Case Report: Successful Treatment With Apremilast of SAPHO Syndrome and Refractory Pain

Key Points

• Apremilast improves pain in SAPHO syndrome.

Dear Editor,

1.

SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome, also classified as chronic non‐bacterial osteitis (CNO) [1], is a rare autoinflammatory disease, characterized by bone erosion and inflammation, bone pain and skin disorders. Pathophysiology remains unclear and involves inflammatory pathways, cytokines, tumor necrosis factor (TNF‐a), interleukin (IL)‐1, 17, 23, and intracellular Janus kinase (JAK) [2]. We present here a case of a 7‐year refractory to treatment SAPHO syndrome. Written informed consent for publication was obtained from the patient.

In 2018, a 50‐year‐old woman with no significant medical history presented with inflammatory sternoclavicular and neck pain, diffuse peripheral arthralgia and no arthritis. She had palmoplantar pustular psoriasis and asthenia. A computer tomography (CT) scan showed osteosclerosis of the sternal manubrium, of costochondral junctions (with slight hyperostosis), of C5, C6, and C7 vertebral bodies and of the anterosuperior corner of T10 (with syndesmophytes at T8‐T9 and T9‐T10), and of L2, L4, and L5, with signs of right sacroiliitis. Full blood count was within normal limits, HLA B27 was negative, and our investigations ruled out any systemic involvement. The diagnosis was SAPHO syndrome.

Between 2018 and October 2023, she had a succession of treatments that improved partially her skin condition but did not help to reduce pain. These included adalimumab, secukinumab, ixekisumab, golimumab, bimekizumab, and non‐steroidal anti‐inflammatory drugs (NSAIDs). Treatments were discontinued because of adverse effects or insufficient efficacy.

In June 2025, she was prescribed infliximab with methotrexate: This improved the skin condition, psoriasis was less florid, but pain intensity was still severe after 2 months when measured with a numeric rating scale (NRS) (8/10).

In October 2025, she presented with severe thoracic pain, most acute at night, and insomnia. Pain was inflammatory, bilateral, affected elbows and ankles, and was severe, NRS = 8/10. The patient was much affected by pain itself and by the past experience of successive treatment failures to relieve pain. Scintigraphy (Figure 1a) showed significant hyperfixation with osteosclerosis of the body of the sternum and sternoclavicular joints on CT. Apremilast (30 mg twice a day) was prescribed in addition to infliximab and methotrexate.

FIGURE 1.

Bone images. (a) Axial computer tomography and bone scan images showing the therapeutic effects of apremilast. Louis's angle and the sternoclavicular joints are indicated by red arrows. (b) Volume rendering technique/maximum intensity projection (left) and maximum intensity projection (right) bone scan images showing the therapeutic effects of apremilast. Left sternoclavicular joint are indicated by red arrows.

After 6 months of treatment with apremilast (infliximab and methotrexate being maintained as initially), significant pain improvement persisted (NRS = 1/10). A CT scan indicated, with limited ability to support treatment efficacy, a relative stability at the level of the sternum, sternoclavicular joints, and right sacroiliac joint, but a bone scan showed a visible reduction in bone remodeling (with no quantitative assessment) (Figure 1). The patient rated the change since the introduction of apremilast as “very much improved”, the highest value, with the Patient Global Impression of Change (PGIC), a 7 point scale [3]. Complete resolution of skin manifestations was also observed, with no objective evidence of improvement in osteitis or disease activity.

Apremilast is used off‐label for dermatological conditions that are refractory to conventional therapy and is approved for the treatment of psoriasis and psoriatic arthritis. Our clinical case confirms previous reports on its usefulness, in addition to other treatments, to alleviate pain that is common and often debilitating in SAPHO syndrome [4]. Many drugs are used in SAPHO syndrome: NSAIDs, often in the first line, corticosteroids, bisphosphonates, conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs), antibiotics, anticytokine biotherapies or Janus Kinase (JAKi) inhibitors [2, 5, 6, 7, 8]. SAPHO syndrome is very heterogeneous, and the absence of an established treatment algorithm despite the increasing use of biologic agents and targeted therapies underlines the limitations of proven therapeutic options [6, 9, 10]. Our case provides additional supportive evidence for the use of apremilast in SAPHO syndrome, but its specific role needs to be defined. The observed improvement may indeed reflect the delayed or cumulative effect of infliximab rather than the specific effect of apremilast, as TNF inhibitors may demonstrate delayed clinical efficacy in SAPHO syndrome, and concomitant methotrexate may improve treatment persistence and efficacy. A case similar to ours [11] with palmoplantar pustulosis and sternoclavicular joint involvement, and successive dose escalations and treatment failures resulted, with apremilast, in stabilization of the skin symptoms and improvement of bone pain without side effects. The efficacy of apremilast on pain was also described previously in one case with a rare association of cutaneous polyarteritis nodosa associated with SAPHO [12].

This case suggests a temporal association between the addition of apremilast and improvement in pain and skin manifestations. However, because apremilast was introduced after infliximab and methotrexate, a delayed effect of the preceding therapy cannot be excluded. Further studies are needed to clarify the specific contribution of apremilast in patients with refractory SAPHO syndrome.

Author Contributions

Dr. M.‐E.P. had full access to all of the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis. All authors have approved the final version of the manuscript before submission. Study concept and design: M.‐E.P. and L.B.; acquisition, analysis, or interpretation of data: M.‐E.P., L.B. and M.C.; drafting of the manuscript: M.‐E.P.; critical revision of the manuscript for important intellectual content: all authors; statistical analysis: NA; study supervision: M.‐E.P. M.‐E.P. supervised the study and is the guarantor for this study. The corresponding author attests that all listed authors meet the authorship criteria and that no others meeting the criteria have been omitted.

Funding

The authors have nothing to report.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.