Behçet’s disease (BD) is a rare chronic, relapsing systemic vasculitis that affects vessels of all types and may involve multiple organ systems. ¹ It typically affects young adults, particularly males ² and is more common in countries along the ancient Silk Road, with an estimated prevalence of 10–20 per 100,000 in endemic regions. ¹

It can cause significant discomfort for patients, which varies depending on the number and type of symptoms. BD often results in fluctuating symptoms such as painful oral and genital ulcers, uveitis, and skin lesions, which significantly impair patients’ daily functioning and quality of life (QoL). In some cases, it can lead to major disability and a marked impairment in QoL. The routine use of QoL assessment in clinical research reflects the growing awareness of its non-inferiority as an outcome measure alongside traditional clinical endpoints. For many years, the assessment of QoL in BD patients has mainly been a surrogate of disease outcomes, but a wider impact of the disease on the patient’s lifestyle has not been considered. The assessment of QoL in BD patients may provide a fundamental measurement for health. This evaluation could serve as a means to assess the efficacy of interventions for this condition, which is characterized by complex patterns of impairment. ³

Different tools were used to evaluate QoL in BD patients were identified. The lack of homogeneity in the adoption of a single, specific tool to evaluate QoL in BD reflects the complexity of measuring such a multi-dimensional domain. ³ Several studies have used both generic instruments and disease-specific tools to measure QoL in BD patients. ⁴ Furthermore, to date, there is a paucity of tools specifically designed for the BD population. TheBehçet’s Disease Quality of Life (BD-QoL), developed in collaboration with BD patients, is one such tool. It is designed to select the most appropriate domains to explore and to emphasize what their health mostly prevents them from doing in daily activities. ⁵ The most frequently used questionnaire was the Short Form-36 Health Survey (SF-36), a generic health status and outcome measures for patients. Beyond general well-being, sexual function is a key but underexplored dimension of health in BD. Sexualdysfunction in BD may be multifactorial, resulting from pain, fatigue, mucocutaneous lesions, psychological distress, and chronic inflammation. Recent research suggests that sexual dysfunction affects a significant proportion of BD patients, yet this issue is rarely addressed during routine care. ^{3, 4, 6}

In clinical research, sexual function is most frequently assessed using validated, standardized tools. In men, the five-item International Index of Erectile Function (IIEF-5) is widely used; it evaluates erectile quality, intercourse satisfaction, and overall sexual confidence. In women, the Female Sexual Function Index (FSFI) is the most commonly applied instrument. Both instruments have been validated in various chronic disease contexts, providing reliable insight into sexual health impairments. Despite their utility, they are seldom integrated into routine assessments for patients with BD. Given the young age of most patients and the chronicity of the disease, addressing sexual health is crucial.

This study aimed to evaluate health-related quality of life (HRQoL) and sexual function in patients with Behçet’s disease (BD), using standardized, validated instruments, and to identify clinical and demographic factors associated with impaired outcomes in both domains.

A total of 35 patients diagnosed with Behçet’s disease (BD) were included in the study; the study flowchart is presented in Figure 1. Sexual function was assessed in 30 of these patients, as 4 reported no sexual activity during the recall period and 1 declined participation. At the time of assessment, the mean age was 45.3 ± 12.9 years, with a clear male predominance (74.3%, n = 26), yielding a male-to-female ratio of 2.8. The mean age at diagnosis was 32.9 ± 9.3 years, and the mean disease duration was 12.5 ± 12.0 years. The majority of patients were married (85.7%, n = 30), among whom five reported primary infertility. Additionally, 22.8% (n = 8) had at least one associated chronic comorbidity, most commonly hypertension (17.1%). Clinically, mucocutaneous manifestations were present in all patients. Recurrent oral aphthosis was reported in 97.1% of patients (n = 34), while genital aphthosis and/or scars from genital ulcers were observed in 77.1% (n = 27).

