A Challenging Diagnosis of Behçet's Disease Starting from Unexplained Fever Recurrence with Pulmonary Embolism: A Case Report.

Purpose: Recurrent inflammatory fevers with multisystem involvement occur clinically and may indicate an autoimmune disease. Case: We present a young male diagnosed with pulmonary embolism who experienced recurrent fever during hospitalization and was unresponsive to antibiotics and antipyretics. A follow-up history revealed chronic oral and genital ulcers, leading to a final diagnosis of Behçet's disease. Conclusion: The patient's temperature normalized rapidly after corticosteroid therapy, and infection markers returned to normal. Complete remission was achieved with immunosuppression and glucocorticoid therapy. Reporting characteristics, treatment experience, and outcomes of such cases are essential to inform future diagnosis and management strategies.

Pseudoaneurysm of profunda femoral artery revealing Bechet's disease treated by embolization.

Behcet's disease is a multisystem inflammatory disorder, whose vascular involvement is very rare. Aneurysmal arterial involvement is the severe form of the disease, it constitutes a therapeutic challenge given its severity, and frequent secondary complications. Profunda femoral artery aneurysms (PFAAs) are extremely rare. The systematic immunosuppressive drug treatment and endovascular or surgical technique thoroughness can reduce relapse rate. We report the case of a young man in whom a false aneurysm of the profunda femoral artery revealed Behcet's disease. He underwent an endovascular treatment by embolization using coils; with good control after 3 months.

Mimickers of nervous system involvement among patients with Behçet's syndrome.

OBJECTIVES: We aimed to identify conditions mimicking nervous system involvement among patients with Behçet's syndrome (BS) and to determine clinical, laboratory and imaging findings that may help in the differential diagnosis. METHODS: We screened the charts of 500 consecutive BS patients to identify those who were referred to neurology at any time during their follow-up. The final diagnoses, presenting signs and symptoms, laboratory and imaging results were retrieved from patient charts. Patients who did not have a follow-up visit during the last 3 months were invited to the clinic. RESULTS: Among the 500 BS patients, 116 (23%) had been referred to neurology. Among these, 29 (5.8%) were diagnosed with typical central nervous system involvement of BS (NeuroBS). The type of NeuroBS was parenchymal involvement in 21 patients, cerebral venous sinus thrombosis in 7 patients, and both in 1 patient. 30 patients (6%) had other conditions related to the nervous system, 46 (9.2%) did not have a nervous system disorder, and their symptoms recovered spontaneously, and 11 (2.2%) were lost to follow-up without a definite diagnosis. Of the 30 BS patients who were diagnosed with another nervous system condition, 14 (46%) had primary headache syndromes, 6 (20%) had psychiatric disorders, 2 had entrapment neuropathy, and 1 each had epilepsy, glial tumor, multiple sclerosis, Meniere's disease, optic neuritis, neuroretinitis, steroid myopathy and polyneuropathy. CONCLUSION: Nervous system conditions other than NeuroBS are frequent among BS patients referred to neurology. Caution is required to avoid misdiagnosis of these patients as NeuroBS.

Examining the Relationship Between Behçet's Disease and Depression, Anxiety, and Sexual Dysfunctions. / Behçet Hastaligi ile Depresyon, Anksiyete ve Cinsel Islev Bozukluklari Arasindaki Iliskinin Incelenmesi.

OBJECTIVE: People with Behçet's Disease, as many individuals with chronic diseases, often face depression, anxiety, poor quality of life and sexual problems. In this study, it was aimed to evaluate depression, anxiety, and sexual dysfuntions in people with Behcet's Disease. METHOD: A total of 100 participants, 50 patients (29 female) and 50 healthy volunteers (28 female), participated in the study. Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Female Sexual Function Index (FSFI), and International Index of Erectile Function (IIEF) were administered to the participants. RESULTS: Depression and sexual dysfunctions were significantly related with Behçet's Disease. In our study, all female participants with Behçet's Disease had problems in sexual functions. Erectile dysfunction was more frequent in participants with Behcet's. The results also showed that there is a significant relationship between depression and orgasmic function (p=0.004), sexual desire (p=0.028), sexual satisfaction (p=0.023), and general satisfaction (p=0.028). There was a significant difference between people with Behçet's Disease (10.54±6.45) and healthy group (7.36 ±6.13) in depression scores (p=0.009). Patients with systemic involvement and those with mucocutaneous involvement were found to be similar in terms of BDI and BAI scores (p>0.05). CONCLUSION: Behçet's Disease was found to be a risk factor for depression and sexual dysfunctions.

