[The disease under chronic urticaria: beyond itching]. / La enfermedad crónica bajo la urticaria: más allá del prurito.

BACKGROUND: Brief erythematous-papular skin rashes suggest the diagnosis of urticaria; However, it may be another type of dermatitis, and complementary examinations must be carried out to establish its diagnosis. CASE REPORT: 53-year-old female patient, diagnosed in 2016 with diffuse large B cell lymphoma, in complete remission. Since 2010, he has had episodes of erythematous-papular lesions lasting 24-36 hours. He received antihistamines, corticosteroids and omalizumab without clinical improvement. The ANA determination was positive (1/320), nuclear mitotic pattern. The skin biopsy was compatible with dermatitis herpetiformis. The study of celiac and locus antibodies showed positivity for HLA-DQ2 and DQ2.5 in heterozygosity. The diagnosis of dermatitis herpetiformis was established. Treatment consisted of a gluten-free diet and prescription of dapsone, with satisfactory results. CONCLUSION: It is important to establish the differential diagnosis of patients with chronic urticaria who do not respond to the reference treatment, in addition to carrying out a thorough clinical examination and physical examination before starting treatment and relying on a multidisciplinary team to establish an accurate diagnosis and treatment. appropriate. Due to the side effects of dapsone, subsequent follow-up of patients is essential.

ANTECEDENTES: Los exantemas cutáneos eritemato-papulares de breve duración sugieren el diagnóstico clínico de urticaria; no obstante, puede tratarse de otro tipo de dermatitis, y para establecer el diagnóstico deben llevarse a cabo exploraciones complementarias. REPORTE DE CASO: Paciente femenina de 53 años, diagnosticada en 2016 con linfoma difuso de células B grandes, en remisión completa. Desde el 2010 manifestó episodios de lesiones eritemato-papulosas, de 24-36 horas de duración. Recibió antihistamínicos, corticoides y omalizumab sin mejoría clínica. La determinación de ANA resultó positiva (1/320), con patrón mitótico nuclear. La biopsia cutánea fue compatible con dermatitis herpetiforme. El estudio de anticuerpos de celiaquía y locus mostró positividad para HLA-DQ2 y DQ2.5 con heterocigosis. Se estableció el diagnosticó de dermatitis herpetiforme. El tratamiento consistió en dieta exenta de gluten y prescripción de dapsona, con resultados satisfactorios. CONCLUSIÓN: Es importante establecer el diagnóstico diferencial de pacientes con urticaria crónica que no responden al tratamiento de referencia, además de efectuar el examen clínico y la exploración física exhaustivos antes de iniciar el protocolo, y apoyarse de un equipo multidisciplinario para establecer el diagnóstico certero y tratamiento adecuado. Debido a los efectos secundarios de la dapsona, es imprescindible el seguimiento posterior de los pacientes.

Evaluation of HLA-DQ2 and HLA-DQ8 haplotypes in patients with endometriosis, A case-control study.

OBJECTIVE: To evaluate the relationship between genetic haplotypes associated with celiac disease (Human Leucocyte Antigen [HLA] DQ2 and DQ8) with the diagnosis, clinical presentation, and location of endometriosis in Brazilian women. METHOD: A retrospective cross-sectional study, was conducted in a Tertiary hospital. PATIENTS: Women aged 18-50 years who underwent HLA-DQ2 and HLA-DQ8 haplotype analysis. INTERVENTION: The patients were divided into endometriosis and control groups and evaluated for symptoms; endometriosis location, American Society for Reproductive Medicine (ASRM) stage, and the presence of anti-tissue transglutaminase IgA (anti-TgA), HLA-DQ2, and HLA-DQ8 markers. RESULTS: A total of 434 consecutive patients with (n = 315) and without (n = 119) endometriosis were included. Pain and infertility were more frequent in the endometriosis group than in the control group. The presence of HLA-DQ2, HLA-DQ8, and anti-TgA was similar between both groups. The presence of HLA-DQ2 and HLA-DQ8 markers did not differ based on age, pain symptoms, ASRM stage, or endometriosis location. CONCLUSION: Although there are similarities in inflammatory markers and pathophysiology between celiac disease and endometriosis, this study found no significant associations in the presence of HLA-DQ2 or HLA-DQ8 haplotypes and endometriosis.