Articular involvement, manifesting as inflammatory arthralgia and/or arthritis, was observed in 54.3% of patients (n = 19), primarily affecting peripheral joints. Ocular involvement was present in 40% of patients (n = 14), presenting with various inflammatory manifestations. The most frequent ones were retinal vasculitis (50%) and posterior uveitis (42.8%). Most vascular involvement was in the form of deep vein thrombosis of the lower limbs (34.3%, n = 12), whereas arterial involvement was observed in only four patients, equally divided between arterial thrombosis and arterial aneurysm. Neurological involvement was noted in 28.6% of patients (n = 10). No patient had cranial nerve involvement or psychiatric disorders. Accelerated erythrocyte sedimentation rate was observed in 45.7% of patients, and HLA-B51 was positive in 33.3% of those tested. All patients were prescribed colchicine during follow-up and systemic corticosteroid therapy was prescribed to the majority (65.7%, n = 23). Biotherapy, including infliximab, was introduced in three patients with refractory neurological and/or ocular involvement. The therapeutic adherence was considered good in 51.4% of patients. Disease activity at the time of the interview was measured by a median BDCAF score of 2 (range 1–3). Around a third of patients (28.6%, n = 10) had active disease. Detailed demographic, clinical, biological, and therapeutic characteristics of the study population are summarized in Table 1.

Assessment of the impact of BD on QoL using the generic SF-36 questionnaire showed that 65.7% of patients (n = 23) reported impairment in at least one SF-36 domain. Among these domains, physical functioning was the most severely affected ( Figure 2). The median BD-QoL score was 11 (range: 0–26), indicating impaired quality of life in 40% of patients (n = 14) ( Table 2). A statistically significant inverse correlation was observed between the total scores of the two QoL instruments. Patients with higher BD-QoL scores (reflecting poorer quality of life) exhibited significantly lower overall SF-36 scores (39.35 vs. 68.08; p < 0.001). An assessment of sexual function revealed that the majority of patients (85.7%, n = 30) had an active sex life. However, erectile dysfunction (ED), predominantly mild, was prevalent among a significant proportion of men (82.6%, n = 19 out of 23). Among women, sexual dysfunction was observed in 71.4% of participants (five out of seven), with constant impairment of the desire domain ( Table 2).

In consideration of factors associated with compromised QoL, the age at diagnosis of BD exhibited an inverse correlation with the physical functioning domain of the SF-36 (p = 0.03), there by indicating that patients diagnosed at a more advanced age reported a greater prevalence of physical limitations. Conversely, gender did not exert an influence on the QoL, as measured by either of the two scores. Furthermore, current tobacco consumption was found to be significantly associated with impaired mental health, as measured by SF-36. The presence of a chronic comorbidity has been identified as a contributing factor to variations in QoL. The latter was found to be significantly associated with a lower total SF-36 score (mean 40.04 vs 61.49; p = 0.032), thus highlighting the negative impact of associated conditions on overall well-being. Among the clinical manifestations observed during follow-up, ocular involvement was the only feature significantly associated with impaired physical functioning, as assessed by the SF-36 physical functioning domain (p = 0.019). Current disease activity, measured by the Behçet’s Disease Current Activity Form (BDCAF), was significantly and inversely correlated with several SF-36 domains, specifically bodily pain, vitality, social functioning, and physical functioning, indicating that higher disease activity was associated with a poorer physical QoL. When focusing on clinical manifestations active within the four weeks prior to assessment, only headache and articular involvement were significantly associated with a decrease in QoL. Headaches predominantly impacted the social functioning domain, while articular manifestations were associated with lower scores in the bodily pain domain. Moreover, patients’ self-perceived disease activity was also found to be negatively associated with global QoL, as reflected by a lower overall SF-36 score (p = 0.049). The findings of this study indicated that a biological inflammatory syndrome, as indicated by an elevated erythrocyte sedimentation rate, was associated with a significant impairment in the physical limitations domain of the SF-36 (p = 0.002). Regarding the impact of treatments, the use of systemic corticosteroids was associated with improved physical component scores of the SF-36 (p = 0.007) as well as better BD-QoL scores (p = 0.007). Conversely, treatment with Cyclophosphamide was associated with significantly lower scores for the total SF-36 (p = 0.032), the social functioning and vitality domains, as well as a more impaired BD-QoL score (p = 0.028). The assessment of sexual function revealed no significant results regarding the influence of age on the sexual lives of males and females. Conversely, neither marital status nor lifestyle habits (tobacco, alcohol, and drug use) exerted a significant influence on the sexual life of either gender. While cutaneous, articular, ocular, and neurological involvement, as well as the presence of neurological sequelae, showed no significant influence on male or female sexual life, the presence of vascular involvement was associated with impaired male sexuality (p = 0.024). It is not worthy that all men with vascular involvement exhibited erectile dysfunction. However, no statistically significant association was found between vascular involvement and the FSFI score in women. These subgroup analyses and their associations with impaired quality of life and sexual function are summarized in Table 3.

