Clinical features and diagnosis of allergic contact dermatitis

INTRODUCTION — Allergic contact dermatitis (ACD) is the classic presentation of a T cell-mediated, delayed-type hypersensitivity response to exogenous agents [1,2]. The words "dermatitis" and "eczema" are often used interchangeably to describe a pattern of inflammation of the skin characterized acutely by erythema, vesiculation, and pruritus (picture 1). Chronic exposure typically leads to reduction of the erythema accompanied by lichenification (thickening and hardening of the skin) and persistence of itch (picture 2). The clinical presentation may vary depending upon the triggering agent and individual's reactivity, but in most cases, the lesions are primarily confined to the site of contact [3,4].

This topic will discuss the clinical presentation, diagnosis, and differential diagnosis of ACD. The pathophysiology, patch testing for, and management of ACD are discussed separately. Eyelid contact dermatitis is also reviewed separately.

●(See "Basic mechanisms and pathophysiology of allergic contact dermatitis".)

●(See "Patch testing".)

●(See "Management of allergic contact dermatitis in adults".)

●(See "Eyelid dermatitis (eczema)".)

EPIDEMIOLOGY AND RISK FACTORS — The incidence and prevalence of ACD in the general population are not known. Data are often extrapolated from surveillance studies on occupational dermatitis. In industrialized nations, up to 30 percent of all occupational diseases involve the skin. Irritant and contact dermatitis account for more than 90 percent of cases of occupational skin disease [5].

Surveillance studies in the United States and United Kingdom have reported an annual incidence of contact dermatitis (including irritant and ACD) of 13 to 34 cases per 100,000 workers [6-8]. The agents most frequently implicated in occupational contact dermatitis included rubber-related materials, protective equipment, soap and cleansers, resins, and acrylics.

Information on the main allergens responsible for ACD in the general population is derived from retrospective studies of patch testing referral centers [9]. In one study, metals, fragrances, topical antibiotics, preservatives, chemicals used in hair care products, topical corticosteroids, glues, plastics, and rubber were the most common allergen groups associated with positive patch test reaction [10].

In a meta-analysis of 28 studies including over 20,000 patch-tested individuals from the general population, the pooled prevalence of contact allergy was 20.1 percent (95% CI 16.8-23.7), with nickel being the most common allergen, followed by fragrance mix, cobalt, and Myroxylon pereirae [11]. Among children, nickel sulfate, ammonium persulfate, gold sodium thiosulfate, thimerosal, and toluene-2,5-diamine (p-toluenediamine) are the most common sensitizers [12]. (See "Common allergens in allergic contact dermatitis".)

Multiple studies from around the world indicate that, of patients presenting for patch testing, 20 to up to 40 percent will be allergic to nickel [13-18]. In North America, the most common cause of ACD is from contact with poison ivy, oak, and sumac. (See "Poison ivy (Toxicodendron) dermatitis".)

Risk factors for ACD include:

●Occupation – Workers at highest risk of ACD include health professionals, chemical industry workers, beauticians and hairdressers, machinists, and construction workers.

●Age – ACD was once considered a disorder of the adult population. Children were thought to be spared because of a low exposure to potential allergens and an immature immune system. However, it is now recognized that contact sensitization begins in early childhood via exposures such as vaccinations, piercing, topical medications, and cosmetics [19,20].

The incidence of ACD increases with age. Repetitive and prolonged exposure to potential sensitizers may account for the high rate of ACD in older adults. Medical comorbidities, including stasis dermatitis and venous ulcerations, are contributing factors [21]. (See "Stasis dermatitis".)

●History of atopic dermatitis – The role of atopy in ACD is controversial, although several studies report a high rate (up to over 50 percent) of positive patch tests among atopic individuals [22-28]. However, a 2017 meta-analysis of 74 studies did not find a difference in the frequency of contact sensitization between individuals with atopic dermatitis and those without (odds ratio [OR] 0.89, 95% CI 0.77-1.03) [29].

CLINICAL FEATURES

Lesion morphology — Acute ACD lesions consist of erythematous, indurated, scaly plaques (picture 3A-C). Vesiculation and bullae may be seen in severe cases (picture 1). Edema may be prominent in areas in which the skin is thin, such as the eyelids, lips, and genitalia (picture 4).

Repeated or continued exposure to allergens results in chronic disease. The skin becomes dry, scaly, and thicker as a result of acanthosis, hyperkeratosis, edema, and cellular infiltration in the dermis (picture 2). Lichenification and fissuring may develop later [30]. Secondary changes include excoriation or impetiginization (picture 5). Subacute dermatitis has a mixture of both acute and chronic features [31].

Lesion distribution — ACD is typically localized to the skin areas that come in contact with the allergen (picture 6A-C). However, patchy or diffuse distributions may occur, depending upon the nature of the allergen or secondary transfer of the allergen from the primary site of contact to distant skin areas:

●The involvement of hands, face, or eyelids, which most commonly come in contact with the environment, occurs most frequently in ACD.

●Allergens applied to the scalp, including hair dyes and shampoos, may elicit dermatitis in adjacent skin.

