Luis Fernández-Salazar

Incidence, Clinical Characteristics, and Management of Psoriasis Induced by Anti-TNF Therapy in Patients with Inflammatory Bowel Disease: A Nationwide Cohort Study

Background:Psoriasis induced by anti–tumor necrosis factor-&agr; (TNF) therapy has been described as a paradoxical side effect. Aim:To determine the incidence, clinical characteristics, and management of psoriasis induced by anti-TNF therapy in a large nationwide cohort of inflammatory bowel disease patients. Methods:Patients with inflammatory bowel disease were identified from the Spanish prospectively maintained Estudio Nacional en Enfermedad Inflamatoria Intestinal sobre Determinantes genéticos y Ambientales registry of Grupo Español de Trabajo en Enfermedad de Croh y Colitis Ulcerosa. Patients who developed psoriasis by anti-TNF drugs were the cases, whereas patients treated with anti-TNFs without psoriasis were controls. Cox regression analysis was performed to identify predictive factors. Results:Anti-TNF–induced psoriasis was reported in 125 of 7415 patients treated with anti-TNFs (1.7%; 95% CI, 1.4–2). The incidence rate of psoriasis is 0.5% (95% CI, 0.4–0.6) per patient-year. In the multivariate analysis, the female sex (HR 1.9; 95% CI, 1.3–2.9) and being a smoker/former smoker (HR 2.1; 95% CI, 1.4–3.3) were associated with an increased risk of psoriasis. The age at start of anti-TNF therapy, type of inflammatory bowel disease, Montreal Classification, and first anti-TNF drug used were not associated with the risk of psoriasis. Topical steroids were the most frequent treatment (70%), achieving clinical response in 78% of patients. Patients switching to another anti-TNF agent resulted in 60% presenting recurrence of psoriasis. In 45 patients (37%), the anti-TNF therapy had to be definitely withdrawn. Conclusions:The incidence rate of psoriasis induced by anti-TNF therapy is higher in women and in smokers/former smokers. In most patients, skin lesions were controlled with topical steroids. More than half of patients switching to another anti-TNF agent had recurrence of psoriasis. In most patients, the anti-TNF therapy could be maintained.

Gastric metastasis from renal cell carcinoma

Metastatic tumours of the stomach are uncommon finding, usually discovered at autopsy (1). In the same way, gastric metastasis from renal cell carcinoma is uncommon. Brain, spinal cord, and lung are prevalent sites of metastasis from primary renal cell carcinoma (2). The occurrence of gastric metastasis might serve as an indicator of advanced disease and commonly shows concomitant tumour spread to other organs (3).

Phenotype and natural history of elderly onset inflammatory bowel disease: a multicentre, case-control study

Onset during old age has been reported in upto 10% of total cases of inflammatory bowel disease (IBD).

Natural history of irritable bowel syndrome

Chronic diarrhea and functional abdominal pain (FAP) in childhood could be an early manifestation of adult irritable bowel syndrome (IBS). The aim of this study was to investigate the presence of chronic functional digestive symptoms in childhood, interviewing adult patients diagnosed with IBS, in an attempt to establish a relationship between them.

Collagenous colitis: Requirement for high-dose budesonide as maintenance treatment

BACKGROUNDnControlled studies show high efficacy of budesonide in inducing short-term clinical remission in collagenous colitis (CC), but relapses are common after its withdrawal.nnnAIMnTo evaluate the need for high-dose budesonide (≥6mg/d) to maintain clinical remission in CC.nnnMETHODSnAnalysis of a multicentre retrospective cohort of 75 patients with CC (62.3±1.5years; 85% women) treated with budesonide in a clinical practice setting between 2013 and 2015. Frequency of budesonide (9mg/d) refractoriness and safety, and the need for high-dose budesonide to maintain clinical remission, were evaluated. Drugs used as budesonide-sparing, including azathioprine and mercaptopurine, were recorded. Logistic regression analysis was performed to evaluate the risk factors associated with the need for high-dose budesonide (≥6mg/d) to maintain clinical remission.nnnRESULTSnBudesonide induced clinical remission in 92% of patients, with good tolerance. Fourteen of 68 patients (21%; 95% CI, 13-32%) needed high-dose budesonide to maintain remission. Only intake of NSAIDs at diagnosis (OR, 8.6; 95% CI, 1.6-44) was associated with the need for high-dose budesonide in the multivariate analysis.nnnTREATMENTnwith thiopurines was effective in 5 out of 6 patients (83%; 95% CI, 44-97%), allowing for withdrawal from or a dose decrease of budesonide.nnnCONCLUSIONSnOne fifth of CC patients, especially those with NSAID intake at diagnosis, require high-dose budesonide (≥6mg/d) to maintain clinical remission. In this setting, thiopurines might be effective as budesonide-sparing drugs.

