Search Results (3,232)

Breast cancer (BC) remains one of the most prevalent malignancies worldwide, and genetic factors may influence its development. Approximately 10–15% of all BCs are hereditary and known as Hereditary Breast Cancer (HBC). A remarkable family history and young onset are the strongest risk factors of HBC. The rapid development of genetic testing techniques has increased the detection rate of pathogenic and likely pathogenic variants in several genes associated with high, moderate, or low risk of HBC. This allowed us to identify the whole family at risk of HBC. Among hereditary cases, pathogenic variants (PVs) in the BRCA1 and BRCA2 genes are particularly notable, especially in certain populations where founder mutations (specific genetic variants originating from a common ancestor) are more prevalent. In this article, an overview of the current state of knowledge on HBC is provided, focusing on the frequency of founder mutations in the BRCA1 and BRCA2 genes in HBC in Poland compared to other countries. We will also highlight the role of genetic counseling in the diagnosis and treatment of BC, emphasizing its crucial importance in identifying genetic predispositions, selecting appropriate therapeutic strategies, and supporting patients and their families in making informed medical decisions. Full article

Background/Objectives: The distribution of body mass index (BMI) categories at celiac disease (CD) diagnosis in children is changing, and the impact of a gluten-free diet (GFD) on BMI status remains incompletely understood. We aimed to evaluate the distribution of BMI categories at CD diagnosis and their changes after 12–18 months on a GFD in Italian children. Methods: Children and adolescents aged 0–18 years who received a new diagnosis of CD at 23 Pediatric Gastroenterology referral centers in Italy were retrospectively enrolled. We analyzed their BMI status at diagnosis, classifying them as underweight, normal weight, overweight, or obese. BMI changes were assessed after 12–18 months on a GFD. Results: Among the 4967 children (mean age 7.1 ± 4.1 years, M:F = 1827:3140), 4.4% were underweight, 77.5% normal weight, 12.7% overweight, and 5.4% obese at diagnosis. Overweight/obese children were more likely to have a family history of CD, associated conditions, and an asymptomatic presentation. After 12–18 months of GFD, 55.7% of underweight children achieved normal weight, and 23% of overweight/obese reverted to normal weight. Conversely, 10.9% of normal-weight children and 3.2% of underweight children became overweight/obese. Conclusions: At diagnosis, most children were normal weight, but 18.1% presented with overweight/obesity. After 12–18 months on a GFD, BMI normalized in over half of underweight but in fewer than one-quarter of overweight/obese subjects. Full article

Optic neuritis (ON) has been recognized since antiquity, but its modern clinical identity emerged only in the late 19th century and was definitively shaped by the Optic Neuritis Treatment Trial (ONTT). The ONTT established the natural history, visual prognosis, association with multiple sclerosis (MS), and therapeutic response to corticosteroids, building the foundation for contemporary ON management. Subsequent discoveries—most notably aquaporin-4 IgG-associated ON (AQP4-ON), myelin oligodendrocyte glycoprotein antibody-associated ON (MOG-ON), and double-negative ON—have fundamentally transformed this paradigm, shifting ON from a seemingly uniform demyelinating syndrome to a group of biologically distinct disorders. These subtypes differ in immunopathology, clinical course, MRI features, retinal injury patterns, CSF profiles, and long-term outcomes, making early and accurate differentiation essential. MRI provides key distinctions in lesion length, orbital tissue inflammation, bilateral involvement, and chiasmal or optic tract extension. Optical coherence tomography (OCT) offers complementary structural biomarkers, including severe early ganglion cell loss in AQP4-ON, relative preservation in MOG-ON, and variable patterns in double-negative ON. CSF analysis further refines diagnosis, with oligoclonal bands strongly supporting MS-ON. Together, these modalities enable precise early stratification and timely initiation of targeted immunotherapy, which is critical for preventing irreversible visual disability. Despite major advances, significant unmet needs persist. Access to high-resolution MRI, OCT, cell-based antibody assays, and evidence-based treatments remains limited in many regions, contributing to global disparities in outcomes. The understanding of the pathogenesis of double-negative optic neuritis, the identification of reliable biomarkers of relapse and visual recovery, and the determination of standardized cut-off values for multimodal diagnostic tools—including MRI, OCT, CSF analysis, and serological assays—remain unresolved challenges. Future research must expand biomarker discovery, refine imaging criteria, and ensure equitable global access to cutting-edge diagnostic platforms and therapeutic innovations. Four decades after the ONTT, ON remains a dynamic field of investigation, with ongoing advances holding the potential to transform care for patients worldwide. Together, these advances expose a fundamental tension between historically MS-centered diagnostic frameworks and the emerging biological heterogeneity of ON, a tension that underpins the structure and critical perspective of the present review. Full article