In this cross-sectional study of 35 patients with Behçet’s disease (BD), we investigated the association between clinical manifestations, quality of life (QoL) and sexual function. Our findings show a significant impact of disease on both physical and psychosocial well-being. BD affects young adults as reported in larger series than ours. ^{14, 22, 23} The present study confirms this finding, showing a mean age at disease onset of 32.9 years in this cohort. On the other hand, it has also been documented a later disease onset, which may indicate variability due to environmental, genetic, or diagnostic factors. ²⁴ The majority of the published data is consistent with the male predominance observed in this study (74.3%). ²³ However, it should be acknowledged that disparities exist across various populations and geographical areas. These discrepancies can be the result of societal, racial, or geographic factors influencing disease expression. In contrast, Zouboulis et al. ²⁵ found no significant age-related effects on QoL. Our data suggest that while age may affect physical functioning in BD, its impact on broader QoL outcomes may be limited. When assessing the influence of gender on QoL, our study did not show any statistically significant association. This finding is consistent with the results of the nationwide German claims database study by, Zouboulis et al. ²⁵ This is in contrast to a number of other research that indicates that male patients mostly score higher on QoL in the physical functioning domain evaluations. For instance, in their cross-sectional study, Masoumi et al. ⁴ found that male sex was associated with significantly better physical QoL scores (mean SF-36 Physical Component Score: 49.7 in men vs. 42.3 in women; p < 0.01).

Disparities in symptom assessment, coping mechanisms, and psychological resilience may account for these apparent inconsistencies, in which male sex is linked to both more severe disease manifestations and better reported QoL. Different authors have suggested that women, in particular, may experience a greater disease burden, and body image concerns due to the chronic and stigmatizing nature of the condition, with societal expectations. Consequently, they may bear a disproportionate level of emotional and psychological stress. ^{14, 26} These findings show that it is worth considering gender-sensitive approaches while clinically assessing and psychologically support patients with BD, particularly for domains beyond objective clinical severity.

Association of chronic comorbidities such as hypertension, type 2 diabetes, and dyslipidemia may further contribute to the overall deterioration of health status. In our cohort, 20% of patients presented with at least one chronic comorbidity. Similarly, a systemic review by Chen et al. ²⁷ found a strong association between BD and components of the metabolic syndrome that may act in conjunction with the systemic inflammation that underlies BD, increasing their clinical impact.

Consistent with most reported series, mucocutaneous involvement remains the most common clinical symptom of BD in our sample (100%) which points out its importance on the disease diagnostic criteria. ¹ A thorough clinical assessment and careful physical examination are also essential, given the systemic and multi systemic nature of BD, a feature that is further highlighted by the frequency of articular (54.3%), ophthalmic (40%), and vascular (34.3%) involvement.

Pseudofolliculitis was a key symptom in the mucocutaneous manifestations since it was significantly associated with role limitations due to emotional problems as measured by SF-36 (p = 0.019). This sign was present in 38.9% of patients without impairment in emotional role limitations, compared to 58.8% to those with impairment in this domain.

This suggests that mucocutaneous involvement, particularly visible lesions such as pseudofolliculitis, may contribute to increased psychological distress and social withdrawal.

Chronic, and visible skin symptoms in BD negatively affect self-esteem and body image, sometimes resulting in stigma and reduced emotional health. ^{28, 10} This has been particularly confirmed in a recent systemic review which particularly singled out ulcerative and follicular lesions as consistent contributors to poorer mental health. ⁴ Consequently, dermatological healthcare should be integrated alongside psychological support in managing patients with cutaneous manifestations.

Neuro-Behcet is one of the most disabling forms of the disease and was observed in a considerable proportion of our patients (28.6%). This particular entity has a substantial impact on QoL. ^{26, 29, 30} Both direct neurological symptoms such as motor impairment, seizures, or cognitive impairment and the possibility of long-term complication including loss of autonomy and functional disability, contribute to this burden.