Frecuencia, factores predictores y consecuencias de la intensificación del tratamiento de mantenimiento con infliximab en la colitis ulcerosa

INTRODUCTIONnInfliximab (IFX) therapy intensification in ulcerative colitis (UC) is more common than established in pivotal studies.nnnOBJECTIVESnTo establish the frequency and form of intensification for UC in clinical practice, as well as predictors, and to compare outcomes between intensified and non-intensified treatment.nnnMETHODSnA retrospective study of 10 hospitals and 144 patients with response to infliximab (IFX) induction. Predictive variables for intensification were analyzed using a Cox regression analysis. Outcome, loss of response to IFX, and colectomy were compared between intensified and non-intensified therapy.nnnRESULTSnFollow-up time from induction to data collection: 38 months [interquartile range (IQR), 20-62]. Time on IFX therapy: 24 months (IQR, 10-44). In all, 37% of patients required intensification. Interval was shortened for 36 patients, dose was increased for 7, and 10 subjects received both. Concurrent thiopurine immunosuppressants (IMM) and IFX initiation was an independent predictor of intensification [Hazard ratio, 0.034; p, 0.006; CI, 0.003-0.371]. In patients on intensified therapy IFX discontinuation for loss of response (30.4% vs. 10.2%; p, 0.002), steroid reintroduction (35% vs. 18%; p, 0.018), and colectomy (22% vs. 6.4%; p, 0.011) were more common. Of patients on intensification, 17% returned to receiving 5 mg/kg every 8 weeks.nnnCONCLUSIONSnIntensification is common and occasionally reversible. IMM initiation at the time of induction with IFX predictsnon-intensification. Intensification, while effective, is associated with poorer outcome.

Increased Intraepithelial Vα24 Invariant NKT Cells in the Celiac Duodenum

Celiac Disease (CD) is an interferon (IFN)γ-mediated duodenal hypersensitivity to wheat gluten occurring in genetically predisposed individuals. Gluten-free diet (GFD) leads to a complete remission of the disease. Vα24-restricted invariant NKT (iNKT) cells are important to maintain immune homeostasis in the gut mucosa because of their unique capacity to rapidly produce large quantities of both T-helper (Th)1 and Th2 cytokines upon stimulation. We studied the presence of these cells in the CD duodenum. Duodenal biopsies were obtained from 45 untreated-CD patients (uCD), 15 Gluten Free Diet-CD patients (GFD-CD), 44 non-inflamed non-CD controls (C-controls) and 15 inflamed non-CD controls (I-controls). Two populations from Spain and Argentina were recruited. Messenger RNA (mRNA) expression of Vα24-Jα18 (invariant TCRα chain of human iNKT cells), IFNγ and intracellular transcription factor Forkhead Box P3 (Foxp3), and flow cytometry intraepithelial lymphocyte (IEL) profile were determined. Both uCD and GFD-CD patients had higher Vα24-Jα18 mRNA levels than non-CD controls (I and C-controls). The expression of Vα24-Jα18 correlated with Marsh score for the severity of mucosal lesion and also with increased mRNA IFNγ levels. uCD and GFD-CD patients had decreased mRNA expression of FoxP3 but increased expression of Vα24-Jα18, which revealed a CD-like molecular profile. Increased numbers of iNKT cells were confirmed by flow cytometry within the intraepithelial lymphocyte compartment of uCD and GFD-CD patients and correlated with Vα24-Jα18 mRNA expression. In conclusion, we have found an increased number of iNKT cells in the duodenum from both uCD and GFD-CD patients, irrespective of the mucosal status. A CD-like molecular profile, defined by an increased mRNA expression of Vα24-Jα18 together with a decreased expression of FoxP3, may represent a pro-inflammatory signature of the CD duodenum.