Purpose: Pineal region tumors are rare tumors in the pediatric population, typically managed with surgical resection or biopsy, and often with radiation therapy and chemotherapy. This study aims to examine the clinical and neurocognitive outcomes of pediatric patients with pineal tumors. Methods: A retrospective analysis was conducted on pediatric patients with pineal region tumors treated at Istituto Giannina Gaslini, Genoa, from January 1998 to July 2023. Data on medical history, surgical approaches, histological findings, administered therapies, long-term outcomes using the Glasgow Outcome Scale (GOS), education level, and employment status were collected. Statistical analysis was performed using SPSS software. Results: We identified 38 patients, with germinoma being the most prevalent tumor (47.4%). Surgical interventions included endoscopic biopsy (20 patients), stereotactic biopsy (5 patients), and excisional surgery (5 patients). Thirty-three patients received chemotherapy, and 35 underwent adjuvant radiotherapy. The mean follow-up duration was 8.79 ± 5.71 years. Significant correlations were found between tumor dissemination at diagnosis and patient outcomes (p-value = 0.03). Notably, patients in GOS classes 5–6 did not significantly differ from those in classes 7–8 regarding the frequency of intervention. School dropout rates significantly differed between GOS classes 5–6 and 7–8. Conclusions: This study highlights that prognosis is strongly associated with tumor aggressiveness, and particularly dissemination at diagnosis. The findings also suggest potential cognitive impairments, possibly linked to melatonin dysfunction induced by tumor-related treatments, as indicated by school dropout and employment data. Implications for Cancer Survivors: Our results underscore the need for further investigation into the impact of pineal involvement and potential therapeutic strategies. Full article

Background and Objectives: Interstitial lung diseases (ILDs) have been increasingly linked to neurological manifestations, including cognitive dysfunction and motor impairments, yet the prevalence and severity of these associations remain underexplored. We aimed to (1) compare the frequency of neurological symptoms between patients with and without ILD; (2) evaluate differences in cognitive and motor function scores; (3) perform subgroup analyses based on MoCA (Montreal Cognitive Assessment) scores; and (4) identify potential risk factors for neurological involvement. Methods: In this cross-sectional study, we enrolled 77 patients (40 with ILD and 37 without ILD). We recorded demographic data, smoking status, and body mass index (BMI). Neurological symptoms (tremor, diminished reflexes, paresthesia, etc.) were documented. Cognitive assessments included the MoCA and Symbol Digit Modalities Test (SDMT). Motor function was evaluated via the Berg Balance Scale (BBS), Timed Up and Go (TUG), Single-Leg Stance (SLS), and Grooved Pegboard Test (GPT). Results: Neurological symptoms were more prevalent in ILD (42.5%) than in non-ILD patients (16.2%; p = 0.003). Tremor appeared in 35% of ILD vs. 11% of non-ILD (p = 0.007). ILD patients showed lower mean SLS scores (7.2 ± 3.1 vs. 9.1 ± 3.8 s, p = 0.03) but similar TUG times (10.3 ± 2.1 vs. 9.6 ± 2.3 s, p = 0.20). MoCA scores < 26 were more common in those with ILDs (45% vs. 19%; p = 0.01). Among ILD participants, those with MoCA < 26 had significantly higher rates of tremor (51% vs. 24%, p = 0.04). Logistic regression revealed ILD diagnosis (OR = 3.12, 95% CI: 1.27–7.65, p = 0.013), older age (OR = 1.09 per year, p = 0.02), and smoking history (OR = 2.01, p = 0.05) as independent risk factors for neurological involvement. Conclusions: Our findings suggest that ILD is associated with a higher burden of neurological symptoms and subtle impairments in cognition and motor performance. Recognizing and addressing these manifestations may improve patient management, underscoring the importance of an integrative, multidisciplinary approach. Full article

