Abstract
Purpose
The primary objectives of this study were: (1) to describe the clinical characteristics and disease burden in a cohort of patients with SAPHO syndrome; (2) to evaluate the impact of SAPHO syndrome on quality of life using DLQI and HAQ; and (3) to identify independent risk factors associated with impaired quality of life.
Methods
We retrospectively analyzed clinical data from 225 SAPHO patients at two tertiary hospitals using Dermatology Life Quality Index (DLQI) and Health Assessment Questionnaire (HAQ) scores. Correlation and regression analyses identified factors influencing QoL and physical function.
Results
There was no significant correlation between bone pain location and total HAQ scores (P = 0.264); skin lesion types showed a significant correlation with DLQI scores (P = 0.039), and PPP was the main factor leading to impaired skin-specific quality of life.Patients were predominantly female (65.3%; mean onset age 35 ± 13 years). Palmoplantar pustulosis (92.9%) and sternoclavicular joint involvement (59.6%) were predominant. There is a statistically significant association between treatment type and DLQI score (P = 0.028), with a significant correlation with HAQ score (P = 0.05).Median DLQI was 17 (78.5% moderate-severe) and HAQ 0.12. Alcohol and education correlated with DLQI (P < 0.05), with education as an independent factor (P = 0.002). Duration and alcohol correlated with HAQ (P < 0.05), with alcohol as an independent factor (P = 0.036).
Conclusion
SAPHO significantly impacts patients' quality of life, worsened by modifiable factors like alcohol and education; targeted interventions may improve prognosis.
Keywords: SAPHO syndrome, Palmoplantar pustulosis, Arthritis, Clinical features, Quality of life, Influencing factors
Background
SAPHO syndrome is a rare autoinflammatory disease characterized mainly by synovitis, acne, pustulosis, hyperostosis, and osteitis. Its cause is unknown, and diagnosis is often difficult due to the diversity and non-specificity of symptoms [1, 2]. Patients commonly present with both bone and joint involvement (such as anterior chest wall pain and spinal lesions) and skin manifestations (such as palmoplantar pustulosis and acne). The disease course is prolonged, affecting not only physical function but also significantly impairing psychological well-being and quality of life. Current research mainly focuses on clinical features and diagnosis and treatment, while systematic analyses of quality of life are limited, especially in-depth explorations of the relationship between clinical features and quality of life in large-sample studies. This study retrospectively analyzed clinical data from a relatively large sample of SAPHO patients from two major tertiary hospitals in eastern and western China, summarizing their characteristics and evaluating quality of life and influencing factors. The aim is to provide a basis for deepening disease understanding, optimizing clinical management, and improving patients' quality of life.
Methods
The subjects of this study were SAPHO syndrome patients who visited Peking Union Medical College Hospital and Qinghai University Affiliated Hospital between April 2021 and October 2024, and met the diagnostic criteria proposed by Kahn et al. [3]. Diagnostic criteria: (1) Multifocal osteomyelitis, with or without skin lesions; (2) Acute or chronic sterile arthritis, associated with pustular psoriasis, palmoplantar pustulosis, or acne; (3) Sterile osteitis accompanied by a characteristic skin lesion. Meeting any one of these three criteria is sufficient for a diagnosis of SAPHO.All patients signed the informed consent form.Data sources include questionnaires completed by patients at the time of diagnosis and medical records, collecting demographic information, clinical symptoms, and quality of life assessments (DLQI and HAQ).In addition, we collect clinical data on patients' drug treatments from medical records. The drugs include: traditional Chinese medicine; biological agents (such as TNF-α inhibitors); glucocorticoids; vitamin D3 ointment; conventional synthetic disease-modifying antirheumatic drugs; non-steroidal anti-inflammatory drugs.Patients often first sought medical attention in orthopedics, dermatology, or rheumatology departments due to bone pain or skin lesions, and some were prompted by worsening symptoms of acute tonsillitis/pharyngitis. Diagnosis and treatment in the two hospitals were carried out through multidisciplinary team (MDT) collaboration, and this study was approved by the Ethics Committee of Qinghai University Affiliated Hospital (Clinical Medical College).
Measurement
This study used the simplified Chinese versions of the DLQI and HAQ scales. We tested the reliability and validity of the DLQI scale against the HAQ scale.The DLQI assesses the impact of skin diseases on quality of life and includes 10 questions across 6 dimensions, with a total score ranging from 0 to 30. The scoring criteria are as follows: 0–1, no effect; 2–5, slight effect; 6–10, moderate effect; 11–20, severe effect; 21–30, extremely severe effect. The HAQ evaluates functional ability and quality of life in patients with chronic diseases, consisting of 20 questions across 8 dimensions, scored from 0 to 3, with higher scores indicating more severe functional impairment. Statistics show that the overall median HAQ score is 0.12.
