Yuxi Liu
Di Jin2†
Chen Li
Xin Li- 1Department of Critical Rheumatology and Immunology, Clinical Immunology Centre, Tianjin Medical University General Hospital, Tianjin, China
- 2Department of Rheumatology, Weifang People’s Hospital, Weifang, Shandong, China
- 3School of traditional Chinese medicine, Beijing University of Chinese Medicine, Beijing, China
- 4Department of Dermatology, Tianjin Institute of Integrative Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, China
Background: SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome is a rare autoinflammatory disease. Paradoxical reactions and immune deviation following biologic therapy are occasionally observed in clinical practice; however, to our knowledge, no previous cases of paradoxical skin rash accompanied by Hyperimmunoglobulinemia E have been reported.
Case presentation: A 35-year-old male with SAPHO syndrome experienced significant exacerbation of palmoplantar pustulosis and a sharp increase in immunoglobulin E(IgE) levels following treatment with secukinumab and infliximab. After one month of upadacitinib therapy, the patient showed marked improvement in cutaneous lesions and bone pain, along with significant normalization of inflammatory markers and a pronounced reduction in IgE levels.
Conclusion: This case suggests that upadacitinib may be a valuable therapeutic option for patients with refractory SAPHO syndrome, particularly those presenting with paradoxical reactions or hypersensitivity. The unique mechanism of action of Janus kinase (JAK) inhibitors may offer superior efficacy in such cases, though further clinical validation and mechanistic studies are warranted.
Introduction
SAPHO(synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome is a rare autoinflammatory disorder characterized by synchronous skin-bone-joint inflammation, presenting clinically with synovitis, acne, pustulosis, hyperostosis, and osteitis (1). Its pathogenesis remains unclear, potentially involving individual genetic differences, immune status, microbial factors, and environmental influences (2).SAPHO syndrome exhibits clinical heterogeneity, rendering diagnosis challenging. Commonly employed therapeutic approaches include antibacterial agents, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, bisphosphonates, and conventional disease-modifying antirheumatic drugs (cDMARDs) such as methotrexate. In recent years, biologic agents such as tumor necrosis factor(TNF)-α inhibitors and interleukin-17/-interleukin23(IL-17/IL-23) inhibitors have become increasingly important therapeutic options (3). However, reports indicate paradoxical manifestations in some patients, though no cases of allergic reactions or Hyperimmunoglobulinemia E have been observed to date. Upadacitinib is a highly selective Janus kinase(JAK)1 inhibitor approved for treating rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, and other conditions (4), demonstrating unique advantages in refractory inflammatory diseases (5). This paper presents the first reported case of upadacitinib treating SAPHO syndrome complicated by biologic-induced paradoxical rash and abnormally elevated immunoglobulin E(IgE) levels. It aims to explore the clinical efficacy and therapeutic targeting of upadacitinib in this specific status, offering a potential treatment option for SAPHO patients who have failed biologic therapy.
Case presentation
Initial presentation and diagnosis(April 2022): The patient is a 35-year-old male who presented three years ago with anterior chest and lower back pain, accompanied by herpetic lesions with ulceration on both hands and feet. Physical examination revealed tenderness over both costal margins and sternoclavicular joints; tenderness between the spinous processes of L5 and S1 vertebrae. Papular vesicles were observed on the palms of both hands and soles of both feet, which ruptured to discharge yellowish fluid, accompanied by crusting and desquamation, with visible erythematous ecchymoses. Whole-body bone scintigraphy revealed abnormal tracer concentration in bilateral articulations sternocostales regions, the sternoclavicular joint areas, the sacrum, and bilateral sacroiliac joints, presenting the classic “bull’s head sign” (Figure 1A). Laboratory investigations revealed an erythrocyte sedimentation rate (ESR) of 47 mm/h, C-reactive protein (CRP) at 17.2 mg/L, and IgE 778.00 IU/mL. Other laboratory results are detailed in Table 1. Diagnosis of SAPHO syndrome was confirmed.