Evaluation of HLA-DQ2 and HLA-DQ8 haplotypes in patients with endometriosis, A case-control study

Abstract Objective To evaluate the relationship between genetic haplotypes associated with celiac disease (Human Leucocyte Antigen [HLA] DQ2 and DQ8) with the diagnosis, clinical presentation, and location of endometriosis in Brazilian women. Method A retrospective cross-sectional study, was conducted in a Tertiary hospital. Patients Women aged 18-50 years who underwent HLA-DQ2 and HLA-DQ8 haplotype analysis. Intervention The patients were divided into endometriosis and control groups and evaluated for symptoms; endometriosis location, American Society for Reproductive Medicine (ASRM) stage, and the presence of anti-tissue transglutaminase IgA (anti-TgA), HLA-DQ2, and HLA-DQ8 markers. Results A total of 434 consecutive patients with (n = 315) and without (n = 119) endometriosis were included. Pain and infertility were more frequent in the endometriosis group than in the control group. The presence of HLA-DQ2, HLA-DQ8, and anti-TgA was similar between both groups. The presence of HLA-DQ2 and HLA-DQ8 markers did not differ based on age, pain symptoms, ASRM stage, or endometriosis location. Conclusion Although there are similarities in inflammatory markers and pathophysiology between celiac disease and endometriosis, this study found no significant associations in the presence of HLA-DQ2 or HLA-DQ8 haplotypes and endometriosis.

HLA-Haplotypes Influence Microbiota Structure in Northwestern Mexican Schoolchildren Predisposed for Celiac Disease or Type 1 Diabetes.

To contribute to and elucidate the participation of microbiota in celiac disease (CD) and type 1 diabetes (T1D) development, we evaluated the influence of HLA haplotypes, familial risk, and diet on the microbiota of schoolchildren. We conducted a cross-sectional study on 821 apparently healthy schoolchildren, genotyping HLA DQ2/DQ8, and registering familial risk. We analyzed the fecal microbiota using 16S rRNA gene sequencing, and autoantibodies for CD or T1D by ELISA. After analyses, we created three groups: at-high-risk children (Group 1), at-high-risk children plus autoantibodies (Group 2), and nonrisk children (Group 3). HLA influenced the microbiota of Groups 1 and 2, decreasing phylogenetic diversity in comparison to Group 3. The relative abundance of Oscillospiraceae UCG_002, Parabacteroides, Akkermansia, and Alistipes was higher in Group 3 compared to Groups 1 and 2. Moreover, Oscillospiraceae UCG_002 and Parabacteroides were protectors of the autoantibodies' positivity (RRR = 0.441 and RRR = 0.034, respectively). Conversely, Agathobacter was higher in Group 2, and Lachnospiraceae was in both Groups 1 and 2. Lachnospiraceae correlated positively with the sucrose degradation pathway, while the principal genera in Group 3 were associated with amino acid biosynthesis pathways. In summary, HLA and familial risk influence microbiota composition and functionality in children predisposed to CD or T1D, increasing their autoimmunity risk.

The Second Highest Prevalence of Celiac Disease Worldwide: Genetic and Metabolic Insights in Southern Brazilian Mennonites.

Celiac disease (CD), despite its high morbidity, is an often-underdiagnosed autoimmune enteropathy. Using a modified version of the Brazilian questionnaire of the 2013 National Health Survey, we interviewed 604 Mennonites of Frisian/Flemish origin that have been isolated for 25 generations. A subgroup of 576 participants were screened for IgA autoantibodies in serum, and 391 participants were screened for HLA-DQ2.5/DQ8 subtypes. CD seroprevalence was 1:29 (3.48%, 95% CI = 2.16-5.27%) and biopsy-confirmed CD was 1:75 (1.32%, 95% CI = 0.57-2.59%), which is superior to the highest reported global prevalence (1:100). Half (10/21) of the patients did not suspect the disease. HLA-DQ2.5/DQ8 increased CD susceptibility (OR = 12.13 [95% CI = 1.56-94.20], p = 0.003). The HLA-DQ2.5 carrier frequency was higher in Mennonites than in Brazilians (p = 7 × 10-6). HLA-DQ8 but not HLA-DQ2.5 carrier frequency differed among settlements (p = 0.007) and was higher than in Belgians, a Mennonite ancestral population (p = 1.8 × 10-6), and higher than in Euro-Brazilians (p = 6.5 × 10-6). The glutathione pathway, which prevents reactive oxygen species-causing bowel damage, was altered within the metabolic profiles of untreated CD patients. Those with lower serological positivity clustered with controls presenting close relatives with CD or rheumatoid arthritis. In conclusion, Mennonites have a high CD prevalence with a strong genetic component and altered glutathione metabolism that calls for urgent action to alleviate the burden of comorbidities due to late diagnosis.