Trisomy 8 presentation by inflammatory manifestations and its response to thalidomide: two case reports and narrative review.

Objective: It has been recognized that there is a nexus among Trisomy 8 (T8), Behcet's disease (BD), and myelodysplastic syndrome (MDS). We reported a series of inflammatory features in 2 children with T8 without hematological involvement. Methods: 2 children with trisomy 8 who were excluded from MDS were retrospectively collected from the Department of Rheumatology and Immunology, Children's Hospital of Nanjing Medical University, Nanjing. Results: Patients developed a range of inflammatory manifestations before a diagnosis of T8. The clinical manifestations of T8 patients vary from normal to severely disabled. Glucocorticoids and thalidomide can effectively relieve inflammation in patients with T8. Conclusion: The early clinical manifestations of T8 in children lack specificity, and the diagnosis is mainly based on karyotype analysis, gastrointestinal endoscopy and bone marrow aspiration findings. Active and effective immunoregulatory therapy and long-term follow-up can improve the prognosis of patients with T8.

Association between COVID-19 infection and uveitis flare in patients with Behcet's disease, a retrospective multicenter cohort study.

PURPOSE: To explore if COVID-19 infection and its subsequent immunosuppressant adjustment as well as previous vaccination status are associated with higher risks of uveitis flare in patients with Behcet's disease. METHODS: This retrospective multicenter cohort study was conducted in January 2023 among patients with Behcet's uveitis, during the second wave of the COVID-19 pandemic in China, with an anticipated sample size of 250. The primary objective was to examine the association between COVID-19 infection and the occurrence of uveitis flare. The potential impact of other exposures, including the patient's vaccination status and treatment adjustments to the risk of uveitis flare and the course of COVID-19 infection were also analyzed. RESULTS: 207 patients with COVID-19 infection and 47 patients without COVID-19 infection were included. A total of 127 uveitis flares occurred in the observational period (14.29 events per 100 person-month). COVID-19 infection was found to be significantly associated with a higher rate of uveitis flare (adjusted rate ratio = 4.8, 95% CI 3.7 to 6.3, P < 0.001). However, neither systemic immunosuppressive adjustment nor COVID-19 vaccination status showed a significant association with uveitis flare or the course of COVID-19 infection. CONCLUSIONS: This study provides evidence of an association between COVID-19 infection and an increased risk of uveitis flare in patients with Behcet's disease. However, there was no significant evidence to support that baseline immunosuppressive therapy regimens, treatment adjustment after COVID-19 infection, or vaccination status were associated with higher risks of uveitis flare or prolonged COVID-19 course.

Neuro-Behçet's Syndrome Without Genital Ulcers: A Case Report and Literature Review.

Behçet's disease is a rare multisystemic vasculitis characterized by oral ulcers, genital ulcers, and skin and ocular lesions. Neuro-Behçet's syndrome is a condition in which individuals with Behçet's disease experience neurological symptoms that cannot be attributed to other neurological diseases. We present a rare case of neuro-Behçet's syndrome with acute internuclear ophthalmoplegia and deteriorating neurological function with a prior history of recurrent oral ulcers with pathergy-like features, acneiform papulopustular rash, retinal hemorrhages, and recurrent epididymitis without genital ulcers. Patient improved with cyclophosphamide. This case underscores the importance of diagnosing and managing neuro-Behçet's syndrome in the absence of genital ulcers.

Behçet disease: epidemiology, classification criteria and treatment modalities.

INTRODUCTION: Behçet disease (BD) is an inflammatory multisystem disorder of unknown etiology, believed to be triggered by infection and environmental factors in genetically predisposed individuals. The significance of understanding BD lies in its impact on global health due to its diverse clinical manifestations and geographical distribution. AREAS COVERED: This review discusses the epidemiology of BD, emphasizing its prevalence estimated at 10.3 (95% CI, 6.1, 17.7) per 100,000 population, with higher rates observed in regions historically linked to the Silk Route. The criteria for diagnosis are explored, focusing on clinical manifestations that guide healthcare professionals in identifying and managing BD. Additionally, the review encompasses treatment strategies, highlighting TNF-alpha inhibitors as pivotal biologics and newer agents like IL-1 inhibitors and Ustekinumab that broaden the therapeutic options for BD. EXPERT OPINION: Our work provides insights into the evolving landscape of treatments for BD, emphasizing the expanding role of newer agents alongside established therapies like TNF-alpha inhibitors.