Figure 1. Patient’s imaging and pathological examination, skin manifestations and changes in indicators. (A) Whole-body bone scintigraphy revealed abnormal tracer accumulation in bilateral costal regions, the sternoclavicular joint areas, the sacrum, and bilateral sacroiliac joints, presenting the classic “bull’s head sign”; (B) Exacerbation of hands pustular psoriasis following treatment with secukinumab; (C) Exacerbation of pustular psoriasis on the feet following treatment with secukinumab; (D) After treatment with infliximab, the hands rash worsened again, accompanied by itching, crusting, and desquamation; (E) After treatment with infliximab, the feet rash worsened again, accompanied by itching, crusting, and desquamation; (F) Skin biopsy revealed hyperkeratosis of the epidermis, mild hyperplasia of the granular and spinous layers, Elongation of the rete ridges, and perivascular lymphocytic infiltration in the dermis; (G) The hands rash has markedly resolved following treatment with upadacitinib; (H) The feet rash has markedly resolved following treatment with upadacitinib; (I) Changes in inflammatory parameters levels during treatment; (J) Changes in IgE levels during treatment.
Table 1. Laboratory results at initial treatment.
First-line therapy and partial response: Initial treatment was commenced with loxoprofen sodium tablets (60 mg po twice a day), methotrexate (10 mg po once a week), and alendronate sodium tablets (70 mg po once a week). The patient’s symptoms improved.
Paradoxical reaction under IL-17 inhibitor (September 2022): After five months of treatment, the patient experienced worsening shoulder and back pain, with herpes lesions spreading from the plantar surface to the dorsum of the feet. Treatment was continued with secukinumab (300 mg S.C once a week) for one month. Follow-up blood tests revealed an ESR 108mm/h, CRP 74.3 mg/L, IgE 6880.00 IU/mL. The patient reported worsening of shoulder-back and lumbar-gluteal pain, extending to both arms. Pustular lesions appeared on the palms and soles, worsening compared to previous episodes (Figures 1B, C). This was considered a paradoxical reaction to IL-17 inhibitors. Thereafter, the patient intermittently and irregularly received secukinumab until March 2025, achieving clinical symptom remission, though serum IgE levels remained persistently elevated.
Worsening and hypersensitivity reaction under TNF-α inhibition (April 2025): Due to persistently elevated IgE levels, therapy was switched to infliximab (100mg IV 3d). Following the third infusion, the patient developed pain in the anterior chest and buttocks, with a recurrence and worsening of the generalized rash, accompanied by pruritus, crusting, and desquamation (Figures 1D, E). Follow-up blood tests revealed an ESR 70 mm/h, CRP 29.3 mg/L, IgE 27,100.00 IU/mL. Skin biopsy revealed hyperkeratosis of the epidermis, mild hyperplasia of the granular and spinous layers, Elongation of the rete ridges, and perivascular lymphocytic infiltration in the dermis (Figure 1F).
Diagnostic reassessment: The patient was considered to have developed a paradoxical rash and allergic reaction following the administration of biologic agents. Infliximab was discontinued. Following one week of symptomatic treatment with anti-allergy medication, the rash has shown slight improvement.
Initiation of JAK inhibitor and therapeutic response (May 2025): Treatment with upadacitinib (15mg po once a day) was then initiated. One month later, follow-up revealed an ESR 14 mm/h, CRP <0.2 mg/L, and IgE 15,800 IU/mL. The patient’s rash had markedly subsided, and bone pain had resolved (Figure 1G, H). Changes in inflammatory parameters and IgE levels during treatment are shown in Figures 1I and J.
Follow-up and long-term response: While drafting and revising this article, the patient continued upadacitinib therapy with sustained clinical stability. At the 3−month follow−up (September 2025), laboratory tests showed further improvement: ESR 8mm/h, CRP 3.35mg/L, and IgE 11,600IU/mL. By the 6−month follow−up (December 2025), the inflammatory markers had declined to ESR 7mm/h, CRP 2.87mg/L, and IgE 10,800IU/mL, with no recurrence or progression of cutaneous or osteoarticular symptoms. No adverse events such as infection or thrombosis were observed; however, a mild elevation of low-density lipoprotein cholesterol (LDL−C) and γ-glutamyl transferase (GGT) was noted at the 6−month assessment. To provide a clearer overview of the clinical course, illustrating the sequence of treatment and the occurrence and progression of paradoxical manifestations, a timeline diagram is presented in Figure 2.
Figure 2. The timeline chart illustrates the sequence of treatment and the occurrence and progression of paradoxical manifestations, providing a clearer overview of the clinical course. ESR: erythrocyte sedimentation rate, CRP: C-reactive protein, IgE: immunoglobulin E, LDL−C: low-density lipoprotein cholesterol, GGT: γ-glutamyl transferase.
