Question

A 25-year-old female presents to your clinic with an intensely pruritic rash on both forearms. She reports that three days ago she went hiking in the woods, and shortly thereafter began noticing redness, swelling, and blistering on the dorsal aspects of her forearms. The rash has since worsened and is now oozing clear fluid. She denies systemic symptoms. Physical exam reveals poorly defined erythematous, red, weeping papules and plaques studded with vesicles on the bilateral dorsal forearms (Figure 1).

Which of the following immunologic mechanisms is responsible for this patient’s eruption?

1. Immune complex deposition in vessel walls causing complement activation and inflammation
2. IgE-mediated release of histamine from mast cells
3. T-cell–mediated immune response causing cytokine release and recruitment of macrophages
4. IgG or IgM antibody binding to cell surface antigens leading to complement activation

Correct Answer

Correct Answer: C. T-cell–mediated immune response causing cytokine release and recruitment of macrophages.

Explanation

C) This answer choice describes a Typer IV (delayed-type) hypersensitivity reaction. The patient is suffering from allergic contact dermatitis (ACD) due to Toxicodendron (poison ivy, oak, or sumac).^1-3 This cell-mediated response occurs when sensitized T lymphocytes recognize the allergen urushiol and release proinflammatory cytokines that recruit macrophages and cytotoxic T cells to the skin. The reaction typically develops 24–72 hours after exposure and presents as pruritic, erythematous, and vesicular plaques in areas of direct contact—often with a linear or streaky configuration. Treatment consists of avoidance of potential offending agents as well as symptomatic treatment. Topical steroids can be used, and in severe cases, systemic corticosteroids can be prescribed over 3 weeks.⁴

Explanation of Incorrect Answers A) This answer choice describes a Type III hypersensitivity reaction, in which circulating antigen–antibody complexes deposit in tissues, triggering complement activation and neutrophilic inflammation. Examples include leukocytoclastic vasculitis, the malar rash of systemic lupus erythematosus as well as serum sickness and serum sickness-like reaction. ⁵

B) This answer choice describes a Type I hypersensitivity reaction, which occurs within minutes of exposure to an allergen. Cross-linking of IgE on mast cells triggers histamine release, leading to edema, erythema, and pruritus. Examples include urticaria, angioedema, and anaphylaxis. ^6,7

D) This answer choice describes a Type II hypersensitivity reaction, in which antibodies target antigens on cell surfaces, causing complement-mediated cell destruction. Examples include pemphigus vulgaris (antibodies against desmoglein-3 and desmoglein-1), bullous pemphigoid (antibodies against hemidesmosomal proteins BP180 and BP230) and epidermolysis bullosa acquisita (antibodies against type VII collagen).⁸

References

1. Kalish RS. Recent developments in the pathogenesis of allergic contact dermatitis. JAMA Dermatology. 1991;127(12):1558-1563. doi:10.1001/archderm.127.12.1558. 2. Adler BL, DeLeo VA. Allergic Contact Dermatitis. JAMA Dermatology. 2021;157(2):200-201. doi:10.1001/jamadermatol.2020.5639. 3. Kim Y, Flamm A, ElSohly MA, et al. Poison Ivy, Oak, and Sumac Dermatitis: What Is Known and What Is New? Dermatitis. 2019;30(3):183-190. doi:10.1097/DER.0000000000000472. 4. Alikhan, Ali, and Thomas L. H Hocker. Review of Dermatology (p. 435). Elsevier, 2024. 5. Carlson JA, Ng BT, Chen KR. Cutaneous vasculitis update: diagnostic criteria, classification, epidemiology, etiology, pathogenesis, and therapeutic options. J Cutan Pathol. 2005;32(9):601-613. doi:10.1111/j.0303-6987.2005.00379.x. 6. Zuberbier T, et al. EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for urticaria. Allergy. 2022;77(3):734-766. doi:10.1111/all.15090. 7. Sampson HA, et al. Mechanisms of IgE-mediated food allergy and other hypersensitivity reactions. J Allergy Clin Immunol. 2018;141(1):41-58. doi:10.1016/j.jaci.2017.11.007. 8. Schmidt E, Zillikens D. The diagnosis and treatment of autoimmune blistering skin diseases. Lancet. 2013;381(9863):320-332. doi:10.1016/S0140-6736(12)61140-4.