Background/Objectives: Autoimmune Polyendocrinopathy with Candidiasis and Ectodermal Dystrophy is an extremely rare autosomal recessive disorder caused by inborn errors of immunity. It is due to a loss-of-function mutation in the AIRE autoimmune regulator gene. Its manifestations include autoimmunity affecting endocrine glands, in addition to non-endocrine manifestations including dental enamel hypoplasia, alopecia areata, hepatitis, and chronic mucocutaneous candidiasis. Globally, 10 cases per million are affected by this condition, with higher incidence in highly consanguineous populations. Here, we describe a novel AIRE gene mutation in a pediatric patient from Lebanon, along with the observed phenotype. Method: A nine-year-old boy with history of craniosynostosis presented with jaundice. His past medical history was significant for recurrent oral thrush, keratoconjunctivitis, nail dystrophy, and alopecia. Upon presentation, he had jaundice, isolated splenomegaly, and severe failure to thrive. Laboratory tests showed transaminitis, cholestasis, and hypergammaglobulinemia. Abdominal ultrasound findings were suggestive of cirrhosis with compensated portal hypertension. The differential diagnosis included viral infection, inborn errors of metabolism, and autoimmune hepatitis. Results: Exome sequencing identified a novel homozygous pathogenic variant in the AIRE gene, NM_000383.4: c.1066dup p.(Arg356Profs*16), confirming the diagnosis. Conclusions: This study expands the genotypic and phenotypic spectrum of a rare inborn error of immunity in a child with chronic mucocutaneous candidiasis, enamel hypoplasia, and hepatitis. Full article

Background and Clinical Significance: Metastatic carcinoma of the lacrimal sac originating from primary nasopharyngeal carcinoma (NPC) is a rare entity, usually presenting with chronic, unilateral epiphora. Case Presentation: A 55-year-old male patient presented with symptoms of chronic persistent dacryocystitis of the left eye for a year. His history revealed a non-keratinizing NPC diagnosed 5 years earlier, which was treated with combined radiotherapy (RT) and chemotherapy (CMT). Following CT and MRI scans, a mass was identified at the left lacrimal sac suggestive of a neoplasm in that region. The patient underwent endoscopic dacryocystorhinostomy (DCR), with tissue samples taken for biopsy. The histopathological diagnosis revealed a metastatic carcinoma of the lacrimal sac originating from the nasopharynx. The postoperative course was uneventful. However, a follow-up positron emission tomography-computed tomography (PET-CT) scan showed a hypermetabolic lesion in the left orbital cavity, infiltration of the lacrimal sac, hypermetabolic lateral cervical lymph nodes (IIA-IIB), and a hypermetabolic parotid lymph node. The patient is currently receiving combined CMT and immunotherapy (IMT) and is scheduled to receive RT thereafter. Conclusions: The non-specific symptomatology of the disease might be a reason for delayed diagnosis. Early recognition requires a high index of suspicion, while therapy mainly focuses on RT, CMT, IMT, and rarely on surgical approaches. A multidisciplinary approach and coordination are indispensable for the best possible treatment outcome. Full article