Severe Occlusive Retinal Vasculitis in an Immunocompetent Patient with Chronic CMV Anterior Uveitis.

PURPOSE: We report a unique case of non-necrotizing occlusive retinal vasculitis presenting two years following chronic hypertensive uveitis. METHODS: Case Report. RESULTS: A 32-year-old Iraqi woman with a history of Posner-Schlossman Syndrome diagnosed 10 years prior presented with blurred vision and redness in her left eye. Examination demonstrated ocular hypertension, keratic precipitates, and inflammatory cells in the anterior chamber. Quantitative real-time PCR confirmed the presence of cytomegalovirus in the aqueous humor, and dilated posterior segment examination was negative for any signs of intraocular inflammation, retinitis, or vasculitis. Her uveitis workup was otherwise negative, and she was treated with valganciclovir for 6 months. Two years after her initial presentation, she was noted to have a new vitreous hemorrhage in the left eye. Fluorescein angiography demonstrated an occlusive retinal vasculitis with extensive neovascularization without retinitis. Quantitative real-time PCR again demonstrated the presence of cytomegalovirus in the anterior chamber. Her uveitis workup was repeated, which has now returned positive for HLA-B51. She otherwise did not demonstrate any systemic signs of Behcet's Disease. She was restarted on valganciclovir and oral prednisone and referred to rheumatology for consideration of adalimumab initiation. Thus far she has responded very well to treatment. CONCLUSION: This case highlights the importance of serial posterior segment examinations and HLA-B51 testing in individuals with cytomegalovirus anterior uveitis.

Macrophage Activation Syndrome in the Setting of Rheumatic Diseases.

Patients with established rheumatic disorders may develop complications of macrophage activation syndrome due to severe flares of the underlying disease (adult-onset Still's disease, SLE); however, in most other rheumatic disorders, MAS develops in association with identified viral or other infectious triggers. It is therefore important to pursue appropriate studies to identify potential infectious triggers in rheumatic disease patients who develop MAS. Management is best directed toward treatment of the triggering infections and combinations of high-dose corticosteroids, calcineurin inhibitors, and biologic therapies targeting IL-1 and/or IL-6 to suppress the associated cytokine storm.

Fever, Leukocytosis, and Ulcerated Vulvar Lesions: An Atypical Presentation Concerning Behcet's Disease.

Behcet's disease (BD) is a variable-vessel vasculitis commonly presenting in early adulthood with painful oral aphthous ulcers, genital ulcers, uveitis, pathergy, and skin lesions. The diagnosis of BD is made clinically based on criteria from the International Study Group (ISG) and the International Criteria for Behcet's Disease (ICBD). Due to the wide constellation of symptoms BD can cause, it can be challenging to diagnose in an acute setting. Here, we discuss a patient who presented with a clinical picture of sepsis, with profound ulcerated vulvar and herpetiform oral mucosal lesions, that led us to a presumptive diagnosis of Behcet's disease.

Screening for familial disease presence in first-degree relatives of Behçet's disease patients: Is measurement of common femoral vein wall thickness valuable for the diagnosis?

OBJECTIVES: We aimed to assess first degree relatives (FDRs) of BD patients for the presence of clinical symptoms and signs of BD and evaluate common femoral vein (CFV) wall thickness measurement for the diagnosis. METHODS: Patients with BD(n=129) and FDRs(n=230) of these patients were included. FDRs were questioned in terms of BD symptoms by phone. Pathergy test and CFV wall thickness measurement were performed among 111 FDRs who accepted the clinical assessment. Clinical assessment group were classified according to the criteria sets for BD. FDRs who did not meet the criteria sets and had at least one clinical finding in addition to oral aphthae(OA) were categorized as the "suspected BD". RESULTS: :We observed increased frequency of isolated BD manifestations in FDRs. Ten FDRs were diagnosed with BD during clinical evaluation. Significantly increased CFV wall thickness was observed in FDRs of BD patients fulfilling diagnostic BD criteria (p<0.001 for both sides) and also in those with suspected BD group (p<0.05 for both sides). Presence of OA, genital ulcer, folliculitis or erythema nodosum were associated with increased CFV wall thickness (p<0.05). CONCLUSION: . Our results suggest that CFV wall thickness measurement can be used in diagnosis of familial BD.