Data Collection
In addition to the DLQI and HAQ questionnaires, we retrospectively collected patients' clinical data on drug treatments. The medications used by patients when attending outpatient visits and simultaneously diagnosed with SAPHO syndrome were recorded, including: traditional Chinese medicine, biological agents (such as TNF-α inhibitors); corticosteroids, vitamin D3 ointment, conventional synthetic disease-modifying antirheumatic drugs; non-steroidal anti-inflammatory drugs;
Data Analysis
All variables were tested for normality; quantitative data that followed a normal distribution were expressed as mean ± standard deviation, while data that did not follow a normal distribution were expressed as median. Qualitative data were expressed as n/%. The data in this study were non-normally distributed. Spearman correlation was used for preliminary screening of clinical features significantly related to DLQI/HAQ dimensions; p < 0.05 indicated a statistically significant difference, and p < 0.01 indicated a highly statistically significant difference.
Definitions of Clinical Manifestations
SAPHO Syndrome: Diagnosis was made based on the presence of characteristic osteoarticular lesions (osteitis, hyperostosis, osteolysis) associated with typical skin manifestations (palmoplantar pustulosis, acne, or psoriasis), according to the criteria by Kahn et al. [Ref]. Infectious bone lesions and malignant tumors were excluded.
Classification of Bone and Joint Symptoms:
Pain alone: Patients reporting pain restricted to specific movements or weight-bearing activities, without clinical or radiological evidence of active inflammation or structural damage (no synovitis, no osteolysis).
Pain with inflammation and/or erosion: Patients reporting pain accompanied by clinical signs of inflammation (swelling, warmth, tenderness) and/or radiological evidence of bone erosion, joint space narrowing, or active osteitis (increased uptake on bone scan or MRI edema).
Non-vascular Joint Symptoms: These were defined as SAPHO-related osteonecrosis or severe bone collapse (e.g., in the hip or shoulder) that mimics avascular necrosis. Unlike primary vascular osteonecrosis, these symptoms were considered a consequence of the SAPHO inflammatory bone process.
Results
Correlation between Lesion Types and Disease Burden: To investigate the impact of specific lesions on disease burden, we analyzed the correlations between bone pain sites/skin types and quality of life scores. There was no significant correlation between different bone pain sites (e.g., anterior chest wall, sacroiliac joint) and HAQ total scores (P = 0.264), indicating that anatomical site of bone pain did not significantly predict physical dysfunction. However, skin lesion types showed a significant correlation with DLQI scores (P = 0.039). Patients with Palmoplantar Pustulosis (PPP) had significantly higher DLQI scores compared to patients with other skin manifestations (such as Psoriasis or Acne), suggesting that PPP is the primary driver of dermatology-specific quality of life impairment in SAPHO syndrome.
Basic Data Statistics Results
Among the 965 patients who voluntarily participated in the on-site survey, 225 complete and valid questionnaires were returned (response rate of 22.5%). In this group, there were 78 male patients (34.7%) and 147 female patients (65.3%), with a male-to-female ratio of 1:1.88. The average age of disease onset was approximately 35 ± 13 years, and the average age at diagnosis was 40 ± 12 years. The median disease course is 4 years.
Among the 225 patients, 54.20% received medication to control symptoms. Specifically, 15.30% of patients used traditional Chinese medicine, 14.10% used biologic agents, 7.40% used glucocorticoids, 6.70% used vitamin D3 ointment, 4.70% received disease-modifying antirheumatic drugs (DMARDs), and 6.00% used non-steroidal anti-inflammatory drugs (NSAIDs). Given the widespread use of these medications, they may alleviate symptoms and improve quality of life scores; therefore, the reported DLQI and HAQ scores may reflect the 'post-treatment' disease burden rather than the natural course of the disease.There was a statistically significant association between treatment type and DLQI scores (P = 0.028), and a significant correlation with HAQ scores was also observed (P = 0.05).
Table 1 summarizes the distribution of skin lesions in SAPHO patients. Among the SAPHO patients included in this study, the most common skin manifestation was palmoplantar pustulosis (PPP), occurring in 209 cases, accounting for 92.9%. Among PPP patients, the distribution of skin lesions was mainly 'involving both hands and feet', with 198 cases, accounting for 94.7% of PPP patients; 15 cases (7.2%) involved only the hands, 9 cases (4.3%) involved only the feet, and 16 cases (7.7%) had lesions affecting other areas. In addition, acne and psoriasis accounted for 1.8% (4 cases) and 3.7% (8 cases) as skin manifestations, respectively, which is much lower than PPP.The incidence of osteoarticular symptoms reached 85.8%, with detailed distribution as follows (Table 2 below): the sternoclavicular joint was most commonly affected (59.6%), followed by the sternum (43.5%) and sacroiliac joint (43.5%); then the knee (30.6%), ribs (26.0%), and scapula (13.0%); lower rates were observed for lumbar spine (4.7%), thoracic spine (4.1%), shoulder joint (2.1%). The coccyx,pubic bone and xiphoid each accounted for 1%, and a few patients had scattered bone pain (such as hip joints, finger joints, etc.), with the incidence at each individual site being < 2%.
