Paradoxical SAPHO Syndrome after Etanercept in a Patient with Psoriasis

Sir, Paradoxical reactions are secondary side effects of biological therapies defined as the worsening or de novo presentation of a pathology that responds to the treatment that induces it. Its mean latency period is around 12–14 months.[1,2] The most commonly described are psoriasiform reactions.[3] Anti-tumour necrosis factor (TNF) alpha drugs can trigger them. These reactions can present as a paradoxical SAPHO (synovitis-acne-pustulosis-hyperostosis-osteitis) syndrome.[4] A 35-year-old woman was referred to the dermatology department with hyperkeratotic plantar lesions of four months duration. She denied previous similar lesions or psoriasis. The patient had a family history of plaque psoriasis. On examination, she presented with palmoplantar hyperkeratosis, along with plantar pustules [Figure 1a], compatible with palmoplantar pustular psoriasis. The culture of the lesions was sterile. Nail affectation was absent. No other symptoms were associated, and psoriatic arthritis was ruled out. Palmoplantar lesions were initially treated with topical corticosteroids without response. Methotrexate was prescribed (7.5 mg/week), which was suspended due to poor tolerance after 5 weeks of treatment. Thus, etanercept was introduced with a favourable response of the palmoplantar lesions (50 mg/week) in four weeks. Six weeks later, the patient reported back with exacerbation. Upon re-examination, scattered pustules, furuncles and acneiform lesions were observed mainly on the trunk, palms, axilla and scalp [Figure 1b and 1c]. No systemic symptoms were evidenced. Bacterial and mycological cultures of the pustules were sterile. Blood tests confirmed the presence of elevated levels of acute-phase reactants. Histopathological examination revealed an acute inflammatory infiltrate with dermal abscesses. No granulomas or epidermal involvement were observed. Additionally, she associated inflammatory joint pain in sternoclavicular and presternal regions. Tecnecium-99 scintigraphy examination revealed increased uptake at the aforementioned locations [Figure 1d]. Subsequently, paradoxical SAPHO syndrome was suspected, leading to the suspension of etanercept. Ustekinumab (90 mg/month) was consequently initiated, leading to the resolution of the cutaneous lesions, but not controlling articular symptoms. Therefore, it was replaced by secukinumab (300 mg/month) three months after. Clinical stability was achieved in eight weeks and persists after three years.Figure 1: (a) Initial presentation of the cutaneous lesions. Bilateral plantar hyperkeratosis is present, combined with pustular lesions settled on an erythematous background. (b and c) Cutaneous lesions after the administration of etanercept. Inflammatory papules, pustules and deeper furuncle-like are scattered all over the body surface. (d) Tecnecium-99 scintigraphy images evidencing signs of inflammatory articular pathology on bilateral sternoclavicular articulations as well as first bilateral sternocostal articulationsDiverse osteoarticular disorders associated with cutaneous manifestations can be included in SAPHO syndrome. It is believed that incomplete forms remain underdiagnosed.[4] Both anti-TNF and anti-interleukin IL 17 and 23 drugs have been reported as effective therapeutic alternatives for this condition.[4] Regarding paradoxical SAPHO syndrome, adalimumab can cause compatible manifestations.[5] In the previously reported case, articular symptoms appeared after 10 weeks, while cutaneous lesions were evidenced 14 weeks after discontinuing the drug. There are no reports of etanercept triggering paradoxical SAPHO. It is challenging to differentiate whether it is an adverse drug reaction or a latent condition unmasked by the drugs. Some reports describe its persistence after suspending the drug.[5] In the present case, it should be discussed whether the patient presented initially with palmoplantar pustular psoriasis or palmoplantar pustulosis (PPP).[6] The nosological distinction between both entities remains unsettled. The aetiology of PPP is unclear, and its association with psoriasis is controversial.[6] Additionally, pustulotic arthro-osteitis (PAO) is a well-described joint comorbidity of PPP, affecting the anterior chest wall, mostly in middle-aged Japanese smoker women. PAO is associated with focal infections. Acneiform cutaneous lesions are more frequently observed in SAPHO syndrome. Even though it is not possible to precisely determine whether it was a paradoxical reaction, the authors believe that the patient initially presented with palmoplantar pustular psoriasis, considering she was not Japanese, the family history of psoriasis and that lesions were only palmoplantar without articular involvement. Regarding the differential diagnosis between SAPHO and PPP with PAO, both the development of clinically different cutaneous lesions and the sudden osteoarticular involvement (lacking the synchronous presence of focal infection), prompted us to suspect it was a paradoxical SAPHO induced by etanercept, previously unreported with this drug. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.