Endometrial cancer is the most common gynaecologic malignancy in high-income countries, with a rising incidence largely driven by reproductive factors, obesity, and prolonged exposure to unopposed oestrogens. Although most cases are sporadic, approximately 2–5% are associated with hereditary cancer syndromes, of which Lynch syndrome represents the most important contributor. Lynch syndrome results from germline mutations in DNA mismatch repair (MMR) genes and is associated with a substantially increased lifetime risk of endometrial cancer, reaching up to 71% in carriers of MutS homologue 6 (MSH6) mutations. Hereditary cancer predisposition typically follows an autosomal dominant inheritance pattern and may be suspected based on clinical warning signs such as early disease onset, multiple primary malignancies, a strong family history, or the presence of microsatellite instability in tumour tissue. In addition to Lynch syndrome, rarer genetic conditions—including Cowden syndrome (PTEN), Li–Fraumeni syndrome (TP53), polymerase proofreading–associated polyposis (POLE/POLD1), and hereditary breast and ovarian cancer syndromes (BRCA1/2)—also contribute to hereditary endometrial cancer risk. Recognition of these genetic backgrounds is essential for accurate diagnosis, personalised surveillance, and the implementation of targeted preventive and therapeutic strategies. Despite major advances in molecular diagnostics, hereditary endometrial cancer remains frequently underdiagnosed, leading to missed opportunities for cancer prevention among affected individuals and their families. This comprehensive review summarises current evidence on hereditary predispositions to endometrial cancer, with a particular emphasis on Lynch syndrome, and discusses underlying genetic mechanisms, inheritance patterns, diagnostic strategies, and clinical implications for screening, genetic counselling, and treatment optimisation. Full article

Background: Spondyloarthritis (SpA) typically develops before 40 years of age, but increasing life expectancy has led to a growing number of cases in older adults. It is well known that age at onset may influence disease presentation, comorbidities, and patient outcomes. Objectives: To assess whether age at onset influences SpA clinical presentation. Methods: We analyzed clinical, demographic, clinimetric, and imaging data in 272 SpA patients, grouped by onset age: early (≤40, n = 119), intermediate (41–59, n = 127), and late (≥60, n = 26). All patients had a minimum follow-up duration of 12 months. Their epidemiologic, clinic, and clinimetric data were collected, as well as patient-reported outcome measures (PROs) [Patient Global Assessment (PGA), Health Assessment Questionnaire (HAQ), FACIT-Fatigue (FACIT-F), SHORT-FORM 36 (SF-36), Hospital Anxiety and Depression Scale (HADS), Work Productivity and Activity Impairment Questionnaire (WPAI), CSI (Central Sensitization Inventory), and Psoriatic Arthritis Impact of Disease (PsAID) questionnaire]. In univariate analyses, differences in categorical variables across onset groups were assessed using Fisher’s exact test; for continuous variables, between-group comparisons were performed using the Mann–Whitney U test (two-tailed) or the Kruskal–Wallis test, as appropriate, with Bonferroni correction for post hoc analyses. Multivariable regression models were subsequently fitted, adjusting for sex, diagnosis, and disease duration. For binary outcomes, multivariable logistic regression models were used, while multivariable linear regression models (ANCOVA) were applied for continuous outcomes. The overall association between onset group and each outcome was formally tested using likelihood ratio tests, comparing models including the onset variable with nested models excluding it. A p-value < 0.05 was considered statistically significant. Results: Patients’ mean age was 60.0 ± 13.7 years; 55.9% of them were males; and there were 188 cases (69.1%) of psoriatic arthritis (PsA) and 84 cases (30.9%) of ankylosing spondylitis (AS). In early-onset patients, inflammatory back pain (IBP) was more frequent, whereas late-onset patients more often presented with joint swelling. A family history of SpA and psoriasis was less common in late-onset forms. Comorbidities, including osteoporosis, osteoarthritis, hypertension, hyperuricemia, and diabetes, were more prevalent in older-onset patients, resulting in a higher overall comorbidity burden in Groups 2 and 3. Patient-reported outcomes were largely similar across age groups, although work activity limitation was more pronounced in younger patients. Conclusions: Age at onset seems to influence SpA phenotypes: early-onset could favor axial involvement, while late-onset may associate with peripheral arthritis. Late-onset forms are associated with a more severe comorbidity burden, in particular for cardiovascular risk factors. Lung involvement proved to be more prevalent with respect to the general population, so it should be checked in the routinary assessment of SpA patients. These findings suggest that rheumatologists could tailor their routine assessments based on patients’ age at disease onset. Interestingly, work productivity seems more impacted in early-onset patients. All these points highlight the importance of age at disease onset in SpA, guiding toward personalized medicine in terms of follow-up, therapy, and more holistic patient management. Full article

