A 34-year-old woman comes to the office due to a 1-year history of pain and swelling in her wrists and hands. The patient has no other medical conditions and takes no medications. Vital signs are normal. No wrinkles are noted on the face and neck. A photograph of her left hand is shown in the exhibit. Interplay among which of the following cells is most likely responsible for this patient's condition?
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This patient has skin thickening in the digits consistent with systemic sclerosis (SS) (also called scleroderma), an autoimmune disease characterized by widespread fibrosis in multiple organ systems. The pathogenesis of SS primarily involves an interplay between immunologic and vascular processes that ultimately results in excess fibrosis and vasculopathy. The main cells involved are endothelial cells, T lymphocytes, and fibroblasts:
Vascular endothelial cells produce excessive endothelin 1, which causes vasoconstriction and activation of underlying fibroblasts. They also increase expression of adhesion molecules, which facilitates binding and extravasation of circulating lymphocytes.
T lymphocytes migrate into the tissues and increase expression of numerous cytokines that further activate tissue fibroblasts.
Dermal fibroblasts produce increasing quantities of collagen and ground substance, leading to thickening and stiffening of the tissue.
The skin in SS undergoes dermal expansion due to diffuse deposition of collagen (eosinophilic connective tissue), resulting in atrophy of the intradermal adipose tissue and obliteration of dermal appendages (eg, hair follicles, glands). Early symptoms often include finger swelling and mild pruritus. With progression of the disease, patients may experience dermal sclerosis (sclerodactyly), dermal ulcers, nail atrophy, and digital calcinosis.
(Choice A) Psoriasis is characterized by activation of antigen-presenting dendritic cells, leading to recruitment and differentiation of T-helper cells, which in turn produce additional inflammatory cytokines that stimulate keratinocyte proliferation and generate a neutrophilic response (eg, focal microabscesses). However, psoriasis presents with well-demarcated, scaly, erythematous plaques rather than skin thickening and ulceration.
(Choice C) The immune response in Mycobacterium tuberculosis infection is characterized by stimulation of CD4 T lymphocytes; these cells subsequently activate macrophages, which can differentiate into epithelioid histiocytes and coalesce into multinucleated Langhans giant cells. Cutaneous tuberculosis may present with a variety of skin lesions (eg, papules, plaques, pustules), but thickening and ulceration of digital skin are more consistent with SS.
(Choice D) Migration of T lymphocytes, eosinophils, and basophils is seen in the late acute phase of asthma as well as in allergic and chronic urticaria. Urticaria manifests as acute erythematous wheals, not chronic sclerodactyly and ulceration.
Educational objective:
The pathogenesis of systemic sclerosis (scleroderma) involves vascular endothelial cells (increased expression of endothelin 1 and adhesion molecules), T lymphocytes (production of cytokines that activate fibroblasts), and dermal fibroblasts (increased production of collagen and ground substance).