[Phenotyping and genotyping in patients with inflammatory bowel disease in a reference center in Colombia]. / Fenotipificación y genotipificación en pacientes con enfermedad inflamatoria intestinal en un centro de referencia de Colombia.

INTRODUCTION: Attempts have been made to identify the genetic factors related to susceptibility to inflammatory bowel disease (IBD), and the current conclusions are in favor of a complex pathology model, without a clear hereditary pattern. OBJECTIVE: To perform phenotypic and genotypic characterization of patients with IBD in Colombian population and to describe its possible association with predisposition. MATERIALS AND METHODS: case series, 16 patients with IBD according to clinical and pathological criteria, onset of gastrointestinal symptoms after 18 years of age. All had pre-test genetic counseling and family trees of at least three generations were made. Also, genotyping, using a multi-gene panel that included genes related to IBD and some autoimmune disorders. Finally, a genomic analysis of variants was performed. RESULTS: 9 women and 7 men, with mean age of diagnosis of IBD of 35 years, and gastrointestinal symptoms appearance of 32 years. 11/16 (68.75%) required biological therapy. 10/16 (62.5%) were refractory to standard therapy. 3/16 (18.75%) had positive family history of IBD. 100% cases presented at least one single nucleotide polymorphism related to IBD risk in more than one gene. The genes most related to ulcerative colitis (UC) were CD48, CD6, and TYK2 for UC, and CD6 and ITGAM for Crohn's disease. The most frequent gene was CD6. It was found presence of up to 5 genes in 3/16 (18.75%), 4 in 3/16 (18.75%), and three in 5/16 (31.25%). CONCLUSION: In IBD there is the presence of genetic variants with associated predisposition, but without confirmed pathogenicity, and whose sum seems to contribute to its pathophysiology.

[HLA genotypes associated with gastrointestinal symptoms in patients with spondyloarthritis without inflammatory bowel disease]. / Genotipos HLA asociados a síntomas gastrointestinales en pacientes con espondiloartritis sin enfermedad inflamatoria intestinal.

OBJECTIVE: This study aimed to establish the association between HLA-A, B, DR genotypes and gastrointestinal variables in patients with SpA without inflammatory bowel disease (IBD). METHODS: Retrospective study of 91 patients with SpA and 401 healthy controls, with typing by Illumina Sequencing/PacBio and LIFECODES HLA-PCR/SSO multiplex sequencing technology. The presence of gastrointestinal symptoms was evaluated by administering a survey, and those who presented 2 or more symptoms were taken for clinical evaluation by rheumatology and gastroenterology, colonoscopy and histopathological study. (Ethics committee approval). RESULTS: The 59,3% of the patients were men, with a mean age of 43,9±11.4 years; 80,2% were classified as ankylosing spondylitis. 14, 28 and 19 genotypes for the HLA-A*, HLA-B* and HLA-DR* loci were identified in both groups, of which a relationship with gastrointestinal symptoms was identified: A*26, A*29 and B*27 were associated to abdominal pain, DRB1*11 and DRB1*16 with abdominal distention, A*30, B*38, DRB1*13 and DRB1*14 with weight loss, B*40 with diarrhea >4 weeks, and presence of mucus in the stools with A*02 and DRB1*11 (p<0.05). Furthermore, the presence of B*15 had a statistical relationship with intolerance to some food, highlighting the B*27 genotype in relation to grains and dairy products, A*23 with grains, vegetables and meats, and B*49 with vegetables and dairy (p<0.05). Regarding the endoscopic variables, macroscopic changes were found in the ileum mucosa related to A*02, B*48, DRB1*14 and the relationship between B*27 and ulcers at this level should be highlighted. Macroscopic changes in the sigmoid colon with B*48 and the rectum with A*30. In microscopic changes, inflammatory alterations of the ileum are mentioned with genotypes DRB1*07, DRB1*13 and DRB1*14, a genotype that is related to changes in the ileum both endoscopically and histologically (p<0.05). CONCLUSIONS: These findings indicate a potential genetic predisposition related to HLA genotypes that may increase the likelihood of food intolerance, gastrointestinal symptoms, and even visible and microscopic changes, specifically in the ileal tissue. The study highlights the presence of B*27 and other noteworthy HLA class I and class II genes (such as DRB1*14) in the diverse Colombian population.

OBJETIVO: Establecer la asociación entre genotipos HLA-A, B, DR y variables gastrointestinales en pacientes con EspA, sin enfermedad inflamatoria intestinal (EII). MÉTODOS: Estudio retrospectivo de 91 pacientes con EspA y 401 controles sanos, con tipificación por tecnología de secuenciación Illumina Sequencing/PacBio, y LIFECODES HLA-PCR/SSO multiplex. Se evaluó la presencia de síntomas gastrointestinales por aplicación de una encuesta, y, aquellos que presentaran dos o más síntomas, fueron llevados a valoración clínica por reumatología y gastroenterología, colonoscopia y estudio histopatológico. (Aprobación del Comité de Ética, HMC, 2022 - 2020). RESULTADOS: El 59,3% de los pacientes fueron hombres, con edad media de 43,9 ± 11,4 años. El 80,2% se clasificó como espondilitis anquilosante. Se identificaron en ambos grupos 14, 28 y 19 genotipos para los loci HLA-A*, HLA-B* y HLA-DR*, de los cuales se identificó relación con síntomas gastrointestinales: A*26, A*29 y B*27, con dolor abdominal; DRB1*11 y DRB1*16, con distensión abdominal; A*30, B*38, DRB1*13 y DRB1*14, con pérdida de peso; B*40, con diarrea >4 semanas y presencia de moco en las deposiciones con A*2 y DRB1*11 (p<0,05). Además, la presencia de B*15, tuvo relación estadística con intolerancia a algún tipo de alimento, a resaltar el genotipo B*27, en relación con granos y lácteos; A*23 con granos, verduras y carnes; y el B*49, con verduras y lácteos (p<0,05). Frente a las variables endoscópicas, se encontraron cambios macroscópicos en la mucosa de íleon relacionados con A*02, B*48, DRB1*14 y, a destacar, la relación B*27 con úlceras a este nivel. Cambios macroscópicos en colon sigmoides con B*48 y en recto con A*30. En cambios microscópicos, se mencionan alteraciones inflamatorias de íleon con genotipos DRB1*07, DRB1*13 y DRB1*14, genotipos que se relaciona a cambios en íleon tanto endoscópica e histológicamente (p<0,05). CONCLUSIONES: Estos resultados sugieren una posible susceptibilidad genética asociada al HLA, con genotipos que pueden predisponer a intolerancia alimentaria, síntomas gastrointestinales, e incluso, a cambios macroscópicos e histológicos, particularmente en tejido de íleon, entre los cuales está presente el B*27, pero resaltan otros interesantes en HLA clase I, como clase II (DRB1*14), en una población de alto mestizaje como la colombiana.