Table 1.
Distribution of skin lesions in SAPHO patients
| item | date |
|---|---|
| PPP | 209(92.9%) |
| both hands and feet | 198(94.7%) |
| hands | 15(7.2%) |
| feet | 9(4.3%) |
| other sites | 16(7.7%) |
| acne | 4(1.8%) |
| psoriasis | 8(3.7%) |
Table 2.
Bone and joint involvement in SAPHO patients
| item | Date(%) |
|---|---|
| bone-joint symptoms | 193(85.8%) |
| sternoclavicular joint | 115(59.6%) |
| sternum | 84(43.5%) |
| sacroiliac joint | 84(43.5%) |
| knee joint | 59(30.6%) |
| ribs | 50(26.0%) |
| scapula | 25 (13.0%) |
| lumbar vertebrae | 9(4.7%) |
| thoracic vertebrae | 8(4.1%) |
| shoulder joint | 4(2.1%) |
| pubis | 2(1.0%) |
| xiphoid process | 2(1.0%) |
| coccygeal vertebrae | 2(1.0%) |
| other parts | 9(4.0%) |
| avascular—joint symptoms | 32(14.2%) |
By educational level, patients with higher education (including college) accounted for 62.7%, while those with low education (high school or below) accounted for 37.3%. 28.9% of patients reported current alcohol consumption (37.2% in males vs. 24.5% in females)., and the drinking rate was significantly higher among those with low education (44%) compared to those with higher education (19.9%). 26.7% of patients had a history of allergies; 21.8% had tobacco exposure (male 28.2% > female 18.4%), and the smoking rate among low-education patients (25%) was slightly higher than that of high-education patients (19.9%). 10.7% of patients had a family history of genetic conditions (such as psoriasis, hypertension, etc.). The main occupations were freelance work (44.0%) and office workers (23.1%); the majority were married (79.1%).
Quality of Life
Reliability and validity testing of the DLQI scale
Reliability: Hotelling's T2 test showed significant differences in item means (F = 164.104, P < 0.001); Cronbach's α = 0.938, indicating excellent internal consistency; the correlation coefficients between each item and the total score were r = 0.647 ~ 0.869, showing strong correlation. Validity: KMO = 0.942, Bartlett’s test of sphericity χ2 = 1689.763 (P < 0.01), indicating suitability for factor analysis; principal component analysis extracted 1 factor (explaining 65% of the variance), with factor loadings for each dimension ranging from 0.622 to 0.833, confirming good construct validity of the scale.
Patient DLQI scores and influencing factors
43.5% (98/225) were level 4, 35% (79/225) were level 5, 13.8% (31/225) were level 3, 4.9% (11/225) were level 2, and 2.7% (6/225) were level 1, with an overall median of 17 (Table 3). The medians of the six DLQI dimensions concentrated around 2.0, with a mean of 1.8 points. The impact of skin disease on quality of life varied by dimension: the 'personal relationships' dimension had a smaller impact and less individual variation, while the other five dimensions had a moderate impact with similar individual differences.
Table 3.
Scoring of 6 dimensions of DLQI
| Measures | Median | Mean value | IQR |
|---|---|---|---|
| symptoms & feelings | 2.0 | 1.9 | 1 ~ 2.5 |
| daily activities | 2.0 | 1.8 | 1 ~ 2.5 |
| work& school | 2.0 | 1.8 | 1 ~ 3 |
| leisure | 2.0 | 1.8 | 1 ~ 2.5 |
| personal relationships | 1.0 | 1.2 | 0.5 ~ 2 |
| treatment | 2.0 | 1.8 | 1 ~ 2.5 |
Table 4 summarizes the factors affecting DLQI and their p-values.
Table 4.
