Search Results (180)

Vasculitides are a heterogeneous group of disorders characterized by inflammation of blood vessel walls, leading to tissue ischemia and organ injury. Traditional inflammatory markers such as the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are widely used but lack diagnostic specificity. This has driven the search for more informative biomarkers across vasculitis subtypes. This review summarizes current evidence for validated and emerging biomarkers in large-, medium-, small-, and variable-vessel vasculitis, as well as single-organ vasculitis. Key analytes reflect systemic inflammation, such as serum amyloid A (SAA) and interleukin-6 (IL-6), as well as endothelial activation, complement pathways, neutrophil and macrophage activation, and organ-specific damage. Promising candidates include pentraxin-3 (PTX3) and matrix metalloproteinase-9 (MMP-9) in large-vessel vasculitis; N-terminal pro-B-type natriuretic peptide (NT-proBNP) and S100 proteins in Kawasaki disease; galactose-deficient immunoglobulin A1 (Gd-IgA1) and urinary angiotensinogen (AGT) in IgA vasculitis; and tissue inhibitor of metalloproteinases-1 (TIMP-1), S100 proteins, complement C3, and PTX3 in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Although these biomarkers provide mechanistic insight, most lack disease-specificity, external validation, or standardized assays. Future progress will require multicenter studies, harmonized testing, and integrated biomarker panels combined with imaging modalities to improve diagnosis, activity assessment, and monitoring. Full article

Background/Objective: In recent years, artificial intelligence (AI) has gained increasing prominence in the fields of diagnostic decision-making in medicine. The aim of this study was to compare multidisciplinary team (MDT: rheumatology, pulmonology, thoracic radiology) decisions with single-session plans generated by ChatGPT-4o. Methods: In this cross-sectional concordance study, adults (≥18 years) with confirmed systemic autoimmune rheumatic disease (SARD) and having MDT decisions within the last 6 months were included. The study documented diagnostic, treatment, and monitoring decisions in cases of SARDs by recording answers to six essential questions: (1) What is the most likely clinical diagnosis? (2) What is the most likely radiological diagnosis? (3) Is there a need for anti-inflammatory treatment? (4) Is there a need for antifibrotic treatment? (5) Is drug-free follow-up appropriate? and (6) Are additional investigations required? Consequently, all evaluations were performed with ChatGPT-4o in a single-session format using a standardized single-prompt template, with the system blinded to MDT decisions. All data analyses in this study were conducted using the R programming language (version 4.3.2). An agreement between AI-generated and MDT decisions was assessed using Cohen’s Kappa (κ) statistic where κ (kappa) values represent the level of agreement: <0.20 = slight, 0.21–0.40 = fair, 0.41–0.60 = moderate, 0.61–0.80 = substantial, >0.80 = almost perfect agreement. These analyses were performed using the irr and psych packages in R. Statistical significance of the models was evaluated through p-values, while overall model fit was assessed using the Likelihood Ratio Test. Results: A total of 47 patients were involved in this study, with a predominance of female patients (61.70%, n = 29). The mean age was 61.74 ± 10.40 years. The most frequently observed diagnosis was rheumatoid arthritis (RA), accounting for 31.91% of cases (n = 15). This was followed by cases of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, interstitial pneumonia with autoimmune features (IPAF), and sarcoidosis. The analyses indicate a statistically significant level of agreement across all decision types. For clinical diagnosis decisions, agreement was moderate (κ = 0.52), suggesting that the AI system can reach partially consistent conclusions in diagnostic processes. The need for an immunosuppressive treatment and follow-up without medication decisions demonstrated a higher level of concordance, reaching the moderate-to-high range (κ = 0.64 and κ = 0.67, respectively). For antifibrotic treatment decisions, agreement was moderate (κ = 0.49), while radiological diagnosis decisions also fell within the moderate range (κ = 0.55). The lowest agreement—though still moderate—was observed in further investigation required decisions (κ = 0.45). Conclusions: In patients with SARDs with pulmonary involvement, particularly in complex cases, concordance was observed between MDT decisions and AI-generated recommendations regarding prioritization of clinical and radiologic diagnoses, treatment selection, suitability for drug-free follow-up, and the need for further diagnostic investigations. Full article

