{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T01:53:06Z","timestamp":1775872386567,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Nicolau syndrome, also known as embolia cutis medicamentosa, is a rare iatrogenic reaction that may occur following parenteral drug administration, including inadvertent intra-arterial or periarterial injection. Its pathophysiology remains poorly understood; however, several mechanisms have been proposed, including vasospasm, embolization, cytotoxic inflammation, and secondary tissue necrosis. We report the case of a 22-year-old transgender woman who received intravenous benzathine penicillin in the left arm without a medical prescription following a reactive syphilis screening performed outside a formal healthcare setting. She subsequently developed severe pain, livedoid dermatitis, pallor, distal cyanosis, and blister formation. Radial and brachial pulses remained palpable, and Doppler ultrasonography revealed no evidence of arterial or venous thrombosis. Medical management included daily wound care, anticoagulation, corticosteroids, peripheral vasodilators, antibiotic therapy, and analgesia. The patient was hospitalized for nine days, with partial clinical improvement. However, persistent distal ischemic changes involving the second through fifth fingers raised concern for evolving necrosis and potential amputation. After counseling regarding these risks, the patient requested voluntary discharge. This case underscores the importance of safe medication administration and appropriate injection practices, particularly in low-resource settings. It also highlights the need for improved training of healthcare personnel to ensure early recognition and prompt management of Nicolau syndrome, as well as strengthened patient education to discourage self-medication and promote timely care by qualified healthcare professionals.<\/jats:p>","DOI":"10.3390\/jcm15051756","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T09:31:32Z","timestamp":1772098292000},"page":"1756","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["An Unusual Presentation of Nicolau Syndrome in the Upper Limb: A Case Report from Northern Ecuadorian Amazonia"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7502-3758","authenticated-orcid":false,"given":"El\u00edas David","family":"Guam\u00e1n-Charco","sequence":"first","affiliation":[{"name":"Emergency Department, Marco Vinicio Iza General Hospital, Nueva Loja 210202, SC, Ecuador"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cesar","family":"Espinoza","sequence":"additional","affiliation":[{"name":"Emergency Department, Marco Vinicio Iza General Hospital, Nueva Loja 210202, SC, Ecuador"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Bel\u00e9n","family":"V\u00e9lez-Altamirano","sequence":"additional","affiliation":[{"name":"Emergency Department, Marco Vinicio Iza General Hospital, Nueva Loja 210202, SC, Ecuador"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0385-1692","authenticated-orcid":false,"given":"Jos\u00e9","family":"Govea","sequence":"additional","affiliation":[{"name":"General Surgery Department, Marco Vinicio Iza General Hospital, Nueva Loja 210202, SC, Ecuador"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Willam","family":"Valdez","sequence":"additional","affiliation":[{"name":"Traumatology Department, Marco Vinicio Iza General Hospital, Nueva Loja 210202, SC, Ecuador"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillermo","family":"Prieto-Mar\u00edn","sequence":"additional","affiliation":[{"name":"One Health Research Group, Faculty of Medicine, Universidad de las Am\u00e9ricas, Calle de los Colimes y Avenida de los Granados, Quito 170137, Ecuador"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Vasconez-Gonzalez","sequence":"additional","affiliation":[{"name":"One Health Research Group, Faculty of Medicine, Universidad de las Am\u00e9ricas, Calle de los Colimes y Avenida de los Granados, Quito 170137, Ecuador"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1178-0546","authenticated-orcid":false,"given":"Juan S.","family":"Izquierdo-Condoy","sequence":"additional","affiliation":[{"name":"One Health Research Group, Faculty of Medicine, Universidad de las Am\u00e9ricas, Calle de los Colimes y Avenida de los Granados, Quito 170137, Ecuador"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1895-7498","authenticated-orcid":false,"given":"Esteban","family":"Ortiz-Prado","sequence":"additional","affiliation":[{"name":"One Health Research Group, Faculty of Medicine, Universidad de las Am\u00e9ricas, Calle de los Colimes y Avenida de los Granados, Quito 170137, Ecuador"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"ref_1","first-page":"48","article-title":"S\u00edndrome de Nicolau posterior a la inyecci\u00f3n de penicilina intramuscular","volume":"20","author":"Gandino","year":"2012","journal-title":"Actual SIDA"},{"key":"ref_2","first-page":"216","article-title":"S\u00edndrome de Nicolau: Afecci\u00f3n rara y prevenible","volume":"68","year":"2024","journal-title":"Dermatol. Rev. Mex."