●Facial lesions may result from direct contact with cosmetic products or tools or from involuntary transfer of allergens to the face (eg, eyelid ACD from nail polish).

●A pendant-like distribution of lesions (berloque dermatitis) in the neck and chest suggests a reaction to fragrances in perfumes and lotions (picture 7A-B).

●A diffuse or patchy dermatitis of the trunk, often with accentuation in the axillary folds, may be caused by cloth dyes or textiles. Rubber components may induce ACD at the site of contact with elastic waistbands (picture 8).

●Periorificial ACD involving periocular, perioral, and genital areas may be induced by fragrances, detergents, or preservatives in hygiene products, including moist wipes [32].

●Dermatitis involving the dorsal aspect of the foot suggests ACD related to shoe chemicals (eg, rubber accelerators or potassium dichromate) (picture 3C).

●Involvement of photoexposed areas suggests photoallergic contact dermatitis. (See "Photosensitivity disorders (photodermatoses): Clinical manifestations, diagnosis, and treatment", section on 'Photoallergy'.)

●Occupational ACD frequently involves the hands and requires a careful ascertainment of occupation-specific exposures.

Symptoms — The dominant symptom of ACD is itch. However, ACD may cause a variety of other symptoms, including burning, stinging, or pain [33].

DISEASE COURSE — If left untreated, ACD can evolve from an acute form to a subacute and then chronic eczematous dermatitis. Chronic dermatitis can negatively impact an individual's health-related quality of life, particularly in social functioning and psychologic wellbeing [34,35]. Successful allergen avoidance can result in clearance of ACD.

Persistence of dermatitis in the face of dutiful allergen avoidance suggests an alternative diagnosis (eg, systemic medication allergy, cutaneous lymphoma) or concurrent diagnosis (ie, atopic dermatitis). (See 'Differential diagnosis' below.)

HISTOPATHOLOGY — The histology of ACD mirrors the clinical picture. In acute ACD, the epidermis is of normal thickness, and spongiosis (intercellular edema leading to the disruption of intercellular adhesion and formation of vesicles) is the dominant feature (picture 9). An additional feature is the exocytosis of lymphocytes and eosinophils into spongiotic foci. The upper dermis contains an infiltrate of lymphocytes, histiocytes, and eosinophils, with perivascular accentuation [36].

In subacute ACD, there are mild to moderate spongiosis, moderate acanthosis (epidermal hyperplasia from increased mitotic activity of keratinocytes), and a denser dermal lymphohistiocytic infiltrate. Chronic lesions may show prominent epidermal acanthosis with hyperkeratosis and areas of parakeratosis. Spongiosis may be present focally but often is minimal. The inflammatory infiltrate is sparse.

DIAGNOSIS — The diagnosis of ACD is based upon a combination of [4]:

●Clinical features (morphology, location, and symptoms) of the eruption

●History of exposure to a putative allergen during work, hobbies, or home activities

●Patch testing results, if performed

●Laboratory tests and/or histopathologic examination

●Lack of recurrence after empirical treatment of the dermatitis and avoidance of the suspected allergen

Clues from clinical examination — The morphology, regional distribution, and temporal course of dermatitis frequently suggest the diagnosis of ACD. (See 'Lesion morphology' above and 'Lesion distribution' above.)

The typical appearance of ACD is a well-demarcated, pruritic, eczematous eruption localized to the area of skin that comes in contact with the allergen (picture 3A-C). The eruption may be acute, with vesiculation and weeping, or chronic (lichenified or scaly plaques).

The eruption may not remain anatomically limited to the initial site of contact. For example, a patient with a neomycin contact allergy may exhibit a modest eruption at the site of application on the torso and a diffuse, concomitant dermatitis of the face due to passive transfer of the allergenic ointment to the face. Body washes or shampoos or cloth dyes and textiles may cause a patchy or diffuse dermatitis.

Less commonly, ACD may present with a photosensitivity reaction: The eruption is limited to photo-exposed skin areas and follows the application of sunscreens, fragrances, or topical nonsteroidal anti-inflammatory drugs (NSAIDs) (picture 10). (See "Photosensitivity disorders (photodermatoses): Clinical manifestations, diagnosis, and treatment", section on 'Photoallergy'.)

History — A comprehensive, multiyear history is helpful for the diagnosis of ACD (table 1). The source of contact with allergens may be identified by reviewing the patient's activities, including occupation and hobbies. Products and objects for personal use, including prescription or over-the-counter topical preparations, cosmetics and toiletries, hair dyes, fragrances, eyeglasses, gloves, and clothing, should be reviewed. A patient's recall may not be complete, and revisiting the history after obtaining the results of patch testing may be useful.

A history of long-term exposure to an allergen does not rule out contact allergy, since multiple exposures are typically necessary for sensitization and dermatitis to occur. In addition, an individual's susceptibility to ACD may change over time because of aging, customs, or comorbidities (eg, stasis dermatitis and leg ulcers) [31]. Infrequently, sensitization may occur after a single exposure.