Conservative management of rotator cuff disorders remains challenging, with no comprehensive, evidence-based framework integrating diagnosis, prognosis, rehabilitation, and biological therapies. Existing recommendations usually address isolated components of care, leading to inconsistent treatment strategies. This article proposes a global, pragmatic protocol for the non-surgical management of rotator cuff lesions, from initial assessment to long-term follow-up. Drawing on clinical expertise supported by recent literature, we outline a stepwise approach that begins with a comprehensive diagnostic process that combines history, clinical examination, and targeted imaging. Based on lesion type, associated shoulder or neurogenic conditions, and patient profile, rotator cuff disorders are stratified into three prognostic categories under conservative care: good, borderline, and poor prognosis, highlighting factors that require treatment adaptation or early surgical consideration. Rehabilitation objectives are structured around four domains: (1) inflammation and pain control, (2) mobility and scapular kinematics, (3) strengthening and motor control with tendon-sparing strategies, and (4) preservation or restoration of anatomy. For each prognostic category, we define a monitoring plan integrating clinical reassessment, ultrasound follow-up, and functional milestones, including return-to-play criteria for athletes. This comprehensive narrative review demonstrates that precise diagnosis and individualized rehabilitation can optimize medical follow-up, active strengthening, and complementary or regenerative therapies. Aligning therapeutic decisions with prognostic and functional goals allows clinicians to optimize patient satisfaction and recovery, providing a clear, evidence-informed roadmap for conservative management of rotator cuff disorders. Full article

Background: Follicular lymphoma (FL) is the second most common B-cell lymphoma in Western countries, typically presenting as an indolent disease with prolonged overall survival. Despite favorable initial responses to therapy, most patients experience relapse, and early progression is associated with poor outcomes. Methods: This guideline provides evidence-based recommendations from the Spanish GELTAMO group on the diagnosis, staging, treatment, and follow-up of FL. A systematic literature review was conducted, and recommendations were graded according to the GRADE system. Results: Histopathological diagnosis should be based on excisional biopsy. PET-CT is recommended for staging and response evaluation. For localized disease, involved-site radiotherapy (ISRT) remains the treatment of choice. In asymptomatic patients with advanced-stage disease and low tumor burden, a watch-and-wait approach is appropriate, although rituximab monotherapy is also acceptable. For advanced-stage disease with high tumor burden, immunochemotherapy with anti-CD20 antibodies (rituximab or obinutuzumab) combined with CHOP, CVP, or bendamustine is recommended, followed by maintenance therapy. Management of relapsed disease is tailored based on tumor burden, treatment history, and timing of relapse. Although novel immunotherapies (CAR-T therapy and bispecific antibodies) are emerging as promising options, autologous stem cell therapies may still be a valid option in young patients with early relapse who are sensitive to immunochemotherapy. Conclusions: FL is a heterogeneous disease requiring individualized management strategies. Recent advances in immunotherapy and molecular diagnostics are reshaping the therapeutic landscape. These updated GELTAMO recommendations aim to provide practical guidance for optimal FL management in clinical practice. Full article