},{"key":"ref_3","first-page":"145","article-title":"S\u00edndrome de Nicolau","volume":"83","author":"Sola","year":"2023","journal-title":"Med. B. Aires"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"92","DOI":"10.4103\/0974-2077.58523","article-title":"Nicolau Syndrome: An Iatrogenic Cutaneous Necrosis","volume":"2","author":"Nischal","year":"2009","journal-title":"J. Cutan. Aesthetic Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"rjad224","DOI":"10.1093\/jscr\/rjad224","article-title":"Nicolau Syndrome Following Intramuscular Diclofenac Injection: A Case Report and Review of the Literature","volume":"2023","author":"Ata","year":"2023","journal-title":"J. Surg. Case Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"102181","DOI":"10.1016\/j.epsc.2022.102181","article-title":"Nicolau Syndrome: A Series of Three Cases Following Drug\u2019s Intramuscular Injection in Children","volume":"80","author":"Goudjo","year":"2022","journal-title":"J. Pediatr. Surg. Case Rep."},{"key":"ref_7","first-page":"17112c6","article-title":"Nicolau Syndrome","volume":"11","author":"Ersoy","year":"2017","journal-title":"J. Turk Acad. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1152\/japplphysiol.00527.2015","article-title":"Sympathetic Control of Reflex Cutaneous Vasoconstriction in Human Aging","volume":"119","author":"Greaney","year":"2015","journal-title":"J. Appl. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"21501319231179936","DOI":"10.1177\/21501319231179936","article-title":"Job Satisfaction and Self-Perceptions Among Ecuadorian Medical Doctors During Their Compulsory Rural Community Social Service: A Countrywide Cross-Sectional Analysis","volume":"14","author":"Hidalgo","year":"2023","journal-title":"J. Prim. Care Community Health"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ortiz-Prado, E., Simba\u00f1a-Rivera, K., Cevallos, G., G\u00f3mez-Barreno, L., Cevallos, D., Lister, A., Fernandez-Naranjo, R., R\u00edos-Touma, B., V\u00e1sconez-Gonz\u00e1lez, J., and Izquierdo-Condoy, J.S. (2022). Waterborne Diseases and Ethnic-Related Disparities: A 10 Years Nationwide Mortality and Burden of Disease Analysis from Ecuador. Front. Public Health, 10.","DOI":"10.3389\/fpubh.2022.1029375"},{"key":"ref_11","first-page":"27","article-title":"Nicolau syndrome: A review of case studies","volume":"28","author":"Mojarrad","year":"2021","journal-title":"Pharm. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.jdcr.2016.09.004","article-title":"Nicolau Syndrome after Lumbar Puncture: A Case Report in a 22-Month-Old Girl","volume":"3","author":"Navrazhina","year":"2017","journal-title":"JAAD Case Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"148","DOI":"10.7224\/1537-2073.2016-038","article-title":"Case Report: Two Cases of Nicolau Syndrome Associated with Glatiramer Acetate","volume":"19","author":"Kimbrough","year":"2017","journal-title":"Int. J. MS Care"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"867","DOI":"10.12688\/f1000research.11705.1","article-title":"Case Report: Nicolau Syndrome Due to Etofenamate Injection","volume":"6","author":"Ozlu","year":"2017","journal-title":"F1000Research"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"ojaa027","DOI":"10.1093\/asjof\/ojaa027","article-title":"A Case Report of Nicolau Syndrome After Aesthetic Breast Surgery: A Review of the Literature and Introduction to a New Treatment Modality","volume":"2","author":"Gal","year":"2020","journal-title":"Aesthetic Surg. J. Open Forum"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.wneu.2020.07.029","article-title":"Nicolau Syndrome, Masquerader of Postinjection Sciatic Nerve Injury: Case Report and Review of Literature","volume":"143","author":"Raju","year":"2020","journal-title":"World Neurosurg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"276","DOI":"10.11604\/pamj.2020.37.276.21850","article-title":"Nicolau Syndrome Following Intramuscular Benzathine Penicillin Injection: A Case Report","volume":"37","author":"Phiri","year":"2020","journal-title":"Pan Afr. Med. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"489","DOI":"10.4103\/ijp.ijp_166_21","article-title":"Nicolau Syndrome Following Subcutaneous Glatiramer Acetate Injection: A Case Report and Review of the Literature","volume":"53","author":"Esme","year":"2021","journal-title":"Indian J. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1177\/08971900211012263","article-title":"Embolia Cutis Medicamentosa (Nicolau Syndrome) Secondary to Intramuscular Fulvestrant Injection: A Case Report","volume":"35","author":"Murdock","year":"2022","journal-title":"J. Pharm. Pract."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1177\/1534734620948768","article-title":"Extensive Deep Tissue Involvement in Nicolau Syndrome and Below-Knee Amputation: A Case Report and Literature Review","volume":"22","author":"Zargarbashi","year":"2023","journal-title":"Int. J. Low. Extrem. Wounds"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2050313X231180747","DOI":"10.1177\/2050313X231180747","article-title":"Nicolau Syndrome Associated with Fluphenazine Depot: A Case Report","volume":"11","author":"Das","year":"2023","journal-title":"SAGE Open Med. Case Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.toxrep.2023.10.002","article-title":"Nicolau Syndrome after Intramuscular Injection of Methocarbamol: A Rare Case Report","volume":"11","author":"Goli","year":"2023","journal-title":"Toxicol. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1177\/02537176241296307","article-title":"Buprenorphine Induced Nicolau Syndrome: A Case Report","volume":"47","author":"Arunima","year":"2024","journal-title":"Indian J. Psychol. Med."},{"key":"ref_24","first-page":"127","article-title":"Nicolau Syndrome: Cutaneous Necrosis Following Diclofenac Intramuscular Injection","volume":"361","author":"Bhuyyar","year":"2025","journal-title":"Georgian Med. News"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1186\/s13256-025-05437-2","article-title":"Nicolau Syndrome in a Pediatric Patient after Corticosteroid Injection: A Case Report and Review of the Literature","volume":"19","author":"Babaie","year":"2025","journal-title":"J. Med. Case Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1159\/000548557","article-title":"Nicolau Syndrome Following Benzathine Benzylpenicillin Injection in a Patient with Syphilis and Type 2 Diabetes: A Case Report","volume":"17","author":"Cheng","year":"2025","journal-title":"Case Rep. Dermatol."},{"key":"ref_27","first-page":"e100623","article-title":"From Needle to Necrosis: A Case Report on Nicolau Syndrome","volume":"18","author":"Ramya","year":"2026","journal-title":"Cureus"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Fekete, G.L., Iantovics, L.B., Fekete, J.E., and Fekete, L. (2023). Embolia Cutis Medicamentosa (Nicolau Syndrome): Case Series. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1216781"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.joen.2021.10.006","article-title":"Nicolau Syndrome after Endodontic Treatment: A Case Report","volume":"48","author":"Tharupeedikayil","year":"2022","journal-title":"J. Endod."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1016\/j.ad.2010.12.018","article-title":"Embolia cutis medicamentosa (s\u00edndrome de Nicolau) tras inyecci\u00f3n de acetato de glatir\u00e1mero","volume":"102","author":"Borbujo","year":"2011","journal-title":"Actas Dermo-Sifiliogr."},{"key":"ref_31","first-page":"860","article-title":"Nicolau Syndrome in an Athlete Following Intra-Muscular Diclofenac Injection","volume":"74","author":"Hamilton","year":"2008","journal-title":"Acta Orthop. Belg."},{"key":"ref_32","first-page":"1","article-title":"Nicolau Syndrome Treated with Triple Therapy of Enoxaparin, Steroids, and Pentoxifylline and Monitored Using Infrared Thermography","volume":"12","author":"Somasundaram","year":"2025","journal-title":"Indian J. Dermatol. Venereol. Leprol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"34","DOI":"10.4103\/ijdd.ijdd_21_23","article-title":"Nicolau Syndrome: A Dreaded Complication of Vitamin-12 Injection","volume":"9","author":"Harode","year":"2023","journal-title":"Indian J. Drugs Dermatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"267","DOI":"10.5999\/aps.2013.40.3.267","article-title":"Nicolau\u2019s Syndrome Complicated by Atypical Necrotizing Fasciitis","volume":"40","author":"Segreto","year":"2013","journal-title":"Arch. Plast. Surg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"35","DOI":"10.61186\/jsurgtrauma.11.1.35","article-title":"The Nicolau Syndrome: A Case Report and a Review of the Literature","volume":"11","author":"Hassan","year":"2023","journal-title":"J. Surg. Trauma"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"51","DOI":"10.47464\/MetroCiencia\/vol29\/1\/2021\/51-57","article-title":"Tratamiento y manejo fibrinol\u00edtico en s\u00edndrome de Nicolau: Caso cl\u00ednico","volume":"29","author":"Godos","year":"2021","journal-title":"Metro Cienc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e62","DOI":"10.1055\/s-0041-1728652","article-title":"Nicolau Syndrome: An Unforeseen Yet Evadable Consequence of Intramuscular Injection","volume":"7","author":"Sasmal","year":"2021","journal-title":"Surg. J."},{"key":"ref_38","first-page":"87","article-title":"Compartment Syndrome of the Calf Due to Nicolau Syndrome","volume":"4","author":"Enshaei","year":"2016","journal-title":"Arch. Bone Jt. Surg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.nrl.2012.04.010","article-title":"S\u00edndrome de Nicolau tras la administraci\u00f3n de acetato de glatir\u00e1mero","volume":"28","year":"2013","journal-title":"Neurolog\u00eda"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/5\/1756\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T10:03:56Z","timestamp":1772100236000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/5\/1756"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,26]]},"references-count":39,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["jcm15051756"],"URL":"https:\/\/doi.org\/10.3390\/jcm15051756","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,26]]}}}