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Archives of Dermatological Research Nov 2023Previous studies found conflicting results about associations of vitiligo with different autoimmune diseases. To evaluate associations of vitiligo with multiple...
Previous studies found conflicting results about associations of vitiligo with different autoimmune diseases. To evaluate associations of vitiligo with multiple autoimmune diseases. A cross-sectional study representative of 612,084,148 US patients from the Nationwide Emergency Department Sample (NEDS) 2015-2019 was performed. Vitiligo and autoimmune diseases were identified using International Classification of Diseases-10 codes. The most frequent autoimmune disorders in patients with vitiligo were type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus (SLE), autoimmune thyroiditis, Addison's disease, and systemic sclerosis (SSc). Vitiligo was associated with any autoimmune disorder (adjusted odds ratio [95% confidence interval] 1.45 [1.32-1.58]). Cutaneous disorders with largest effect-sizes were alopecia areata (186.22 [115.31-300.72]) and SSc (32.13 [25.28-40.82]). Non-cutaneous comorbidities with largest effect-sizes were primary sclerosing cholangitis (43.12 [18.98-97.99]), pernicious anemia (41.26 [31.66-53.78]), Addison's disease (33.85 [26.68-42.9]), and autoimmune thyroiditis (31.65 [26.34-38.02]). Vitiligo is associated with multiple cutaneous and non-cutaneous autoimmune diseases, especially in females and older age.
Topics: Female; Humans; Vitiligo; Cross-Sectional Studies; Thyroiditis, Autoimmune; Addison Disease; Autoimmune Diseases; Skin; Hashimoto Disease
PubMed: 37405428
DOI: 10.1007/s00403-023-02661-y -
Journal of Molecular Graphics &... Nov 2023The quest in finding an everlasting panacea to the pernicious impact of sickle cell disease (SCD) in the society hit a turn of success since the recent discovery of a...
The quest in finding an everlasting panacea to the pernicious impact of sickle cell disease (SCD) in the society hit a turn of success since the recent discovery of a small molecule reversible covalent inhibitor, Voxelotor. A drug that primarily promotes the stability of oxygenated hemoglobin and inhibit the polymerization of HbS by enhancing hemoglobin's affinity for oxygen has opened a new frontier in drug discovery and development. Despite eminent efforts made to reproduce small molecules with better therapeutic targets, none has been successful. To this end, we employed the use of structure-based computational techniques with emphasis on the electrophilic warhead group of Voxelotor to harness novel covalent binders that could elicit better therapeutic response against HbS. The PubChem database and DataWarrior software were used to design random molecules using Voxelotor's electrophilic functionality. Following the compilation of these chemical entities, a high-throughput covalent docking-based virtual screening campaign was conducted which revealed three (Compound_166, Compound_2301, and Compound_2335) putative druglike candidates with higher baseline energy value compared to the standard drug. Subsequently, in silico ADMET profiling was carried out to evaluate their pharmacokinetics and pharmacodynamics properties, and their stability was evaluated for 1 μs (1 μs) using molecular dynamics simulation. Finally, to prioritize these compounds for further development in drug discovery, MM/PBSA calculations was employed to evaluate their molecular interactions and solvation energy within the HbS protein. Despite the admirable druglike and stability properties of these compounds, further experimental validations are required to establish their preclinical relevance for drug development.
Topics: Humans; Anemia, Sickle Cell; Benzaldehydes; Pyrazines; Molecular Dynamics Simulation; Hemoglobins; Molecular Docking Simulation
PubMed: 37339569
DOI: 10.1016/j.jmgm.2023.108549 -
Cureus May 2023A 52-year-old woman with no significant past medical history presented to the emergency room (ER) with nonspecific systemic symptoms, including fatigue, dyspnea on...
A 52-year-old woman with no significant past medical history presented to the emergency room (ER) with nonspecific systemic symptoms, including fatigue, dyspnea on exertion, easy bruising, and palpitations. She was found to have significant pancytopenia. Hemolytic anemia, thrombocytopenia, and elevated PLASMIC score (6, High risk; PLASMIC = Platelet count; combined hemoLysis variable; absence of Active cancer; absence of Stem-cell or solid-organ transplant; MCV; INR; Creatinine) score at the time of presentation led to a concern for thrombotic thrombocytopenic purpura (TTP). Therapeutic plasma exchange (TPE) was deferred pending additional investigation. Workup revealed the true diagnosis of severe B12 deficiency, which would not have benefited from TPE and instead would have placed the patient at risk for harm, making the decision to defer treatment the correct and judicious approach. This is a case where anchoring on lab results may result in reaching the incorrect diagnosis. This case reminds clinicians of the importance of creating a broad differential and ensuring thorough history-taking is done for all patients.