Background: Antineutrophil cytoplasmic antibody-associated systemic vasculitis (AAV) most often involves the kidneys, upper airways and lungs, and peripheral and central nervous systems (PNS, CNS). However, in contrast to PNS, the involvement of the CNS is rarely taken into account in the recognition and assessment of systemic vasculitis, probably because of nonspecific symptoms such as headaches and dizziness, aphasia, memory disorders, or mood changes. In addition, it is not clear whether treatment of systemic vasculitides reduces cerebral vascular alterations. In this study, we aimed to evaluate the effects of AAV treatment on vascular and vasogenic alterations in the brain in patients with acute vasculitis onset with renal involvement. Methods: Twenty-nine patients (17F, 12M, age 60.4 ± 9.8) with AAV relapse with renal involvement were included in the study. The initial baseline assessment and the second evaluation, performed 12.6 ± 2.5 months after the beginning of immunosuppressive treatment, included clinical, neurological, and renal function assessments, along with a brain MRI. Results: Compared with baseline, improvement in clinical, neurological, and renal function was observed during the second clinical evaluation. A significant reduction in the occurrence of vascular dilatation and narrowing in secondary (37.9% vs. 17.2%; p = 0.031) and tertiary (37.9% vs. 10.3%; p = 0.008) cerebral vascular branches was observed. However, the number of vasogenic cerebral white matter lesions detected on the FLAIR sequence increased significantly (36.0 vs. 48.0%; p < 0.001). Conclusions: Intensive immunosuppressive treatment of acute-onset systemic AAV with renal involvement decreases disease activity, improves kidney function, and decreases central nervous system vascular but not vasogenic alterations. Full article

Objectives: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of vasculitides sharing a common pathophysiology, which affects small and medium blood vessels. Sinonasal involvement is one of the most common manifestations of AAV. The goal of this study was to find the most suitable method to assess paranasal sinus changes in a group of patients with ANCA-associated vasculitis and renal involvement. Subjective scales like Lund–Mackay and Zinreich were compared with a three-dimensional (3D) volumetric method. Pre- and post-treatment computer tomography were compared. Methods: Computer tomography, nasal symptoms, and endoscopy of 28 patients hospitalized at the Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Medicine—National Research Institute were assessed retrospectively. Paranasal sinus tomography was performed during treatment induction and after achieving disease remission (BVAS = 0) to assess treatment effectiveness. Radiological analysis was performed with the Lund–Mackay scoring system, Zinreich scoring system, and 3D volumetric scoring system with the usage of Slicer 3D analysis. The radiologic scoring systems were compared. Results: The statistically significant differences in treatment effectiveness were observed for the Zinreich scale on both the right and left side. Similar to the 3D volumetric scoring system, the right and left maxillary sinuses demonstrated statistically significant differences. On the other hand, no statistically significant differences were found between the first and second visits for the Lund–Mackay or total Global Osteitis scores on either side. The strongest correlation was achieved between the Zinreich scoring system and 3D volumetric scale. Conclusions: The three-dimensional CT volumetric analysis demonstrated higher SRM (standardized response mean) values than the Zinreich score on both sides, but the differences were not statistically significant. The Zinreich scoring system should be used instead of the Lund–Mackay scale in everyday clinical practice. Full article