Factors affecting DLQI and their P-values
| Factors | symptoms&feelings | Daily activities |
work& school | leisure | Personal relationships | treatment | Total score |
|---|---|---|---|---|---|---|---|
| gender | 0.950 | 0.862 | 0.426 | 0.521 | 0.133 | 0.712 | 0.371 |
| age of onset | 0.283 | 0.468 | 0.156 | 0.713 | 0.742 | 0.932 | 0.458 |
| age of diagnosis | 0.318 | 0.541 | 0.231 | 0.745 | 0.651 | 0.978 | 0.496 |
| duration of disease | 0.584 | 0.165 | 0.353 | 0.456 | 0.626 | 0.957 | 0.362 |
| occupation | 0.498 | 0.162 | 0.121 | 0.212 | 0.102 | 0.524 | 0.152 |
| marital status | 0.412 | 0.893 | 0.625 | 0.821 | 0.776 | 0.776 | 0.939 |
| education level | 0.010 | 0.018 | 0.070 | 0.005 | 0.001 | 0.071 | 0.003 |
| current smoking consumption | 0.160 | 0.411 | 0.074 | 0.557 | 0.529 | 0.596 | 0.278 |
| current alcohol consumption | 0.020 | 0.093 | 0.052 | 0.012 | 0.005 | 0.027 | 0.007 |
| genetic disorders | 0.330 | 0.455 | 0.469 | 0.333 | 0.896 | 0.575 | 0.451 |
| allergy history | 0.560 | 0.241 | 0.270 | 0.336 | 0.113 | 0.253 | 0.180 |
| location of skin lesions | 0.386 | 0.959 | 0.432 | 0.557 | 0.839 | 0.522 | 0.550 |
Alcohol consumption history and education level are the main factors significantly associated with various dimensions or the total DLQI score, while most other factors, such as gender and age of onset, show no significant association (P > 0.05). Specifically: Alcohol consumption history: patients who drink alcohol are more significantly affected in the 'symptoms & feelings,' 'leisure,' 'personal relationships,' and 'treatment' dimensions, as well as in the total score (P < 0.05); Gender: males show significant associations in the five above-mentioned dimensions (for females, all P-values > 0.05); Education level: except for 'treatment' (P > 0.05) and 'work & school' (0.05 < P < 0.10), patients with lower education levels (high school and below) are significantly more affected in the other dimensions and total score compared to those with higher education levels (college and above) (P < 0.05).
To ensure more robust results, we conducted a multifactor linear regression model (Table 5), which showed that education level (β = −1.217, P = 0.002) was an independent factor affecting the total DLQI score, while a history of alcohol consumption did not reach statistical significance after adjusting for confounding factors (β = 2.363, P = 0.064), showing only a marginally significant trend; other variables including gender, age at diagnosis, disease duration, occupation, marital status, smoking history, family history of disease, allergy history, and lesion location did not show an independent effect on the total DLQI score in the multivariate model (all P > 0.05).
Table 5.
Multivariate Analysis of Factors Influencing DLQI Total Score
| Influencing factors | β | SE | Beta | T | P |
|---|---|---|---|---|---|
| Constant | 24.552 | 3.248 | 7.559 | ＜0.001 | |
| gender | 0.058 | 1.074 | 0.004 | 0.054 | 0.957 |
| age of diagnosis | ﹣0.101 | 0.052 | ﹣0.159 | ﹣1.933 | 0.055 |
| duration of disease | ﹣0.080 | 0.089 | ﹣0.060 | ﹣0.894 | 0.372 |
| occupation | ﹣0.244 | 0.282 | ﹣0.059 | ﹣0.867 | 0.387 |
| marital status | ﹣0.226 | 1.395 | ﹣0.013 | ﹣0.162 | 0.871 |
| education level | ﹣1.217 | 0.393 | ﹣0.220 | ﹣3.096 | 0.002 |
| smoking history | 0.565 | 1.348 | 0.031 | 0.419 | 0.676 |
| alcohol history | 2.363 | 1.269 | 0.141 | 1.861 | 0.064 |
| genetic disorders | 0. 833 | 1. 655 | 0.034 | 0.503 | 0.078 |
| allergy history | 1.439 | 1.166 | 0.084 | 1.234 | 0.218 |
| location of skin lesions | ﹣0.165 | 0.459 | ﹣0.024 | ﹣0.359 | 0.720 |
The results of the reliability and validity tests of the patient HAQ (Health Assessment Questionnaire) scale indicate
Reliability: Hotelling's T2 test showed significant differences between groups (F = 21.397, P < 0.001); the correlation coefficients between each item and the total score ranged from r = 0.665 to 0.816, showing strong correlations; Cronbach's α = 0.959, indicating excellent internal consistency. Validity: KMO = 0.946, Bartlett's test of sphericity χ2 = 3807.311 (P < 0.001), indicating suitability for factor analysis; principal component analysis extracted 2 factors (cumulative variance explained 72.146%), confirming that the scale effectively reflects the core dimension of 'bone-joint impact on quality of life'.
2.2.4 Patient HAQ Scores and Influencing Factors (Table 6): "grip": mean 0.84 (highest among all dimensions), suggesting that grip function is most significantly impaired; "walking": mean 0.02 (lowest), IQR 0–0.01, indicating that walking function is generally mildly affected with small individual differences; "hygiene": IQR 0–0.93, reflecting large differences in the degree of functional impairment among individuals; "dressing" and "eating": median both 1.00, mean 0.55, showing that some patients have significant limitations in basic daily activities; "arising": median 0.00, mean 0.43, suggesting moderate overall impairment in getting up, with some patients not significantly affected.
Table 6.
