INFLAMMATORY DISORDERS OF THE SKIN AND SUBCUTIS:
A PRACTICAL AND ANALYTICAL APPROACH
CASE #1: ALLERGIC CONTACT DERMATITIS
Cynthia M. Magro, M.D., A.Neil Crowson, M.D., and Martin C. Mihm Jr., M.D.
Allergic contact dermatitis and pityriasis rosea represent the two histomorphological poles of spongiotic
dermatitis. Irrespective of etiology, the hallmarks of spongiotic dermatitis are exocytosis of lymphocytes
into an epidermis which shows spongiosis with variable vesiculation and a parakeratotic scale. Additional
light microscopic features may be present which point to a precise etiology. Lesions comprise erythematous
papules, vesicles or exudative plaques which are often itchy and develop twelve to forty-eight hours after
re-exposure to antigen. Lesions will resolve 2 or 3 weeks after the allergen is removed and respond quickly
to topical steroid application. The specific allergen may be identified in a patch test.
Patients with allergic contact dermatitis to nickel and nonallergic individuals display different
nickel-specific T cell responses. Specifically patients with nickel allergy exhibit a clonal
hyperproliferative response of CD8 positive lymphocytes to nickel while interleukin 10 production by CD4
positive cells is an important regulator of the immune response. The interleukin 10 production is lower in
patients with nickel allergy relative to those without a specific allergy to nickel.
Cutaneous immune responses involve T helper (TH) type 1 (TH1) and type 2 (TH2) T cells, characterized by
secretion of interferon-gamma (Ifn-gamma) and interleukin-4 (IL-4). IL-4 immunoreactivity has been found in
cells in the dermal infiltrate in lesional skin of some patients with allergic contact dermatitis however
not all patients exhibit this pattern of a Th2 dominant cytokine milieu. In addition the expression of IL-4
receptors by cutaneous mast cells provides a route through which local effects of IL-4 might be mediated.
Allergic contact dermatitis characteristically shows spongiotic vesiculation of the epidermis; in
consequence, the parakeratotic scale often contains plasma.
Acute allergic contact dermatitis shows
pronounced exocytosis of lymphocytes and eosinophils, with vesicles comprising lymphocytes, eosinophils and
Langerhans' cells an almost ubiquitous finding. The papillary dermis shows variable edema. The dermis
contains an interstitial and perivascular lymphocytic, histiocytic and eosinophilic infiltrate of variable
intensity. An allergic contactant such as neomycin, zinc and nickel can provoke a purely dermal-based
reaction with no epithelial spongiosis, but often accompanied by pronounced papillary dermal edema. With
persistence of exposure to the allergen, epidermal proliferation becomes more striking, the intra-epidermal
inflammatory infiltrate becomes less exuberant, the degree of spongiosis diminishes, and the intensity of
the dermal infiltrate may increase with concomitant fibroplasia. This variable maturation of the process
yields subacute dermatitis (when spongiosis is still easily recognized) and chronic dermatitis (when
pronounced epidermal hyperplasia with minimal spongiosis ensues). Complicating these pictures may be the
presence of excoriation artefacts, namely, wedge-shaped areas of eosinophilia of the superficial layers of
the stratum spinosum often imbued with a neutrophil-rich crust.
Allergic contact dermatitis represents a delayed-type hypersensitivity reaction following re-exposure to an
allergen: medication, a plant product, food stuff, cosmetic or industrial chemical. Delay-type
hypersensitivity reactions occur when an allergen, usually a low molecular weight Hapten which is lipid
soluble, penetrates the skin and binds to a structural or cell-surface protein to form the complete antigen
which is then processed by Langerhans' cells which present the modified antigen to memory T-helper
lymphocytes. The latter migrate to regional lymph nodes where clonal expansion of lymphocytes sensitized to
that specific antigen ensues. Following re-exposure, a proliferation of T-lymphocytes occurs both within
the skin and the regional lymph nodes; the activated lymphocytes elaborate cytokines, including IL-2 and
IFN-gamma which cause a further influx of inflammatory cells including lymphocytes, eosinophils and
basophils. Homing of lymphocytes to the skin involves specific interactions of lymphocyte function antigens
(LFA's) with endothelial adhesion molecules which are up-regulated in the site of inflammation. Another
effect of the cytokine elaboration by T-helper cells is epidermal proliferation.
When the mononuclear cell reaction is pronounced and/or includes transformed lymphocytes, the appellation
"lymphomatoid hypersensitivity reaction" is sometimes applied, as these reactions can histologically
simulate mycosis fungoides. Allergic contact dermatitis can be mimicked by arthropod-bite responses; on
occasion a wedge-shaped insect bite punctum shows a necrotizing neutrophilic reaction within the epidermis.
As well, blood vessels frequently show perivascular and mural fibrin deposition and additional level
sections may disclose components of insect mouth parts in the dermis or the stratum corneum.
Oral ingestion, inhalation or transcutaneous application of a drug to which a person has been previously
sensitized via contact exposure may elicit an eczematous dermatitis clinically and light microscopically
indistinguishable from allergic contact dermatitis. Affected sites frequently correspond to those involved
in a prior contact dermatitis, the onset of symptoms being within two to twenty-four hours after an oral
dose. The term baboon syndrome has been used to describe bright red, well-demarcated ano-genital lesions
associated with a symmetric eczematous eruption involving elbow flexures, axillae, eyelids and the sides of
the neck. Among the classic drugs associated with eczematous reactions are antibiotics and ethylene
diamine-containing antihistamenic and aminophylline preparations. Oral administration of sulfonyl urea
hypoglycemic drugs in patients sensitized to para-immuno compounds such as sulfanilamide results in
flare-ups of dermatitis. The histomorphology is indistinguishable from that described for allergic contact
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