[HLA alleles heterogeneity in a sample of colombian patients with a diagnosis of psoriatic arthritis]. / Heterogeneidad de alelos HLA, en una muestra de pacientes con diagnóstico de artritis psoriásica en Colombia.

OBJECTIVE: The objective is to describe the HLA allelic frequency in PsA and correlate it with demographic and clinical variables. METHODS: Retrospective study of adult patients with a diagnosis of PsA (n=23) and healthy controls (n=46), all with a request for HLA-A, B, C, DR. Typing was performed using HLA-PCR/SSO LifeCodes and analyzed on the LUMINEX IS100/200 xMAP® system. (Ethics/Code HMC2022-014). RESULTS: One hundred thirty-eight alleles were included from 69 individuals, 43,5% women, aged 44,5±16,5 years in patients with PsA, with a mean age of disease onset of 33.4±14 years. Only 9.5% had a high Body Mass Index and dyslipidemia was the most frequent comorbidity (34.8%), followed by high blood pressure (26,1%). 82% debuted with skin manifestation and once the joint disease was established, the predominance was peripheral (74%) due to arthritis/arthralgia in 74%, enthesitis in 30% and dactylitis in 13%. The allele frequencies were for HLA*A 2402 (13%), 3201 (13%) and 2427 (8,7%), for HLA*B 1402 (17,4%), 4002 (17,4%), 3801 (13%) and HLA*DR 0404 (17,4%), 0407 (13%). No HLA*B27 was identified and HLA*C0602 was only 2,2%. HLA A*0201 and DR*1301 were less frequent in controls versus PsA (p=0.024 and 0,029, respectively), while HLA*B1302 was frequent in PsA (p=0,035). CONCLUSIONS: Curiously, there were no positive results for HLAB*27, which may be related to the population mix. HLA Cw6 is traditionally associated with psoriasis. However, its absence has been linked to nail disorders and PsA; consequently, in our study, it had a low frequency (2,2%). On the other hand, HLA*B1302 has been related to the disease and its early onset; in the healthy Colombian population, it has been described in 0,92%; in our group, it is found to be significant in patients without establishing a clinical association. Few previous studies report HLA results in PsA in Colombia.

OBJETIVO: Describir la frecuencia alélica de HLA en APs y asociarlo con variables demográficas y clínicas. MÉTODOS: Estudio retrospectivo de pacientes adultos con diagnóstico de APs (n=23), y controles sanos (n=46), todos con solicitud de HLA-A, B, C y DR. La tipificación se realizó por medio de HLA-PCR/SSO LifeCodes, y se analizó en el sistema LUMINEX IS 100/200 xMAP®. (Ética/Código HMC2022-014). RESULTADOS: Se incluyeron 138 alelos de 69 individuos, 43,5% mujeres, con edad 44,5±16,5 años, en pacientes con APs, con edad media de inicio de la enfermedad de 33,4±14 años. Solo el 9,5% tuvo Índice de Masa Corporal alto y la dislipidemia fue la comorbilidad más frecuente (34,8%), seguida de hipertensión arterial (26,1%). El 82% debutó con manifestación en piel y una vez establecida la enfermedad articular, el predominio fue periférico (74%), por artritis/artralgias en un 74%, entesitis en 30%, y dactilitis 13%. Las frecuencias alélicas fueron para HLA*A 2402 (13%), 3201 (13%) y 2427 (8,7%), para HLA*B 1402 (17,4%), 4002 (17,4%), 3801 (13%) y HLA*DR 0404 (17,4%), 0407 (13%). No se identificó HLA*B27 y HLA*C0602 fue solo del 2,2 %. HLA A*0201 y DR*1301 fueron menos frecuentes en controles versus APs (p=0,024 y 0,029, respectivamente), mientras que HLA*B1302 frecuente en APs (p=0,035). CONCLUSIÓN: Curiosamente no hubo resultados positivos para HLAB*27 y esto puede relacionarse con el mestizaje de la población. HLA Cw6 es tradicionalmente asociado a psoriasis, sin embargo, su ausencia se ha relacionado con mayor reporte de alteraciones ungueales y Aps; como consecuencia, en nuestro estudio tuvo una baja frecuencia (2,2%). Por otro lado, el HLA*B1302 ha tenido relación con la enfermedad y su inicio temprano, en población sana colombiana se ha descrito en 0,92%, en nuestro grupo se encuentra de manera significativa en los pacientes sin establecerse asociación clínica. Pocos estudios previos refieren resultados de HLA en APs en Colombia.

[Faecal microbiota study reveals specific dysbiosis in spondyloarthritis according to subtype, disease activity and treatment]. / Estudio de microbiota fecal revela disbiosis específica en espondiloartritis, según subtipo, actividad de la enfermedad y tratamiento.

OBJECTIVE: To compare the diversity and composition of the gastrointestinal microbiome of patients with SpA. METHODS: MiSeq sequencing of the V3-V4 region of the 16S ribosomal RNA gene was performed on DNA isolated from stool. Patients with concurrent SpA and IBD were excluded. Differences were assessed for richness and diversity indices by QIIME 2™. Differences between means >0,2% with a p-value<0,05 were assumed significant. Institutional Ethics Committee endorsement. RESULTS: 69 individuals included, 49 with SpA (ankylosing spondylitis-AS 72,9%, psoriatic arthritis-PsA 18,8%, reactive arthritis-ReA 8,3%) 5 positive controls-dysbiosis and 15 controls-eubiosis. Conventional treatment in 42,9%, anti-IL-17 16,3% and anti-TNF 40,8%. By subtype, statistically significant differences in favour of AS were found for the diversity indices. AS vs PsA there was a difference in favour of AS for Clostridium clostridioforme (p=0,002), Gemmiger formicilis (p=0,009), Roseburia inulivorans (p=0,008) and Lachnospira pectinoschiza. AS vs ReA there was a difference in favour of AS for L. pectinoschiza (p=0,009), Ruminococcus callidus (p=0.006), Clostridium ruminantium (p=0.031); G. formicilis (p=0,034). Diversity and richness showed differences in patients with high activity for Simpson's and Pielou's indices. In high activity, lower enrichment of Bacteroides eggerthii (p= 0,0003), C. ruminantium (p= 0,026) and Alistipes putredinis (p=0,035) was found. The number of ASV was higher in the anti-IL-17 vs conventional group (p=0.025) and a trend between anti-IL-17 vs anti-TNF (p=0.09). In anti-TNF there was a lower proportion for C. clostridioforme (p=0.023), G. formicilis (p=0.030) and R. callidus (p= 0.003). In anti IL-17, Alistipes indistinctus (p= 0.012) was decreased. CONCLUSIONS: There are differences in microbial diversity for SpA subtypes. The level of disease activity is plausible to influence the composition of the faecal microbiota. Anti-TNFα treatment may influence the microbiome environment favouring restoration of the gut microbiota, while anti-IL-17 may maintain an inflammatory environment.

