Impact of age at diagnosis, sex, and immunopathological manifestations in 886 patients with pediatric chronic immune thrombocytopenia

Abstract

Pediatric chronic immune thrombocytopenia (cITP) is a heterogeneous condition in terms of bleeding severity, second‐line treatment use, association with clinical and/or biological immunopathological manifestations (IMs), and progression to systemic lupus erythematosus (SLE). No risk factors for these outcomes are known. Specifically, whether age at ITP diagnosis, sex, or IMs impact cITP outcomes is unknown. We report the outcomes of patients with pediatric cITP from the French nationwide prospective cohort OBS'CEREVANCE. We used multivariate analyses to investigate the effect of age at ITP diagnosis, sex, and IMs on cITP outcomes. We included 886 patients with a median (min‐max) follow‐up duration of 5.3 (1.0–29.3) years. We identified an age cutoff that dichotomized the risk of the outcomes and defined two risk groups: patients with ITP diagnosed <10 years (children) and ≥ 10 years (adolescents). Adolescents had a two to four‐fold higher risk of grade ≥3 bleeding, second‐line treatment use, clinical and biological IMs, and SLE diagnosis. Moreover, female sex and biological IMs were independently associated with higher risks of biological IMs and SLE diagnosis, second‐line treatment use, and SLE diagnosis, respectively. The combination of these three risk factors defined outcome‐specific risk groups. Finally, we showed that patients clustered in mild and severe phenotypes, more frequent in children and adolescents, respectively. In conclusion, we identified that age at ITP diagnosis, sex, and biological IMs impacted the long‐term outcomes of pediatric cITP. We defined risk groups for each outcome, which will help clinical management and further studies.

Clinical significance of antinuclear antibodies in primary immune thrombocytopenia

“…In children, the incidence of systemic lupus in the large cohort of chronic ITP patients by Pincez et al ( n = 886) was 4.3% ( n = 38) with a median follow‐up of 5.3 years (min–max: 1.0–29.3). Systemic lupus developed with a median time from ITP diagnosis of 2.8 years (min–max: 0.1–15.5), and 33 (86.8%) were girls with a median age at lupus diagnosis of 15 years (min–max: 5.8–21.0) 21 . Of note, only children with chronic ITP (lasting ≥12 months) were included in this prospective cohort, which is the subgroup probably the most as risk to develop systemic autoimmune disease as compared with ITP in remission before 12 months of evolution.…”

“…In the recently published prospective study of 886 children with chronic ITP, the presence of ANAs (titre ≥1:160) was associated with a higher probability to be exposed to second‐line treatments 21 . No data are available in adults with this regards.…”

“…Systemic lupus developed with a median time from ITP diagnosis of 2.8 years (min-max: 0.1-15.5), and 33 (86.8%) were girls with a median age at lupus diagnosis of 15 years (min-max: 5.8-21.0). 21 Of note, only children with chronic ITP (lasting ≥12 months) were included in this prospective cohort, which is the subgroup probably the most as risk to develop systemic autoimmune disease as compared with ITP in remission before 12 months of evolution. Data from other clinical cohorts in both children and adults should be taken with caution due to the low number of included patients, the low number of expected cases and the short follow-up resulting in very unprecise estimates.…”

“…In the cohort by Pincez et al, all the 38 children who developed systemic lupus had ANAs at a titre ≥1:160. Conversely, 147 children with chronic ITP and the presence of ANAs at a titre ≥1:160 did not develop systemic lupus during the follow‐up 21 . However, clinical experience and ancient descriptions of cases favour the interest of regular assessment of signs of autoimmune systemic diseases during the follow‐up of patients with a high titre of ANAs and/or ANAs specifically directed towards DNA or ENA (SSA/La, SSB/Ro or Sm) 11,20,32 …”

“…Large series identified a higher prevalence of ANAs in adolescent girls than in boys and younger children. 17,21 No association with bleeding and platelet count at diagnosis was identified in a retrospective series of 365 children. 13 In adults, no association was found in a prospective series of 215 patients with primary ITP aged ≥18 years between the presence of ANA (≥1:160, n = 92) and age, sex, history of autoimmune disease, the presence of bleeding at ITP diagnosis, type of bleeding (cutaneous, mucosal, serious) and platelet count at diagnosis.…”