Primary immunodeficiency and autoimmunity: A comprehensive review.

The primary immunodeficiency diseases (PIDs) include many genetic disorders that affect different components of the innate and adaptive responses. The number of distinct genetic PIDs has increased exponentially with improved methods of detection and advanced laboratory methodology. Patients with PIDs have an increased susceptibility to infectious diseases and non-infectious complications including allergies, malignancies and autoimmune diseases (ADs), the latter being the first manifestation of PIDs in several cases. There are two types of PIDS. Monogenic immunodeficiencies due to mutations in genes involved in immunological tolerance that increase the predisposition to develop autoimmunity including polyautoimmunity, and polygenic immunodeficiencies characterized by a heterogeneous clinical presentation that can be explained by a complex pathophysiology and which may have a multifactorial etiology. The high prevalence of ADs in PIDs demonstrates the intricate relationships between the mechanisms of these two conditions. Defects in central and peripheral tolerance, including mutations in AIRE and T regulatory cells respectively, are thought to be crucial in the development of ADs in these patients. In fact, pathology that leads to PID often also impacts the Treg/Th17 balance that may ease the appearance of a proinflammatory environment, increasing the odds for the development of autoimmunity. Furthermore, the influence of chronic and recurrent infections through molecular mimicry, bystander activation and super antigens activation are supposed to be pivotal for the development of autoimmunity. These multiple mechanisms are associated with diverse clinical subphenotypes that hinders an accurate diagnosis in clinical settings, and in some cases, may delay the selection of suitable pharmacological therapies. Herein, a comprehensively appraisal of the common mechanisms among these conditions, together with clinical pearls for treatment and diagnosis is presented.

Juvenile polyautoimmunity in a rheumatology setting.

Overt polyautoimmunity (PolyA) corresponds to the presence of more than one well-defined autoimmune disease (AD) manifested clinically in a single patient. The current study aimed to describe the main characteristics of juvenile PolyA in a pediatric rheumatology setting and analyze the chronological aspects, index cases, familial autoimmunity, and clustering pattern. This was a cross-sectional and multicenter study in which 313 children with overt PolyA were included. Patients were systematically interviewed and their medical records reviewed using a questionnaire that sought information about demographic, clinical, immunological, and familial characteristics. A hierarchical cluster analysis was done to determine similarities between autoimmune diseases based on PolyA. PolyA occurred simultaneously in 138 (44%) patients. Multiple autoimmune syndrome was observed in 62 (19.8%) patients. There were 25 index diseases of which, systemic lupus erythematosus (SLE, n = 134, 42.8%), juvenile idiopathic arthritis (JIA, n = 40, 12.7%), Hashimoto's thyroiditis (HT, n = 24, 7.66%), immune thrombocytopenic purpura (ITP n = 20, 6.39%), antiphospholipid syndrome (APS, n = 15, 4.79%), and vitiligo (VIT, n = 15, 4.79%) were the most frequent and represented 79.23% of the total number of patients. Familial autoimmunity influenced PolyA. A high aggregation of autoimmunity was observed (λr = 3.5). Three main clusters were identified, of which SLE and APS were the most similar pair of diseases (based on the Jaccard index) followed by HT and JIA, which were related to ITP and Sjögren's syndrome. The third cluster was composed of localized scleroderma and VIT. Our findings may assist physicians to make an early diagnosis of this frequent condition. Pediatric patients with ADs should be systematically assessed for PolyA.

Posición anatómica y longitud del apéndice vermiforme en una población de raza mestiza de la ciudad de Bucaramanga - Colombia / Anatomical position and length of caecal appendix in a mixtured population from Bucaramanga

Antecedentes: La posición y longitud del apéndice vermiforme en el ser humano no son constantes y los datos sobre sus variaciones son limitados. Estudios previos soportan que algunas posiciones particulares o apéndices muy largas pueden confundir los signos clínicos de una apendicitis. Algunos autores afirman que el curso de una apendicitis puede estar influenciada por la posición del apéndice. Método: La posición y longitud del apéndice cecal fueron estudiados en 100 especímenes cadavéricos de población mestiza en Bucaramanga - Colombia. La posición del apéndice se dividió en 6 grupos: pélvica, retrocecal, preileal, postileal, subcecal y paracecal. La posición fue estudiada in situ. Resultados: La posición predominante fue el retrocecal 41%. Igualmente, se encontró un porcentaje elevado de posición pélvica 28%. El promedio de la longitud del apéndice fue de 7.1 cm. Conclusión: El porcentaje de la posición retrocecal de nuestro estudio concuerda con otros estudios realizados en especímenes cadavéricos. Algunos autores han reportado porcentajes elevados de posición pélvica especialmente en poblaciones de raza negra. La posición pélvica del apéndice cecal puede producir dolor hipogástrico confundiendo los síntomas clínicos principalmente en mujeres. Los resultados de este tipo de investigaciones son importantes porque las relaciones de variables anatómicas son usadas en imágenes clínicas de apendicitis aguda; además éstas observaciones pueden alentar la mayor realización de apendicectomías por laparoscopia. [Corzo EG, Forero PL, Amaya L, Bohórquez D, Bohórquez S. Posición antómica y longitud del apéndice vermiforme en una población de raza mestiza de la ciudad de Bucaramanga. MedUNAB 2009; 12:116-120].

Background: The position and length of the vermiform appendix in humans has no constant and the data on the variations in its position are limited. Previous studies support that particular positions and very long appendix could confuse the clinical signs of appendicitis. Some authors affirm that the course of acute appendicitis is influenced by the position of the appendix. Methods: The position and length of the vermiform appendix were studied in one hundred cadaverous specimens of mestizo population from Bucaramanga - Colombia. The appendix positions were divided into six groups: pelvic, retrocaecal, preileal, postileal, subcaecal and paracecal. The position were studied in situ. The data analysis was made from Universidad Autónoma de Bucaramanga's Medical Faculty's Anatomy Department. Results: The predominant position was retrocaecal 41%. Also we found a high percentage of pelvic position 28%. The average length of the appendix was 7.1 cm. Conclusion: Our percentaje of retrocaecal position agreement with other studies in cadaveroys specimens. Some authors have reported high pelvic position especially in black population. Pelvic position in caecal appendix could generate hypogastric pain confusyng the clinical symptoms principaly in women. The results of these investigations are important because the variable anatomical relations are used in clinical imagen of acute appendicitis; furthemore this observations may encourage greater utilization of laparoscopic appendectomy. [Corzo EG, Forero PL, Amaya L, Bohórquez D, Bohórquezx S. Anatomical position and length of caecal appendix in a mixtured population from Bucaramanga. MedUNAB 2009; 12:116-120].