OBJETIVO: Comparar la diversidad y composición del microbioma gastrointestinal de pacientes con EspA. MÉTODOS: La secuenciación MiSeq de la región V3-V4 del gen ARN ribosomal 16, se realizó en ADN aislado de heces. Se excluyeron pacientes con EspA y EII simultánea. Se evaluaron diferencias para los índices de riqueza y diversidad por medio de QIIME 2™. Las diferencias entre medias> 0,2%, con un valor de p< 0,05, se asumieron significativas. Aval del Comité de Ética Institucional. RESULTADOS: 69 individuos incluidos, 49 con EspA (espondilitis anquilosante-EA 72,9%, artritis psoriásica-APs 18,8%, artritis reactiva-ARe 8,3%), cinco controles positivos-disbiosis y 15 controles-eubiosis. El tratamiento convencional en 42,9%, anti-IL-17 16,3%, y anti-TNF 40,8%. Por subtipo-EasP, se encontraron diferencias estadísticamente significativas a favor de EA para los índices de diversidad. Entre EA vs APs, hubo diferencia a favor de EA para Clostridium clostridioforme (p=0,002), Gemmiger formicilis (p=0,009), Roseburia inulivorans (p=0,008) y Lachnospira pectinoschiza. Entre EA vs ARe hubo diferencia a favor de EA para L. pectinoschiza (p=0,009), Ruminococcus callidus (p = 0,006), Clostridium ruminantium (p=0,031); G. formicilis (p=0,034). La diversidad y riqueza mostraron diferencias en pacientes con alta actividad para los índices de Simpson y Pielou. En alta actividad, se encontró menor enriquecimiento de Bacteroides eggerthii (p=0,0003), C. ruminantium (p= 0,026) y Alistipes putredinis (p= 0,035). El número de ASV fue superior en el grupo de anti IL-17 vs convencional (p=0.025), y una tendencia entre anti IL-17 vs anti-TNF (p=0,09). En anti TNF hubo menor proporción para C. clostridioforme (p=0,023), G. formicilis (p=0,030) y R. callidus (p= 0,003). Y en anti IL-17, Alistipes indistinctus (p= 0,012), estuvo disminuida. CONCLUSIONES: Existen diferencias en la diversidad microbiana para los subtipos de EspA. El nivel de actividad de la enfermedad es plausible para influir en la composición de microbiota fecal. El tratamiento con anti-TNFα, puede influenciar el ambiente del microbioma favoreciendo la restauración de la microbiota intestinal, mientras los anti IL-17 podrían mantener un ambiente inflamatorio.

Posttranslational modifications in psoriatic arthritis: A systematic literature review.

BACKGROUND AND AIMS: Psoriatic arthritis (PsA) is an inflammatory complex condition. Posttranslational modifications influence almost all aspects of normal cell biology and pathogenesis. The aim of this systematic review was to collect all published evidence regarding posttranslational modifications in PsA, and the main outcome was to evaluate an association between disease outcomes and specific posttranslational modifications in PsA. METHODS: A systematic electronic search was performed in Medline, PubMed, Cochrane, Virtual Health Library, and Embase databases. A total of 587 articles were identified; 59 were evaluated after removing duplicates and scanning, of which 47 were included. A descriptive analysis was conducted, with results grouped according to the type of posttranslational modification evaluated. The protocol was registered at the PROSPERO database. RESULTS: Seven posttranslational modifications were identified: citrullination, carbamylation, phosphorylation, glycosylation, acetylation, methylation, and oxidative stress. Anti-citrullinated peptide and anti-carbamylated protein have been evaluated in rheumatoid arthritis. There is now information suggesting that these antibodies may be helpful in improving the diagnosis of PsA and that they may demonstrate a correlation with worse disease progression (erosions, polyarticular involvement, and poor treatment response). Glycosylation was associated with increased inflammation and phosphorylation products related to the expression of SIRT2 and pSTAT3 or the presence of Th17 and cytokine interleukin-22, suggesting a possible therapeutic target. CONCLUSIONS: Posttranslational modifications often play a key role in modulating protein function in PsA and correlate with disease outcomes. Citrullination, carbamylation, phosphorylation, glycosylation, acetylation, methylation, and oxidative stress were identified as associated with diagnosis and prognosis.

Differences in the distribution of hemoglobin variants according to the geographic regions in a Colombian population

ABSTRACT Introduction: Colombia has been subject to intense genetic and cultural currents due to its geographical location. Hemoglobinopathies are the most common recessive diseases found worldwide and represent an important public health problem, according to the region and ancestry of each country. Objectives: To evaluate the frequency of hemoglobin variants according to the geographical region in a population group adjusted to sex and age in Colombia. Methods: This was a descriptive retrospective study of hemoglobin variants performed by electrophoresis in patients treated at and/or referred to specialized care institutions in Bogota, Colombia between January 2009 and December 2020. Results: A total of 2,224 results were analyzed, 48.4% male and 51.5% female; 63.3% of patients were without alterations, 14.3% presented with thalassemia, 17.3%, HbS, 2.3%, HbS/C, 1.8%, HbC, 0.5%, HbE and 0.5% persistent HbF, with HbS being more prevalent in males (p = 0.005). When assessing the geographical regions of Colombia, a higher prevalence of HbS was found in the Pacific (p = 0.005) and Caribbean regions, while Thalassemia and HbS were more prevalent in the Andean and Orinoquia regions, and it was rare to find any hemoglobinopathies (p = 0.0001) in the Amazonian region. Conclusions: The main hemoglobinopathies found in Colombia are HbS, predominantly in males, and Thalassemia. The distribution of hemoglobinopathies in different geographical regions of Colombia is influenced by ancestry.

Metastatic Crohn's disease: a difficult diagnosis from different perspectives

Metastatic Crohn's disease (MCD) is a rare cutaneous manifestation of Crohn's disease (CD). The simultaneous involvement of the vulva and oral region is uncommon in clinical presentations of MCD. We present the case of a middle-aged woman with a family history of autoimmunity who initially presented with oral and vulvoperineal involvement. Initially, Behçet's disease was ruled out, but histopathological studies of the vulva revealed findings compatible with MCD. The patient had no gastrointestinal symptoms, and fecal calprotectin levels were normal. Upper and lower endoscopic examinations and capsule endoscopy of the small intestine (SI) did not reveal any significant findings. Treatment with anti-tumor necrosis factor (anti-TNF) agents was initiated but resulted in paradoxical psoriasis with adalimumab and infliximab. Cyclosporine was also used, but the patient experienced intolerable tachycardia. After 18 months, the patient developed episcleritis and experienced diarrhea accompanied by cramp-like abdominal pain. Repeat upper and lower endoscopic examinations showed normal results, while capsule endoscopy of the SI revealed CD enteritis. The patient was diagnosed with CD of the small intestine, along with extraintestinal manifestations of vulvoperineal MCD, oral involvement, and episcleritis. Management with azathioprine and ustekinumab was initiated, resulting in significant clinical improvement. MCD poses a diagnostic challenge due to its unusual manifestations. It may present without gastrointestinal tract involvement, mimicking other conditions. Therefore, timely diagnosis and the selection of the most appropriate therapeutic strategy are crucial.

