Subscribe to RSS
Pediatric Presentation of Antiphospholipid Syndrome: A Review of Recent Literature With Estimation of Local Prevalence
We aimed to investigate the epidemiology, the clinical and laboratory characteristics of the pediatric involvement of antiphospholipid syndrome (APS), by performing a review of the current evidence and reviewing local experience in the Northwest Italy. To achieve this, we performed a detailed literature search to identify articles describing clinical and laboratory characteristics of pediatric APS. In concomitance, we conducted a registry-based study collecting data from the Piedmont and Aosta Valley Rare Disease Registry including pediatric patients diagnosed with APS in the last 11 years. The literature review led to inclusion of six articles with a total of 386 pediatric patients (65% females, 50% with systemic lupus erythematosus (SLE) as concomitant diagnosis). Rates of venous and arterial thrombosis were 57 and 35%, respectively. “Extra-criteria manifestations” included mostly hematologic and neurologic involvement. Almost one-quarter of patients (19%) reported recurrent events and 13% manifested as catastrophic APS. A total of 17 pediatric patients (mean age 15.1 ± 2.8, 76% female) developed APS in the Northwest of Italy. In 29% of cases, SLE was a concomitant diagnosis. Deep vein thrombosis was the most frequent manifestation (28%) followed by catastrophic APS (6%). The estimated prevalence of pediatric APS in Piedmont and Aosta Valley Region is 2.5/100,000 people, whereas the estimated annual incidence is 0.2/100,000 inhabitants. In conclusion, clinical manifestations of pediatric APS seem to be more severe and with a high prevalence of noncriteria manifestations. International efforts are needed to better characterize this condition and to develop new specific diagnostic criteria to avoid missed/delayed diagnosis in children with APS.
Data will be available upon reasonable request.
* These authors equally contributed to the manuscript
Article published online:
20 March 2023
© 2023. Thieme. All rights reserved.
Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA
1 Anon. Rare diseases | Public Health. Available at: . Accessed February 20, 2020. Accessed July 16, 2022 https://ec.europa.eu/health/non_communicable_diseases/rare_diseases_en
- 2 Petri M. . Epidemiology of antiphospholipid syndrome. In:Hughes Syndrome. London: Springer-Verlag;2006:22–28.
- 3 Andreoli L, Chighizola CB, Banzato A, Pons-Estel GJ, Ramire de Jesus G, Erkan D. Estimated frequency of antiphospholipid antibodies in patients with pregnancy morbidity, stroke, myocardial infarction, and deep vein thrombosis: a critical review of the literature. Arthritis Care Res (Hoboken) 2013; 65 (11) 1869-1873
- 4 Hwang J-J, Shin S-H, Kim Y-J. et al. Epidemiology of antiphospholipid syndrome in Korea: a nationwide population-based study. J Korean Med Sci 2020; 35 (05) e35
- 5 Sciascia S, Radin M, Unlu O, Erkan D, Roccatello D. Infodemiology of antiphospholipid syndrome: merging informatics and epidemiology. Eur J Rheumatol 2018; 5 (02) 92-95
- 6 Duarte-García A, Pham MM, Crowson CS. et al. The epidemiology of antiphospholipid syndrome: s population-based study. Arthritis Rheumatol 2019; 71 (09) 1545-1552
- 7 Sciascia S, Sanna G, Khamashta MA. et al; APS Action. The estimated frequency of antiphospholipid antibodies in young adults with cerebrovascular events: a systematic review. Ann Rheum Dis 2015; 74 (11) 2028-2033
- 8 Miranda S, Park J, Le Gal G. et al. Prevalence of confirmed antiphospholipid syndrome in 18‐50 years unselected patients with first unprovoked venous thromboembolism. J Thromb Haemost 2020; 18 (04) 926-930
