SAPHO syndrome is an uncommon auto inflammatory disease characterized by osteoarticular and cutaneous manifestations. Although its pathogenesis remains unclear, SAPHO syndrome could be the consequence of the complex interactions between polygenic and exogenous factors triggering the disease burden2.
In our case acne fulminans had preceded the onset of sacroiliitis. The patient experienced osteoarticular symptoms 10 weeks after being on isotretinoin. This drug has been already found to be associated with acute spondyloarthritis, in adults and in adolescents8. It has been shown that isotretinoin alters the formation of cytokines, such as tumour necrosis factor (TNF) and interleukin 1 (IL1). In addition, isotretinoin has detergent-like properties and could alter cell membrane structures, promoting the degenerative process of joints. Finally, retinol and acid retinoic has been shown to induce metalloproteinases activity, which increase degradation of membranes5.
Isotretinoin was documented as a possible provoking factor for articular symptoms in SAPHO only in a few cases6910 Likewise, we herein present a case where SAPHO was possibly precipitated with isotretinoin. Indeed, the temporal sequence between isotretinoin introduction and musculoskeletal disease suggests an inducing role of this drug in the pathogenesis of sacroiliitis.
Therefore, the previous use of isotretinoin should be investigated by paediatricians approaching adolescents affected by acne and osteoarticular symptoms, especially if the axial skeleton is involved. Further studies are needed to better clarify isotretinoin role in patients with SAPHO syndrome.
In our case the patient did not favourably respond to the NSAIDs therapy. Considering the severe osteoarticular involvement, acne fulminans and the occurrence of HS we decided to start biologic therapy as second line treatment. A rapid clinical improvement with ADA administration every 2 weeks was observed and confirmed by radiological 12-month follow-up. In addition, stable clinical remission of both cutaneous and osteoarticular symptoms was confirmed up to 24 months.
Available literature has reported that TNF-antagonists have been successfully used for the treatment of acne fulminans. Moreover, most cases of refractory SAPHO syndrome were treated with anti-TNF agents, such as infliximab and adalimumab. Furthermore, ADA is considered the first-choice biologic agent in moderate/severe HS after failure of conventional treatments with antibiotics11. In our patient, ADA determined a rapid response of cutaneous and musculoskeletal involvement with maintenance of clinical disease remission during the treatment period.
Finally, our patient who had complained depression since the worsening of acne, still maintained his severe psychiatric disorder in the following years, despite the sertraline therapy and the dermatological and rheumatological stable remission. The association between many immuno-mediated inflammatory diseases and depressive mood disorders is already reported. However, there is no related literature concerning psychiatric symptoms in SAPHO patients, out of a recent study by Lu et al, revealing a high prevalence (46%) of depression in SAPHO patients.
The association between isotretinoin and sacroiliitis has been already described but its pathogenetic mechanism remains undefined; in contrast, the role of isotretinoin as trigger of musculoskeletal involvement in SAPHO has been rarely reported.
In severe cases of SAPHO syndrome, ADA therapy proved to be efficacious determining persistent clinical remission of cutaneous and osteoarticular symptoms.
SAPHO patients may have the potential to develop depressive symptoms, but this mood disorder seems to be independent from the course of the disease.