{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:54:31Z","timestamp":1789620871010,"version":"build-2803163510"},"reference-count":53,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T00:00:00Z","timestamp":1756252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinics and Practice"],"abstract":"<jats:p>Sickle cell disease (SCD) is a hereditary hemoglobin disorder characterized by chronic hemolysis and recurrent vaso-occlusive crises, leading to a wide spectrum of complications. While common SCD manifestations have well-established management protocols, rare and atypical complications pose significant diagnostic and therapeutic challenges. A critical barrier is diagnostic overshadowing, where common SCD symptoms (pain, fever, respiratory distress) mask infrequent but life-threatening conditions, resulting in delayed recognition and suboptimal outcomes. This narrative review synthesizes the literature from 2000\u20132025 on rare SCD complications, including atypical neurological events (e.g., spontaneous epidural or subdural hematoma, central retinal artery occlusion, cerebral arteriovenous malformations, posterior reversible encephalopathy syndrome), uncommon hematologic syndromes (acute leukemia, extramedullary hematopoiesis in unusual sites, hemophagocytic lymphohistiocytosis), severe cardiopulmonary emergencies (acute multiorgan failure and fat embolism syndromes), unusual hepatic crises (acute hepatic sequestration, intrahepatic cholestasis), and others (e.g., compartment syndrome). Key insights underscore the need for high clinical suspicion and prompt use of advanced diagnostics (e.g., MRI, specialized laboratory tests) when patients present with atypical or disproportionate symptoms. Clinical implications: Heightening clinician awareness of these rare complications and implementing structured diagnostic strategies can facilitate earlier intervention, improving outcomes and reducing the high morbidity and mortality associated with these infrequent but severe events.<\/jats:p>","DOI":"10.3390\/clinpract15090156","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T09:14:05Z","timestamp":1756286045000},"page":"156","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Diagnostic Overshadowing and the Unseen Spectrum: A Narrative Review of Rare Complications in Sickle Cell Disease"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9401-810X","authenticated-orcid":false,"given":"Abdulrahman","family":"Nasiri","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11432, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manal","family":"Alshammari","sequence":"additional","affiliation":[{"name":"Hematology Department, King Salman Specialist Hospital, Hail 55471, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem","family":"Alkharras","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Security Forces Hospital, Riyadh 11481, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albaraa","family":"Madkhali","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Armed Forces Hospital, Jizan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mostafa F.","family":"Mohammed Saleh","sequence":"additional","affiliation":[{"name":"Hematology Department, King Faisal Specialist Hospital & Research Centre, Riyadh 12713, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazza","family":"Alzahrani","sequence":"additional","affiliation":[{"name":"Hematology Department, King Faisal Specialist Hospital & Research Centre, Riyadh 12713, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18010","DOI":"10.1038\/nrdp.2018.10","article-title":"Sickle cell disease","volume":"4","author":"Kato","year":"2018","journal-title":"Nat. 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