Bone scintigraphy and SPECT/CT imaging characteristics in patients with synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome

Introduction

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare inflammatory disorder that predominantly affects the anterior chest wall, leading to significant pain and discomfort. It encompasses a broad spectrum of clinical manifestations primarily affecting bones, skin, and joints. The epidemiological data is not reliable, however, it has been estimated to have a prevalence of less than one in 10,000 (1,2).

SAPHO syndrome primarily affects adults, and is more common in females than males (3,4). The enigmatic nature of this condition is underscored by the absence of broadly accepted and independently validated diagnostic criteria, which makes its diagnosis a complex task for clinicians. Currently, the diagnosis of SAPHO syndrome relies on identifying a combination of clinical features, including sterile bone inflammation, arthritis, and inflammatory dermatological disorders. Its diagnosis also involves ruling out other potential conditions like infectious diseases, neoplasms, and Langerhans cell histiocytosis (5).

Imaging plays a pivotal role in confirming the diagnosis and monitoring the progression of the disease (6,7). Conventional radiographic imaging, including plain radiographs and computed tomography (CT), lays the groundwork for visualizing bony changes. However, these modalities often lack the sensitivity required to detect early or subtle osseous involvement characteristic of SAPHO syndrome. Magnetic resonance imaging offers excellent soft tissue contrast, enabling the detection of inflammatory changes in the bone marrow and surrounding structures. Further, positron emission tomography (PET)/CT combines the benefits of molecular imaging with high-resolution anatomical detail, providing a robust method to differentiate malignant from benign processes. Bone scintigraphy is an invaluable diagnostic tool due to its heightened sensitivity to metabolic bone changes (8,9). Due to its resemblance to other diseases, the diagnosis of SAPHO syndrome can be challenging, often resulting in delayed treatment (2,3,10). This study aimed to characterize the scintigraphic pattern of SAPHO syndrome.

Patients and clinical presentation

This case series included nine patients with SAPHO syndrome recruited from the First Hospital of Lanzhou University from February 2021 to April 2024. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of the First Hospital of Lanzhou University (No. LDYYLL-2024-803), and the requirement of individual consent for this retrospective analysis was waived.

In this case series, we reviewed the medical records of nine patients with confirmed SAPHO syndrome (Table 1). The patients had an average age of 43.8±15.8 years, five were male (55.6%), and four were female (44.4%). The duration of illness varied widely, ranging from 1 to 60 months (mean: 20.9 months), highlighting the chronic nature of the disease and the potential for prolonged symptomatic periods. The most common chief complaint was chest pain, particularly in the sternal region, which was reported by eight of the nine patients. Seven (77.8%) patients also had accompanying skin lesions, indicating the diverse expression of SAPHO syndrome in relation to dermatological involvement. The laboratory tests included the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complement levels (C3, C4), and complete blood count. The results revealed that the ESR was elevated in three patients (33.3%), CRP was elevated in four patients (44.4%), and both ESR and CRP were simultaneously elevated in two patients (22.2%). No abnormalities were found in the complement levels or the complete blood count.

Table 1. Clinical characteristics.

Patients No.	Gender	Age (years)	Disease duration (months)	Skin lesions	ESR (ref: 0–15 mm/h)	CRP (ref: 0–4 mg/L)
1	Male	53	36	Yes	29	3.27
2	Female	31	34	No	6	3.00
3	Male	68	1	Yes	81	181.27
4	Male	56	25	Yes	5	3.20
5	Female	33	1	Yes	14	24.02
6	Male	49	24	Yes	10	2.18
7	Female	20	3	Yes	5	3.50
8	Male	30	60	Yes	2	4.32
9	Female	54	4	No	82	27.81

CRP, C-reactive protein; ESR, erythrocyte sedimentation rate.

Single-photon emission computed tomography/CT (SPECT/CT) imaging acquisition

The technetium-99m methylene diphosphonate (^99mTc-MDP) was produced using a technetium generator, and commercially supplied and delivered to our institution by Beijing Atom High Tech Co., Ltd (China). Each patient received an intravenous injection of ^99mTc-MDP with a radiochemical purity of over 95% at a dosage of 740 MBq. The patients were instructed to drink plenty of water, and empty their bladder approximately three hours after the injection, with minor variations (±10 minutes) due to logistical factors.