The patient reported feeling markedly better after switching to upadacitinib, with resolution of the skin rash and relief of bone pain. The improvement in symptoms led to a substantial enhancement in his overall quality of life and sleep.
Discussion
Currently, there is no universally accepted treatment protocol for SAPHO syndrome. Although biologics such as TNF-α inhibitors (e.g., infliximab) and IL-17/23 inhibitors (e.g., secukinumab) have demonstrated therapeutic potential, their efficacy varies considerably between individuals. In clinical practice, immune drift, treatment failure, or paradoxical effects are frequently observed. A considerable body of literature has documented these findings, with relevant summaries presented in Table 2.
Table 2. Literature summary of biologics-induced paradoxical manifestations in SAPHO syndrome.
The exacerbation of palmoplantar pustulosis (PPP) following biologic therapy remains incompletely understood, though it is hypothesized to represent a severe allergic reaction associated with T helper 2 (Th2)-type inflammation, which is characterized by elevated eosinophil counts and/or high serum IgE levels (6). The pathogenesis of PPP is centrally driven by Th2 immune responses, operating independently of the IL-23/Th17 axis characteristic of classical psoriasis. Th2 cytokines (IL-4/IL-13) play the most fundamental role in this process. They bind to corresponding receptors on the surface of B cells, activating the JAK/(signal transducer and activator of transcription) STAT signaling pathway. This initiates the crucial Ig class switching and recombination, causing B cells to transition from producing IgM, IgG and other types to specifically generating IgE (7). Furthermore, focal infection as an initiating factor amplifies Th2 inflammation and indirectly promotes the dysregulation of IgE-mediated immune responses by releasing superantigens to activate T cells and inducing Treg dysfunction. Post-infection resolution of Th2 markers correlates with symptom improvement (8). Results from a cohort study involving 24,997 cases exposed to biological agents indicate that patients receiving IL-17 inhibitors and TNF-α inhibitors face the highest risk of developing paradoxical psoriasis (9). Infliximab may induce immune complex-mediated Type III hypersensitivity reactions and shift the Th1/Th2 immune balance (10), whilst also potentially impairing neutrophil function. This may lead to the reactivation of slow-growing microorganisms such as Propionibacterium acnes, exacerbating cutaneous manifestations (11). Secukinumab may disrupt cytokine homeostasis by inhibiting IL-17A’s immune surveillance function, potentially increasing upstream cytokines such as IL-23 and Interferon(IFN)-α (12), thereby exacerbating Th2 immunological skewing and elevated IgE levels (13). Within the local microenvironment, Th17 cells undergo a phenotypic shift towards Th2, while IL-4 attenuates IL-23/Th17 axis activity by inhibiting STAT3 phosphorylation (14). This mechanism explains the limited efficacy observed with IL-17/IL-23 inhibitors.
A substantial amount of clinical literature supports the use of JAK/STAT inhibitors for treating SAPHO syndrome. These agents effectively alleviate clinical symptoms, reduce inflammatory marker levels, and demonstrate good overall tolerability in patients, as summarised in Table 3. The therapeutic rationale for employing upadacitinib, a highly selective JAK1 inhibitor, in SAPHO syndrome lies in its broad inhibitory effects on multiple inflammatory signaling pathways. The drug competitively inhibits the binding of adenosine triphosphate(ATP) to the tyrosine kinase domain of JAK1 (15). This high selectivity enables it to effectively block the signaling of multiple pro-inflammatory cytokines while minimizing interference with JAK2/JAK3-dependent physiological processes (16), thereby demonstrating superior therapeutic efficacy and safety. Upadacitinib addresses paradoxical reactions induced by biologics by concurrently inhibiting the signal transduction of multiple Th2 cytokines—including IL-4, IL-13, thymic stromal lymphopoietin(TSLP), IL-5, and IL-31—thereby suppressing their biological effects (17). This dual action reverses both upstream Th2 polarization and downstream inflammatory responses, ultimately ameliorating Th2 inflammation and cytokine dysregulation (18).
Table 3. Literature summary of JAK/STAT inhibitor therapy for SAPHO syndrome.