Ocular involvement was significantly associated with impairment in the physical functioning domain of the SF-36 (p = 0.019). Among patients without physical impairment, ocular involvement was present in only 32.3% (n = 10 out of 31), while it was found in 100% (n = 4) of those with physical functioning limitations. This finding is particularly relevant in the Tunisian context, where ocular manifestations affect over one-third of patients with BD. ^{2, 14} As previously reported, ocular inflammation not only causes pain but also leads to visual impairment, especially in bilateral cases, thereby interfering with patients’ autonomy, academic performance, and professional activities. ³¹ Vision loss or persistent ocular pain may thus be a major contributor to impaired physical quality of life. Notably, several studies have identified panuveitis as the form most strongly associated with a marked decline in physical domain scores of the SF-36. ¹⁰

In the present study, disease activity as measured by the Behçet’s Disease Current Activity Form (BDCAF) was significantly associated with impairment in the bodily pain domain of the SF-36 (p = 0.015). Patients with active BD reported more severe pain and greater interference of pain with daily activities. In contrast, no statistically significant relationship was found between disease activity and the BD-QoL score, suggesting that the generic SF-36 may be more sensitive to variations in physical symptoms such as pain. In our study, among the clinical manifestations that were active within the four weeks preceding the assessment, only headache and articular involvement were significantly associated with impaired QoL, specifically affecting the social functioning and bodily pain domains of the SF-36. These findings align with previous literature emphasizing the impact of active musculoskeletal and neurological symptoms on patients’ daily life in BD. ^{29, 32} Several studies have demonstrated that recurrent joint pain and neurological symptoms, particularly headaches, significantly impair both the physical and social dimensions of HRQoL. ^{29, 32} The high prevalence of arthralgia and inflammatory joint involvement in BD is well documented. Although typically non-destructive, articular involvement can be recurrent and painful, leading to impaired mobility and reduced functional independence. This may account for the significant association observed in our cohort between recent articular manifestations and impairment in the bodily pain domain of the SF-36 (50% vs. 8.7%; p = 0.011). Similarly, headaches, whether occurring in the context of parenchymal neuro-Behçet or as isolated symptoms, have been associated with reduced social participation and poorer mental well-being. In our study, 60% of patients with impaired social functioning reported headaches, compared to only 8% of those with preserved social functioning (p = 0.043). This finding aligns with prior reports demonstrating that patients with neuro-Behçet’s disease exhibit significantly lower scores in several SF-36 domains, including physical functioning, role limitations due to physical problems, bodily pain, and general health perception, compared to healthy controls. ³²

These findings indicate the need for specific symptom management, particularly for joint inflammation, and chronic headaches, as well as for addressing the impact of pain-related and cognitive symptoms on the quality of life, even when those manifestations are not life-threatening. Multidisciplinary care involving rheumatologists, psychiatrists, and pain specialists may help these patients achieve better outcomes by addressing both the physical and psychological dimensions of the BD.

The association between elevated inflammatory markers, particularly erythrocyte sedimentation rate (ESR), and reduced physical health scores on the SF-36 underscores the central role of systemic inflammation in BD–related morbidity. In our cohort, increased ESR correlated with decreased physical functioning. This aligns with findings from a study by Bodur et al. ¹¹ which demonstrated that disease activity, particularly reflected by inflammatory markers such as ESR and C-reactive protein (CRP), was inversely correlated with SF-36 scores, especially in the domains of bodily pain, general health, and physical functioning. A meta-analysis-like cross-sectional study by Ilhan et al. ³³ demonstrated that fatigue, a symptom closely linked to elevated inflammatory markers, was significantly associated with lower SF-36 physical and mental component scores, regardless of flare status. These data corroborate our findings and support a model of active BD in which chronic inflammation perpetuates pain, fatigue, and functional impairment, even during quiescent disease phases. This highlights the importance of monitoring and addressing both clinical and subclinical inflammatory activity to preserve patients’ physical well-being and overall QoL.

The impact of therapeutic strategies is another key finding of this study. The use of systemic corticosteroids was associated with improved QoL, both in the SF-36 physical domain (p = 0.007) and BD-QoL scores (p = 0.007). This effect may be due to the short-term efficacy of corticosteroids in alleviating symptoms and controlling inflammatory flares. This is supported by a recent review highlighting that glucocorticoids remain a mainstay of induction therapy for major organ involvement in BD, often resulting in rapid symptomatic relief and functional improvement despite limited long-term data. ³⁴ However, the known long-term adverse effects of corticosteroids, such as osteoporosis, metabolic syndrome, and psychological impacts, must be carefully weighed. By contrast, cyclophosphamide use was associated with significantly poorer QoL in our cohort. The mean total SF-36 score was substantially lower in patients receiving cyclophosphamide compared to those who were not (36.78 vs. 60.68; p = 0.032). In addition, this treatment was associated with significantly worse BD QoL scores (p = 0.028) and the social functioning and vitality domains of the SF-36. These results are in line with earlier research which demonstrated that cyclophosphamide was associated with lower HRQoL scores, particularly in social functioning and vitality domains. ²⁶