Imaging was performed using a GE Discovery 670Pro SPECT/CT system (GE Healthcare, Chicago, IL, USA) with a low-energy high-resolution, parallel hole collimator. The acquisition parameters were as follows: matrix size: 256×1,024, zoom: 0.92, and scanning speed: 22 cm/min. The scanner used dual probes to acquire images simultaneously in both the anterior and posterior positions. If any abnormal focal accumulation of the tracer was observed during the acquisition process, additional SPECT/CT imaging was immediately performed after the completion of the planar images. The SPECT/CT scan parameters were as follows: matrix size: 128×128, zoom: 1.0, and number of frames acquired: 60 (each lasting 10 seconds). For the CT scan, the voltage was 120 kV, the current was 240 mA, the acquisition matrix was 512×512, and the slice thickness was 1.25 mm.

The image reconstruction for SPECT on the GE Discovery 670Pro system used ordered subset expectation maximization to improve image quality. CT-based attenuation correction was applied using the attenuation map from the concurrent CT scan. Model-based scatter correction with the dual-energy window method was used to reduce scatter artifacts. Resolution recovery techniques were implemented to enhance spatial resolution. A Gaussian filter with a size of 4–6 mm was applied during reconstruction to balance noise reduction and spatial resolution. These methods collectively optimized the image quality and quantification accuracy.

The image analysis was conducted by two experienced nuclear medicine physicians who characterized the distribution, number, and location of areas showing increased radiotracer uptake. They also analyzed the bone and joint morphology and the characteristics of the CT images. Any discrepancies in interpretation were resolved through discussion and consensus.

Imaging findings and diagnosis

The SPECT/CT imaging revealed the “bullhead” sign in six patients, indicating cortical hyperostosis and sclerosis of the sternal manubrium and bilateral clavicles with intense ^99mTc-MDP uptake (Figure 1), while the remaining patients displayed incomplete “bullhead” signs (Figure 2). The “bullhead” sign is considered pathognomonic for SAPHO syndrome, and helps differentiate it from other conditions such as tumors or infections that may present similarly.

Figure 1.

A 68-year-old male presented with a full-body rash of varying sizes. The rash was pale red in color, non-raised, and non-itchy, and was accompanied by a fever. The rash was particularly prominent on the anterior chest area, and the patient reported experiencing an associated burning sensation and pain for one month. SPECT imaging revealed increased metabolic activity in both clavicles and the sternum, showing typical “bullhead” changes. CT scans revealed sclerosis in both clavicles and the sternal bone, increased density around the joints, and fusion and enlargement of the sternoclavicular joints. The ESR was 81 mm/h (reference range, 0–15 mm/h) and CRP was 181.27 mg/L (reference range, 0–4 mg/L); both were elevated. CRP, C-reactive protein; CT, computed tomography; ESR, erythrocyte sedimentation rate; SPECT, single-photon emission computed tomography.

Figure 2.

A 20-year-old woman with a three-month history of lumbago. Whole-body planar imaging showed increased bone metabolism in the bilateral clavicles, thoracic spine, and sacrum; however, the CT scans did not show thickening or heterogeneously increased density of bilateral clavicle bones. The physical examination revealed a rash on the anterior chest; both the ESR and CRP levels were within normal ranges. CRP, C-reactive protein; CT, computed tomography; ESR, erythrocyte sedimentation rate.

Among all the patients, five had abnormal metabolism in the sacroiliac joints, and one had abnormal uptake in the thoracic spine and sacrum.

Discussion

The current case series contributes to the expanding body of literature on SAPHO syndrome, a rare and complex chronic inflammatory disorder that affects the musculoskeletal and dermatologic systems (1). Our findings reinforce the notion that a high index of clinical suspicion is necessary for the diagnosis of SAPHO syndrome, especially in patients presenting with unexplained anterior chest pain and associated skin lesions. The mean age of our patient cohort aligns with previous reports, suggesting this syndrome affects patients across a broad age range; however, it appears to be more prevalent in middle-aged individuals.

Interestingly, our study revealed a nearly equal gender distribution, which contrasts with some previous studies that reported a female predominance (2,4). This observation may indicate a need for further research to elucidate potential gender-related factors in the epidemiology of SAPHO syndrome.

The predominant symptom of chest pain, often described as sternal or chest wall pain, is recognized as one of the most characteristic features of SAPHO syndrome. In our series, eight (88.9%) patients complained primarily of chest pain, underscoring its importance as a leading symptom. Further, the presence of skin lesions in seven of these patients highlights the diagnostic value of recognizing the cutaneous manifestations that can accompany the osteoarticular symptoms.