Background and Objectives: This study investigated and compared the efficacy of therapeutic plasma exchange (PEX) between antineutrophil cytoplasmic antibody (ANCA)-positive and ANCA-negative patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) presenting with diffuse alveolar haemorrhage (DAH) and rapidly progressive glomerulonephritis (RPGN). Materials and Methods: A total of 336 patients with ANCA-associated vasculitis were screened, and 34 patients with MPA/GPA receiving PEX for DAH or RPGN were included. PEX was performed a total of 5–6 times consecutively (three times a week × 2 weeks) in all 34 patients. All-cause mortality (ACM) and end-stage kidney disease (ESKD) were evaluated as poor outcomes of MPA/GPA. Clinical data and poor outcomes were compared between ANCA-positive and ANCA-negative MPA/GPA patients receiving PEX. Results: The median age of the 34 MPA/GPA patients was 67 years (15 men and 19 women), of whom two were diagnosed with ANCA-negative vasculitis. Among the 34 patients, 28 (82.4%) received PEX owing to RPGN, and 6 (17.6%) due to DAH. During follow-up, 13 patients (38.2%) died, and 15 (44.1%) progressed to ESKD. Serum protein and C-reactive protein levels at AAV diagnosis were higher in ANCA-positive MPA/GPA patients than in ANCA-negative patients, although the difference was not statistically significant. Similarly, there were no differences in ACM or ESKD between the two groups during follow-up. Survival analysis showed that ANCA-positive MPA/GPA patients did not have significantly different cumulative patient or ESKD-free survival rates compared to ANCA-negative patients. Conclusions: This pilot study is the first to demonstrate the clinical feasibility of PEX in managing severe and refractory ANCA-negative MPA and GPA. Full article

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis characterized by asthma, eosinophilia, and necrotizing inflammation of small- to medium-sized vessels. Accumulating evidence indicates that EGPA is a polygenic and heterogeneous disorder comprising distinct antineutrophil cytoplasmic antibody (ANCA)–defined endotypes with divergent genetic backgrounds, immune pathways, and clinical phenotypes. Its pathogenesis reflects the convergence of epithelial–alarmin signaling, type 2 inflammation, eosinophil effector mechanisms, and B-cell/autoantibody responses, with myeloperoxidase (MPO)-ANCA serving as a hallmark of the vasculitic subset. Recent advances in genomics, immunology, and multi-omics profiling have uncovered biomarkers and molecular circuits sustaining disease activity and guiding therapeutic stratification. The identification of the interleukin (IL)-5–eosinophil axis, epithelial-derived alarmins, and B-cell/IgG4 networks as central pathogenic nodes has enabled the development of targeted biologic therapies that are redefining treatment paradigms. Benralizumab (anti-IL-5Rα) has recently been approved for EGPA following the phase 3 head-to-head MANDARA trial, which demonstrated non-inferiority to mepolizumab in achieving remission (BVAS = 0 with ≤4 mg/day prednisone equivalent) at weeks 36 and 48. These results, together with the established efficacy of mepolizumab, inform practical selection between IL-5 and IL-5Rα blockade and support glucocorticoid-sparing approaches. A structured literature search (2015–2025) was conducted in PubMed, Scopus, and Web of Science to identify recent advances in epidemiology, genetics, biomarkers, and targeted therapies for EGPA. This updated review integrates molecular insights, clinical endotypes, and therapeutic innovations to outline current evidence and future precision-medicine strategies aimed at improving long-term patient outcomes. Full article

Background and Objectives: To investigate whether myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA) titres at diagnosis are associated with the risk of end-stage kidney disease (ESKD) progression in patients with microscopic polyangiitis (MPA) treated with rituximab. Materials and Methods: This retrospective cohort study included 34 patients with MPA who received rituximab. Clinical data, including MPO-ANCA titres at diagnosis and ESKD progression during follow-up, were assessed. Receiver operating characteristic (ROC) curve analysis was performed to assess whether MPO-ANCA titres could predict ESKD progression. The optimal cut-off value of MPO-ANCA titres was determined where the sum of sensitivity and specificity was at a maximum. Based on this cut-off value, patients were categorised into two groups, and the relative risk (RR) of ESKD progression was estimated. Results: During a median follow-up of 39.5 months, seven patients (20.6%) progressed to ESKD. ROC curve analysis showed a significant inverse association between MPO-ANCA titres and ESKD progression (AUC 0.254, 95% confidence interval [CI] 0.046, 0.462 p = 0.048). The optimal cut-off of MPO-ANCA titres was 81.0 IU/mL, which yielded a sensitivity and specificity of 70.4% and 85.7%, respectively. The RR of ESKD progression was significantly higher in those with MPO-ANCA titres ≤ 81.0 IU/mL than in those with MPO-ANCA titres > 81.0 IU/mL (42.9% vs. 5.0%, RR 14.250, 95% CI 1.469, 138.271). Conclusions: Lower MPO-ANCA titres at diagnosis may be associated with a higher risk of ESKD progression in rituximab-treated MPA patients. These findings suggest that MPO-ANCA titres may be useful in guiding therapeutic decisions for MPA. Full article

