Cutaneous adverse drug reactions in patients with congenital heart disease: a systematic review with focus on perioperative outcomes.

backgroundCutaneous adverse drug reactions (CADRs) are uncommon but clinically significant complications among patients with congenital heart disease (CHD), particularly those with pulmonary arterial hypertension (PAH) or perioperative hemodynamic instability. The complex pharmacologic regimens required in CHD—often involving prostaglandins, vasodilators, antibiotics, and antiepileptics—predispose patients to idiosyncratic and immune-mediated reactions. Despite increasing recognition of CADRs in cardiovascular medicine, systematic evidence focusing on CHD populations remains limited.

methodsA systematic search of MEDLINE (PubMed), Embase, Web of Science, and CENTRAL was conducted from database inception to October 31, 2024, covering all types of congenital heart disease, both cyanotic and acyanotic, isolated and syndromic forms. Eligible studies included randomized controlled trials, observational studies, and case reports that reported CADRs in patients with structural CHD, regardless of age or surgical status. Extracted outcomes included type of CADR, implicated drug, temporal association, histopathology, management, and clinical outcome. Study quality was assessed using the Joanna Briggs Institute (JBI) checklist for case reports and case series.

resultsThirteen studies encompassing 22 patients met the inclusion criteria. Most patients (68%) were neonates or infants with duct-dependent congenital heart disease receiving prostaglandin E₁ (alprostadil) for lesions such as transposition of the great arteries, hypoplastic left heart syndrome, and Taussig–Bing anomaly. The most frequently reported CADRs were prostaglandin-associated vasomotor eruptions, including migratory urticaria and erythematous patches (n = 4, 18%), as well as radiographically detected brown fat necrosis and soft-tissue calcification following prolonged prostaglandin infusion (n = 9, 41%). Severe hypersensitivity reactions—including drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens–Johnson syndrome (SJS)—occurred in patients receiving antiepileptics or antibiotics (n = 3, 14%), typically in postoperative or intensive care settings. Additional reports described bosentan-associated indurated erythema in an adult with repaired tetralogy of Fallot and amoxicillin-associated morbilliform exanthem in pediatric patients after surgical repair. Overall, prostaglandin analogs accounted for the majority of implicated drugs (77%), followed by antiepileptics (9%), antibiotics (9%), and pulmonary vasodilators (5%). Methodological quality of the included studies was generally low according to the Joanna Briggs Institute appraisal tools due to descriptive study designs and limited follow-up.

conclusionsCADRs, though infrequently reported, occur across the therapeutic continuum of CHD management—from neonatal prostaglandin therapy to adult antimicrobial and antiepileptic use. The predominance of prostaglandin-associated reactions underscores the importance of dermatologic and metabolic surveillance during infusion therapy, while severe whereas severe hypersensitivity reactions underscore the interface between cardiology and dermatology. Larger multicenter studies are warranted to clarify incidence, risk factors, and outcomes, guiding safer pharmacologic management in congenital cardiology.