La enfermedad de Crohn metastásica (ECM) es una entidad rara, es una manifestación cutánea en enfermedad Crohn (EC), y en su presentación clínica es inusual el compromiso vulvar y oral de modo concomitante. Se describe el caso de una mujer de edad media que tiene historia familiar de autoinmunidad, presenta inicialmente compromiso oral y vulvoperineal. En su abordaje inicial se descartó enfermedad de Behçet, pero los estudios histopatológicos a nivel vulvar tuvieron hallazgos compatibles para ECM. Hubo ausencia de síntomas gastrointestinales y sus niveles de calprotectina fecal eran normales. Los estudios endoscópicos altos y bajos, y la cápsula endoscópica del intestino delgado (ID) no tuvieron hallazgos relevantes. Se inició el tratamiento con antifactor de necrosis tumoral (anti-TNF) y presentó una psoriasis paradójica con adalimumab e infliximab. También se utilizó ciclosporina y presentó una taquicardia intolerable. 18 meses después de estos síntomas tuvo epiescleritis e inició con diarrea asociada a dolor abdominal tipo cólico, por lo que se repitieron los estudios endoscópicos altos y bajos, que resultaron normales, y cápsula endoscópica de ID mostró una enteritis por EC. Se consideró EC de ID con manifestaciones extraintestinales y con ECM vulvoperineal, compromiso oral y epiescleritis. Se requirió manejo con azatioprina y ustekinumab, con una mejoría clínica significativa. La ECM es un reto diagnóstico, pues es una manifestación inusual; en su debut puede haber ausencia de compromiso en el tracto gastrointestinal y también simular otras entidades. Debe buscarse lograr el diagnóstico oportuno y la estrategia terapéutica más segura.

Porphyromonas gulae and PPAD antibodies are not related to citrullination in rheumatoid arthritis.

INTRODUCTION: Porphyromonas gulae have the enzyme PPAD, as P. gingivalis, which is responsible for citrullination related to the pathophysiology of rheumatoid arthritis and periodontitis; this implies the presence of two species of PPAD-producing bacteria in the mouth as well as the presence of citrullinated proteins. There are no previous reports or studies investigating an association between P. gulae PPAD in rheumatoid arthritis (RA). OBJECTIVE: To assess the presence of P. gulae and anti-citrullinated peptide antibodies of P. gulae PAD in patients with RA and their possible relationship with clinical activity markers. SUBJECTS AND METHODS: A total of 95 patients with RA and 95 controls were included. Erythrocyte sedimentation rate (ESR), C-reactive protein, anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF) were measured. Activity index-28 (DAS28) and SCDAI. The periodontal diagnosis was established. Presence of P. gulae and P. gingivalis. An ELISA was used to determine antibodies against citrullinated peptides of P. gulae PAD. RESULTS: A P. gulae frequency of 15.8% was observed in the RA group and 9.5% in the control group. Higher levels of ACPA were found in the P. gulae-positive patients of the RA group, finding no significant difference, but if in patients positive for P. gingivalis with statistical significance (p = 0.0001). The frequency of anti-VDK-cit and anti-LPQ-cit9 antibodies to PPAD of P. gulae was higher in the RA group than in the control group without significant difference. No relationship was found with the clinical variables despite the presence of P. gulae and anti-citrullinated peptide antibodies of P. gulae PPAD in patients with RA CONCLUSIONS: It was not possible to establish a connection with clinical variables in RA and P. gulae; as a result, the presence of P. gingivalis continues to contribute significantly to the increase in antibodies against citrullinated proteins/peptides from exogenous sources of citrullination in RA and periodontitis.

The Interaction Effect of Anti-RgpA and Anti-PPAD Antibody Titers: An Indicator for Rheumatoid Arthritis Diagnosis.

Porphyromonas gingivalis secretes virulence factors like Arg-gingipains and peptidyl arginine deiminase (PPAD), that are associated with rheumatoid arthritis (RA) pathogenesis. However, there is no information regarding the antibody titers for these bacterial enzymes as systemic indicators or biomarkers in RA. In this cross-sectional study, 255 individuals were evaluated: 143 were diagnosed with RA, and 112 were without RA. Logistic regression models adjusted for age, sex, basal metabolic index, smoking, and periodontitis severity were used to evaluate the association of RA with rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPAs), erythrocyte sedimentation rate, high sensitivity C-reactive protein, anti-RgpA, anti-PPAD, and double positive anti-RgpA/anti-PPAD. It was found that RF (odds ratio [OR] 10.6; 95% confidence interval [CI] 4.4-25), ACPAs (OR 13.7; 95% CI 5.1-35), and anti-RgpA/anti-PPAD double positivity (OR 6.63; 95% CI 1.61-27) were associated with RA diagnoses. Anti-RgpA was also associated with RA (OR 4.09; 95% CI 1.2-13.9). The combination of anti-RgpA/anti-PPAD showed a high specificity of 93.7% and 82.5% PPV in identifying individuals with RA. RgpA antibodies were associated with the periodontal inflammatory index in RA individuals (p < 0.05). The double positivity of the anti-RgpA/anti-PPAD antibodies enhanced the diagnosis of RA. Therefore, RgpA antibodies and anti-RgpA/anti-PPAD may be biomarkers for RA.

Colonoscopy aspiration lavages for mucosal metataxonomic profiling of spondylarthritis-associated gastrointestinal tract alterations.

The study of the GI-tract microbiota of spondylarthritis (SpA) patients has focused on the analysis of feces samples, that picture mostly the luminal microbiota. The aim of this study was to determine the contribution of mucosal and luminal microbiome to the gut dysbiosis in SpA, using colonoscopy aspiration lavages (CAL), a recent alternative for regional studies of the GI-tract. We analyzed 59 CAL (from sigmoid colon and distal ileum), and 41 feces samples, from 32 SpA patients and 7 healthy individuals, using 16S rRNA gene-targeted metataxonomic profiling. It was found high prevalence of GI-tract manifestations among SpA patients (65.3%). Metataxonomic profiling, confirmed CAL samples from the lower GI tract (colon or ileum) presented a distinctive and undifferentiated bacteriome and separate from that found in feces' samples or in the beginning of the GI tract (oral cavity (OC)). Lower GI-tract samples and feces of SpA patients exhibited similar behavior to the microbiota of IBD group with reduced microbial richness and diversity, comparing to the healthy controls. Interestingly, it was found increase in proinflammatory taxa in SpA patients, such as Enterobacteriaceae family (mostly in the ileum), Succinivibrio spp. and Prevotella stercorea. Conversely, SpA patients presented significant decrease in the SCFA producers Coprococcus catus and Eubacterium biforme. Our data support the value of CAL samples for the regional study of GI-tract and contribute with information of potential "disruptor taxa" involved in the GI-tract associated disorders observed in SpA patients.