Imaging plays a crucial role in the diagnostic workup of SAPHO syndrome, with SPECT/CT significantly contributing to revealing the disease’s characteristic patterns. The “bullhead sign” (indicating active osteoblastic activity in the sternal manubrium and bilateral clavicles) was observed in 66.7% of patients. It is pathognomonic for SAPHO syndrome, and helps differentiate it from other conditions like infections, tumors, and inflammatory disorders that can affect the sternoclavicular region (8,11). This sign could also uncover unexpected skeletal system locations (55.6% of the patients had abnormal metabolism in the sacroiliac joints).

There are no specific laboratory findings for SAPHO syndrome. Among the patients, the ESR was elevated in three of the nine patients (33.3%), CRP was elevated in four of the nine patients (44.4%), and both ESR and CRP were simultaneously elevated in two of the nine patients (22.2%). This may indicate that the elevated inflammatory markers (ESR and CRP) occurred during the active phase of the disease.

Diagnosis is crucial for SAPHO syndrome, as it lacks specific diagnostic findings and is often underrecognized. A comprehensive evaluation of the patient’s medical history is also crucial (2). This was a retrospective study with a small sample size, which is inherent to case series analyses. These factors may limit the generalizability of our findings. However, given the rarity of SAPHO syndrome, case series continue to provide valuable insights into its diagnosis and management. Prospective studies with larger cohorts are needed to further delineate the clinical spectrum and optimal treatment strategies for SAPHO syndrome.

Recognition of the “bullhead sign” on imaging should prompt clinicians to consider SAPHO syndrome in the differential diagnosis of patients with unexplained anterior chest pain. This recognition can guide appropriate therapeutic interventions to alleviate symptoms and improve the patient’s quality of life.

Given the diagnostic uncertainties inherent in SAPHO syndrome, the integration of multimodal imaging is key to its diagnosis. The comprehensive understanding and utilization of these imaging techniques is essential for establishing a timely diagnosis, differentiating disease mimics, guiding appropriate therapeutic interventions, and improving patient outcomes. Further research into the diagnostic efficacy and pathophysiological correlates of advanced imaging modalities will provide insights into the enigmas surrounding SAPHO syndrome.

Our case series analysis contributes to the expanding body of literature on SAPHO syndrome by emphasizing the demographic and clinical characteristics of patients in a specific timeframe. The study reaffirms the complexity of diagnosing this rare syndrome and emphasizes the importance of multidisciplinary collaboration in managing patients with SAPHO syndrome. Recognizing the “bullhead sign” on SPECT/CT imaging is crucial for prompt and accurate diagnosis. This recognition enables early therapeutic interventions that can significantly enhance patient outcomes. This study also showed that the uptake of lesions in ^99mTc-MDP SPECT/CT decreased after treatment. Therefore, SPECT/CT can also be used to evaluate treatment efficacy (9). Further research into the pathogenesis and optimal treatment strategies for SAPHO syndrome is warranted to enhance the quality of life of those affected by this debilitating condition.

Bone scintigraphy becomes positive in affected bones primarily due to increased osteoblastic activity and bone turnover associated with inflammation, osteitis, and hyperostosis, which are characteristic pathological features of SAPHO syndrome. Although the modality has relatively low specificity and cannot differentiate SAPHO syndrome from infectious or neoplastic conditions, its high sensitivity makes it valuable in early detection and for assessing the extent of skeletal involvement through whole-body evaluation. Due to the multifocal and heterogeneous nature of SAPHO syndrome, bone scintigraphy remains a critical tool in the diagnostic algorithm. While SPECT/CT provides the additional benefit of anatomic localization, further improving diagnostic accuracy.

Conclusions

Bone scintigraphy is the preferred imaging modality for diagnosing skeletal involvement in SAPHO syndrome. SPECT shows the typical uptake of the sternal manubrium and bilateral clavicles, and can reveal unexpected locations in the skeletal system, with most cases showing bullhead-like tracer uptake. The “bullhead sign” is the typical and particular SPECT manifestation of SAPHO syndrome and aids in medical treatment.

Supplementary

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Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of the First Hospital of Lanzhou University (No. LDYYLL-2024-803), and the requirement of individual consent for this retrospective analysis was waived.