The lack of significant correlations between most clinical or demographic factors and sexual outcomes was a noteworthy finding. This could be partly explained by the small sample size especially in the female subgroup, and the resulting statistical power. Male sexual function was assessed using the IIEF-5, ²¹ a validated instrument that primarily evaluates erectile capacity and satisfaction during intercourse. However, the IIEF-5 is unable to cover other domains that contribute to the male sexual dysfunction, such as disturbances in libido, ejaculation, and overall sexual satisfaction. Despite this limitation, the instrument revealed a significant association between vascular involvement and erectile dysfunction (ED). None of the patients from the group with normal IIEF-5 scores presented vascular abnormalities, whereas 63.2% of the patients with altered scores had vascular manifestations (p=0.037). This supports the hypothesis that vascular pathology may directly impair sexual performance in BD through mechanisms such as endothelial dysfunction and compromised penile blood flow. In line with this, the existing literature identifies vasculitis and systemic vascular inflammation as major causes of organic ECD in chronic inflammatory disorders. ^{35, 36} Conversely, no significant association was found between female sexual dysfunction as measured by the FSFI and vascular involvement. The multifaceted character of female sexual dysfunction, frequently including emotional, relational, hormonal, and psychological components, may help to explain this disparity. ³⁷ The small number of actively active female participants in this study explains the low statistical power for this subgroup analysis.

In light of these results, it is important to evaluate the vascular comorbidity to better assess the sexual dysfunction in male patients, and to follow a more comprehensive, sex-specific approach.

Although not specifically explored in this study, psychological factors, particularly depressive symptoms, have been emphasized in several studies ³⁶ for their role in the male sexual dysfunction. These factors are of particular interest due to their interaction with physical symptoms and their potential to further exacerbate sexual health impairment.

It is important to acknowledge the limitations of this study. The single-center, cross-sectional design and relatively small sample size of the study limit the generalizability of the findings and reduce the statistical power to detect weaker associations. The use of self-reported questionnaires may have limited sexual assessment. This could be explained to memory loss, or the tendency of the patients to give socially accepted responses when using these types of questionnaires. The low number of the female participants restricted the subgroup analysis of the sexual function.

During future research, it is recommended to conduct larger, multicenter, and longitudinal cohorts to further evaluate the temporal relationship between clinical features, QoL, and sexual function. Additionally, psychosocial and inflammatory biomarkers should be included in order to elucidate the disease burden in BD.

This study provides a descriptive and analytical assessment of a cohort of Behçet’s disease patients from Tunisia, emphasizing on the impact on sexual health and quality of life. Older age at diagnosis, the presence of chronic comorbidities, ocular involvement and active disease were significantly associated with lower quality of life.

Interestingly, the extent of patients’ discomfort did not always correlate with clinical severity. Symptoms like mouth ulcers, headaches, and joint pain, even if seen as moderate, had a big effect on the quality of life. In this context, tools such as SF-36 and BD-QoL help assess and capture the patient’s experience.

Both physical and psychological factors contribute to the multifactorial causes of the sexual dysfunction in Behçet’s disease. In our study, vascular involvement was significantly associated with erectile dysfunction, highlighting the need to actively address sexual health in these patients, particularly those with vascular or neurologic involvement. Consequently, these findings underline the necessity of adopting a patient-centered approach to the management of Behçet’s disease including monitoring organ-specific involvement, particularly ocular and vascular, and monitoring inflammatory flares. Optimizing the outcomes requires acknowledging the patient’s subject experience.

Further large-scale, multicenter, longitudinal studies are needed to validate these associations, explore underlying mechanisms, and inform evidence-based strategies to improve the comprehensive care and quality of life of individuals living with Behçet’s disease.

This study was approved by the Ethics Committee of Sahloul University Hospital of Sousse (Approval No. [HS56-2025]).

The authors used ChatGPT (OpenAI, GPT-4, 2025 version) to assist in correcting minor language errors and improving the sentence formulation in the manuscript. All authors reviewed and approved the final manuscript to ensure its accuracy and integrity.

Verbal informed consent was obtained from all participants because the study involved minimal risk, only required completion of validated questionnaires, and was conducted in a routine clinical context where patients were already under medical care. This approach was approved by the local ethics committee. Written consent was therefore not considered necessary, and verbal consent ensured greater participation and feasibility in this setting.