Expression of Homing Receptors in IgM+IgD+CD27+ B Cells and Their Frequencies in Appendectomized and/or Tonsillectomized Individuals.

BACKGROUND: In humans, blood circulating IgM+IgD+CD27+ B cells are considered analogous to those described in the marginal zone of the spleen and are involved in important immunological processes. The homing receptors they express, and the organs involved in their development (for example, intestinal organs in rabbits) are only partially known. We recently reported that this population is heterogeneous and composed of at least two subsets: one expressing high levels of IgM - IgMhi B cells - and another low levels - IgMlo B cells. OBJECTIVES: To evaluate the expression of homing receptors on IgD+CD27+ IgMhi and IgMlo B cells and quantify their frequencies in blood of control and appendectomized and/or tonsillectomized volunteers. MATERIALS AND METHODS: Using spectral flow cytometry, the simultaneous expression of 12 previously reported markers that differentiate IgMhi B cells and IgMlo B cells and of α4ß7, CCR9, CD22 and CCR10 were evaluated in blood circulating B cells of control and appendectomized and/or tonsillectomized volunteers. RESULTS: The existence of phenotypically defined IgMlo and IgMhi B cell subsets was confirmed. They differentially expressed intestinal homing receptors, and the expression of α4ß7 and CCR9 seems to determine new IgM subpopulations. IgMlo and IgMhi B cells were detected at lower frequencies in the appendectomized and/or tonsillectomized volunteers relative to controls. CONCLUSIONS: Human blood circulating IgD+CD27+ IgMlo and IgMhi B cell subsets differentially express homing receptors, and it is necessary to investigate if mucosal organs are important in their development.

Shared epitope classification methods according to Gregersen and de Vries allow adequate characterization of patients with rheumatoid arthritis in a Colombian population

Introduction: The most important genetic association in rheumatoid arthritis (RA) is presented with some alleles from the HLA-DRB1 gene that encode the shared epitope (SE). Objectives: To apply the SE classification methods of Gregersen, de Vries, Raychaudhuri, Mattey, and Tezenas du Montcel in a group of Colombian patients with RA and determine the most common HLA-DRB1 alleles in the population. Methods: RA diagnosis, genetic study of the HLA-DRB1 region using Luminex technology in 50 RA and 50 healthy subjects. For the classification analysis, Fisher's exact test and chi-squared test were applied. Tables were created to count the RA-related alleles. We used odds ratio to determine the risk between the presence of the shared epitope (SE) and anti-cyclic citrullinated peptides (Anti-CCP). Results: Gregersen and de Vries methods were suitable for the characterization of RA in this population (p = .006). The most prevalent HLA-DRB1 alleles in the RA group were 14:02,04:04, 08:02,04:05, and 10:01. High frequencies of the 07:01, 03:01,13:02,01:02, and 12:01 HLA-DRB1 alleles were found in the healthy population. HLA-DRB1 alleles with similar distribution in both populations were 04:07, 15:01, 11:01, 16:02, and 01:01. A high frequency of SE + was observed in Anti-CCP + individuals (63.15%); however, this was not statistically significant [OR2.4 (.63-9.01); p = .19]. Conclusion: The SE classification methods of Gregersen and de Vries were adequate in characterizing RA in a Colombian population group. An equivalence of 100% was verified between the susceptibility alleles defined by de Vries and the alleles assigned as SE according to Gregersen.

Introducción: La asociación genética más importante en artritis reumatoide (AR) se presenta con algunos alelos del gen HLA DRB1 que codifican el epítope compartido (EC). Objetivos: Aplicar los métodos de clasificación de EC de Gregersen et al., de Vries et al., Raychaudhuri et al., Mattey et al., y Tezenas du Montcel et al., en un grupo de pacientes colombianos con AR, y determinar los alelos HLA DRB1 más frecuentes en esta población. Métodos: Diagnóstico para AR, estudio genético de la región HLA DRB1 por tecnología Luminex® de 50 sujetos AR y 50 sanos. Para análisis comparativos de clasificaciones EC, se aplicaron las pruebas test exacto de Fisher y Chi-cuadrado y se realizaron tablas de conteos para los alelos relacionados con AR. Se estimó la razón de odds para determinar el riesgo entre la presencia de EC y los anticuerpos antipéptidos cíclicos citrulinados (anti-PCC). Resultados: Los métodos de Gregersen et al. y de Vries et al. fueron adecuados para la caracterización de AR en esta población (p = 0,006). Los alelos HLA DRB1 más prevalentes en el grupo AR fueron 14:02, 04:04, 08:02, 04:05 y 10:01. Se encontraron altas frecuencias de los alelos HLA DRB1 07:01, 03:01,13:02, 01:02 y 12:01 en población sana. Alelos HLA DRB1 con distribución similar en ambas poblaciones fueron: 04:07, 15:01, 11:01, 16:02 y 01:01. Se observó alta frecuencia de individuos EC+ en el grupo AR anti-PCC+ (63,15%); no obstante, sin asociación estadística (OR: 2,4 [0,63-9,01]; p = 0,19). Conclusión: Los métodos de clasificación para EC de Gregersen et al. y de Vries et al. fueron adecuados caracterizando AR en un grupo de población colombiana. Se corroboró equivalencia del 100% entre los alelos de susceptibilidad definidos por de Vries y los alelos asignados como EC según Gregersen et al.

Adipokine Profile on Joint and Periodontal Conditions in First-degree Relatives of Patients with Rheumatoid Arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by joint inflammation and destruction. OBJECTIVE: Establish the association between Porphyromonas gingivalis (P. gingivalis) infection, body mass index (BMI), joint involvement, and serum adipokines in first-degree relatives (FDR) of patients with rheumatoid arthritis (RA). METHODS: The cross-sectional study evaluated 124 FDR and 124 healthy controls (HC). The clinical examination included joint and radiographic evaluation and calculation of BMI. Serum adipokine levels were measured (leptin, vaspin, adiponectin, resistin, and adipsin), as were the erythrocyte sedimentation rate, C-reactive protein, and anti-citrullinated protein antibodies. Investigations were performed to detect P. gingivalis, and anti-P. gingivalis antibodies. Statistical analyses were performed to confirm associations. RESULTS: Leptin levels in FDR were associated with BMI >25 (OR, 2.64; 95%CI, 1.17-5.97; P=0.019), radiographic damage (Simple Erosion Narrowing Score [SENS])/hands, total SENS, and joint space narrowing in feet (P=0.037, 0.026, 0.020, respectively). FDR had more tender joints (P=0.018); this finding was associated with high levels of leptin and resistin and low levels of adipsin (P=0.040, 0.040, and 0.019, respectively). The presence of P. gingivalis was related to FDR, low levels of adipsin, resistin, adiponectin, and a trend toward higher levels of leptin (P=0.002, 0.001, 0.003, and 0.060, respectively), whereas anti-P. gingivalis antibodies were related to low levels of adipsin (P=0.001). CONCLUSION: In FDR, serum adipokine levels were associated with overweight and the presence of P. gingivalis. Adipokine levels were also associated with joint involvement. Hence, adipokines may be involved in the pathogenesis of RA in FDR and warrant further investigation.