In summary, the emergence of paradoxical reactions accompanied by Hyperimmunoglobulinemia E in SAPHO syndrome patients during biologic therapy reflects a complex immunological dysregulation. We posit that this phenomenon may be associated with the following mechanisms: first, a pre-existing Th2 inflammatory predisposition in patients, characterized by overactivation of the Th2 immune pathway (IL-4/IL-13), which directly drives antibody class switching in B cells; second, the administration of biologics may disrupt immune homeostasis, leading to impaired immune surveillance and further exacerbating Th2 bias and cytokine imbalance; additionally, focal infections as initiating factors amplify Th2 inflammation. Any therapeutic intervention that disrupts immune equilibrium risks being “counteracted” or even “reversed” by the Th2 pathway, triggering paradoxical manifestations and hypersensitivity reactions.
This case report presents the first documented instance of a patient with SAPHO syndrome developing a severe paradoxical cutaneous reaction accompanied by hyperimmunoglobulinaemia following treatment with IL-17 and TNF-α inhibitors, ultimately controlled by the JAK1 inhibitor upadacitinib. This unique clinical trajectory not only offers novel therapeutic insights for such multiply refractory cases but also suggests a potential biologically triggered subtype centred on Th2 immunological bias.
However, this case study carries limitations. Firstly, as a single case report, it is inherently observational and descriptive, incapable of establishing causality and thus offering limited generalisability. The success of this case carries selection bias, and the influence of placebo effects, natural disease fluctuations, or unidentified confounding factors cannot be entirely excluded. Secondly, our interpretation of the Th2-biased mechanism relies primarily on serum IgE as an indirect biomarker, lacking direct immunological evidence from lesion tissue. Finally, despite a six-month follow-up period, this remains insufficient for assessing long-term efficacy and safety in a chronic condition.
Moreover, when considering the use of upadacitinib or similar JAK inhibitors for SAPHO syndrome, their known class-related risks must be systematically assessed and managed. Based on large clinical trial data from diseases such as rheumatoid arthritis, risks requiring attention with JAK inhibitors include: increased risk of infections, major adverse cardiovascular events and venous thromboembolism, as well as laboratory parameter changes such as dyslipidaemia (19). Therefore, a comprehensive baseline risk assessment must be conducted before clinical use, with close monitoring throughout treatment.
Conclusion
Conclusively, this case offers significant insights for SAPHO syndrome patients who develop paradoxical reactions to biologic therapy. However, its widespread application requires further validation through additional clinical cases and more extensive research. Treatment decisions should be individualized based on disease characteristics, treatment history, and risk assessment.
Data availability statement
The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.
Ethics statement
In accordance with Chinese law and relevant institutional policies, this retrospective case analysis qualifies for exemption from ethical review. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article. Written informed consent was obtained from the participant/patient(s) for the publication of this case report.
Author contributions
YL: Data curation, Writing – original draft, Conceptualization, Formal Analysis, Methodology, Visualization, Writing – review & editing. DJ: Investigation, Writing – original draft, Conceptualization, Methodology, Resources, Visualization, Writing – review & editing. WL: Data curation, Formal Analysis, Investigation, Visualization, Writing – original draft, Writing – review & editing. SZ: Writing – review & editing. CL: Conceptualization, Funding acquisition, Resources, Supervision, Writing – review & editing. XL: Conceptualization, Funding acquisition, Resources, Supervision, Writing – review & editing.
Funding
The author(s) declared that financial support was received for this work and/or its publication. This study was funded by the Weifang Health Commission’s scientific research program (grant No. WFWSJK-2023-222 and WFWSJK-2023-240); Weifang Youth Medical Talent Lift Project; and the National Natural Science Foundation of China (82374272).
Conflict of interest
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Generative AI statement
The author(s) declared that generative AI was not used in the creation of this manuscript.
Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
1. Minhchau Thi N, Andrea B, Carlo S, Stanley MN, Gurtej C, and M Eric G. The SAPHO syndrome. Semin Arthritis Rheumatol. (2012) 42. doi: 10.1016/j.semarthrit.2012.05.006
2. Przepiera-Będzak H and Brzosko M. SAPHO syndrome: pathogenesis, clinical presentation, imaging, comorbidities and treatment: a review. Postepy Dermatol Alergol Dec. (2021) 38:937–42. doi: 10.5114/ada.2020.97394
3. Li SWS, Roberts E, and Hedrich C. Treatment and monitoring of SAPHO syndrome: a systematic review. RMD Open. (2023) 9. doi: 10.1136/rmdopen-2023-003688
4. Iain B M, Jaclyn K A, Marina M, Joseph F M, Yi L, Mitsumasa K, et al. Trial of upadacitinib and adalimumab for psoriatic arthritis. N Engl J Med. (2021) 384. doi: 10.1056/NEJMoa2022516
5. Tanaka Y. A review of upadacitinib in rheumatoid arthritis. Mod Rheumatol. (2020) 30:779–87. doi: 10.1080/14397595.2020.1782049
6. Criado PR, Miot HA, and Ianhez M. Eosinophilia and elevated IgE serum levels: a red flag: when your diagnosis is not a common atopic eczema or common allergy. Inflammation Res. (2023) 72:541–51. doi: 10.1007/s00011-023-01690-7
7. Oscar P, Dirk E, Peter MI, Xavier J, and Paolo T. Regulatory T cells and immunoglobulin E: A new therapeutic link for autoimmunity? Allergy. (2022) 77. doi: 10.1111/all.15449
8. Michiyoshi K, Akihiro N, Masaki M, Naohiko I, Kenichiro U, Takeshi N, et al. Retrospective analysis of the clinical response of palmoplantar pustulosis after dental infection control and dental metal removal. J Dermatol. (2017) 44. doi: 10.1001/jamadermatol.2023.4846
9. Ali A-J, Oras A A, Zenas Z N Y, Amy C F, Steve E, Adnan R K, et al. Risk of paradoxical eczema in patients receiving biologics for psoriasis. JAMA Dermatol. (2023) 160. doi: 10.1001/jamadermatol.2023.4846
10. Jarrett SJ, Cunnane G, Conaghan PG, Bingham SJ, Buch MH, Quinn MA, et al. Anti-tumor necrosis factor-alpha therapy-induced vasculitis: case series. J Rheumatol. (2003) 30:2287–91.
11. Kotilainen P, Merilahti-Palo R, Lehtonen OP, Manner I, Helander I, Möttönen T, et al. Propionibacterium acnes isolated from sternal osteitis in a patient with SAPHO syndrome. J Rheumatol. (1996) 23:1302–4.
12. Carlo Alberto M, Mario V, Chiara M, Maurizio R, Silvia Mariel F, Michel G, et al. Paradoxical psoriasis: an updated review of clinical features, pathogenesis, and treatment options. J Invest Dermatol. (2024) 144. doi: 10.1016/j.jid.2024.05.015
13. Daniel W, François A, Frank V, and Clément P. IL-23/Th17 targeted therapies in SAPHO syndrome. A case series. Joint Bone Spine. (2017) 84. doi: 10.1016/j.jbspin.2017.05.016
14. Daniel M, Natashia B-O, Satveer K M, Niina Karoliina H, Christian T W, A David B, et al. Single-cell analysis implicates T(H)17-to-T(H)2 cell plasticity in the pathogenesis of palmoplantar pustulosis. J Allergy Clin Immunol. (2022) 150. doi: 10.1016/j.jaci.2022.04.027
15. Daniella MS, Michael B, Massimo G, and John JOS. Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases. Nat Rev Rheumatol. (2015) 12. doi: 10.1038/nrrheum.2015.167
16. Parmentier JM, Voss J, Graff C, Schwartz A, Argiriadi M, Friedman M, et al. In vitro and in vivo characterization of the JAK1 selectivity of upadacitinib (ABT-494). BMC Rheumatol. (2018) 2:23. doi: 10.1186/s41927-018-0031-x
17. I-Hsin H, Wen-Hung C, Po-Chien W, and Chun-Bing C. JAK-STAT signaling pathway in the pathogenesis of atopic dermatitis: An updated review. Front Immunol. (2022) 13. doi: 10.3389/fimmu.2022.1068260
18. Chisa N, Shigeto Y, and Atsushi O. Innovation in the treatment of atopic dermatitis: Emerging topical and oral Janus kinase inhibitors. Allergol Int. (2021) 71. doi: 10.1016/j.alit.2021.10.004
