A young woman with generalized pustular psoriasis and synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome treated successfully with upadacitinib

Dear Editor, Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a chronic auto-inflammatory disease characterized by osteoarticular and cutaneous involvement.[1] In view of the rarity of the SAPHO syndrome, a standard treatment strategy is not available. Generalized pustular psoriasis (GPP) is another skin disease characterized by pustular rashes distributed widely on inflamed erythematous skin. Biological agents may be used as the first-line treatment for severe acute GPP.[2] For the first time, the successful use of the Janus kinase (JAK) inhibitor upadacitinib to treat SAPHO syndrome with GPP has been reported here. A 40-year-old woman developed palmoplantar pustulosis and pain in the sternum and rib. Subsequently, she also developed fever and dense sterile superficial pustules on the whole body [Figure 1a and b]. Laboratory tests showed elevated erythrocyte sedimentation rate (36 mm/h) and C-reactive protein (4 mg/L). 99Tc-labeled methylene diphosphonate whole-body bone scintigraphy demonstrated abnormal radiotracer uptake in the bilateral sternoclavicular joint [Figure 1c]. A pustule in the thigh was biopsied, which indicated hyperkeratosis of the epidermis, partial parakeratosis, a small amount of neutrophil aggregation in the stratum corneum (Munro's microabscess), thinning of the granular layer with epidermal hyperplasia, and edema in the papillary dermis [Figure 1d and e].Figure 1: (a and b) Clinical image of the palm, perineum, and thigh showed dense sterile superficial pustules all over the body fused into "pus lakes." (c) A whole-body bone scan indicated increased radioactive uptake in the sternoclavicular and sacroiliac joints accompanied by bone sclerosis. (d and e) Original magnification × 40/×200 of the skin tissue indicated hyperkeratosis of the epidermis, partial parakeratosis, a small amount of neutrophil aggregation in the stratum corneum (Munro's microabscess), thinning of the granular layer with epidermal hyperplasia, and edema in the papillary dermis, partially extending upward to the top of the papilla. (f and g) After treating with upadacitinib, skin lesions in the palm, perineum, and thigh disappeared.Based on the symptoms, imaging studies, and pathology results, SAPHO syndrome with GPP was diagnosed.[1] Owing to nonresponse to etoricoxib, methotrexate, and adalimumab treatment, 15 mg of the JAK inhibitor upadacitinib was administered once daily. The bone pain and skin lesions were relieved entirely after 3 months [Figure 1f and g]. SAPHO and GPP have similar pathogenesis and are auto-inflammatory disorders associated with interleukin (IL)-1, tumor necrosis factor-alpha (TNF-α), IL-17A, IL-36, and IL-12 dysregulation. Hence, therapy targeting cytokines may be effective.[3,4] Treatment for these two diseases is challenging. For SAPHO syndrome, the use of TNF-α, IL-17, and JAK inhibitors has also been frequently reported.[3] GPP may be triggered by an inflammatory response resulting from the activation of innate immunity. This condition might be considered a severe variant of psoriasis with high levels of IL-1 and IL-36; therefore, biological agents, including JAK inhibitors, may be a suitable choice.[4] Previous studies have suggested that upadacitinib is effective in treating psoriasis; however, few studies have shown efficacy in GPP. Upadacitinib has been approved for treating rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, atopic dermatitis, and nonradiographic axial spondyloarthritis. A study demonstrated that treating SAPHO syndrome is one of its off-label uses.[5] However, case reports on the successful use of upadacitinib to treat SAPHO syndrome with GPP have not been published. Our patient was treated with upadacitinib, which is a type of selective JAK1 inhibitor. ILs (IL-2, IL-4, IL-15, and IL-21) can activate the downstream JAK1 pathway through the gamma-chain receptor. Pro-inflammatory cytokines, including IL-6 and IFN, are also involved in the JAK1/STAT pathway.[6] JAK1 is predominantly involved in inflammatory and innate immune responses. By blocking this pathway, JAK1 inhibitor can inhibit the production of inflammatory factors to exert an anti-inflammatory effect. Thus, the use of JAK1 inhibitor might be a potential therapeutic strategy for GPP combined with SAPHO syndrome. Inhibition of JAK2/3 may contribute to adverse events owing to its role in regulating immune cell proliferation and homeostasis.[7] Compared with tofacitinib that blocks JAK1/3, the second-generation JAK inhibitor upadacitinib may potentially alleviate the exhaustion of immune cells by the highly selective inhibition of individual JAK proteins. In conclusion, this is the first report on the successful use of the JAK1 inhibitor upadacitinib to treat GPP with SAPHO syndrome. Ethical approval The study protocol was approved by the committee on human research of Fangshan Hospital of Beijing University of Chinese Medicine with the following reference numbers: FZJ JS-2021-002. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Financial support and sponsorship This work was supported by the National Natural Science Foundation of China (No. 82074246) and the construction project of a clinical key specialty in the Fengtai District of Beijing. Conflicts of interest There are no conflicts of interest.