PubMed: 37332426
DOI: 10.7759/cureus.39080 -
The Journal of the Royal College of... Sep 2023Current guidelines recommend surveillance for gastric adenocarcinoma in patients with extensive chronic atrophic gastritis (CAG), which is considered a premalignant... (Review)
Review
Current guidelines recommend surveillance for gastric adenocarcinoma in patients with extensive chronic atrophic gastritis (CAG), which is considered a premalignant condition. Although the association between vitamin B12 deficiency and CAG is well described, the indication for endoscopic investigation is only advised in patients with pernicious anaemia. Our case did not have evidence of autoimmune or but despite this she had CAG. We suggest considering gastroscopy for severe, unexplained vitamin B12 deficiency, particularly in this patient group.
Topics: Female; Humans; Gastritis, Atrophic; Vitamin B 12 Deficiency; Helicobacter Infections; Gastroscopy; Vitamin B 12
PubMed: 37329268
DOI: 10.1177/14782715231180965 -
Clinics and Research in Hepatology and... Aug 2023Autoimmune gastritis (AIG) is a prominent risk factor for pernicious anemia (PA) and gastric neoplasia. This study aimed to investigate the clinicopathological...
BACKGROUND AND AIM
Autoimmune gastritis (AIG) is a prominent risk factor for pernicious anemia (PA) and gastric neoplasia. This study aimed to investigate the clinicopathological characteristics of AIG patients in China, with a focus on those who had positive anti-intrinsic factor antibodies (AIFA).
METHODS
A total of 103 AIG patients who were diagnosed between January 2018 and August 2022 were reviewed in a large academic tertiary teaching hospital. Patients were divided into two groups based on the presence or absence of AIFA, and their serologic and histopathological characteristics were analyzed.
RESULTS
The mean age of the 103 AIG patients was 54.16±11.92 years (range 23-79), with 69 (66.99%) being women. AIFA were present in 28.16% of patients. Patients with AIFA-positive had a higher risk of PA than those with AIFA-negative, as demonstrated by a larger mean corpuscular volume (MCV), lower hemoglobin level, and lower vitamin B-12 level (P<0.05). There were no statistically significant differences in gastric histopathology, gastrin level, and pepsinogen level when patients were divided into AIFA-positive and AIFA-negative group. Of the 103 cases, 34 (33.01%) were concomitant with other autoimmune diseases, with autoimmune thyroid diseases being the most common (25.24%, 26/103). Thyroid peroxidase antibody, which accounted for 45.45% (25/55), was the most prevalent thyroid antibody, followed by anti-thyroglobulin antibody (34.55%, 19/55), thyroid stimulating antibody (12.73%, 7/55), and thyrotropin receptor antibody (3.64%, 2/55).
CONCLUSION
This study highlights the increased risk of severe anemia in AIFA-positive AIG patients, particularly for PA. Clinicians should consider the presence of AIFA as a warning sign for PA and prioritize early diagnosis and appropriate treatment to prevent serious complications.
Topics: Humans; Female; Young Adult; Adult; Middle Aged; Aged; Male; Retrospective Studies; Gastritis; Autoantibodies; Autoimmune Diseases; Anemia, Pernicious
PubMed: 37311519
DOI: 10.1016/j.clinre.2023.102154 -
Clinical Case Reports Jun 2023Autoimmune polyglandular syndrome type 2 (APS II) is a rare autoimmune disease that affects many endocrine glands. We present a case of a 32-year-old man with Addison's...
Autoimmune polyglandular syndrome type 2 (APS II) is a rare autoimmune disease that affects many endocrine glands. We present a case of a 32-year-old man with Addison's disease, autoimmune thyroiditis, and pernicious anemia. Multi-line and timely management are crucial for each association.
PubMed: 37305884
DOI: 10.1002/ccr3.7413 -
Heliyon May 2023A 47-year-old, north african, male patient, has recently been diagnosed with pernicious anemia, treated with weekly intramuscular hydroxocobalamin. 6 weeks after its...
A 47-year-old, north african, male patient, has recently been diagnosed with pernicious anemia, treated with weekly intramuscular hydroxocobalamin. 6 weeks after its initiation, the patient presented a sudden, extensive and monomorphic eruption of inflammatory papulo-pustules and nodules, affecting the face, and the trunk. The eruption was pruritic, and comedones were also present, on the chest. The patient was diagnosed with vitamin B12-induced acneiform eruption. Levels of vitamin B12 were normalized. Hydroxocobalamin was therefore stopped and lymecycline was started, allowing a complete resolution of the lesions within 3 months. Drug intake, sudden and uncommon age of onset, pruritus, a monomorphic pattern and an involvement of extra-seborrheic areas are features that distinguish acneiform eruptions from acne vulgaris.
PubMed: 37305488
DOI: 10.1016/j.heliyon.2023.e16120 -
Chemico-biological Interactions Sep 2023Vitamin B (cyano- or hydroxo-cobalamin) acts, via its coenzymes, methyl- and adenosyl-cobalamin, as a partner for enzymatic reactions in humans catalysed by methionine...
