A 50-year-old woman comes to the office due to cough, shortness of breath, fatigue, and weight loss. The patient does not use tobacco or alcohol. Blood pressure is 110/70 mm Hg, pulse is 88/min and regular, and oxygen saturation on room air is 96%. Lung examination reveals scattered crackles. Serum calcium levels are elevated. Imaging studies reveal mediastinal fullness and diffuse, bilateral, ground-glass lung opacities. Biopsy of the lung lesions shows granulomas with multinucleated giant cells; no microorganisms or particulates are present. Appropriate pharmacotherapy is initiated. At follow-up a few days later, the symptoms have improved but blood glucose is elevated. Which of the following additional changes is most likely present in this patient due to her treatment?

Question

A 50-year-old woman comes to the office due to cough, shortness of breath, fatigue, and weight loss.  The patient does not use tobacco or alcohol.  Blood pressure is 110/70 mm Hg, pulse is 88/min and regular, and oxygen saturation on room air is 96%.  Lung examination reveals scattered crackles.  Serum calcium levels are elevated.  Imaging studies reveal mediastinal fullness and diffuse, bilateral, ground-glass lung opacities.  Biopsy of the lung lesions shows granulomas with multinucleated giant cells; no microorganisms or particulates are present.  Appropriate pharmacotherapy is initiated.  At follow-up a few days later, the symptoms have improved but blood glucose is elevated.  Which of the following additional changes is most likely present in this patient due to her treatment?

Quizplus · Accepted Answer

11ec160b_3b70_761b_9249_85b047e78cd0_MD0001_00 This patient with cough, shortness of breath, and fatigue has multiple findings characteristic of granulomatous inflammation in sarcoidosis, including the following: Elevated serum calcium due to increased 1,25-dihydroxyvitamin D production by activated macrophages Mediastinal and hilar adenopathy Granulomas (noncaseating) with multinucleated giant cells and no microorganisms on lung biopsy Glucocorticoids are commonly used as initial therapy in patients with sarcoidosis because of their ability to reduce inflammation, improving symptoms and limiting end-organ damage while having relatively minor adverse effects (eg, weight gain, glucose intolerance) with short term use. Glucocorticoids improve sarcoidosis symptoms by decreasing transcription of proinflammatory genes, leading to reduced activation of lymphocytes and macrophages with decreased expression of cytokines necessary for granuloma formation (eg, IL-1, interferon-gamma) (Choice D). Glucocorticoids also impair neutrophil margination, extravasation, and migration to inflammatory sites by reducing adhesion molecule expression on neutrophils (eg, L selectin) and endothelial cells and limiting production of cytokines (eg, IL-8) that promote neutrophil emigration. The result is increased circulating levels of neutrophils (ie, neutrophilia). In addition to these changes, glucocorticoids have a variety of other effects on immune function, as follows: Increased production of anti-inflammatory cytokines (eg, IL-10) (Choice A) Decreased apoptosis of neutrophils, reinforcing neutrophilia (Choice C) Promoting apoptosis of eosinophils, monocytes, and lymphocytes, decreasing circulating levels Reduced macrophage activation (decreasing overall 1,25-dihydroxyvitamin D synthesis) (Choice E) Decreased production of prostaglandins and leukotrienes through the inhibition of phospholipase A2 (Choice F) Educational objective: Glucocorticoids have a variety of effects that can be useful in reducing inflammation and limiting end-organ damage in inflammatory diseases (eg, sarcoidosis). These include decreased proinflammatory cytokine (IL-1, interferon-gamma) production, increased anti-inflammatory cytokine (eg, IL-10) production, and impaired migration of leukocytes (eg, neutrophils) to sites of inflammation.

A 50-Year-Old Woman Comes to the Office Due to Cough