Scoring of 8 dimensions of HAQ
| Measures | Median | Mean value | IQR |
|---|---|---|---|
| dressing | 1.00 | 0.55 | 0 ~ 1.00 |
| arising | 0.00 | 0.43 | 0 ~ 0.60 |
| eating | 1.00 | 0.55 | 0 ~ 1.00 |
| walking | 0.00 | 0.02 | 0 ~ 0.01 |
| hygiene | 0.00 | 0.48 | 0 ~ 0.93 |
| reach | 0.00 | 0.15 | 0 ~ 0.50 |
| grip | 0.50 | 0.84 | 0 ~ 1.50 |
| activities | 0.30 | 0.59 | 0 ~ 1.00 |
Table 7 shows multivariate analysis results of factors significantly associated with HAQ and their exact p-values. Only disease duration and alcohol history significantly affected partial HAQ dimensions (or total score), while factors like gender, age, occupation, and smoking history showed no significant effects.Disease duration: ≤ 1 year vs. 2–10 years: Higher impact on "dressing" and "activities" dimensions; ≥ 11 years vs. < 11 years: Higher impact on "dressing" and "activities" dimensions; ≤ 1 year: Higher impact on "total score".Alcohol history: Drinkers vs. non-drinkers: Higher impact on "dressing" and "eating" dimensions.Gender: Females vs. males: Higher impact on "eating" dimension.
Table 7.
Factors affecting HAQ and their P-values
| Factors | dressing | arising | eating | walking | hygiene | reach | grip | activities | totalscore |
|---|---|---|---|---|---|---|---|---|---|
| gender | 0.767 | 0.312 | 0.524 | 0.767 | 0.806 | 0.589 | 0.982 | 0.900 | 0.984 |
| age of onset | 0.828 | 0.855 | 0.160 | 0.604 | 0.951 | 0.458 | 0.562 | 0.847 | 0.325 |
| age of diagnosis | 0.627 | 0.708 | 0.311 | 0.770 | 0.497 | 0.432 | 0.894 | 0. 667 | 0.941 |
| duration of disease | 0.033 | 0.202 | 0.087 | 0.312 | 0.152 | 0.585 | 0.175 | 0.034 | 0.009 |
| occupation | 0.371 | 0.989 | 0.700 | 0.960 | 0.802 | 0.380 | 0.530 | 0.783 | 0.597 |
| marital status | 0.595 | 0.700 | 0.614 | 0.400 | 0.672 | 0.703 | 0.747 | 0.453 | 0.884 |
| education level | 0.541 | 0.660 | 0.256 | 0.755 | 0.570 | 0.284 | 0.910 | 0.781 | 0.998 |
| smoking history | 0.398 | 0.864 | 0.679 | 0.343 | 0.510 | 0.120 | 0.587 | 0.814 | 0.835 |
| alcohol history | 0.046 | 0.063 | 0.007 | 0.355 | 0.328 | 0.837 | 0.113 | 0.252 | 0.209 |
| genetic disorders | 0.757 | 0.768 | 0.820 | 0.555 | 0.390 | 0.069 | 0.129 | 0.730 | 0.648 |
| allergy history | 0. 924 | 0. 949 | 0.675 | 0.460 | 0.445 | 0. 043 | 0.433 | 0.864 | 0.854 |
| painful bone area | 0.381 | 0.949 | 0.342 | 0.400 | 0.252 | 0.147 | 0.957 | 0.503 | 0.413 |
As shown in Table 8, the results of the subsequent multivariate linear regression model indicated that a history of alcohol consumption (β = 0.176, P = 0.036) was an independent factor affecting the total HAQ score, while the duration of the disease did not show a significant independent effect after adjusting for confounding factors (β = −0.007, P = 0.386); the remaining variables mentioned above also did not show an independent effect on the total HAQ score in the multivariate model (all P > 0.05).
Table 8.
