This review characterizes VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) as a prototype of adult-onset autoinflammation that challenges traditional autoimmune paradigms. Driven by constitutive activation of innate myeloid cells via Ubiquitin-Like Modifier Activating Enzyme 1 (UBA1) mutations, VEXAS affects the nervous system in approximately 6-10% of cases. We identify the peripheral nervous system as the primary target (70%), typically manifesting as refractory axonal polyneuropathy, while central involvement may present as neutrophilic meningoencephalitis. Crucially, we highlight the "hematologic paradox"-hyperinflammation co-occurring with macrocytic anemia rather than thrombocytosis-as the key biomarker distinguishing VEXAS from vasculitic mimics, necessitating early genetic sequencing for targeted clone suppression.

Background/Objectives: VEXAS (Vacuoles, E1-Enzyme, X-linked, Autoinflammatory, and Somatic) syndrome is a recently described adult-onset autoinflammatory disorder. It is characterized by somatic mutations in the UBA1 gene, systemic inflammation, macrocytic anemia, cytopenias, and bone marrow vacuolization and frequently overlaps with Sweet's syndrome, relapsing polychondritis, and myelodysplastic syndrome (MDS). Because treatment options are evolving, we reviewed the current and latest evidence of clinical features and therapeutic methods. Methods: A comprehensive literature review was conducted using PubMed and MEDLINE for studies published between 1 January 2020 and 1 July 2025. Search terms included "VEXAS" and "treatment." Eligible publications comprised clinical trials, multicenter and observational studies, and case reports containing therapeutic data. Findings were analyzed narratively with emphasis on treatment response, steroid-sparing effects, survival outcomes, and molecular responses. Results: Glucocorticoids remain the first-line therapy for acute management; however, this comes with near-universal steroid dependence. DMARDs and TNF-α inhibitors showed limited benefits. IL-6 inhibitors and JAK inhibitors showed improvement in overall response, with JAK inhibitors demonstrating a superior effect. Ruxolitinib showed a higher complete response rate and transfusion independence compared to other JAK inhibitors. Hypomethylating agents, particularly azacitidine, improved hematologic responses in patients with co-existing MDS and reduced UBA1 variant allele burden. Allogeneic hematopoietic stem cell transplantation may be the only current curative method, though with notable transplant-related mortality. Conclusions: JAK inhibitors and hypomethylating agents offer promising disease-modifying potential, while transplant may provide curative intent in selected patients. Ongoing clinical trials are taking place to dictate the treatment direction of VEXAS syndrome.

This study aimed to assess the prevalence and characteristics of previously undiagnosed anemia among children in Taif. The objective was to estimate the prevalence of undiagnosed anemia in a broader pediatric population (aged 2-12 years) across 3 hospitals, and to evaluate severity and morphological patterns. A cross-sectional study was conducted across Taif region's main hospitals serving children; including Taif Children's Hospital, King Faisal Hospital, and Taif Armed Forces Hospitals. A total of 264 children aged 2 to 12 years, presenting to outpatient clinics or emergency departments for acute, non-hematological conditions, were included. Children with previously diagnosed anemia or chronic diseases were excluded. Blood samples were collected to measure hemoglobin (Hb) levels, and anemia was diagnosed based on age-specific Hb thresholds. Descriptive statistics, chi-square tests, and independent t tests were used for data analysis. Out of 264 children, 28 (10.6%) were found to have undiagnosed anemia. The majority (75%) were aged 2 to 5 years, and a higher prevalence was noted among males (67.9%) compared to females (32.1%), though the gender difference was not statistically significant. There was a significant association between younger age and anemia (P < .001). Mean Hb levels were significantly lower in anemic children (10.13 ± 0.90 g/dL) than in non-anemic children (13.11 ± 0.93 g/dL; P < .001). Most cases were mild (71.4%), followed by moderate anemia (28.6%). Normocytic normochromic anemia was the most common type (53.6%), followed by microcytic hypochromic (39.3%) and macrocytic anemia (7.1%). This study highlights a notable prevalence of undiagnosed anemia among children in Taif, particularly in the preschool age group. The findings underscore the need for routine screening in pediatric outpatient and emergency settings, even in the absence of overt symptoms. Early detection and intervention are essential to prevent long-term developmental complications. Public health efforts should focus on nutritional education, iron supplementation, and comprehensive diagnostic evaluations to address this hidden burden.