19. Almoallim HM, Omair MA, Ahmed SA, Vidyasagar K, Sawaf B, and Yassin MA. Comparative efficacy and safety of JAK inhibitors in the management of rheumatoid arthritis: A network meta-analysis. Pharm (Basel). (2025) 18. doi: 10.3390/ph18020178
20. Massara A, Cavazzini PL, and Trotta F. In SAPHO syndrome anti-TNF-alpha therapy may induce persistent amelioration of osteoarticular complaints, but may exacerbate cutaneous manifestations. Rheumatol (Oxford). (2006) 45:730–3. doi: 10.1093/rheumatology/kei221
21. Eleftheriou D, Gerschman T, Sebire N, Woo P, Pilkington CA, and Brogan PA. Biologic therapy in refractory chronic non-bacterial osteomyelitis of childhood. Rheumatol (Oxford). (2010) 49:1505–12. doi: 10.1093/rheumatology/keq122
22. Branimir A, Ivan P, Marko B, and Stanko T. The lobster sign in SAPHO syndrome: unusually extensive osteitis of the anterior chest wall partially responsive to infliximab. Rheumatol Int. (2012) 34. doi: 10.1007/s00296-012-2606-y
23. Xinlu Z, Xia W, and Chen L. Successful treatment of synovitis, acne, pustulosis, hyperostosis, and osteitis and paradoxical skin lesions by Tripterygium wilfordii hook f: a case report. J Int Med Res. (2020) 48. doi: 10.1177/0300060520949100
24. Chen L, Xia W, Yihan C, Yueping Z, Weihong Z, Shuo Z, et al. Paradoxical skin lesions induced by anti-TNF-α agents in SAPHO syndrome. Clin Rheumatol. (2018) 38. doi: 10.1007/s10067-018-4083-5
25. Luxia C, Qichang L, Sijia C, and Hao C. Case Report: Successful treatment of refractory synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome and palmoplantar pustulosis with ustekinumab. Front Immunol. (2025) 16. doi: 10.3389/fimmu.2025.1628279
26. Danyang F, Fuqiu L, Zhe L, Zhanhan T, and Sha L. Successful treatment of refractory synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome and paradoxical psoriasis with secukinumab: A case report. Clin Cosmet Investig Dermatol. (2024) 17. doi: 10.2147/ccid.S454057
27. Mario F, Luigi F, Elisabetta G, Eneida C, Mauro F, Alberto B, et al. Risankizumab efficacy in synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) remission: A case report on rheumatologic and dermatologic disease manifestations with literature review. Case Rep Immunol. (2024) 2024. doi: 10.1155/2024/9076852
28. Cheng X, Xiayan X, and Yongmei H. Awareness of the risk of paradoxical psoriasis in patients with SAPHO syndrome undergoing treatment with secukinumab: A case series. J Inflammation Res. (2025) 18. doi: 10.2147/jir.S510006
29. S A, J N, A K, U S, A C, L E F, et alSuccessful treatment of SAPHO syndrome with apremilast. Br J Dermatol. (2017) 179. S A, J N, A K, et al. doi: 10.1111/bjd.16071
30. Man L, Patrick W, Su-Boon Y, and Pui-Ying L. Case report: successful treatment of secukinumab-induced SAPHO syndrome with tofacitinib. Int J Rheum Dis. (2025) 28. doi: 10.1111/1756-185x.70305
31. Fujita S, Kosaka N, Mito T, Hayashi H, and Morita Y. Development of aseptic subcutaneous abscess after tocilizumab therapy in a patient with SAPHO syndrome complicated by amyloid A amyloidosis. Int J Rheum Dis. (2015) 18:476–9. doi: 10.1111/1756-185X.12525
32. Sun XC, Liu S, Li C, Zhang S, Wang M, Shi XH, et al. Failure of tocilizumab in treating two patients with refractory SAPHO syndrome: a case report. J Int Med Res. (2018) 46:5309–15. doi: 10.1177/0300060518806105
33. Na D, Jingyi Y, Yiwen Z, Xinyan L, Lei C, and Wei M. Successful treatment of refractory palmoplantar pustulosis by upadacitinib: report of 28 patients. Front Med (Lausanne). (2024) 11. doi: 10.3389/fmed.2024.1476793