Background/Objectives: Mesalazine agents are essential drugs for treating ulcerative colitis (UC). Biomarkers that can differentiate mesalazine intolerance from exacerbated UC are needed because of the similarity of their symptoms and increasing prevalence of mesalazine intolerance. The study aim was to assess the usefulness of proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) to identify mesalazine intolerance in patients with UC. Methods: In this single-center retrospective study, patients with UC in whom serum PR3-ANCA was measured were included, and the serum levels were compared between the mesalazine-intolerant and -tolerant patient groups. The predictability of the marker to discriminate between these patients was analyzed. Results: Among 406 patients with UC with measured serum PR3-ANCA levels, 68 (17%) had mesalazine intolerance. The PR3-ANCA levels were significantly higher in the intolerance group than in the tolerance group [4.5 U/mL (0.8–26.2 U/mL) vs. 1.5 U/mL (0.0–8.5 U/mL), p = 0.001]. The area under the curve of the receiver operating characteristic curve analysis of the predictability of PR3-ANCA in differentiating mesalazine-intolerant patients from clinically active patients with UC was 0.755 (95% confidence interval: 0.634–0.876, cutoff value: 15.05 U/mL; sensitivity: 0.625, specificity: 0.813). Multivariate logistic regression analysis using various clinical factors revealed that serum PR3-ANCA > 15.0 U/mL was an independent risk factor of mesalazine intolerance (odds ratio: 8.25, 95% confidence interval: 2.52–27.02, p < 0.001). Conclusions: Serum PR3-ANCA could be a useful marker to identify mesalazine-intolerant patients with UC. Full article

Background: The complement system factors’ role in the pathogenesis of autoimmunological diseases is known, but the influence of autoantibodies against complement factors’ receptors on the course of specific glomerular diseases remains unclear. Methods: We measured the levels of anti-C3aR and anti-C5aR antibodies in patients with membranous nephropathy (n = 18), primary focal and segmental glomerulosclerosis (FSGS) (n = 25), lupus nephritis (LN) (n = 17), IgA nephropathy (n = 14), mesangial proliferative (non-IgA) glomerulonephritis (n = 6), c-ANCA (cytoplasmic anti-neutrophil cytoplasmic antibodies) vasculitis (n = 40), and p (perinuclear)-ANCA vasculitis (n = 16). These conditions were compared to a healthy control group (n = 22). Then, for up to two years, we tracked the patients’ clinical progress (in terms of creatinine, total protein, and albumin levels) and compared the outcomes with their antibody levels. Results: The lupus nephritis group had higher levels of anti-C3aR and anti-C5aR antibodies than the other groups. The lupus nephritis group’s anti-C3aR antibody level showed a negative correlation with albumin and total protein at several time points of observation. Additionally, at numerous observational points, the anti-C3aR antibody level showed a positive correlation with both the basic albumin level in the FSGS group and the total protein level. Conclusions: The anti-C3aR and anti-C5aR antibodies are higher in lupus nephritis patients compared to other glomerulonephritis patients and healthy individuals. Albumin and total protein levels appear to be correlated positively with anti-C3aR antibody levels in FSGS and negatively in lupus nephritis. Full article

