R. Mohamad Javier, Savira Salsabila, Errini Sabilla Lilhawa Ditsi, Irma Rahmawati Madrik, Felly Moelyadi, Aninda Zunia Pratiwi, Jonathan, Yosua Darmadi Kosen, Indah Ayu Tri Artha Simanjuntak, Angela Anjelina Cita, Aldo Aulia Rahman, Arkan Zikri Berlian, Mahardika Adhitya Nugraha, Michelle Anisa Ujianto, Theresia Verawati Lumban Gaol, Ericko Julian Limanto, Andra Purwanto Yogatama Putra, Clearardo Grayson Giantambrani, Ave Maria, Bernadus Bernardino Bramantyo, Akhdan Baghaskara Rahmatullah, Nikko Shidqi Iman, Kristian Kurniawan, Muhammad Reva Aditya
Background: Cutaneous 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. Methods: A 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. Results: Thirteen 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. Conclusions: CADRs, 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. © The Author(s) 2026.
Department of Cardiology and Vascular Medicine, Universitas Indonesia Hospital, Jakarta, Indonesia; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, RSUP Fatmawati, Jakarta, Indonesia; Subang Regional General Hospital (RSUD Subang), Subang, Indonesia; RSUD Pasirian, Lumajang, Indonesia; Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia; Department of Internal Medicine, Wangaya Regional General Hospital, Denpasar, Bali, Indonesia; Faculty of Medicine, Universitas Islam Indonesia, Yogyakarta, Indonesia; Kalideres Regional General Hospital (RSUD Kalideres), Jakarta, Indonesia; Faculty of Medicine, Maranatha Christian University, Bandung, Indonesia; Faculty of Medicine, Universitas Kristen Duta Wacana, Yogyakarta, Indonesia; Faculty of Medicine, Universitas Sriwijaya, Palembang, Indonesia; Department of Internal Medicine, Division of Endocrinology, Metabolism, and Diabetes, Cipto Mangunkusumo National General Hospital (RSUPN Dr. Cipto Mangunkusumo), Jakarta, Indonesia; Division of Psychosomatic and Palliative Medicine, Department of Internal Medicine, RSUPN Dr. Cipto Mangunkusumo, Jakarta, Indonesia; Sunan Kalijaga Regional General Hospital (RSUD Sunan Kalijaga), Demak, Indonesia; Bhayangkara Hospital Kediri (RS Bhayangkara Kediri), Kediri, Indonesia; Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia; Dr. Sardjito General Hospital (RSUP Dr. Sardjito), Yogyakarta, Indonesia; Faculty of Medicine, Universitas Ahmad Dahlan, Yogyakarta, Indonesia; Buton Regional General Hospital (RSUD Buton), Buton, Indonesia; Bhayangkara Hospital Yogyakarta (RS Bhayangkara Yogyakarta), Yogyakarta, Indonesia; Faculty of Medicine, Universitas Katolik Indonesia Atma Jaya, Jakarta, Indonesia