35. Mingwei M, Siyi L, Xiujuan H, and Chen L. Novel JAK-1 inhibitor upadacitinib as a possible treatment for refractory SAPHO syndrome: A case report. Int J Rheum Dis. (2023) 26. doi: 10.1111/1756-185x.14774
36. Yang Q, Zhao Y, Li C, Luo Y, Hao W, Zhang W, et al. Case report: successful treatment of refractory SAPHO syndrome with the JAK inhibitor tofacitinib. Med (Baltimore). (2018) 97:e11149. doi: 10.1097/MD.0000000000011149
37. Chen L, Zhaohui L, Yihan C, Li L, Feng L, Yueting L, et al. Rapid remission of refractory synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome in response to the Janus kinase inhibitor tofacitinib: A case report. World J Clin Cases. (2020) 8. doi: 10.12998/wjcc.v8.i19.4527
38. Yueting L, Jianwei H, Yihan C, Meiyan Y, Yanan Z, Zhaohui L, et al. Efficacy of tofacitinib in synovitis, acne, pustulosis, hyperostosis and osteitis syndrome: a pilot study with clinical and MRI evaluation. Ann Rheum Dis. (2020) 79. doi: 10.1136/annrheumdis-2020-217250
39. Chen L, Zhaohui L, Yihan C, Li L, Feng L, Yueting L, et al. Tofacitinib for the treatment of nail lesions and palmoplantar pustulosis in synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome. JAMA Dermatol. (2020) 157. doi: 10.1001/jamadermatol.2020.3095
40. Shuang L, Chen L, Ming-Wei T, Wen-Shuai X, Ke-Qi C, Xin S, et al. Improvement of lymphangioleiomyomatosis following successful tofacitinib treatment for refractory synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome. Chin Med J (Engl). (2019) 132. doi: 10.1097/cm9.0000000000000441
41. Fangfang Y, Jing L, and Qiong Y. SAPHO syndrome complicated by ankylosing spondylitis successfully treated with tofacitinib: A case report. Front Immunol. (2022) 13. doi: 10.3389/fimmu.2022.911922
42. Chen R, Tangliang Q, Xiaoping L, Chaoxin W, Weizhong L, Xiujuan H, et al. SAPHO syndrome with Takayasu arteritis successfully treated with tofacitinib. Int J Rheum Dis. (2023) 26. doi: 10.1111/1756-185x.14628
43. Fengjiao C, Xiujuan H, Tianlun K, Xiaojun S, Weiguo M, Yuan Z, et al. SAPHO syndrome complicated with relapsing polychondritis: A case report. Int J Rheum Dis. (2023) 26. doi: 10.1111/1756-185x.14693
44. Ruoyi W, Yingzi L, Yuyue L, Xiujuan H, and Chen L. Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome with henoch-schönlein purpura: A case report. Clin Cosmet Investig Dermatol. (2023) 16. doi: 10.2147/ccid.S392909
45. Wuriliga, Xia W, Yihan C, and Chen L. Successful treatment of hip involvement in SAPHO syndrome with baricitinib. Rheumatol Adv Pract. (2022) 6. doi: 10.1093/rap/rkac084
46. Jianqiu Y, Chunyu Y, Shengru Z, Zhicheng T, and Min L. Successful treatment of refractory synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome with baricitinib, a janus kinase inhibitor. Clin Cosmet Investig Dermatol. (2024) 17. doi: 10.2147/ccid.S446468
Keywords: Hyperimmunoglobulinemia E, JAK inhibitors, paradoxical manifestation, SAPHO syndrome, upadacitinib
Citation: Liu Y, Jin D, Li W, Zhang S, Li C and Li X (2026) Case Report: Upadacitinib for SAPHO syndrome with biologics-induced paradoxical manifestation and Hyperimmunoglobulinemia E. Front. Immunol. 17:1728245. doi: 10.3389/fimmu.2026.1728245
Received: 19 October 2025; Accepted: 22 January 2026; Revised: 30 December 2025;
Published: 05 February 2026.
Edited by:
Animesh A Sinha, University at Buffalo, United StatesReviewed by:
Hao Cheng, Second Hospital of Shanxi Medical University, ChinaMustafa Alhayali, Ibn Sina University for Medical and Pharmaceutical Sciences, Iraq
Copyright © 2026 Liu, Jin, Li, Zhang, Li and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Xin Li, bGltYm91cmdAMTYzLmNvbQ==; Chen Li, Y2FzaW8xOTgxQDE2My5jb20=
†These authors share first authorship