Rheumatoid Arthritis and CLOVES Syndrome: A Tricky Diagnosis

• Main Authors: Laura Damian, Andrei Lebovici, Cristina Pamfil, Cristina Belizna, Romana Vulturar
• Format: Article
• Language: English
• Published: MDPI AG 2020-07-01
• Series: Diagnostics
• Subjects: CLOVES syndrome; rheumatoid arthritis; macrodactyly; PIK3/AKT/mTOR pathway; <i>PIK3CA</i>-related overgrowth spectrum
• Online Access: https://www.mdpi.com/2075-4418/10/7/467

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 <i>PIK3CA</i>-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 “sandal gap” 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 <i>PIK3CA</i>-related overgrowth spectrum. Nevertheless, lack of detection of a <i>PIK3CA</i> mutation does not exclude the diagnosis in patients fulfilling clinical criteria. Due to the patient’s 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.