Frequency of HLA-DQ, susceptibility genotypes for celiac disease, in Brazilian newborns.

BACKGROUND: The frequency of HLA-DQ2 and DQ8 predisposing genotypes for celiac disease (CD) has shown significant variation among different world regions and has not been previously determined among the highly interbred Brazilian population. The aim of this study was to investigate the frequency of these genotypes among Brazilian newborns (NB). METHODS: We typed DQA1*05 - DQB1*02 (DQ2.5) and DQA1*03 - DQB1*03:02 (DQ8) alleles in 329 NB using qPCR technique. Subsequently we confirmed our results by PCR-SSP using a reference kit which further identified DQ2.2 (DQA1*02:01 - DQB1*02). RESULTS: Among the 329 NB, using qPCR technique: 5 (1.52%) carried both DQ2.5 and DQ8 variants; 58 (17.63%) carried only DQ2.5 (DQA1*05 and DQB1*02) and 47 (14.29%) carried only the DQ8 (DQA1*03 and DQB1*03:02) variant. The use of the PCR-SSP method yielded further information; among the 329 samples: 34 (10.34%) tested positive for DQ2.2 and among the 47 previously DQ8 positives samples, we found 10 (3.04%) that also tested positives for DQ2.2. CONCLUSION: 43.7% of the analyzed individual tested positive for at least one of the CD predisposing HLA-DQ genotypes in our group of Brazilian NB. The highest frequency was found for DQ2.5 positive subjects (17.6%) followed by DQ8 (11.3%); DQ2.2 (10.3%); DQ8 and DQ2.2 (3.0%); DQ2.5 and DQ8 (1.5%). We found no positive sample for DQ2.5 associated with DQ2.2.

Is celiac disease better identified through HLA-DQ8 than through HLA-DQ2 in Mexican subjects? / ¿Es posible una mejor identificación de la enfermedad celiaca en sujetos mexicanos por medio de HLA-DQ8 que de HLA-DQ2?

INTRODUCTION AND AIMS: A strong genetic association between celiac disease (CD) and the human leukocyte antigen (HLA) has been widely demonstrated. In Europe, the HLA-DQ2 allele is predominant. However, studies in Latin America indicate that HLA-DQ8 could be more frequent. In Mexico, the frequency of those alleles has not been reported in subjects with CD. Therefore, the aim of the present study was to evaluate the distribution of HLA-DQ2 and HLA-DQ8 in Mexican individuals with CD. MATERIAL AND METHODS: An exploratory study was conducted on a cohort of 49 subjects with chronic diarrhea. Autoantibodies for CD, duodenal atrophy, and HLA haplotypes were determined. RESULTS: Thirty individuals had CD (23 women, mean age 54.2 ± 15.5 years), 24 (80%) of whom expressed HLA-DQ8, 15 (50%) expressed HLA-DQ2, and 11 (37%) presented with both alleles. However, neither the HLA-DQ2 nor the HLA-DQ8 allele was found in 5 (10%) individuals. In subjects with chronic diarrhea that did not have CD, 12 (63%) presented with HLA-DQ2, and 7 (37%) with HLA-DQ8. Individuals with CD expressed the combinations of the HLA-DQ8/DQ2 alleles (37 vs. 5%) and the HLA-DR4/DQ8 alleles (60 vs. 26%) more frequently than the subjects without CD. CONCLUSIONS: In Mexican subjects with CD, HLA-DQ8 distribution was more frequent than that of HLA-DQ2, indicating a possible similarity to the frequency reported in other Latin American countries. However, given the nature of the present study and its sample size, further conclusions could not be reached.

Genetics, environment, and asthma associated with celiac disease in the extended family of an affected child. / Genética, ambiente y asma asociados a enfermedad celiaca en la familia extendida de un niño afectado.