Multivariate Analysis of Factors Influencing HAQ Total Score
| Influencing factors | β | SE | Beta | T | P |
|---|---|---|---|---|---|
| Constant | 0.656 | 0.213 | 3.079 | 0.002 | |
| gender | ﹣0.039 | 0.071 | ﹣0.038 | ﹣0.550 | 0.583 |
| age of diagnosis | ﹣0.004 | 0.003 | ﹣0.088 | ﹣1.036 | 0.301 |
| duration of disease | ﹣0.007 | 0.089 | ﹣0.066 | ﹣0.869 | 0.386 |
| occupation | ﹣0.003 | 0.019 | ﹣0.012 | ﹣0.172 | 0.864 |
| marital status | ﹣0.022 | 0.091 | 0.021 | 0.245 | 0.807 |
| education level | ﹣0.002 | 0.026 | ﹣0.006 | ﹣0.076 | 0.940 |
| smoking history | ﹣0.077 | 0.089 | ﹣0.066 | ﹣0.869 | 0.386 |
| alcohol history | 0.176 | 0.083 | 0.164 | 2.107 | 0.036 |
| genetic disorders | 0. 068 | 0. 109 | 0.043 | 0.618 | 0.537 |
| allergy history | 0.015 | 0.077 | 0.014 | 0.199 | 0.842 |
| painful bone area | ﹣0.001 | 0.008 | ﹣0.009 | ﹣0.132 | 0.895 |
Discussion
The exact epidemiological data of SAPHO syndrome are not clear (it is easily misdiagnosed or missed). Existing data show a global incidence of about 1/100,000 (mainly in white populations) [4, 5]. The latest statistics indicate its distribution in Northern Europe, the United States, Latin America, and Asia (Japan 0.00144/100000) [6]. The disease is more common in women than in men [7], and it can occur at any age (peak incidence at 30–50 years), with cases also reported in children [8] and the elderly [9–11]. In this study, the male-to-female ratio was 1:1.88, the average onset age was 35 ± 13 years (consistent with the literature [12]), and the average time to diagnosis was 5.67 years.
In this study, 21.8% of patients had a history of smoking (lower than the national adult smoking rate of 23.2%) [13], with a smoking rate of 18.4% among women (significantly higher than the national rate of 1.8% for women) and 28.2% among men (lower than the national rate of 43.9% for men). In terms of alcohol consumption, the overall drinking rate among patients was 28.9% (lower than the national adult rate of 42.9%) [14]: 37.2% for men (much lower than the national rate of 62.3% for men) and 24.5% for women (higher than the national rate of 22.9% for women).
This study showed that the incidence of skin lesions was 98.4% (with PPP accounting for 92.9%), significantly higher than reported in the literature (skin involvement 68% [15], PPP 60% [16]), and 94.7% showed simultaneous accumulation of hands and feet.; other skin lesions and scattered lesions in multiple locations were all less than 8%. Among bone and joint lesions, involvement of the anterior chest wall reached 65%, consistent with the literature (52.5% ~ 97.8% [17]). The top five bone involvement sites (sternoclavicular joint, sternum, sacroiliac joint, knee joint, and ribs) accounted for more than 20% cumulatively. The incidence of unilateral/limb-specific PPP, atypical skin sites, and scattered bone pain was ≤ 2%. Symmetrical PPP combined with sternoclavicular/sternum/sacroiliac joint lesions is the most characteristic combination of SAPHO syndrome and can serve as a core diagnostic criterion. Among 14.2% of patients without bone and joint symptoms, bone scans revealed the 'bullhead sign' or osteomyelitis, confirming the diagnosis, indicating the presence of occult bone lesions; timely treatment may prevent the progression of bone pain. Therefore, prioritizing control of skin PPP and axial joint inflammation can improve quality of life.
Patients with SAPHO syndrome have a complex and extensive spectrum of associated diseases, encompassing chronic inflammatory, autoimmune, metabolic, and infection-related disorders across multiple systems. Multidisciplinary team (MDT) coordinated diagnosis and treatment is key to controlling the condition. Some patients, in addition to skin and osteoarticular symptoms, also have other systemic diseases (not detailed). Previous studies have shown that 67.2% of patients have concurrent chronic tonsillitis [18], and 33.3% experience sore throat and a sensation of a foreign body in the throat; in this study, 32% of patients had chronic tonsillitis.
Implications of differences in treatment-related quality of life: The significant correlation between treatment type and DLQI scores (P = 0.028) should be interpreted with caution. This correlation is likely reflective of "indication bias": patients with more severe skin lesions are more likely to be prescribed medication, and therefore, despite receiving treatment, they still report higher DLQI scores. This finding highlights a key limitation of current pharmacological treatments—although the medication controls inflammation, it may not fully alleviate the psychosocial burden (DLQI) of patients with severe SAPHO, especially those with recalcitrant palmoplantar pustulosis (PPP). This reinforces our previous finding that, compared to bone lesions, skin lesions have a relatively greater impact on the heterogeneity of quality of life.
As a dermatology-specific quality of life assessment scale, the DLQI has been widely used in studies of PPP, psoriasis, and other skin diseases. This study confirmed its excellent reliability and validity in SAPHO syndrome: 78.5% of patients experienced moderate to severe quality of life impairment due to skin disease (moderate 43.5%, severe 35%), with an overall DLQI median score of 17. Among the dimensions, 'symptoms & feelings,' 'daily activities,' 'work & school,' 'leisure,' and 'treatment' were significantly affected, while the impact on 'personal relationships' was mild. Patients who consume alcohol perform worse on the DLQI scale, particularly in the dimensions of 'symptoms and feelings', 'leisure', 'personal relationships', 'treatment', and 'total score', with female patients being more susceptible. Alcohol may be associated with a more severe symptom burden, as studies have reported that alcohol worsens the symptoms of skin diseases such as psoriasis, acne, and palmoplantar pustulosis, thereby impairing patients' overall experience, daily activities, and treatment adherence. The impact of alcohol on the DLQI of female patients with skin diseases is more pronounced, possibly due to a higher incidence among women, hormonal differences, the effects of alcohol on mood and social relationships, and lower alcohol metabolism efficiency. However, this study did not include inflammatory biomarkers (such as CRP or ESR) or longitudinal disease activity data to assess the direct impact of alcohol/tobacco on inflammation progression, and its exact mechanism in SAPHO still requires further longitudinal research to verify.
