An 8-year-old girl is brought to the office by her mother due to chronic pruritus affecting her arms. The mother states that the patient is always scratching herself. She scratches through the night, affecting her ability to sleep. Her sister has similar, but less severe, symptoms. The patient also has intermittent asthma. The rash is shown in the exhibit.

First-line therapy for this patient's condition works by which of the following mechanisms of action?

Question

An 8-year-old girl is brought to the office by her mother due to chronic pruritus affecting her arms. The mother states that the patient is always scratching herself. She scratches through the night, affecting her ability to sleep. Her sister has similar, but less severe, symptoms. The patient also has intermittent asthma. The rash is shown in the exhibit.

First-line therapy for this patient's condition works by which of the following mechanisms of action?

Quizplus · Accepted Answer

11ec160b_3b6e_ef77_9249_e392945831d0_MD0001_00 This patient has pruritic lichenified plaques on the bilateral antecubital fossae, findings consistent with atopic dermatitis. Atopic dermatitis is an inflammatory condition caused by genetically mediated epidermal barrier dysfunction and immune dysregulation favoring a Th2-skewed response. Patients typically have a family history and comorbid atopic conditions (eg, asthma, allergic rhinitis), as in this patient. First-line therapy is topical corticosteroids. Corticosteroids bind to cytoplasmic receptors and translocate to the nucleus, where they act primarily by inhibiting transcription of genes encoding inflammatory mediators. Specific mechanisms include the following: ? Local tissue production of proinflammatory prostaglandins and leukotrienes through the inhibition of phospholipase A₂ ? Synthesis of proinflammatory cytokines (eg, IL-4, IL-13) ? Production of anti-inflammatory mediators In addition, corticosteroids act on nonimmune cells and can cause impaired wound healing due to reduced fibroblast growth. They also reduce epithelial proliferation and type I collagen synthesis in the dermis, which can lead to skin atrophy with chronic use. (Choice A) Leukotriene receptor blockers (eg, montelukast) block the effects of leukotrienes (released by mast cells and eosinophils). These medications are used as adjunct therapy for allergic rhinitis and asthma and can help reduce mucus secretion, edema, and bronchoconstriction. (Choice B) Topical corticosteroids decrease, not increase, dendritic cell populations, in part by inducing dendritic cell apoptosis. These antigen-presenting cells activate naïve T cells and are thought to play a role in initiating inflammation in atopic dermatitis. (Choice C) Keratinocyte apoptosis induced by ultraviolet phototherapy is effective for treating psoriasis, which causes plaques with silvery scales on the extensor elbows, knees, and gluteal cleft (not the antecubital fossae). Phototherapy is also sometimes used for refractory atopic dermatitis (ie, not first-line therapy), but functions primarily by inducing T-cell apoptosis. (Choice E) IL-4 normally stimulates B-cell production of IgE and is suppressed with topical corticosteroids. However, corticosteroids also increase CD40-ligand expression on T cells, which stimulates IgE production to a greater degree than IL-4 suppression, and the net effect is a rise in IgE. Educational objective: Topical corticosteroids are the first-line therapy for atopic dermatitis. Their mechanism of action includes decreasing tissue production of proinflammatory prostaglandins and leukotrienes through the inhibition of phospholipase A₂; they also inhibit transcription of many other proinflammatory mediators.

An 8-Year-Old Girl Is Brought to the Office by Her