INTRODUCTION: Celiac disease (CD) is an autoimmune enteropathy associated with gluten ingestion. In extended families of celiac patients that live in close proximity of one another, shared genetic and environmental factors can predispose them to CD. AIM: The aim of this study was to provide evidence about the genetic and environmental factors involved in the development of CD in the extended family of a pediatric patient. METHODS: The medical history, environmental conditions, and participant weight, height, and peripheral blood samples were evaluated. The HLA-DQ2/DQ8 haplotypes were genotyped through qPCR testing and the IgA anti-gliadin and anti-transglutaminase antibodies were quantified using the ELISA test. RESULTS: Twelve close-living maternal relatives of the index case participated in the study. Eight of them presented with the HLA-DQ2 haplotype, inherited from the grandfather, and 7/12 and 9/12 were positive for IgA anti-gliadin and IgA anti-transglutaminase antibodies, respectively. The main intestinal symptoms stated by the participants were abdominal bloating, excess flatulence, constipation, and gastroesophageal reflux. The most frequent extra-intestinal symptoms were fatigue, stress, and anxiety. In addition, 6/13 participants had bronchial asthma. CONCLUSION: The extended family living in close proximity of one another shared a genetic predisposition, environmental conditions, and asthma, which could have predisposed them to celiac disease.

Patrón clínico y sensibilidad de la serología frente a la histología en niños celiacos HLA DQ2/DQ8 / PATTERNS IN CLINICAL PRESENTATIONS, SEROLOGY SENSITIVITY IN FRONT OF HISTOLOGY IN THE CHILDREN CELIACS HLA DQ2/DQ8

Introducción: En áreas tropicales donde el diagnóstico diferencial para enfermedad celíaca está presente, la determinación de HLA DQ2/DQ8 es útil para confirmar la existencia de la enfermedad en pacientes sintomáticos o no con serología negativa y lesión mucosal o anticuerpo positivo y mucosa nor- mal, con la limitante del costo elevado. Objetivo: conocer el patrón clínico en niños celiacos con determinación HLA DQ2/DQ8 e investigar la sensibilidad de la serología frente a la histología en el despistaje diagnóstico de la enfermedad. Pacientes y método: estudio prospectivo y transversal, que incluyo 18 niños celíacos con determinación de DQ2/DQ8. Se registró: edad, sexo, clínica, serología, biopsia y genética. Resultados: edad promedio 3,39 años (8meses-13 años),55,55% hembras. Patrón clínico clásico en 12/18 (66,67%), atípico 3/18 (16,67%), latente 2/18 (11,11%), potencial 1/18 (5,55%). En total 12/18 pacientes (66,67%) con serolo- gía positiva. A la histología: 2/18 mucosa normal (11,11%) y 16/18 alterada (88,89%), de ellos, 4 Marsh I, 5 Marsh II, 7 Marsh III. En todos los niños con serología positiva se observo lesión intestinal, 25% con atrofia de vellosidades. Con serología negativa, 4 con atrofia vellositaria (2/4 con déficit de Ig A) y 2 mucosa normal. Se encontró una sensibilidad de la serología para el diagnóstico en 75%, specificidad 100%. Exactitud diagnóstica en 77,77% de la serología frente a la histología. Conclusiones: la serología resulto con una sensibilidad aceptable para el despistaje diagnóstico de celíaca y la determinación de HLA DQ2/DQ8 fue de utilidad en la caracterización del patrón clínico y la detección de la enfer- medad un grupo de pacientes.

Introduction: In tropical areas where the differential diag- nosis for celiac disease is present, the determination of HLA DQ2/DQ8 is useful to confirm the existence of the disease in symptomatic patients or HIV negative and positive mucosal injury and mucosal antibody or normal with limiting the high cost. Objective: To determine the clinical pattern in celiac children with HLA determination DQ2/DQ8 and investigate the sensitivity of the serology screening histology in the diagnosis of disease. Patients and methods: Prospective, cross-sectional, which included 18 children with celiac DQ2/ DQ8 determination. Was recorded: age, sex, clinical, sero- logy, biopsy and genetics. Results: mean age 3.39 years (8m-13), 55.55% females. Classic clinical pattern in 12/18 (66.67%), atypical 3/18 (16.67%), latent 2/18 (11.11%), potential 1/18 (5.55%). In total 12/18 patients (66.67%) with positive serology. A histology: 2/18 normal mucosa (11.11%) and 16/18 altered (88.89%), of whom 4 Marsh I, 5 Marsh II, 7 Marsh III. In all children with positive serology bowel injury was observed, 25% villus atrophy. With negative serology, 4 with villous atrophy (2/4 with IgA deficiency) and 2 normal mucosa. We found a sensitivity of serology for diagnosis in 75%, specificity 100%. 77.77% diagnostic accuracy of serology against histology. Conclusions: resulted serology with acceptable sensitivity for the screening and diagnosis of celiac HLA determining DQ2/DQ8 was useful in characterizing the clinical pattern and disease detection a group of patients in characterizing the clinical pattern and detection of the disease a group of patients.