Purification of RgpA from external outer membrane vesicles of Porphyromonas gingivalis.

INTRODUCTION: Purification of native gingipains is challenging because these proteases are frequently associated with the cell surface, which affects yield. This study aimed to purify native Arg-gingipain (RgpA) from Porphyromonas gingivalis Outer Membrane Vesicles (OMV). METHODS: Native RgpA was purified from P. gingivalis strain ATCC33277 OMV using a strategy including ultracentrifugation, sonication, and successive anionic and cationic fast protein liquid chromatography (FPLC). The presence and purity of the protease were confirmed by SDS-PAGE and detection of protease activity using fluorogenic substrates. Rat antibodies produced against the unique adhesin hemagglutinin (H1) domain of RgpA (amino acids 719-865) were titrated by ELISA at a 1:100 dilution using whole P. gingivalis lysate as an antigen and western blotting to detect a 75 kDa band corresponding to RgpA. RESULTS: Double anionic-cationic FLPC yielded prominent peaks with evident amidolytic gingipain activity of the appropriate molecular weight, as confirmed by western blotting. The final RgpA yield from 1 L of bacterial culture with colony forming unit (CFU) (Log10) 7.4 ± 0.08/mL was of 12.6% (2 mg/mL), with 3.2 FU/µg of amidolytic activity. CONCLUSIONS: This protocol allows purification of native RgpA from OMV that retains protease activity.

2021 clinical practice guideline for the early detection, diagnosis, treatment, and monitoring of patients with axial spondyloarthritis. Colombian Association of Rheumatology / Guía de práctica clínica 2021 para la detección temprana, el diagnóstico, el tratamiento y el seguimiento de los pacientes con espondiloartritis axial. Asociación Colombiana de Reumatología

Abstract Introduction: Axial spondyloarthritis is a rheumatic condition affecting young patients with social and occupational consequences. Diagnosis delay is associated with functional impairment and impact on quality of life, requiring a multidisciplinary approach. Objective: To develop a set of recommendations based on the best available evidence for the early detection, diagnosis, treatment, and monitoring of adult patients with axial spondy-loarthritis. Methods: A working group was established, questions were developed, outcomes were graded, and a systematic search for evidence was conducted. A multidisciplinary panel of members was established (including patient representatives), minimizing bias in relation to conflicts of interest. The GRADE approach "Grading of Recommendations Assessment, Development and Evaluation" was used to assess the quality of the evidence as well as the direction and strength of recommendations. In total, 11 recommendations on diagnosis (n=2), pharmacological treatment (n=6), non-pharmacological treatment (n=2) and monitoring (n=1) are presented. Results: Sacroiliac joint radiography as the first diagnostic method, and the use of disease activity scales for patient monitoring (ASDAS or BASDAI), are recommended. Nonsteroidal anti-inflammatory drugs are the first treatment option; in case of intolerance or residual pain, acetaminophen or opioids are recommended. In patients with axial involvement, it is recommended not to use conventional disease-modifying antirheumatic drugs or systemic or local glucocorticoids. In patients with failure to non-steroidal anti-inflammatory drugs, anti-TNF or anti-IL17A are recommended. In those patients presenting with anti-TNF failure, starting an anti-IL17A is recommended. Exercise, physical and occupational therapy are recommended as part of treatment. It is recommended not to use unconventional therapies as the only treatment option. Conclusions: This set of recommendations provides an updated guideline for the diagnosis, treatment, and monitoring of patients with axial spondyloarthritis.

RESUMEN Introducción: La espondiloartritis axial es una enfermedad reumatológica que afecta a individuos jóvenes y tiene una gran repercusión sociolaboral. El retraso en el diagnóstico y el tratamiento se asocia con un mayor deterioro funcional y un impacto negativo en la calidad de vida, por lo que requiere un abordaje multidisciplinario. Objetivo: Desarrollar y formular un conjunto de recomendaciones específicas basadas en la mejor evidencia disponible para la detección temprana, el diagnóstico, el tratamiento y el seguimiento de los pacientes adultos con espondiloartritis axial. Métodos: Se configuró un grupo desarrollador, se formularon preguntas clínicas contestables, se graduaron los desenlaces y se realizó la búsqueda sistemática de la evidencia. El panel de la guía fue multidisciplinario (incluyendo representantes de los pacientes) y balanceado, minimizando el sesgo por conflictos de intereses. Se utilizó la aproximación Grading of Recommendations Assessment, Development and Evaluation (GRADE) para evaluar la calidad de la evidencia, al igual que la dirección y la fortaleza de las recomendaciones. Se presentan 11 recomendaciones relacionadas con diagnóstico (n = 2), tratamiento farmacológico (n = 6), tratamiento no farmacológico (n = 2) y seguimiento (n = 1). Resultados: Se recomienda la radiografía de articulaciones sacroilíacas como primer método diagnóstico, y el uso de escalas de actividad para el seguimiento de los pacientes (ASDAS o BASDAI). Los antiinflamatorios no esteroideos son la primera opción de tratamiento; en caso de intolerancia o dolor residual se recomienda acetaminofén u opioides. En pacientes con compromiso axial se recomienda abstenerse de utilizar medicamentos antirreumáticos modificadores de la enfermedad convencionales ni glucocorticoides sistémicos o locales. En pacientes con falla a los antiinflamatorios no esteroideos, se recomienda un anti-TNFα o un anti-IL17A. En pacientes con falla a anti-TNFα, se recomienda iniciar un anti-IL17A. El ejercicio y la terapia física y ocupacional se recomiendan como parte del tratamiento. Se recomienda no utilizar las terapias no convencionales como única opción de tratamiento. Conclusiones: Este conjunto de recomendaciones proporciona una guía actualizada sobre el diagnóstico y el tratamiento de la espondiloartritis axial.

2021 clinical practice guideline for the early detection, diagnosis, treatment, and monitoring of patients with axial spondyloarthritis. Colombian Association of Rheumatology.