Central nervous system (CNS) involvement is an extremely rare manifestation in eosinophilic granulomatosis with polyangiitis (EGPA), associated with a poor prognosis. Here we present a case of 50-year-old female patient with long-term asthma treatment who presented initially with extreme eosinophilia (56%) and severe progressive ascending paresis, similar to Guillain–Barré syndrome, leading to tetraplegia. After navigating through diagnostic mazes, the diagnosis of EGPA was established based on eosinophilia, myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) positivity, asthma, eosinophil granulomatosis in the gastrointestinal tract, and severe peripheral nervous system involvement, complicated with rare central nervous granulomas and ischemia. With combined immunosuppressive and immunomodulatory treatment including high-dose corticosteroids, rituximab and intravenous immunoglobulin along with symptomatic treatment and planned rehabilitation over 6 months, our patient recovered gradually from tetraplegia and adverse events such as severe infections and osteoporotic fractures. Now, from a 2-year perspective, we can conclude a successful treatment leading to decrease in all of her symptoms. Due to persistent eosinophilia after steroid tapering, she was switched to mepolizumab maintenance treatment and demonstrated continuous improvement of motor and sensory functions. Thanks to periodically repeated rehabilitation, she became self-sufficient and returned to her previous job. Our case highlights that EGPA patients should be treated in a center of expertise due to the rarity of the disease and complexity of diagnosis and treatment. Careful multidisciplinary cooperation, the huge effort of the patient, and a supportive environment can show a way back from immune-mediated tetraplegia. Full article

Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare systemic vasculitis with eosinophilic inflammation and variable clinical presentations. Although skin manifestations are frequent, current classification criteria do not include them, which may underestimate their diagnostic value. This prospective observational study aimed to assess systemic and skin involvement as well as eosinophilia, anti-neutrophil cytoplasmic antibody (ANCA), and Anti-nuclear antibodies (ANA) serum levels in 20 EGPA patients followed for one year at the University Hospital of Messina, Italy, before starting Mepolizumab, 300 mg. Eosinophilia, ANCA status, systemic and skin involvement were also evaluated at 6 and 12 months; a literature review on these data supplements our findings. Skin involvement was present in 55% of patients, including purpura, urticarial vasculitis, angioedema, maculopapular rash, and nodules, mostly in ANCA-negative patients, though purpura was more frequent in ANCA-positive cases but without any statistically significant correlation. ANAs were present in 50% of patients, together with ANCA in two subjects and without in eight. Mepolizumab significantly reduced eosinophil levels, BVASs, and corticosteroid dependence, with notable improvement in skin symptoms. In conclusion, skin manifestations are common in EGPA and may represent useful indicators of disease activity. Their integration with ANCA status, eosinophil counts, and positivity to other autoantibodies could enhance diagnostic and monitoring strategies identifying different clusters of EGPA patients even if the small sample size limits the generalizability of the findings. Full article

Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a heterogeneous group of small-vessel vasculitides, characterized by the presence of antibodies binding to myeloperoxidase (MPO) and proteinase-3 (PR3) found in neutrophil granules. Apart from being the target of ANCA, neutrophils actively contribute to the vicious cycle of inflammation and vascular damage in AAV. On the other hand, platelets have recently been recognized as essential for thrombosis and as inflammatory effectors that collaborate with neutrophils, reinforcing the generation of reactive oxygen species (ROS) and the formation of neutrophil extracellular traps (NETs) in those diseases. Neutrophils exhibit morphological and functional heterogeneity in AAV, reflecting the complexity of their contribution to disease pathogenesis. Since long-term immunosuppression may be related to serious infections and malignancies, there is an urgent need for reliable biomarkers of disease activity to optimize the management of AAV. This review summarizes the current understanding of the role of neutrophils and platelets in the pathogenesis of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), focusing on their crosstalk, and highlights the potential for identifying novel biomarkers relevant for predicting the disease course and its relapses. Full article

