The French paediatric cohort of Castleman disease: a retrospective report of 23 patients

Charlotte Borocco (1) , Claire Ballot-Schmit (2) , Oanez Ackermann (1) , Nathalie Aladjidi (3) , Jeremie Delaleu (4) , Vannina Giacobbi-Milet (5) , Sarah Jannier (6) , Eric Jeziorski (7, 8) , François Maurier (9) , Yves Perel (3) , Christophe Piguet (10) , Eric Oksenhendler (11) , Isabelle Koné-Paut (1) , Caroline Galeotti (1)

1 Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre]
2 Hôpital JeanMinjoz
3 Hôpital Pellegrin
4 GRC 28 - GRAASU - Groupe de recherche clinique Amylose AA Sorbonne Université
5 Service de Pédiatrie [CH Le Mans]
6 Hôpital de Hautepierre [Strasbourg]
7 Hôpital Arnaud de Villeneuve [CHRU Montpellier]
8 Pathogénèse et contrôle des infections chroniques (PCCI)
9 HPMetz - Hôpitaux Privés de Metz
10 Service de Pédiatrie médicale [CHU Limoges]
11 AP-HP - Hopital Saint-Louis [AP-HP]

Abstract Background Castleman disease (CD) is a rare non-malignant lymphoproliferation of undetermined origin. Two major disease phenotypes can be distinguished: unicentric CD (UCD) and multicentric CD (MCD). Diagnosis confirmation is based on histopathological findings in a lymph node. We attempted to survey all cases of paediatric CD identified to date in France to set up a national registry aiming to improve CD early recognition, treatment and follow-up, within the context of a new national reference center ( http://www.castleman.fr ). Methods In 2016, we e-mailed a questionnaire to members of the French paediatric immunohaematology society, the paediatric rheumatology society and the Reference Centre for Castleman Disease to retrospectively collect cases of paediatric CD (first symptoms before age 18 years). Anatomopathological confirmation was mandatory. Results We identified 23 patients (12 girls) with a diagnosis of UCD ( n = 17) and MCD ( n = 6) between 1994 and 2018. The mean age at first symptoms was 11.47 ± 4.23 years for UCD and 8.3 ± 3.4 years for MCD. The mean diagnosis delay was 8.16 ± 10.32 months for UCD and 5.16 ± 5.81 years for MCD. In UCD, the initial symptoms were isolated lymph nodes ( n = 10) or lymph node associated with other symptoms ( n = 7); fever was present in 3 patients. Five patients with MCD presented fever. No patients had HIV or human herpesvirus 8 infection. Autoinflammatory gene mutations were investigated in five patients. One patient with MCD carried a K695R heterozygous mutation in MEFV , another patient with MCD and Duchenne myopathy carried two variants in TNFRSF1A and one patient with UCD and fever episodes carried two heterozygous mutations, in IL10RA and IL36RN , respectively. Treatment of UCD was mainly surgical resection, steroids, and radiotherapy. Treatment of MCD included tocilizumab, rituximab, anakinra, steroids, chemotherapy, and splenectomy. Overall survival after a mean of 6.1 ± 6.4 years of follow-up, was 100% for both forms. Conclusion Paediatric CD still seems underdiagnosed, with a significant diagnosis delay, especially for MCD, but new international criteria will help in the future. Unlike adult CD, which is strongly associated with HIV and human herpesvirus 8 infection, paediatric CD could be favored by primary activation of innate immunity and may affect life expectancy less.

Mots clés: Multicentric; Paediatric Castleman disease; Tocilizumab; Unicentric

Domaines: Sciences du Vivant [q-bio]

Charlotte Borocco, Claire Ballot-Schmit, Oanez Ackermann, Nathalie Aladjidi, Jeremie Delaleu, et al.. The French paediatric cohort of Castleman disease: a retrospective report of 23 patients. Orphanet Journal of Rare Diseases, 2020, 15 (1), pp.95. ⟨10.1186/s13023-020-1345-5⟩. ⟨hal-03528898⟩