BACKGROUND: Axial Spondyloarthritis is a rheumatic condition affecting young patients with social and occupational consequences. Diagnosis delay is associated with functional impairment and impact on quality of life, requiring a multidisciplinary approach. OBJECTIVE: To develop a set of recommendations based on the best available evidence for early detection, diagnosis, treatment and monitoring adult patients with axial spondyloarthritis. METHODS: A working group was established, questions were developed, outcomes were graded, and a systematic search for evidence was conducted. A multidisciplinary panel of members was established (including patient representatives), minimizing bias in relation to conflicts of interest. The GRADE approach "Grading of Recommendations Assessment, Development and Evaluation" was used to assess the quality of the evidence as well as the direction and strength of recommendations. In total, 11 recommendations with regard to diagnosis (n = 2), pharmacological treatment (n = 6), non-pharmacological treatment (n = 2) and monitoring (n = 1) are presented. RESULTS: Sacroiliac joint radiography as the first diagnostic method, and the use of disease activity scales for patient monitoring (ASDAS or BASDAI), are recommended. Nonsteroidal anti-inflammatory drugs are the first treatment option; in case of intolerance or residual pain, acetaminophen or opioids are recommended. In patients with axial involvement, it is recommended not to use conventional disease-modifying antirheumatic drugs or systemic or local glucocorticoids. In patients with failure to non-steroidal anti-inflammatory drugs, anti-TNF or anti-IL17A is recommended. In those patients presenting with anti-TNF failure, starting an anti-IL17A is recommended. Exercise, physical and occupational therapy are recommended as part of treatment. It is recommended not to use unconventional therapies as the only treatment option. CONCLUSIONS: This set of recommendations provides an updated guide on the diagnosis, treatment and monitoring of patients with axial spondyloarthritis.

2021 clinical practice guidelines for the diagnosis, treatment, and follow-up of patients with peripheral spondyloarthritis. Colombian Association of Rheumatology / Guía de práctica clínica 2021 para el diagnóstico, el tratamiento y el seguimiento de pacientes con espondiloartritis periférica. Asociación Colombiana de Reumatología

ABSTRACT Background: Peripheral spondylarthritis is a chronic Inflammatory disease whose clinical presentation is related to the presence of arthritis, enthesitis and/or dactylitis. This term is used interchangeably with some of its subtypes such as psoriatic arthritis, reactive arthritis, and undifferentiated spondyloarthritis. Objective: To develop and formulate a set of specific recommendations based on the best available evidence for the diagnosis, treatment, and monitoring of adult patients with peripheral spondyloarthritis. Methods: A working group was established, clinical questions were formulated, outcomes were graded, and a systematic search for evidence was conducted. The guideline panel was multidisciplinary (including patient representatives) and balanced. Following the for mal expert consensus method, the GRADE methodology "Grading of Recommendations Assessment, Development and Evaluation" was used to assess the quality of the evidence and generate the recommendations. The clinical practice guideline includes ten recommendations related to monitoring of disease activity (n = 1) and treatment (n = 9). Results: In patients with peripheral spondyloarthritis, the use of methotrexate or sulfasalazine as the first line of treatment is suggested, and local injections of glucocorticoids are conditionally recommended. In patients with failure to cDMARDs, an anti TNFα or an anti IL17A is recommended. In case of failure to bDMARDs, it is suggested to use another bDMARD or JAK inhibitor. In patients with peripheral spondylarthritis associated with inflammatory bowel disease, it is recommended to start treatment with cDMARDs; in the absence of response, the use of an anti TNFα over an anti-IL-17 or an anti-IL-12-23 is recom mended as a second line of treatment. In patients with psoriatic arthritis, the combined use of methotrexate with a bDMARD is conditionally recommended for optimization of dosing. To assess disease activity in Psoriatic Arthritis, the use of DAPSA or MDA is suggested for patient monitoring. Conclusions: This set of recommendations provides an updated guideline on the diagnosis and treatment of peripheral spondyloarthritis.

RESUMEN Antecedentes: La espondiloartritis periférica es una patología Inflamatoria crónica cuya presentación clínica está determinada por la presencia de artritis, entesitis y/o dactilitis. Este término se utiliza indistintamente con algunos de sus subtipos como artritis psoriásica, artritis reactiva y espondiloartritis indiferenciada. Objetivo: Desarrollar y formular un conjunto de recomendaciones específicas basadas en la mejor evidencia disponible para el diagnóstico, el tratamiento y el seguimiento de pacientes adultos con espondiloartritis periférica. Métodos: Se constituyó un grupo desarrollador, se formularon preguntas clínicas, se graduaron los desenlaces y se realizó la búsqueda sistemática de la evidencia. El panel de la guía fue multidisciplinario (incluyendo representantes de los pacientes) y balanceado. Siguiendo el método de consenso formal de expertos, se utilizó la metodología GRADE (Grading of Recommendations Assessment, Development and Evaluation) para para evaluar la calidad de la evidencia y generar las recomendaciones. La guía de práctica clínica incluye 10 recomendaciones: una sobre seguimiento de la actividad de la enfermedad y nueve sobre tratamiento. Resultados: En pacientes con espondiloartritis periférica se sugiere usar metotrexato o sulfasalazina como primera línea de tratamiento y se recomienda en forma condicional la inyección local de glucocorticoides. En los pacientes que fallan a cDMARDs, se recomienda iniciar un anti TNFα o un anti IL17A. Ante falla terapéutica a la primera línea con bDMARDs, se sugiere usar otro bDMARD o un inhibidor JAK. En pacientes con espondiloartritis periférica y enfermedad inflamatoria intestinal asociada, se recomienda iniciar tratamiento con cDMARDs; en ausencia de respuesta, se recomienda el uso de un anti TNFα sobre un anti IL-17 o un anti IL-12-23 como segunda línea de tratamiento. En pacientes con artritis psoriásica se recomienda, de forma condicional, el uso combinado de metotrexato con bDMARD para favorecer la optimización de la dosis de estos. Para evaluar la actividad de la enfermedad en artritis psoriásica, se sugiere el uso del DAPSA o MDA para el seguimiento de los pacientes. Conclusiones: Este conjunto de recomendaciones proporcionan una guía actualizada sobre el diagnóstico y el tratamiento de la espondiloartritis periférica.

Aspectos clave en la vacunación contra la COVID-19 en pacientes con enfermedad inflamatoria intestinal / Key aspects in vaccination against COVID-19 in patients with inflammatory bowel disease

Resumen Actualmente, la pandemia por la enfermedad por coronavirus de 2019 (COVID-19) ha sido uno de los grandes retos para el personal de la salud y se ha convertido en un mayor desafío cuando hay pacientes con enfermedad inflamatoria intestinal (EII); debido a la fisiopatología de la enfermedad y los tratamientos utilizados, se pueden generar interrogantes difíciles de contestar ante el corto tiempo de evidencia científica existente sobre la vacunación para coronavirus del síndrome respiratorio agudo grave de tipo 2 (SARS-CoV-2). Es claro que la vacunación es una de las intervenciones de salud pública más efectivas para lograr una inmunidad colectiva en esta pandemia; por tal motivo, se realiza una revisión enfocada en los aspectos claves frente a la vacunación para la infección por SARS-CoV-2 en los pacientes con EII según la evidencia disponible.