De novo manifestations during adalimumab treatment in Behçet's syndrome.

OBJECTIVES: Treatment response may be variable across organ manifestations of Behçet syndrome (BS). We aimed to determine the frequency of de novo manifestations during adalimumab treatment. METHODS: We conducted a chart review of all BS patients who received adalimumab in our center between 2008 and 2023. Demographic data, reasons for initiating adalimumab, concurrent medications, previous treatments, and outcomes were recorded. We defined de novo manifestations as new BS manifestations that occurred for the first time during treatment with adalimumab. For patients with vascular involvement, a new vascular event at another vessel was also considered as a de novo manifestation. RESULTS: Among the 335 patients, a de novo manifestation developed in 14 (4%) patients. De novo manifestations were vascular involvement in 5 patients, arthritis in 3, anterior uveitis in 2, nervous system involvement in 2, gastrointestinal involvement in 1, and epididymitis in 1 patient. The primary reasons for adalimumab treatment were vascular involvement in 5 patients, uveitis in 4, arthritis in 3, mucocutaneous involvement in 1, and epididymitis in 1 patient. Upon the development of de novo manifestation, adalimumab was switched to another biologic in 4 patients, dose was intensified in 3, colchicine, conventional immunosuppressives, and/or glucocorticoids were added in 5, and topical eye drops were added in 2 patients, leading to remission of de novo manifestations in all patients. CONCLUSION: De novo manifestations were infrequent (4%) among BS patients treated with adalimumab. Of these, 57% were major organ involvement, mainly vascular involvement. None of the patients developed posterior uveitis.

Carpal tunnel syndrome related to rheumatic disease (Review).

Carpal tunnel syndrome (CTS) is the most commonly occurring type of entrapment neuropathy in the world. Several conditions may contribute to the development of CTS, such as obesity, repetitive wrist movements, pregnancy, genetic predisposition and rheumatoid arthritis (RA) inflammation. CTS is characterized by a wide range of pathophysiological factors, including increased pressure, mechanical trauma and ischemic damage to the median nerve that runs through the wrist tunnel. In the present narrative literature review, the way rheumatic diseases (RDs) contribute to CTS occurrence is investigated. The epidemiological, clinical, paraclinical and pathogenesis aspects of the relationship are examined. CTS is the most common neurological finding in RA, and incidences of RA, psoriatic arthritis and CTS are closely related. The association of CTS with systemic lupus erythematosus, Sjögren's syndrome, Behcet's disease and systemic sclerosis is weaker. In these cases, the prevalence of CTS is similar to that in the general population. As the occurrence of CTS is increasing, understanding the common mechanism and making an early diagnosis are required to limit pain and costs. When patients with RD present with symptoms such as wrist pain, tingling sensations or numbness in their fingers, CTS should be suspected. This suspicion should not be interpreted in terms of RD. To accurately evaluate patients with RD, a detailed electrophysiological examination should be included in the evaluation process. A diagnostic algorithm should include neuromuscular ultrasound or magnetic resonance imaging for patients with RD.

Diffusion tensor imaging in behcet's disease with and without neurological involvement patients: evaluation of microstructural white matter abnormality with a tract-based spatial statistical analysis.

