Towards the definition of disease phenotypes in paediatric SAPHO syndrome: a national multicentric study

Objectives: The objective of this study was to confirm the presence of different disease phenotypes of paediatric SAPHO syndrome (pSAPHO) based on their skin manifestations in a large cohort of Italian patients. Methods: Patients with pSAPHO were enrolled in the Eurofever Registry and the data retrospectively analysed. The patients were categorized according to their skin manifestations into an acne - hidradenitis suppurativa (Acne-HS) group and a palmoplantar pustulosis - psoriasis vulgaris (PPP-PV) group and were compared with patients without skin manifestations (chronic non-bacterial osteomyelitis, CNO). Comparisons of frequencies between groups were performed using the χ2 test or the Fischer's exact test. Results: A total of 54 pSAPHO patients with skin manifestations (35 Acne-HS, 19 PPP-PV) were enrolled and compared with 167 patients with chronic recurrent multifocal osteomyelitis (CRMO). In the Acne-HS group, 82.9% were males, in the PPP-PV, 84.2% were females, while in the chronic non-bacterial osteomyelitis (CNO) group, no gender differences were observed (P < 0.0001). The three groups differed significantly with respect to age at disease onset: Acne-HS median 13.3 years, PPP-PV median 10.2 years, CNO median 9.5 years (P = 0.0001). An axial pattern was more frequent in the Acne-HS (91.4%) group and the PPP-PV group (89.4%) compared with in the CNO group (46%) (P < 0.0001). Both the Acne-HS (82.9%) and the PPP-PV (63.2%) groups required a biologic therapy more frequently than the CNO group (36.8%), but patients with Acne-HS presented with a refractory skin disease requiring steroids and other lines of treatment, while PPP-PV responded well to biologics. Conclusion: Our data have identified two different phenotypes of pSAPHO based on skin manifestations, with different age of onset, gender, and response to treatments. These two groups have peculiar clinical features that differ from those of the CNO group. A new classification encompassing these phenotypes is warranted.