HLA-DQ genetic risk gradient for type 1 diabetes and celiac disease in northwestern Mexico.

BACKGROUND: Type 1 diabetes (T1D) and celiac disease (CD) are the 2 most common autoimmune childhood diseases that share their HLA-DQ2 and DQ8 genetic origin. There has currently been an increase in both diseases worldwide. In children from the low-population State of Sonora (15 inhabitants/km(2)) in north-western Mexico, there is no information on their genetic risk or the distribution of the related alleles in the general population. AIMS: To compare the HLA-DQ allele frequency in a representative sample of newborns from Sonora with that of T1D and CD patients to determine the risk gradient, and to identify the presence of celiac autoimmunity in the T1D group. METHODS: The study included 397 Sonoran newborns, with 44 cases of T1D, and 25 CD cases. The CD and T1D cases were clinically diagnosed by specialists at the Hospital Infantil del Estado de Sonora, and the autoantibodies were determined by ELISA. Whole blood was collected, gDNA was extracted, and HLA-DQ2 and DQ8 were typed by PCR-SSP. The risk gradient was calculated by comparing the allele frequencies of the cases with those of the newborns. RESULTS: The Sonoran HLA-DQ risk heterodimer proportion was 16.1% for HLA-DQ2 and 13.6% for HLA-DQ8, with an HLA-DQ2:HLA-DQ8 ratio of 1.2:1. The DQ8/DQ2 genotype represented a 1:14 risk for T1D, whereas the DQ8/DQB1*0201 combination showed a 1:6 risk for CD. The prevalence of CD autoimmunity in T1D children was 7%. CONCLUSION: The Sonoran population has a distinctive HLA-DQ allele distribution due to its ancestry. The HLA-DQ8 combinations with DQ2 or one of its alleles conferred the highest risk for both diseases, and T1D and CD frequently appear together.

DQ2, DQ7 and DQ8 Distribution and Clinical Manifestations in Celiac Cases and Their First-Degree Relatives.

HLA-linked genes are relevant to celiac disease (CD); the potential genetic differences present worldwide are not fully understood. Previous results suggest that the distribution of HLA-DQ2/DQ7/DQ8 in Chile may differ from that in Europe and North America. In celiac patients and their first-degree relatives (FDRS), we assessed their clinical, serological and histological characteristics, determined HLA-DQ2, HLA-DQ7 and HLA-DQ8 alleles and genotypes, and evaluated the relations between them. A total of 222 individuals were assessed (56 cases, 166 FDRs). 16.9% of FDRs were tTG positive; 53.6% of them showed overweight/obesity and 3% undernourishment; they spontaneously declared being asymptomatic, but detailed questioning revealed that 60.7% experienced symptoms, which had not been investigated. DQ2 was present in 53.9% and 43.9.0% of cases and FDRs (p < 0.05). The most frequent genotype distribution was DQ2/DQ7 (fr 0.392 (cases) and 0.248 (FDRs), respectively, p < 0.02). The next most common genotypes were HLA-DQ2/DQ8 (fr 0.236 in FDRs and 0.176 in cases, p < 0.05). 3.92% cases were not HLA-DQ2/DQ8 carriers. Among tTG positive FDRs, 57.4%, 22.3% and 20.2% carried DQ2, DQ7 and DQ8, respectively. In cases, 72.7% of the biopsies classified Marsh ≥ 3 carried at least one DQ2; 91.7% of DQ2/DQ2 and 88.3% of DQ2/DQ7 were Marsh ≥ 3. Thus, DQ2 frequency is lower than reported; the higher frequency found for DQ8 and DQ7 concur with recent publications from Argentine and Brazil. These results suggest that although CD may manifest clinically in ways similar to those described in other populations, some genetic peculiarities in this region deserve further study.