OBJECTIVE: This study aims to assess the microstructural abnormalities in white matter (WM) among Behcet's Disease (BD) patients, both with and without neurological involvement, utilizing tract-based spatial statistics (TBSS) to elucidate the underlying causes of WM microstructural changes. METHODS: This prospective study comprised 43 BD patients without neurological involvement, 15 Neuro-Behcet's Disease (NBD) patients with normal conventional MRI, and 54 healthy controls matched for age and sex. TBSS was applied in this diffusion tensor imaging study to conduct a whole-brain voxel-wise analysis of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of WM. RESULTS: Compared to the control group, BD patients exhibited decreased FA and increased MD and RD in nearly all WM tracts, along with increased AD in the left corticospinal tract (CST), left inferior longitudinal fasciculus (ILF), and left superior longitudinal fasciculus (SLF). NBD patients also showed a widespread decrease in FA and increased MD and RD, similar to BD patients without neurological involvement. Additionally, NBD patients had increased AD in the left CST, left ILF, left SLF, left inferior fronto-occipital fasciculus (IFOF), and right CST. Compared to BD patients without neurological involvement, NBD patients exhibited a greater reduction in FA and an increase in MD and RD in WM tracts, with no significant differences in AD. CONCLUSION: These results suggest that the main mechanism of microstructural changes in the WM of BD patients may be related to impaired fiber integrity, demyelination, decreased myelin sheath integrity. ADVANCES IN KNOWLEDGE: This study demonstrated BD patients without neurological involvement and NBD patients a decrease in FA and an increase in MD and RD were observed in larger areas of major WM tracts, while an increase in AD values was observed in fewer tracts. Our findings may be useful in understanding the pathophysiology underlying subclinical parenchymal involvement and neurological dysfunction in BD patients and in the management of BD patients.

Clinical profiling, treatment characteristics and outcome in Behcet's Disease (BD)-A retrospective cohort study from Karnataka Rheumatology Association (KRA).

BACKGROUND: Behcet's disease (BD) has a heterogeneous and unpredictable phenotype that differs in various geographical areas. OBJECTIVE: To describe the clinical phenotype & outcome of Behcet's disease(BD) from Karnataka, India and compare them with large cohorts from endemic regions. METHODS: Databases of practising rheumatologists from Karnataka were reviewed to retrieve clinical characteristics, course of illness, prescribing information and outcome at last follow-up of patients clinically diagnosed as BD. The classification criteria, namely revised International criteria for Behcet's disease (rICBD) and International study group (ISG) criteria were applied. Outcome was defined as complete or partial remission, persistent disease or relapse. RESULTS: We included 72 patients, equal gender distribution and mean age 37.4 ± 12.8 years from 8 rheumatology centres. Commonest presentations were recurrent oral aphthosis 58(80.6%), genital ulcers 36(50%) and ocular manifestations 40(55.6%). Three-quarters [51/72(70.8%)] fulfilled rICBD criteria whereas only half [36/72(50%)] fulfilled ISG criteria. Apart from glucocorticoids [53/72(73.6%)], frequently prescribed therapies were colchicine 39(54.2%) and azathioprine 35(48.6%). Eleven-patients received biologics(anti-TNF-α) and JAK inhibitors to treat severe organ involvement. HLA-B*51 and pathergy tests were positive in 27/45(60%) and 12/34(35.3%) patients respectively. Outcomes were documented in 94.4%(68/72) patients at median follow-up of 24 (12;36) months. Majority [46/68(67.6%)] had complete remission, 17/68(25%) had partial remission, 4/68(5.9%) had persistent while 1/68(1.5%) had relapsing course. CONCLUSION: Majority of BD patients had orogenital aphthosis and ocular manifestations and an excellent response to treatment. Key Points • In our region, Behçet's Disease primarily manifests with recurrent oral aphthae and ocular involvement, with comparatively lower incidence of severe genital ulcers and neurological involvement than in endemic regions. • Apart from glucocorticoids, colchicine and azathioprine are the most commonly used agents. Biologics and JAK inhibitors are prescribed infrequently, primarily in cases of severe organ involvement. • A significant proportion of patients achieved either complete or partial remission during follow-up, with no observed mortality suggesting a milder disease course and better outcome compared to endemic regions. • Gender, HLA-B*51 status, and pathergy response did not exert any significant influence on the clinical profile or outcome in BD patients in Karnataka.

Sexual dysfunction among female patients with rheumatic diseases.