Vitamin B (cyano- or hydroxo-cobalamin) acts, via its coenzymes, methyl- and adenosyl-cobalamin, as a partner for enzymatic reactions in humans catalysed by methionine synthase and methylmalonyl-CoA mutase. As well as its association with pernicious anaemia, human B deficiency may also be a risk factor for neurological illnesses, heart disease and cancer. In the present work the effect of vitamin B (hydroxocobalamin) on the formation of DNA adducts by the epoxide phenyloxirane (styrene oxide), a genotoxic metabolite of phenylethene (styrene), has been studied using an in vitro model system. Styrene was converted to its major metabolite styrene oxide as a mixture of enantiomers using a microsomal fraction from the livers of Sprague-Dawley rats with concomitant inhibition of epoxide hydrolase. However, microsomal oxidation of styrene in the presence of vitamin B gave diastereoisomeric 2-hydroxy-2-phenylcobalamins. The quantitative formation of styrene oxide-DNA adducts was investigated using 2-deoxyguanosine or calf thymus DNA in the presence or absence of vitamin B. Microsomal incubations containing either deoxyguanosine or DNA in the absence of vitamin B gave 2-amino-7-(2-hydroxy-1-phenylethyl)-1,7-dihydro-6H-purin-6-one [N7-(2-hydroxy-1-phenylethyl)-guanine], and 2-amino-7-(2-hydroxy-2-phenylethyl)-1,7-dihydro-6H-purin-6-one [N7-(2-hydroxy-2-phenylethyl)guanine] as the principal adducts. With deoxyguanosine the level of formation of guanine adducts was ca. 150 adducts/10 unmodified nucleoside. With DNA the adduct level was 36 pmol/mg DNA (ca. 1 adduct/0.83 × 10 nucleotides). Styrene oxide adducts from deoxyguanosine or DNA were not detected in microsomal incubations of styrene in the presence of vitamin B. These results suggest that vitamin B could protect DNA against genotoxicity due to styrene oxide and other xenobiotic metabolites. However, this potential defence mechanism requires that the 2-hydroxyalkylcobalamins derived from epoxides are not 'anti-vitamins' and ideally liberate, and therefore, recycle vitamin B. Otherwise, depletion of vitamin B leading to human deficiency could increase the risk of carcinogenesis initiated by genotoxic epoxides.
Topics: Animals; Rats; Humans; DNA Adducts; Vitamin B 12; Xenobiotics; Rats, Sprague-Dawley; Epoxy Compounds; DNA Damage; DNA; Guanine; Deoxyguanosine; Styrenes; Styrene
PubMed: 37302460
DOI: 10.1016/j.cbi.2023.110591 -
Family Practice Jun 2024Pseudo-thrombotic microangiopathy (pseudo- thrombotic microangiopathy (TMA)) is a rare presentation of B12 deficiency. Overlapping features like elevated LDH/total...
Unusual case of pernicious anaemia masquerading as thrombotic thrombocytopenic purpura in the setting of multiple normal vitamin B12 deficiency parameters: preventing anchoring and overdiagnosis.
BACKGROUND
Pseudo-thrombotic microangiopathy (pseudo- thrombotic microangiopathy (TMA)) is a rare presentation of B12 deficiency. Overlapping features like elevated LDH/total bilirubin with low haemoglobin/haptoglobin/platelets could deceivingly suggest thrombotic thrombocytopenic purpura (TTP) resulting in avoidable procedures/treatments.
CASE PRESENTATION
A 36-year-old female with hypothyroidism initially presented to clinic with fatigue, palpitations, lightheadedness, and dyspnoea over a 3-month duration and was found to have a haemoglobin of 5.7 g/dL. She received two packed red blood cell units in the emergency room and subsequently discharged with outpatient follow-up and empiric oral iron. During her follow-up visit, she was found to have easy bruisability, gum bleeding, and generalized weakness from hemolytic anaemia (mean corpuscular volume (MCV) 90 fL, haptoglobin <8 mg/dL, LDH >4,000 U/L and schistocytosis on CBC) and thrombocytopenia of 52 K/uL. Due to PLASMIC score of 6 and suspicion for TTP, she was transferred to our facility and tr eated with three cycles of plasma exchange and prednisone but were discontinued when ADAMTS13 levels returned normal. While the patient had normal B12 levels, further testing revealed positive intrinsic factor antibodies (IF-Ab) and an elevated MMA level of 1.56 umol/L. Replacement with cobalamin led to normalization of labs and symptoms.
CONCLUSIONS
Timely diagnosis of pseudo-TMA was exceptionally challenging due to several overlapping features with TTP including normal B12 and normal MCV. B12 levels may falsely appear normal in pernicious anemia due to IF-Ab interference with chemiluminescent immunoassay. Schistocytes lower the MCV in automated cell counters. Lower reticulocyte index (<2%), presence of immature/large platelets and teardrop cells, elevated MMA and a higher LDH (>2500) are indicative of B12 deficiency.
Topics: Humans; Female; Purpura, Thrombotic Thrombocytopenic; Adult; Anemia, Pernicious; Vitamin B 12 Deficiency; Diagnosis, Differential; Vitamin B 12
PubMed: 37294666
DOI: 10.1093/fampra/cmad065