Abstract Currently, the coronavirus disease 2019 (COVID-19) pandemic has been one of the great challenges for health personnel and has become a greater challenge when we have patients with inflammatory bowel disease (IBD); because of the pathophysiology of the disease and the treatments used, it can generate questions that are difficult to answer given the short time of scientific evidence that we have on vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The vaccination is one of the most effective public health interventions to get immunity in this pandemic; for this reason, we made a review with the key aspects about vaccination for infection by SARS-CoV-2 in patients with IBD according to the available evidence.

P048 Metastatic Crohn's Disease Debuting with Severe Oral Manifestation and Vulvar Involvement - A Diagnostic Challenge.

CASE: Background: Metastatic Crohn's disease (MCD) is an unusual cutaneous manifestation in Crohn's disease (CD), and concomitant oral and vulvar involvement is even more unusual. It can debut with cavity lesions oral such as canker sores, ulcers, lip edema, granulomatosis, dry mouth, abscesses in the salivary ducts, erythema, gingivitis, glossitis, among others, however, simultaneous compromise with several oral lesions and so severe with loss of multiple pieces dental is very rare. CASE PRESENTATION: Patient in the fourth decade of life with a family history of autoimmunity who debuts with severe oral manifestations with a requirement for extraction of 14 teeth, severe gingivitis, smooth tongue and glossitis, aphthous stomatitis, ulcers, lip edema and angular cheilitis, without clear cause, and in management by the oral pathology group. Associated with this, there was vulvo-perineal compromise with ulcerated, inflammatory, erythematous and infiltrated lesions. It was initially suspected of Behçet's disease, HLA B51 was performed, it was negative, also, negative pathergy test, and no other suggestive systemic findings. A vulvar biopsy was performed with marked edema of the dermis, dilated lymphatics with perivascular and interstitial lymphoplasmacytic infiltrate and noncaseating granulomas, negative for microorganisms. At this level, it was compatible with MCD, without presence of gastrointestinal symptoms and calprotectin levels in stool in normal range. High and low endoscopic studies and capsule endoscopy were performed in small intestine, without alterations, it was managed by dermatology with topical steroids and by dentistry with dental implants. It was considered patient with inflammatory bowel disease (IBD) type CD with severe extraintestinal manifestations (EIM), although it did not present compromise intestinal treatment, it was decided to start treatment with anti-TNF initially with adalimumab developing paradoxical psoriasis, later treatment with infliximab, again with presentation of severe paradoxical psoriasis, for which it was suspended. Cyclosporine was also used as an immunomodulator, presenting intolerable tachycardia. 18 months after these symptoms, she presented episcleritis of the left eye and begins with colicky abdominal pain and average diarrheal stools 5-a-day, it was performed high and low endoscopic studies without alterations and new capsule endoscopic of small intestine documenting Crohn's enteritis involving the duodenum, jejunum and ileum, considering a patient with IBD type CD, with EIM with vulvo-perineal compromise, severe oral involvement and episcleritis. Currently is under management with azathioprine and Ustekinumab, with clinical improvement significant. CONCLUSIONS: MCD represents a diagnostic challenge, it can debut without gastrointestinal involvement, and its clinical and histopathological findings simulate other entities. A timely diagnosis is required to seek early benefit in the patient.

P050 Oral Inflammatory Changes Associated With Inflammatory Bowel Disease in Spondyloarthritis Associated With Early Endoscopic Findings.

BACKGROUND: Spondyloarthritis (SpA) is a heterogeneous group of chronic autoinflammatory disorders that can present extra-articular gastrointestinal manifestations. Among them is mainly inflammatory bowel disease (IBD). Although IBD mainly affects the intestinal tract, it can include early manifestations evident in the oral cavity. No comparative data on these oral manifestations in patients with SpA were found in the literature. OBJECTIVE: To identify oral clinical manifestations due to changes in the oral mucosa associated with IBD in patients with SpA without a diagnosis of IBD and associate them with endoscopic and histological findings. METHODS: 80 patients with SpA and 52 healthy controls were evaluated. They were assessed intra- and extra-orally, following the modified World Health Organization guideline. In addition, by clinical parameters of rheumatological, gastrointestinal and laboratory activity. Ileocolonoscopy was performed with digital chromoendoscopy with magnification and histological analysis. Comparative analyzes were performed by Chi square tests, Fisher's exact tests, confirmed by univariate regression and discriminant analysis of multiple correspondences. Institutional ethics committee approval cod-2017-023. RESULTS: The patients with SpA had 56% male gender, mean age of 42.8 years (SD ± 10.4) and a BMI in the range of 23.9 - 28.4. The healthy controls, 54% of the male gender with an average age of 41 years (SD ± 13.6) and a body mass index-BMI in the range of 22.9 - 27.6. The patients reported smoking only in 6.2%, however as a smoking history in 31% and passive smokers (15%), the majority employed (41%), married (56%) and professionals (49%). Of the healthy controls, they smoked (15%), with a history of smoking (31%), passive smokers (21%), the majority employed (77%), with their own home (67%), and professionals (54%). The patients with SpA reported a greater presence of some signs and symptoms of gastrointestinal origin 69%, while in the controls it was 7.7% (p = 0.001). Forty one of them were referred to colonoscopy with magnification being in 17.1 % changes in the mucosa of the rectum and in the same frequency changes in the mucosa of the sigmoid colon. Regarding the ileum, changes in the mucosa were evidenced in 41.5% of the cases. The presence of oral lesions was evident and predominated in them (63%) compared to controls p = 0.050. The main oral lesions associated with IBD were gingivitis (55%) (p = 0.001), followed by aphthous stomatitis (3.8%), angular cheilitis (2.6%) and perioral erythema with scaling (1.3%). 100% of the patients who presented alteration of the colonic mucosa presented oral lesions associated with IBD (p = 0039), which was also significantly associated with the presence of gingivitis/aphthous stomatitis (p = 0.029). CONCLUSION: Patients with SpA without a diagnosis of IBD have more oral signs and symptoms compared to healthy controls. Gingivitis is important given its association with early endoscopic and histological findings. Manifestations in the oral cavity can precede intestinal manifestations, therefore the clinical assessment by the oral pathologist in conjunction with gastroenterology and rheumatology allows a timely referral to gastroenterology and an endoscopic and histological evaluation, impacting the quality of life of patients.