To demonstrate the burden of sexual dysfunction (SD) among females with rheumatic diseases, we conducted a cross-sectional comparative study in patients with systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and Behçet's syndrome (BS) along with suitable healthy controls (HCs). Age-matched female patients with SSc (n = 50), SLE (n = 49), and BS (n = 54), along with 52 female HCs were included in this study between April and October, 2021. Sociodemographic features were recorded, and psychometric tests, i.e., female sexual function index (FSFI), Beck depression inventory (BDI), body cathexis scale, and marital adjustment test (MAT) were performed. Scale scores were compared, and binary logistic regression was used to identify predictors for SD in the whole group. The total FSFI and body cathexis scores among the patient groups were significantly lower than those of the HCs (p < 0.001). Depression was significantly more frequent in the patient groups. MAT scores did not differ significantly between the study groups. Patients with SSc had the worst scores in each psychometric index, including MAT. Decreased body cathexis score [OR 0.974, 95% CI (0.957-0.991), p = 0.003] and low MAT score [OR 0.937, 95% CI (0.896-0.980), p = 0.005], and being diagnosed with SSc [OR 6.6, 95% CI (1.975-22.498), p = 0.002], SLE [OR 2.7, 95% CI (0.998-7.753), p = 0.050], and BS [OR 2.8, 95% CI (1.100-7.359), p = 0.031], were identified as independent predictors for SD. Body cathexis seems to be the most important independent predictor for SD, and the burden of SD appears heavier in patients with SSc, probably due to poor body image satisfaction.

Possible Association between Behçet's Disease and Periodontal diseases.

AIM: This study explores the connection between Behçet's disease (BD), characterized by persistent oral and genital ulcers alongside iritis, and periodontal disease. It examines the levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and nitric oxide (NO) in gingival crevicular fluid (GCF) and saliva. METHODS: Forty Behçet's patients with gingivitis or periodontitis and 47 patients with either gingivitis or periodontitis but without BD were studied. Periodontal status was recorded with standard clinical indexes. GCF and saliva samples were obtained. NO, IL-1ß and TNF-α levels were analysed. Current Behçet's symptoms and medications usage were recorded. RESULTS: Mean salivary IL-1ß was elevated (p = .045), and mean NO level was decreased in BD patients with gingivitis compared to patients without BD (p = .000). In contrast, mean NO level in crevicular fluid was higher in Behçet's patients with periodontitis than in patients without BD (p = .009). Furthermore, among Behçet's patients, those with vascular involvement had lower salivary NO level compared to patients without vascular involvement (p = .000). CONCLUSIONS: Based on our findings, the elevated levels of IL-1ß in the saliva of Behçet's patients with gingivitis, along with the decreased NO level, indicate an altered inflammatory response in the oral cavity.

Long-term outcomes of infliximab treatment in neuro-Behcet syndrome: A single-center retrospective study.

INTRODUCTION: Behcet's syndrome is a rare inflammatory disorder characterized by oral and genital ulcers, skin lesions, and uveitis. It exhibits a higher prevalence along the historic Silk Road. Neuro-Behcet syndrome (NBS) affects the central nervous system and poses significant morbidity and mortality risks. Infliximab, a TNF-alpha antagonist, has shown potential in NBS management, although the current evidence is mainly derived from case series due to the lack of randomized controlled trials. OBJECTIVE: This retrospective study aimed to evaluate the disease outcomes during the first and second years following infliximab treatment in NBS patients experiencing attacks despite prior conventional immunosuppressive therapy. The study also sought to investigate the safety profile and adverse effects associated with infliximab. METHODS: Fifty-three NBS patients were examined, with 22 receiving infliximab as either monotherapy or in combination with other therapies. Retrospective analysis was conducted on demographic data, clinical characteristics, and treatment responses. Treatment efficacy was measured using the Expanded Disability Status Scale (EDSS) modified for NBS. The study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist guidelines. RESULTS: Among the study cohort, 60.4% had parenchymal NBS, and 39.6% had nonparenchymal NBS. Treatment with infliximab resulted in remission or disease stabilization in 95% of patients after one year and 68.7% after 2 years. Relapse rates were 4.5% at 1 year and 18.7% at 2 years, with disease progression observed in two cases. Adverse effects were primarily mild to moderate, with no reports of serious adverse events. CONCLUSION: Infliximab exhibited efficacy in achieving remission or stabilization in NBS patients, maintaining a favorable safety profile. The timing of infliximab treatment may prevent the accumulation of disability and hinder disease progression. Nonetheless, future prospective studies are necessary to confirm these findings and refine treatment strategies for this complex condition.