- 9 Trindade VC, Carneiro-Sampaio M, Bonfa E, Silva CA. An update on the management of childhood-onset systemic lupus erythematosus. Paediatr Drugs 2021; 23 (04) 331-347
- 10 Harry O, Yasin S, Brunner H. Childhood-onset systemic lupus erythematosus: a review and update. J Pediatr 2018; 196: 22-30.e2
- 11 Miyakis S, Lockshin MD, Atsumi T. et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 4 (02) 295-306
- 12 Wilson WA, Gharavi AE, Koike T. et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum 1999; 42 (07) 1309-1311
- 13 Taruscio D, Kodra Y, Ferrari G, Vittozzi L. National Rare Diseases Registry Collaborating Group. The Italian National Rare Diseases Registry. Blood Transfus 2014; 12 (Suppl 3, Suppl 3): s606-s613
- 14 Berman H, Rodríguez-Pintó I, Cervera R. et al; Catastrophic Registry Project Group (European Forum on Antiphospholipid Antibodies). Pediatric catastrophic antiphospholipid syndrome: descriptive analysis of 45 patients from the “CAPS Registry”. Autoimmun Rev 2014; 13 (02) 157-162
- 15 Nageswara Rao AA, Elwood K, Kaur D, Warad DM, Rodriguez V. A retrospective review of pediatric antiphospholipid syndrome and thrombosis outcomes. Blood Coagul Fibrinolysis 2017; 28 (03) 205-210
- 16 Ma J, Song H, Wei M, He Y. Clinical characteristics and thrombosis outcomes of paediatric antiphospholipid syndrome: analysis of 58 patients. Clin Rheumatol 2018; 37 (05) 1295-1303
- 17 Islabão AG, Mota LMH, Ribeiro MCM. et al; Brazilian Childhood-Onset Systemic Lupus Erythematosus Group.. Childhood-onset systemic lupus erythematosus-related antiphospholipid syndrome: a multicenter study with 1519 patients. Autoimmun Rev 2020; 19 (12) 102693
- 18 Sloan E, Wright T, Zuo Y. Identifying additional risk factors for arterial and venous thrombosis among pediatric antiphospholipid antibodies carriers. Lupus 2021; 30 (05) 828-832
- 19 Madison JA, Gockman K, Hoy C, Tambralli A, Zuo Y, Knight JS. Pediatric antiphospholipid syndrome: clinical features and therapeutic interventions in a single center retrospective case series. Pediatr Rheumatol 2022; 20: 17-20
- 20 Gattorno M, Falcini F, Ravelli A. et al. Outcome of primary antiphospholipid syndrome in childhood. Lupus 2003; 12 (06) 449-453
- 21 Berkun Y, Padeh S, Barash J. et al. Antiphospholipid syndrome and recurrent thrombosis in children. Arthritis Rheum 2006; 55 (06) 850-855
- 22 Avčin T, Cimaz R, Rozman B. Ped-APS Registry Collaborative Group. The Ped-APS Registry: the antiphospholipid syndrome in childhood. Lupus 2009; 18 (10) 894-899
- 23 Sciascia S, Amigo M-C, Roccatello D, Khamashta M. Diagnosing antiphospholipid syndrome: 'extra-criteria' manifestations and technical advances. Nat Rev Rheumatol 2017; 13 (09) 548-560
Istat.it Popolazione e famiglie.. https://www.istat.it/storage/ASI/2021/capitoli/C03.pdf . Accessed September 16, 2022. Accessed October 22, 2022
- 25 Sciascia S, Lopez-Pedrera C, Roccatello D, Cuadrado MJ. Catastrophic antiphospholipid syndrome (CAPS). Best Pract Res Clin Rheumatol 2012; 26 (04) 535-541
- 26 Alijotas-Reig J, Ferrer-Oliveras R. EUROAPS Study Group. The European Registry on Obstetric Antiphospholipid Syndrome (EUROAPS): a preliminary first year report. Lupus 2012; 21 (07) 766-768
- 27 Demir S, Keskin A, Sağ E. et al. The challenges in diagnosing pediatric primary antiphospholipid syndrome. Lupus 2022; 31 (10) 1269-1275
- 28 Groot N, de Graeff N, Avcin T. et al. European evidence-based recommendations for diagnosis and treatment of childhood-onset systemic lupus erythematosus: the SHARE initiative. Ann Rheum Dis 2017; 76 (11) 1788-1796