—  SHORT COURSE  —

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.

Histomorphology
Allergic contact dermatitis characteristically shows spongiotic vesiculation of the epidermis; in consequence, the parakeratotic scale often contains plasma.


Allergic Contact Dermatitis
Allergic Contact Dermatitis

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.

Pathogenesis
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.

Differential Diagnosis
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 dermatitis.

References

  1. Cohen LM, Skopicki DK, Harrist TJ, Clark Jr WH. Noninfectious vesiculobullous andvsiculopustular diseases. In : Elder D, Elenitsas R, Jaworsky C, Johnson B, Ed's. Lever's Histopathology of the skin, 8th Ed'n, Philadelphia: Lippincott-Raven, 1997:209-252.
  2. Crowson AN, Magro CM. Drug eruptions. In : Barnhill R, Crowson AN, Busam K, Granter S ed's. Textbook of Dermatopathology. New York : McGraw-Hill Co,1998:257-270.
  3. Hood AF, Kwan TH, Mihm MC Jr, Horn TD. Primer of Dermatopathology. Second edition. Boston: Little, Brown & Co, 1993.
  4. Kwan TH. Spongiotic dermatitis. In: Barnhill R, Crowson AN, Busam K, Granter S ed's. Textbook of Dermatopathology. New York : McGraw-Hill Co, 1998:17-32.
  5. Toussaint S, Kamino H. Noninfectious erythematous, papular, and squamous diseases. In: Elder D, Elenitsas R, Jaworsky C, Johnson B, Ed's. Lever's Histopathology of the skin, 8th Ed'n, Philadelphia: Lippincott-Raven, 1997:151-184.
  6. Weedon D. The spongiotic reaction pattern. In : Skin Pathology. Edinburgh : Churchill Livingstone. 1997:83-107.