Background and Clinical Significance: Radiation-induced lumbosacral plexopathy (RILP) is a rare but potentially debilitating complication of radiotherapy, typically affecting patients treated for pelvic malignancies. We report the first documented case of asymmetric RILP following radiotherapy for breast cancer. Case Presentation: A 64-year-old woman developed progressive left lower limb weakness, foot drop, and sensory disturbances four years after receiving locoregional radiotherapy extending to the left thoracoabdominal and lumbar areas. Electrophysiological studies revealed an asymmetric sensorimotor axonal neuropathy predominantly involving the left lower limb, without conduction block and sparing the upper limbs, whereas needle electromyography of the lower limbs showed fibrillation potentials, positive sharp waves, and fasciculations in the vastus lateralis, tibialis anterior, and medial gastrocnemius muscles on the left. Magnetic resonance imaging demonstrated edema and contrast enhancement of bilateral L2–L4 nerve roots with paraspinal muscle atrophy. Cerebrospinal fluid analysis showed albuminocytologic dissociation and elevated neurofilament levels. After exclusion of alternative diagnoses, including amyotrophic lateral sclerosis and inflammatory neuropathies, a diagnosis of radiation-induced peripheral neuropathy and RILP was made. The patient’s condition stabilized with physiotherapy and symptomatic treatment. Conclusions: This case highlights the need for heightened awareness of RILP as a late complication of breast cancer radiotherapy, underscoring the importance of accurate diagnosis to avoid misclassification and unnecessary treatments. Clinicians should carefully integrate all clinical elements—including a thorough remote medical history—since radiation-related neurological damage may manifest many years after the initial insult. Full article

Background: Dermatitis affecting the earlobe is a highly frequent clinical presentation, predominantly attributed to Allergic Contact Dermatitis (ACD) caused by metallic ions like nickel from earrings. However, a significant subset of patients presents with recurrent eczematous lesions highly suggestive of ACD but with inconclusive or negative patch test results, posing a profound diagnostic and therapeutic dilemma. Objective: This comprehensive review critically evaluates the differential diagnosis of earlobe eczema in the context of negative patch tests. Drawing from a representative case of a 30-year-old female with recurrent earlobe eczema and a strong family history of psoriasis, we explore alternative non-immunological and endogenous mechanisms, specifically Irritant Contact Dermatitis (ICD) and the Koebner Phenomenon on a background of Psoriatic Diathesis. Methods: We performed an extensive review of the current literature focusing on the epidemiology and pathogenesis of metal ACD, non-allergic mechanisms of jewelry-induced dermatitis (ICD), the molecular basis of the Koebner phenomenon, and the clinical overlap between eczema and psoriasis (Eczematous Psoriasis). Results: The localized nature of the inflammation, coupled with the absence of generalized nickel sensitivity, strongly suggests that the mechanical and occlusive trauma from earrings can induce a purely irritant reaction. Crucially, the presence of a familial psoriatic diathesis supports the hypothesis that this local irritation acts as a Koebner phenomenon trigger, leading to an eczematous manifestation of an underlying psoriatic tendency. Conclusions: Not all recurrent eczematous lesions at common contact sites are caused by ACD. Clinicians must adopt an integrated diagnostic approach, factoring in personal and family history alongside patch test results, to differentiate true allergy from ICD and the Koebner phenomenon. This nuanced perspective is vital for providing appropriate counseling (strict jewelry avoidance) and targeted, often steroid-sparing, management (e.g., topical calcineurin inhibitors) for a durable therapeutic outcome. Full article