The results of this study indicate that educational level is an independent factor affecting the total DLQI score. Compared with those with higher education, patients with lower education levels are more affected in the five dimensions of the DLQI.excluding the "treatment" dimension, compared to those with higher education. Individuals with lower education often face psychological health issues (depression/anxiety) and difficulties in disease management due to low income, life stress, and lack of medical resources, leading to symptom aggravation and delayed treatment [24]. Table 3 shows that people with lower education levels have significantly higher rates of smoking and drinking, which is related to the influence of low socioeconomic status on behavior through four pathways: health awareness, psychological stress, knowledge level, and cultural environment [22].Smoking and drinking exacerbate symptoms through three aspects: directly triggering inflammation (such as psoriasis), promoting sebaceous metabolism (acne), and increasing systemic inflammatory burden, with the dose-dependent effect of alcohol and its immune interference being the core mechanisms. Drinking not only directly lowers baseline DLQI scores but also worsens emotional/social dimensions through psychosocial burden and reduces treatment adherence, forming a vicious cycle of 'symptom loss of control and decreased quality of life'. Based on these association analyses, we recommend that SAPHO patients quit smoking (as smoking can aggravate PPP, and symptoms may improve after quitting[25]), and the mechanisms behind this are worth investigating in the future.
It is noteworthy that although a history of drinking did not emerge as an independent factor affecting the total DLQI score, it was significantly associated with the 'treatment' and 'personal relationships' dimensions in univariate analysis. This finding suggests that drinking may not affect overall quality of life comprehensively, but rather exerts a localized impact by influencing specific aspects such as patients' acceptance of treatment, treatment experience, or social relationships. The loss of significance in the multivariate model may be related to the adjustment for confounding factors such as education level, and may also reflect the complex interactions between drinking behaviour and other psychosocial factors. Future research could further explore its underlying mechanisms.
Implications of Skin Lesion Type on Quality of Life The finding that skin lesion types, rather than bone pain sites, are correlated with DLQI scores (P = 0.039) underscores the disproportionate impact of cutaneous symptoms on patients' perception of quality of life. As DLQI focuses specifically on skin-related issues (itching, appearance, treatment inconvenience), the chronic, visible, and relapsing nature of Palmoplantar Pustulosis (PPP) appears to impose a heavier psychological and social burden compared to other skin manifestations like Psoriasis or Acne in this cohort. This highlights the necessity of a comprehensive treatment approach that not only controls bone pain but also effectively manages skin lesions to improve overall patient well-being.
The HAQ scale showed good reliability and validity in SAPHO studies. The results indicate that patients’ upper limb function (especially 'grip') is most severely affected, while 'walking' function is relatively preserved. Lesions primarily involve the anterior chest wall and acromioclavicular areas. Some patients have limitations in basic daily living abilities and require targeted rehabilitation interventions. The 'hygiene' dimension showed significant differences, highlighting the need for individualized assessment. Disease duration is U-shaped associated with functional impairment: acute inflammation (disease duration ≤ 1 year) leads to rapid functional decline, while chronic joint lesions (disease duration ≥ 11 years) cause secondary functional disabilities. Patients with rheumatoid arthritis [26], pustular arthritis [27], and synovitis [28] also exhibit long-term inflammation that accelerates joint damage and reduces the ability to perform daily activities. However, in the multiple linear regression model, the effect of disease duration on the total HAQ score was no longer statistically significant, suggesting that the association between disease duration and HAQ may be confounded by other factors and that its impact on physical function does not exist independently. This phenomenon may be related to patients with longer disease duration, whose disease severity, comorbidities, and treatment regimens are more complex, and when other clinical characteristics are included in the model, the independent effect of disease duration is attenuated.
Univariate analysis indicated that a history of alcohol consumption is an important risk factor for impaired eating function in SAPHO patients. The mechanism lies in the fact that alcohol not only exacerbates joint inflammation and pain, but also affects neuromuscular coordination and fine motor control of the hands. In addition, oestrogen enhances the inflammatory activation effect of alcohol through the ERα receptor, explaining why temporomandibular joint symptoms in women are prone to worsening. These pathological changes form a vicious cycle of 'alcohol → increased inflammation → restricted joint function → eating disorder', leading to prolonged meal times and limited food choices. Further multivariate regression analysis confirmed that a history of alcohol consumption is an independent risk factor affecting the HAQ total score (β = 0.176, P = 0.036), suggesting that alcohol may directly or indirectly affect physical function through musculoskeletal, neurological, or overall health pathways, and also reflects its complex interactions with lifestyle and disease management. This finding emphasises that in clinical assessment and the improvement of patients' physical function, a history of alcohol consumption should be regarded as an important independent indicator.