We describe major changes in the nitrous oxide market fueling recreational use with a focus on prevalence, desired effects, adverse events, treatments, and public health interventions. Nitrous oxide is currently sold with easy and discreet access for children and young adults in formulations that attract them. Over 13 million people in the United States have ever used nitrous oxide recreationally and inhalants are mostly used by pre-teen to early 20-year-olds. Poison control center calls have increased 1,300% from 2003 to 2024 and deaths have risen 6-fold from 2010 to 2023. There are many acute adverse events ranging from frostbite to asphyxia. Adverse effects from chronic use are related to cobalt oxidation which impairs vitamin B12 functioning. The resulting dysfunction of methionine synthase induces methionine deficiency frequently causing paresthesia, ataxia, unsteady gait, and cognitive issues. Less commonly, paralysis, bladder and erectile dysfunction, macrocytic anemia and thromboembolism can occur. The European Federation of Clinical Chemistry and Laboratory Medicine guidance specifies diagnostic parameters, supportive care, and replenishment of vitamin B12 levels with intramuscular cyanocobalamin.

Vitamin B12 deficiency can manifest with hematological and neurological abnormalities, though intracranial involvement is less common than spinal cord or peripheral nerve manifestations. We report the case of a man in his 70s who developed acute cognitive decline over 4 days, accompanied with left lower limb weakness and visual disturbances. Neurological examination revealed reduced verbal output, dysarthria, significant cognitive impairment (Mini-Mental State Examination score, 7/30), and left lower limb weakness (Medical Research Council grade, 4/5). Laboratory tests showed pancytopenia (white blood cell count, 2.7 × 10[9]/L; red blood cell count, 1.34 × 10[12]/L; hemoglobin level, 6.3 g/dL; platelet count, 55 × 10[9]/L), with macrocytic anemia (mean corpuscular volume, 134 fL; mean corpuscular hemoglobin, 47 pg) and markedly low serum vitamin B12 levels (<83 pg/mL). Brain magnetic resonance imaging demonstrated distinctive bilateral periventricular hyperintensities on T2‑weighted and diffusion‑weighted imaging, suggestive of cytotoxic edema, a finding often associated with metabolic disturbances. A diagnosis of acute metabolic encephalopathy due to vitamin B12 deficiency was established. Following vitamin B12 supplementation, the patient's symptoms resolved completely (Mini-Mental State Examination score: 24/30, Montreal Cognitive Assessment score, 23/30, adjusted for educational level). This case illustrates that vitamin B12 deficiency can present with acute cognitive dysfunction and may manifest on magnetic resonance imaging as symmetrical periventricular brain cytotoxic edema. Early recognition and treatment are crucial for achieving both clinical and radiographic recovery.

Mixed autoimmune hemolytic anemia (mAIHA) is a rare clinical condition where both warm and cold antibodies lead to autoimmune red cell destruction and progressive anemia. Herein, we report a rare case of combined warm and cold agglutinin-mediated autoimmune hemolytic anemia in a 61-year-old male who initially presented with incidental macrocytic anemia during a preoperative evaluation for pterygium surgery. Investigations showed the presence of both warm (IgG) and cold (IgM) autoantibodies, evidenced by a positive direct Coombs test (both anti-IgG and anti-C3), and elevated serum IgM levels. Type and cross-isolate revealed two distinct autoantibodies with different thermal amplitudes. Further workup did not reveal a definitive underlying etiology for the hemolysis. Mycoplasma pneumoniae and Epstein-Barr virus antibody panels were not suggestive of active infection. He was treated with corticosteroids and rituximab, resulting in an improvement in his hemoglobin levels, a reduction in splenomegaly, and ultimately remission of his autoimmune hemolytic anemia. This case emphasizes the need for a thorough workup to identify the cause of anemia, even in the context of seemingly unrelated surgical procedures.