A 36-year-old woman comes to the office due to worsening shortness of breath. The patient has a long-standing history of nasal congestion and frontal headaches that partly improved after nasal polyp removal a year ago. Over the past several months, she has experienced increasingly frequent episodes of chest tightness and wheezing. The patient has noted that the symptoms worsen after she takes over-the-counter analgesics. She has no pets, and there have been no changes in her environment. She does not use tobacco or alcohol. Which of the following is the main driver of pathogenesis of this patient's symptoms?

Question

A 36-year-old woman comes to the office due to worsening shortness of breath.  The patient has a long-standing history of nasal congestion and frontal headaches that partly improved after nasal polyp removal a year ago.  Over the past several months, she has experienced increasingly frequent episodes of chest tightness and wheezing.  The patient has noted that the symptoms worsen after she takes over-the-counter analgesics.  She has no pets, and there have been no changes in her environment.  She does not use tobacco or alcohol.  Which of the following is the main driver of pathogenesis of this patient's symptoms?

Quizplus · Accepted Answer

Explanation: 11ec25c8_d301_f38a_bc81_0b9abee46973_MD0003_00 This patient's presentation is most consistent with aspirin-exacerbated respiratory disease (AERD), a nonimmunologic reaction to aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs). AERD should be suspected when the Samter triad is present: Asthma (eg, intermittent wheezing, chest tightness) Chronic rhinosinusitis (eg, nasal congestion, frontal headaches) with nasal polyps NSAID-induced respiratory reactions (eg, worsening symptoms after over-the-counter analgesics [eg, ibuprofen]) AERD pathogenesis involves increased production of proinflammatory leukotrienes and decreased production of anti-inflammatory prostaglandins. NSAIDs inhibit the cyclooxygenase arm of the arachidonic acid pathway (COX-1, COX-2) to block prostaglandin synthesis, shunting it toward the leukotriene production arm. AERD symptoms are due to this leukotriene excess and mimic asthma or rhinosinusitis flares. Patients may not always relate the symptoms to NSAID use, especially if they are taken habitually. Some patients may exhibit more dramatic symptoms, including facial flushing, urticarial eruptions, angioedema, and anaphylactoid reactions (eg, bronchospasm, hypotension), usually occurring 30 minutes to 3 hours after NSAID ingestion. Unlike anaphylactic reactions, these pseudoallergic reactions are not IgE-mediated. Treatment includes avoidance of NSAIDs. If NSAIDs are absolutely required, desensitization is sometimes necessary. Leukotriene pathway inhibitors (eg, zileuton, montelukast) can also improve respiratory and nasal symptoms. (Choice A) Antineutrophil cytoplasmic autoantibodies are associated with eosinophilic granulomatosis with polyangiitis, which often presents with prodromal asthma and nasal polyposis before the onset of overt systemic vasculitis. However, the history of NSAID sensitivity is more strongly suggestive of AERD. (Choice B) Bradykinin is an inflammatory vasoactive peptide involved in the pathogenesis of ACE inhibitor cough, as well as ACE inhibitor and hereditary angioedema. The patient does not take an ACE inhibitor and has no evidence of angioedema. (Choice C) IgE is the primary upstream player in type 1 (immediate) hypersensitivity reactions such as anaphylaxis, angioedema, extrinsic allergic asthma (eg, dust mites, pollen), and allergic rhinitis and conjunctivitis (ie, hay fever). However, it is not involved in the pathogenesis of AERD. (Choice D) IL-5 is a T helper type 2 (Th2) cytokine that plays a central role in the pathogenesis of intrinsic asthma (eg, in response to weather, exercise) and chronic rhinosinusitis with nasal polyposis. With intrinsic asthma, the sinus and pulmonary symptoms would not be aggravated by NSAID exposure. Educational objective: Aspirin-exacerbated respiratory disease is a nonimmunologic reaction that occurs when cyclooxygenase inhibitors (eg, aspirin, other nonsteroidal anti-inflammatory drugs [NSAIDs]) promote the imbalanced production of leukotrienes over prostaglandins. The classic triad includes asthma, chronic rhinosinusitis with nasal polyposis, and NSAID sensitivity. References: Aspirin-Exacerbated Respiratory Disease (http://www.ncbi.nlm.nih.gov/pubmed/30207919)

A 36-Year-Old Woman Comes to the Office Due to Worsening