A 72-year-old man presented with a 2-month history of fever of unknown cause. Before presenting to our clinic, he had been evaluated for this concern at another clinic. He had no respiratory, abdominal, urinary, or focal musculoskeletal symptoms, and no known personal or family history of malignancy, inflammatory musculoskeletal disease, or pustular skin disease. His regular medications were mirogabalin, valsartan, rosuvastatin, and triazolam, all of which were discontinued at his initial visit to our clinic because drug fever was considered.
He had a 3-year history of intermittent erythematous eruptions on the trunk and extremities, without palmoplantar, psoriatic, or acneiform lesions. The rash resolved after a 1-month course of minocycline prescribed by physicians at the previous clinic; the patient completed the minocycline course 2 weeks before he presented to our clinic.
There was no tenderness or swelling of the sternoclavicular joints.
Laboratory testing showed a white blood cell count of 5.9 × 109/L (reference range 4–11) with 66.9% neutrophils, C-reactive protein level of 7.99 mg/dL (0–0.3), and an elevated erythrocyte sedimentation rate. Renal function tests, testing to evaluate for liver injury, thyroid-stimulating hormone level, and urinalysis were within normal limits. The alkaline phosphatase level was 110 U/L (38–113). Results of serial blood cultures, interferon gamma release assay, and relevant viral serologies were negative.
Contrast-enhanced computed tomography (CT) of the chest, abdomen, and pelvis showed no abscess or malignancy.
POSITRON EMISSION TOMOGRAPHY AND PROBABLE DIAGNOSIS
The patient was prescribed acetaminophen. After more than 1 month of acetaminophen, fever and elevated inflammatory markers persisted. The workup for fever of unknown origin included 18fluorine-fluorodeoxyglucose positron emission tomography–CT (18F-FDG PET/CT), which showed focal intense uptake at the sternoclavicular joints bilaterally without additional abnormal foci (Figure 1A). Targeted rereview of the chest CT images identified juxta-articular cortical thickening and subchondral sclerosis compatible with osteitis or hyperostosis, without cortical breakthrough, fluid collection, or lytic destruction (Figure 1B).
Imaging findings of bilateral sternoclavicular osteitis and hyperostosis. (A) Whole-body maximum-intensity-projection 18fluorine-fluorodeoxyglucose positron emission tomography–computed tomography (CT), obtained during the workup of fever of unknown origin, showing focal intense uptake limited to the bilateral sternoclavicular joints. (B) Axial chest CT bone-window image showing bilateral juxta-articular cortical thickening and subchondral sclerosis at the sternoclavicular joints (arrowheads), without cortical breakthrough, lytic destruction, or fluid collection.
Other causes of sternoclavicular osteitis were considered, including septic arthritis or osteomyelitis, malignancy, crystal-induced disease, and Paget disease. These alternatives were less likely given the bilateral involvement; nondestructive CT findings; negative microbiologic studies; absence of weight loss, local tenderness, or an identified primary tumor; and normal alkaline phosphatase. Although a biopsy was not performed, the anterior chest wall involvement supported a probable diagnosis of SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome.1 Biopsy was reserved in the event the patient did not show clinical improvement with SAPHO-targeted medical therapy.
Naproxen was started and acetaminophen was stopped, resulting in prompt defervescence and improvement in inflammatory markers, further supporting the clinical diagnosis.
The absence of classic SAPHO-related skin lesions, peripheral arthritis, or inflammatory back pain made the diagnosis challenging. Dermatologic evaluation after SAPHO syndrome was suspected, including review of a previous skin biopsy specimen, showed nonspecific perivascular dermatitis with vascular changes and dermal eosinophils, without evidence of SAPHO-related skin disease. Human leukocyte antigen (HLA)-B27 status was not assessed.
UTILITY OF 18F-FDG PET/CT IN SAPHO SYNDROME
SAPHO syndrome is a rare autoinflammatory disorder with heterogeneous bone, joint, and skin manifestations.2 The anterior chest wall is a characteristic site of bone lesions in SAPHO syndrome, typically with pain. However, in some patients, the lesions do not cause pain, which may contribute to the diagnosis going unrecognized.3 When the workup of fever of unknown origin reveals focal 18F-FDG uptake in the sternoclavicular region, clinicians should seek structural correlates of osteitis or hyperostosis and add SAPHO syndrome to the differential diagnosis, even without classic skin findings. In addition to highlighting the sternocostoclavicular region, 18F-FDG PET/CT provides practical whole-body inflammatory mapping in fever of unknown origin and can identify clinically silent lesions, complementing CT and helping to diagnose SAPHO syndrome.4
In clinically stable patients with imaging concordant with SAPHO syndrome and negative cultures, a trial of nonsteroidal anti-inflammatory drugs as first-line therapy is reasonable, reserving biopsy for atypical, progressive, or refractory cases. Recent consensus supports the early use of 18F-FDG PET/CT in patients with fevers of unknown origin to localize elusive inflammatory foci and guide targeted management.5
DISCLOSURES
Dr. Shojima disclosed teaching and speaking for Daiichi Sankyo, Inc. Dr. Nagasawa disclosed teaching and speaking for Bayer, Boehringer Ingelheim, Daiichi Sankyo, Inc., Eli Lilly, KOWA, Kyowa Hakko Kirin Co. Ltd., Mitsubishi Tanabe, Mochida Pharmaceutical Co., Ltd., Novartis Pharmaceuticals, Otsuka Pharmaceuticals, Shionogi Inc., Taisho Pharmaceutical, and Teijin. The other authors report no relevant financial relationships which, in the context of their contributions, could be perceived as a potential conflict of interest.
The authors disclosed use of ChatGPT (GPT-5.4) for language editing and translation. The authors take full responsibility for the published content.
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REFERENCES
- 1↵Kahn MF, Khan MA. The SAPHO syndrome. Baillieres Clin Rheumatol 1994; 8(2):333–362. doi:10.1016/s0950-3579(94)80022-7
- 2↵Benhamou CL, Chamot AM, Kahn MF. Synovitis-acne-pustulosis hyperostosis-osteomyelitis syndrome (SAPHO). A new syndrome among the spondyloarthropathies? Clin Exp Rheumatol 1988; 6(2):109–112. pmid:2972430
- 3↵Nguyen MT, Borchers A, Selmi C, Naguwa SM, Cheema G, Gershwin ME. The SAPHO syndrome. Semin Arthritis Rheum 2012; 42(3): 254–265. doi:10.1016/j.semarthrit.2012.05.006
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- 5↵Buchrits S, McNeil R, Avni T, Fredman D, Guz D, Gafter-Gvili A. The contribution of 18F FDG PET-CT for the investigation of fever of unknown origin and inflammation of unknown origin. Am J Med 2024; 137(7):629–639. doi:10.1016/j.amjmed.2024.03.017