The significance of gut epithelial cell autoantibodies (GECAs), human leukocyte antigen (HLA) alleles, and other scientifically relevant factors has been largely overlooked, despite their potential importance in the medical management of HIV-infected individuals, in understanding the pathogenesis of AIDS, and in improving epidemiological and diagnostic approaches. This review may be considered as a hypothesis-driven narrative paper mostly considering GECAs and some easily detectable genetic markers. Thus, the aim is to highlight these neglected medical and scientific issues. Addressing them may contribute to a deeper understanding of HIV pathology at both the individual and population levels. Autoantibodies against enterocytes (GECAs) are present in the majority of HIV-positive patients. These intestinal epithelial cells are crucial for nutrient absorption and because of their role as antigen-presenting cells (APCs) within the immune system. Furthermore, the number of CD4-positive lymphocytes depends largely on daily antigenic stimulation rather than on thymic function, which becomes residual or inactive after puberty. The fall of CD4+ lymphocyte counts observed in HIV-infected patients may therefore be exacerbated by enterocyte dysfunction/damage, as indicated by the presence of GECAs. These autoantibodies either cause or reflect damage to these important antigen-presenting cells, which may impair intestinal antigen presentation by their surface HLA proteins to the clonotypic T-cell receptor of lymphocytes. Additionally, the association between specific HLA alleles and a CCR5 variant affects HIV disease progression or transmission and should be considered in both adults and mother–infant pairs. In particular, HLA-B35 and HLA-B57 allelic groups have been implicated in influencing both the transmission and progression of HIV infection. Moreover, several aspects of the natural history of HIV infection remain unresolved and controversial, and these issues warrant urgent clarification. For instance, diagnostic tests are not yet standardised globally, and viral abundance in HIV-infected individuals or AIDS patients’ cells may be relatively low. In summary, the neglected facets of HIV infection demand renewed investigation, particularly now that an HIV diagnosis is no longer the devastating prognosis it once was. The objective of this work is to emphasise additional factors that may influence the course of AIDS, such as enterocyte injury reflected by presence of GECAs. Ultimately, we propose that GECAs may impair enterocytes’ HLA (MHC II)-mediated antigen presentation by enterocytes to CD4+ T lymphocytes (through T-cell receptors), thereby diminishing T-cell proliferation, reducing CD4+ cell numbers, and impairing immune function. Full article

Food allergy diagnosis remains challenging due to the difficulty of distinguishing true clinical allergy from asymptomatic sensitization. Inaccurate diagnosis may result in unnecessary dietary restrictions, reduced quality of life, or, conversely, failure to identify individuals at risk of severe allergic reactions. This review critically analyzes the efficacy, limitations, and clinical utility of currently available diagnostic tests for food allergy, with particular emphasis on their ability to predict true clinical reactivity. A comprehensive literature review was conducted to evaluate the sensitivity, specificity, and predictive values of both traditional and emerging diagnostic modalities. English-language guidelines, systematic reviews, and key clinical studies published primarily within the past 15 years (up to 2025) were identified through PubMed and Google Scholar. Classic diagnostic tools, including skin prick testing (SPT) and serum-specific IgE (sIgE), were assessed alongside novel approaches such as component-resolved diagnostics (CRD), basophil activation test (BAT), mast cell activation test (MAT), atopy patch testing (APT), cytokine profiling, and omics-based diagnostics. Particular attention was given to how these tests compare with the oral food challenge (OFC), which remains the diagnostic gold standard. The findings demonstrate that while conventional tests offer high sensitivity and are valuable for initial risk assessment, their limited specificity often leads to overdiagnosis. Emerging molecular and cellular assays show improved specificity and functional relevance, especially in complex cases involving polysensitization or unclear clinical histories and may reduce reliance on OFCs in the future. However, accessibility, cost, and lack of standardization currently limit their widespread clinical application. Advances in artificial intelligence and data integration hold promise for improving diagnostic accuracy through enhanced interpretation of complex immunological data. Based on the synthesized evidence, this review proposes an evidence-based, stepwise, and individualized diagnostic algorithm for food allergy. Integrating clinical history, targeted testing, and selective use of OFCs can improve diagnostic certainty, enhance food safety, minimize unnecessary dietary avoidance, and optimize patient outcomes. The review underscores the need for continued research, standardization, and validation of novel diagnostic tools to support personalized and precise food allergy management. Full article