Limitations This study has the following limitations:
Methodological limitations: The study has limitations in assessing disease burden because the Dermatology Life Quality Index (DLQI) may not adequately reflect the musculoskeletal symptoms of SAPHO syndrome. Using a dermatology tool might underestimate the impact of joint and bone problems on patients' lives, leading to inaccurate DLQI scores. Future research should integrate assessments of both skin and musculoskeletal issues or develop a specific tool for SAPHO syndrome to better evaluate disease burden.
Study design: The cross-sectional survey did not control for confounding factors, requiring longitudinal follow-up with adjustment for confounding variables to strengthen causal inference.
Sample size: The patient population was limited, and future studies should include multiple centers with patients from different occupational backgrounds and varying disease severity.
Subgroup analysis: Subgroup differences and interactions between variables were not fully explored, and stratified analyses and multifactorial models are recommended.
Psychological assessment: We did not assess anxiety and depression in our patients, which are important confounding factors that can significantly influence DLQI and HAQ scores. The absence of this data represents a methodological defect that may affect the interpretation of the disease burden. Future studies should include psychological evaluations to provide a more comprehensive assessment of the quality of life in SAPHO patients.
Medication confounding: Medication in some patients may affect the assessment of disease burden, as those receiving treatment may report lower Dermatology Life Quality Index (DLQI) and Health Assessment Questionnaire (HAQ) scores due to symptom relief. Although we categorized the main treatments, detailed information on adherence and dosage was lacking during the assessment. Therefore, quality of life scores may more accurately reflect disease burden during treatment rather than in the untreated state. Future prospective studies should consider drug use as a time-dependent factor to accurately assess the impact of SAPHO.
Low response rate: The response rate was relatively low (22.5%). However, given the debilitating nature of SAPHO syndrome and the outpatient setting of the survey, refusal to participate was largely attributed to patients' physical discomfort or time constraints during visits, rather than disease-specific selection bias.
Lack of objective indicators: We did not systematically collect detailed imaging data (e.g., MRI, PET-CT findings) or inflammatory biomarkers (CRP, ESR) to objectively assess the degree of inflammation or bone lesions, which limits the objectivity of the disease burden assessment.
Conclusion
Patients with SAPHO syndrome commonly experience significant skin lesions and musculoskeletal symptoms, which seriously affect their quality of life. DLQI assessment showed that 78.5% of patients had impaired quality of life (median score 17), primarily affecting five dimensions: symptom perception, daily activities, work/study, leisure, and treatment. HAQ assessment found that 'grip' function was the most significantly impaired, while 'walking' function was the least affected. Alcohol consumption affects local quality of life, while education level is an independent key factor affecting skin-related quality of life, with drinkers and those with lower education levels experiencing more severe impairment.Disease duration and alcohol consumption history are the main factors affecting physical function, with more severe functional limitations seen in patients with disease durations of ≤ 1 year and ≥ 11 years, and drinkers exhibiting poorer neuromuscular coordination. Clinically, early intervention and symptom management should be emphasized to improve quality of life. Future research can focus on optimizing quality of life assessment tools and developing individualized treatment strategies.
Acknowledgements
We are grateful to the patients who participated in this study.We are grateful to Peking Union Medical College Hospital and the Affiliated Hospital of Qinghai University., for providing facilities and resources.
Author Contributions
Methodology: Ren Benhong, Zhang Qingping; Investigation: Ye Juan, Guo Bin, Zhang Ying; Liu Wei, Su Peng, Xing Xionghua, Zhang Xiaoli; Writing—Original Draft: Gan Wenyuan, Li Zhaowei; Writing—Review & Editing: Wang Yi,Su Juan.
Funding
No specific funding was received.
Data Availability
Data and materials are available upon request.
Declarations
Ethical Approval & Consent
This study obtained ethical approval from the Ethics Committee of Qinghai University Affiliated Hospital and participant consent; consent for publication was granted.
Competing interests
The authors declare no competing interests.
Footnotes
Su Juan contributed equally to this work and should be considered co-corresponding authors.
Li Zhaowei’s contributions mirror the first author’s in significance and labor; co-first authorship is the only ethically and academically valid recognition.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Contributor Information
Yi Wang, Email: wegreatgroup@126.com.
Juan Su, Email: sujuanqh@163.com.
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Associated Data
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Data Availability Statement
Data and materials are available upon request.