitis to leather shoes. Note the correspondence to sites of exposure. Courtesy of Yale Residents Slide Collection.

44. Because ICD and ACD are not always discernable clinically, patch testing is required to help identify an allergen or exclude an allergy to a suspected allergen. • Allergic contact dermatitis. Chronic hand dermatitis due to ACD to mercaptobenzothiazole found in rubber gloves

45. Epidemiology of ACD • Affects the old and young, individuals of all races, and both sexes • Differences in genders usually based on exposure patterns, such as nickel allergy being seen more frequently in women, presumably due to greater exposure to jewelry • Occupations and avocations play an important role • Allergens differ from region to region, e.g. preservatives used in personal care products can vary based on government legislation

46. Pathogenesis of ACD • ACD is a type IV hypersensitivity response • Requires prior sensitization to the chemical in question • Subsequent re-exposure of individual leads to allergen being presented to a primed T-cell milieu leading to release of numerous cytokines and chemotactic factors leading to the clinical picture of eczema • Once sensitized a low concentration of causative chemical elicits a response

47. Induction of contact hypersensitivity. Application of contact allergens (Ag) induces the release of cytokines by keratinocytes, Langerhans cells and other cells within the skin. These cytokines in turn activate Langerhans cells which uptake the antigen and emigrate into the regional lymph nodes. During this process, the Langerhans cells mature into dendritic cells. In addition, the antigen is processed, re-expressed on the surface and finally presented to naïve T cells in the regional lymph node. Upon appropriate antigen presentation, T cells bearing the appropriate T cell receptor clonally expand and become effector T cells. These alter their migratory behavior due to the expression of specific surface molecules like CLA. Effector T cells recirculate into the periphery where they may later meet the antigen again. Ag, antigen; KC, keratinocyte.

48. Elicitation of contact hypersensitivity. Application of contact allergens (Ag) into a sensitized individual causes the release of cytokines by keratinocytes and Langerhans cells. These cytokines induce the expression of adhesion molecules and activation of endothelial cells which ultimately attracts leukocytes to the site of antigen application. Among these cells, T effector cells are present which are now activated upon antigen presentation either by resident cells or by infiltrating Langerhans cells. Antigen-specific T cell activation again induces the release of cytokines by T cells. This causes the attraction of other inflammatory cells including granulocytes and macrophages which ultimately cause the clinical manifestation of contact dermatitis. Ag, antigen; DDC, dermal dendritic cell; KC, keratinocyte; CLA, cutaneous lymphocyte antigen.

49. Clinical features of ACD • Acute blistering and weeping • Chronic lichenified and scaly plaques • Patchy and diffuse distributions may be seen with body washes and shampoos • Acute bullous allergic contact dermatitis due to poison ivy. This distribution is seen in patients who wear gloves. Courtesy of Yale Residents Slide Collection • Chronic allergic contact dermatitis due to glutaraldehyde. The patient was an optometrist

50. Pathology of ACD • ACD is the prototype of spongiotic dermatitis • Acute stage: variable degree of spongiosis with mixed dermal inflammatory infiltrate containing lymphocytes, histiocytes, and variable numbers of eosinophils • Moderate to severe reactions show intraepidermal vesiculation • Subacute to chronic stages have epidermal hyperplasia, often psoriasiform