Health professionals, chemical industry workers, beauticians and hairdressers, machinists, and construction workers have an increased risk of developing occupational ACD [37]. However, exposure to common industrial allergens, including cements, glues, plasters, and solvents, may also occur at home.

A history of improvement during weekends or holidays suggests an occupational origin, whereas worsening during weekends or holidays suggests recreational exposure to allergens. A seasonal variation may indicate photo-aggravation or photoallergy [30]. (See "Photosensitivity disorders (photodermatoses): Clinical manifestations, diagnosis, and treatment", section on 'Photoallergy'.)

A previous history of contact dermatitis may provide a clue to the origin of a relapse. For example, earring dermatitis may precede nickel dermatitis of the hands by several years.

Patients with ACD often report a history of atopy (childhood flexural eczema, asthma, hay fever, or conjunctivitis).

Patch testing — Patch testing is an essential investigation in patients with persistent eczematous eruptions when contact allergy is suspected or cannot be ruled out [1,9,38]. Patch testing may help to identify allergens that should be avoided and is discussed separately. (See "Patch testing".)

Laboratory tests and biopsy — Laboratory tests are not routinely necessary in the evaluation of patients for ACD but may be helpful in excluding other disorders with similar clinical features. For example, a KOH examination of scale from the eruption or swab cultures may rule out a fungal or bacterial infection [31].

Histologic examination on itself may provide little help in differentiating ACD from other eczematous dermatitides (including irritant contact dermatitis (ICD), atopic, nummular, dyshidrotic, and seborrheic dermatitis), since all present eosinophilic spongiosis as the key feature. However, histologic examination may be helpful when the diagnosis is not clear.

Response to empiric therapy — When the possible offending allergen is identified on the basis of clinical features and history, response to empiric therapy may avoid the need for patch testing. Improvement or resolution of the dermatitis with allergen avoidance and empiric treatment supports the diagnosis of ACD [39]. (See "Management of allergic contact dermatitis in adults".)

DIFFERENTIAL DIAGNOSIS

Clinical — ACD can mimic or complicate other types of eczema and other dermatoses as listed in the table (table 2 and picture 11A-C) [40].

Differentiating ACD from irritant contact dermatitis (ICD) is particularly difficult since they have a similar clinical and histopathologic morphology [41]. Patch testing may be useful to confirm the diagnosis of ACD. There is no specific test for the diagnosis of ICD. (See "Irritant contact dermatitis in adults".)

Histopathologic — Eosinophilic spongiosis and exocytosis of eosinophils and lymphocytes are the key features of ACD and other eczematous dermatitides but may be seen also in other skin diseases.

For example, eosinophilic spongiosis may be the only histologic feature in the early, urticarial phase of bullous pemphigoid [42]. Direct immunofluorescence staining and measurement of circulating anti-BP antibodies will differentiate ACD from bullous pemphigoid.

Early, patch stage mycosis fungoides (MF) may be difficult to differentiate from subacute or chronic ACD. Both diseases show minimal or no spongiosis and lymphocytic exocytosis. However, in MF, lymphocytic exocytosis is more prominent, lymphocytes may have atypical features (hyperchromatic, cerebriform nuclei), and clusters of atypical lymphocytes (Pautrier microabscesses) may be seen in the epidermis (picture 12).

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Contact dermatitis".)

SUMMARY AND RECOMMENDATIONS

●Overview – Allergic contact dermatitis (ACD) is a T cell-mediated, delayed-type hypersensitivity response to exogenous agents. Workers at highest risk of ACD include health professionals, chemical industry workers, beauticians and hairdressers, machinists, and construction workers. Contact allergens may be found at home or in the workplace and may include metals, glues, plastics, rubber, fragrances, topical antibiotics, preservatives, and chemicals used in hair care and cosmetic products. (See 'Introduction' above and 'Epidemiology and risk factors' above.)

●Clinical presentation – Acute ACD lesions consist of pruritic, erythematous, indurated, scaly plaques, typically localized to the skin areas that come in contact with the allergen (picture 3A-C). Vesiculation and bullae may be seen in severe cases (picture 1). Edema of the eyelids, lips, and genitalia may be prominent (picture 4).

In chronic ACD, the skin is dry, scaly, and thicker. Lesions are typically localized in the skin areas that come in contact with the allergen (picture 6A-B). (See 'Lesion morphology' above and 'Lesion distribution' above.)

●Diagnosis – The diagnosis of ACD is based on a combination of clinical features (ie, morphology and location of lesions, symptoms), history of exposure to a putative allergen, and patch testing results, if performed. The involvement of hands, feet, eyelids, and lips, which most commonly come in contact with the environment, suggest the diagnosis of ACD.

The source of contact allergens can be identified through a detailed review of the patient's exposures at home and in the workplace (table 1). Patch testing may be required to confirm the diagnosis and differentiate ACD from other types of eczematous dermatitis (table 2). (See 'Diagnosis' above and 'Differential diagnosis' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges James Yiannias, MD, who contributed to earlier versions of this topic review.