Background and objective. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) affects small- to medium-sized vessels and is characterized by the production of ANCAs. The ANCA-negative term is used if the patient otherwise fulfills the definition for AAV but has negative results on serologic testing for ANCAs. The objective of this study was to compare ANCA-positive and -negative vasculitis patients and to evaluate the main differences possibly related to the presence of ANCAs. Material and methods. A cross-sectional study of 73 patients treated at the tertiary Rheumatology Centre of University Hospital from the 1 January, 2001, to the 31August, 2023, with diagnoses of AAV was carried out. Clinical characteristics and laboratory data were collected at the onset or at the first year of the disease. Results. Forty-eight (65.8%) patients were ANCA-positive, while twenty-five (34.3%) were ANCA-negative. Distribution by gender was similar in both groups, with a female–male ratio of 2:1. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were elevated for all AAV patients, but values were higher in the ANCA-positive patients’ group. The median hemoglobin was 106 g/L in the seropositive group and 127 g/L in the seronegative group. A higher prevalence of kidney involvement (60.4%) with elevated serum creatinine level (93.5 µmol/L) was observed in the ANCA-positive group compared with 24% and 70 µmol/l in the ANCA-negative group (p < 0.05). Neurological involvement was more frequently found in the ANCA-positive patient group, too: 29.2% compared to 20%. Among patients with ANCA-negative vasculitis, 88% had pulmonary; 92% ear, nose, throat (ENT); 48% joint; and 28% skin presentation. In comparison, involvement of these organs was less common in the ANCA-positive patients’ group, at 79.2%, 60.4%, 31.3%, and 25 %, respectively. Conclusions. ANCA-positive patients appear to be in a more difficult clinical situation in terms of organ involvement and laboratory changes. Full article

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA), represent a spectrum of systemic disorders characterized by necrotizing inflammation of small- to medium-sized vessels. Nailfold videocapillaroscopy (NVC) is a validated, non-invasive technique routinely employed in the assessment of microvascular involvement in systemic sclerosis and in the differential diagnosis of Raynaud’s phenomenon; its application in the context of AAV, particularly EGPA, has not been investigated yet. The present study aims to assess the presence and the possible pattern of microcirculatory abnormalities detected by NVC in EGPA patients, and to explore potential correlations between capillaroscopic findings and disease activity status. Methods: A total of 29 patients with EGPA (19 women and 10 men), aged between 51 and 73 years, and 29 age- and sex-matched healthy controls were retrospectively enrolled between October 2023 and April 2025, after providing informed consent and meeting the inclusion and exclusion criteria. NVC was conducted in both groups to assess various morphological parameters, and mean capillary density was also calculated. Results: This study observed the presence of capillaroscopic alterations in the EGPA group, including decreased capillary density (38%), neoangiogenesis (72%), rolling (100%), pericapillary stippling (66%), and inverted capillary apex (52%). Overall, when comparing healthy controls with EGPA patients, microcirculatory abnormalities were significantly more prevalent in the latter. Specifically, scores for neoangiogenesis, capillary rolling, pericapillary stippling, and inverted capillary apex showed p-values < 0.001. Conclusions: Our study demonstrates a higher prevalence of four nailfold videocapillaroscopic abnormalities in patients with EGPA compared to healthy controls. However, the identification of these capillaroscopic alterations as specific to EGPA requires further confirmation. Ongoing studies aim to explore the potential role of NVC as a diagnostic marker and to investigate its correlation with the clinical manifestations of EGPA. Full article

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and interstitial lung disease (ILD) represent a complex interplay between autoimmune and fibrotic processes that poses significant diagnostic and therapeutic challenges. The distinction between isolated ANCA-ILD and AAV-ILD remains a subject of ongoing debate, with some researchers proposing that ANCA-ILD may be an early or restricted form of systemic vasculitis. Immunosuppressive therapy is the cornerstone of treatment for both diseases. However, there is increasing evidence that supports the potential role of antifibrotic agents in the management of progressive fibrosis. Management of these diseases requires a personalized approach that incorporates evaluation of biomarkers, imaging findings, and clinical risk factors to guide treatment decisions. Although current therapeutic strategies primarily target systemic inflammation, addressing the fibrotic components of these diseases is crucial for improving outcomes. Furthermore, emerging therapeutic options, such as B-cell depletion and antifibrotic therapies, offer promising outcomes. However, their roles in the treatment of AAV-ILD require further exploration. In this review, we discuss clinical insights and evolving therapeutic strategies for managing AAV and ANCA-positive ILD. In addition, we highlight the importance of early diagnosis and individualized treatment plans in improving the prognosis and quality of life of affected patients. Full article