Regarding Hypersensitivity Reactions...

A 20-year-old woman had her ears pierced when she was 16 years old. Since that time, she has had only two pairs of earrings, both given to her by her parents; both were 18 karat gold. Last week her
21-year-old boyfriend gave her a new pair of earrings for Valentine’s Day, which she started to wear immediately. Three days later, she developed localized areas of erythema and vesicle formation where she had pierced her ears.

The mechanism responsible for this reaction most closely resembles which of the following?
(A) Type I hypersensitivity
(B) An Arthus reaction
(C) A positive purified protein derivative (PPD) skin reaction
(D) Antibody-dependent cell-mediated cytotoxicity
(E) An immune complex disease

Answer:
(C) A positive purified protein derivative (PPD) skin reaction

Discussion:
It seems highly probable that the earrings given to her by her boy friend were not 18 karat gold, but rather a cheaper alloy containing nickel, and she developed contact dermatitis.

Contact dermatitis is a common inflammatory disorder of skin that is associated with exposure to various antigens and irritating substances.

Four types have been described—

1. allergic contact dermatitis, 
2. irritant contact dermatitis, 
3. contact photodermatitis, and 
4. contact urticaria. 

Allergic contact dermatitis, of which this case is an example, is a cell-mediated type IV hypersensitivity reaction. Three conditions must be present for this reaction to occur; namely, a genetic predisposition, absorption of sufficient antigen through the skin surface, and a competent immune system. Antigenic substances of low molecular weight penetrate the skin, are phagocytized by Langerhans’ cells, and are then transported to regional lymph nodes, where they are presented to T lymphocytes. The T lymphocytes release cytokines that are responsible for the inflammatory response in the tissue. Antigenic substances include rhus (found in poison ivy and poison oak), nickel (jewelry such as earrings, hair dyes), potassium dichromate (household cleaners, leather, cement), formaldehyde (cosmetics, fabrics), ethylenediamine (dyes, medications), mercapto-benzothiazole (rubber products), and paraphenylenediamine (hair dyes,
chemicals used in photography).

Because allergic contact dermatitis is a type IV hypersensitivity reaction, the positive purified protein derivative (PPD) skin reaction (choice C), which involves the interaction of T cells and macrophages, most closely resembles the mechanism of inflammatory response observed in this patient.

Irritant contact dermatitis is not a cell-mediated immune response. It is due to the local toxic effect of the chemical on the skin.
Contact photodermatitis is similar to allergic contact dermatitis except that reaction depends on ultraviolet light.
Contact urticaria is a wheal-and-flare reaction that may be secondary to a type I hypersensitivity (immunoglobulin E [IgE]-mediated) reaction or a nonimmunologic reaction.

The clinical presentation of contact dermatitis, regardless of the mechanism, ranges from localized areas of erythema with vesicle formation to erythematous plaques of thickened skin in chronic disease.

The treatment involves removal of the offending agent along with the use of wet compresses with Burow’s solution in acute disease, followed by local application of steroid cream to suppress inflammation.
Subacute or chronic cases should be treated with local steroid creams without the compresses. Extensive disease may require the use of systemic corticosteroid therapy.

In terms of the other mechanisms listed in the question, type I hypersensitivity (choice A) involves the interaction of IgE antibodies developed against specific antigens and mast cells. Reexposure to the antigen causes mast cell degranulation, with the release of histamine and other chemical mediators that produce increased vessel permeability, tissue swelling, and an inflammatory reaction.

An Arthus reaction (choice B) is a localized immune complex disease (type III hypersensitivity) that activates the complement system to produce anaphylatoxins and chemotactic agents that cause the inflammatory reaction. An example of an Arthus reaction is farmer’s lung, in which exposure to thermophilic actinomycetes in the air results in a localized immune complex deposition in the alveoli, with subsequent inflammation and hypersensitivity pneumonitis.
Systemic immune complex diseases such as systemic lupus erythematosus (SLE) or serum sickness are also associated with immune complex deposition in various tissues, including the joints, skin, and vessels in the skin and glomerulus.

Antibody-dependent cell-mediated cytotoxicity (ADCC) (choice D) is a variant of type II hypersensitivity. It involves the presence of antibody against a target tissue, which attracts killer cells, natural killer cells, or macrophages. These cells interact with the antibodies and destroy the target tissue. Warm autoimmune hemolytic anemia (AIHA), with destruction of immunoglobulin G (IgG) antibody-coated red blood cells (RBCs) by macrophages in the spleen, is a classic example of an ADCC reaction.

An immune complex disease (choice E), such as serum sickness, is a type III hypersensitivity disease.