{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:01:41Z","timestamp":1760238101321,"version":"build-2065373602"},"reference-count":12,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,7,9]],"date-time":"2020-07-09T00:00:00Z","timestamp":1594252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>The PI3K\/AKT\/mTOR signaling pathway is significantly activated in rheumatoid arthritis. In addition, somatic activating mutations of the PI3K\/AKT\/mTOR pathway may result in PIK3CA-related overgrowth spectrum diseases, including CLOVES (Congenital Lipomatous Overgrowth, Vascular malformation, Epidermal nevi, Skeletal abnormalities\/Scoliosis) syndrome. We describe the case of a young female patient, with anti-citrullinated peptide antibodies-positive rheumatoid arthritis, referred for persistent finger pain and stiffness. Examination revealed discrete macrodactyly involving two fingers, scoliosis, asymmetrical calves, venectasias, a shoulder nevus and triangular feet with a \u201csandal gap\u201d between two toes. These mild dysmorphic features with early-onset and the history of surgeries for thoracic lipoma and venous malformation were strongly suggestive of CLOVES syndrome. Confirmatory mutation analysis was not performed, as blood or saliva testing is not contributive for tissue-specific localized effects in the PIK3CA-related overgrowth spectrum. Nevertheless, lack of detection of a PIK3CA mutation does not exclude the diagnosis in patients fulfilling clinical criteria. Due to the patient\u2019s wish to plan a pregnancy, therapy consisted in sulfasalazine and hydroxychloroquine, along with orthotic correction of leg length discrepancy. Overgrowth syndromes and arthritis may share common pathways. Mild macrodactyly should be differentiated from dactylitis. Diagnosing patients with minimal dysmorphic features within the PI3K-related overgrowth spectrum may help design better care strategies, in the quest for personalized medicine.<\/jats:p>","DOI":"10.3390\/diagnostics10070467","type":"journal-article","created":{"date-parts":[[2020,7,9]],"date-time":"2020-07-09T10:45:19Z","timestamp":1594291519000},"page":"467","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Rheumatoid Arthritis and CLOVES Syndrome: A Tricky Diagnosis"],"prefix":"10.3390","volume":"10","author":[{"given":"Laura","family":"Damian","sequence":"first","affiliation":[{"name":"Cab. Reumatologie Dr. Damian, 6-8 Petru Maior St, 400002 Cluj-Napoca, Romania"},{"name":"Rheumatology Department, Emergency Clinical County Hospital Cluj, Center for Rare Musculoskeletal Autoimmune and Autoinflammatory Diseases, 2\u20134 Clinicilor St, 400006 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrei","family":"Lebovici","sequence":"additional","affiliation":[{"name":"Radiology Department, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy Cluj, 8 Victor Babe\u0219 St, 400023 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Pamfil","sequence":"additional","affiliation":[{"name":"Center for Rare Musculoskeletal Autoimmune and Autoinflammatory Diseases, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy Cluj, 8 Victor Babe\u0219 St, 400023 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Belizna","sequence":"additional","affiliation":[{"name":"Vascular and Coagulation Department, University Hospital Angers, 49100 Angers, France"},{"name":"UMR CNRS 6015, INSERM U1083, Rue Haute de Recul\u00e9e, 40945 Angers CEDEX 01, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2476-9706","authenticated-orcid":false,"given":"Romana","family":"Vulturar","sequence":"additional","affiliation":[{"name":"Department of Molecular Sciences, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy Cluj, 6, Pasteur St., 400349 Cluj-Napoca, Romania"},{"name":"Cognitive Neuroscience Laboratory, University Babe\u0219-Bolyai, 30, Fantanele St., 400294 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1016\/j.ajpath.2012.01.030","article-title":"PI3 Kinase \u03b4 Is a Key Regulator of Synoviocyte Function in Rheumatoid Arthritis","volume":"180","author":"Bartok","year":"2012","journal-title":"Am. J. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1002\/ajmg.a.36552","article-title":"Clinical delineation and natural history of the PIK3CA-related overgrowth spectrum","volume":"164","author":"Sapp","year":"2014","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1093\/rheumatology\/key038","article-title":"Activation of mechanistic target of rapamycin complex 1: The common link between rheumatoid arthritis and diabetes mellitus","volume":"58","author":"Melnik","year":"2019","journal-title":"Rheumatology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/nrrheum.2015.172","article-title":"Activation of mTOR (mechanistic target of rapamycin) in rheumatic diseases","volume":"12","author":"Perl","year":"2016","journal-title":"Nat. Rev. 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