Serial Tuberculin Skin Tests Improve the Detection of Latent Tuberculosis Infection in Patients With Inflammatory Bowel Disease

AimnTo assess the likelihood of detecting latent tuberculosis infection [LTBI] by the positive conversion of a serial tuberculin skin test [TST] at 1 year in inflammatory bowel disease [IBD] patients with negative baseline two-step TST.nnnMethodsnIn this multicentre prospective cohort study, we evaluated rate and predictors of conversion of TST at 1 year in patients with negative baseline TST. We also evaluated management of patients who had a positive TST at baseline or a conversion at 1 year. In all patients we assessed TB cases occurring during follow-up.nnnResultsnOf the 192 IBD patients receiving anti-tumour necrosis factor [TNF] and 220 IBD controls not receiving anti-TNF, 35 [8.5%, 95% CI 5.7-11.3] had positive conversion (median TST induration 13 mm, interquartile range [IQR] 9-16). Ten anti-TNF cohort patients [5.2%, 95% CI 2.5-9.5] versus 25 controls [11.4%, 95% CI 7.5-16.3] had TST conversion [p = 0.029]. In multivariate analysis, conversion was associated with smoking habit (odds ratio [OR] 2.19, 95% CI 1.08-3.97; p = 0.028). Anti-TNF-treated patients had a lower conversion rate [OR 0.41, 95% CI 0.20-0.83; p = 0.013]. The likelihood of conversion correlates with fewer immunosuppressive therapies between baseline TST and TST at 1 year [p = 0.042]. One case of active TB [isoniazid-resistant strain] occurred in a patient with positive baseline TST receiving anti-TNF [0.05 events/100 patient-years].nnnConclusionsnSerial TST at 1 year can detect LTBI in IBD patients receiving anti-TNF therapy with negative baseline TST. Serial TST seems to be advisable to reduce the risk of TB cases associated with inability to detect LTBI in pre-treatment screening.

Early Tuberculin Skin Test for the Diagnosis of Latent Tuberculosis Infection in Patients with Inflammatory Bowel Disease

Background and AimnSensitivity of tuberculin skin test [TST] during screening for latent tuberculosis infection [LTBI] is affected by steroid and/or immunosuppressant therapy. The aim of this study was to compare performance of the two-step TST in inflammatory bowel disease patients immediately before anti-tumour necrosis factor [TNF] therapy as part of routine screening for LTBI vs control patients when the TST was carried out at an early stage.nnnMethodsnIn this multicentre prospective controlled study, we evaluated the performance of two-step TST with 5-mm threshold. Factors associated with TST results were determined by logistic regression.nnnResultsnWe evaluated 243 candidates for anti-TNF therapy and 337 control patients. Overall, 105 patients [18.1%] had an induration ≥ 5 mm in the first TST or in TST retest. LTBI was diagnosed in 25% of patients by TST retest. Twenty-eight [11.5%] anti-TNF group patients vs 77 [22.8%] control patients had a positive TST (odds ratio [OR] 0.44, 95% confidence interval [CI] 0.28-0.70; P < 0.001]. In multivariate analysis, positive TST was associated with higher age [OR 2.63, 95% CI 1.21-5.72; P < 0.001] and 5-aminosalicylate therapy [OR 1.86, 95% CI 1.14-3.05; P = 0.013]. Negative TST was associated with steroid therapy [OR 0.36, 95% CI 0.16-0.83; P = 0.016], immunosuppressant therapy [OR 0.36, 95% CI 0.21-0.62; P < 0.001], or steroids + immunosuppressant therapy [OR 0.20, 95% CI 0.07-0.59; P = 0.004].nnnConclusionsnThe sensitivity of routine TST performed just before starting anti-TNF therapy is low. TST performed at an early stage enables screening in the absence of immunosuppressive treatment and thus maximises the diagnostic yield of TST for detecting LTBI.

Las preocupaciones de los pacientes españoles con enfermedad inflamatoria intestinal medidas con el cuestionario RFIPC

BACKGROUND AND OBJECTIVESnConcerns impact the quality of life for patients with inflammatory bowel disease (IBD). We attempted to identify the concerns of IBD patients in our practice, and to assess the applicability of the Rating Form of IBD Patients Concerns (RFIPC) questionnaire to Spanish patients.nnnPATIENTS AND METHODSnOne hundred and thirty-one patients seen in our practice filled out the Spanish version of RFIPC. The questionnaires reliability, validity, and discriminating power were analyzed.nnnRESULTSnThe total score was 46.93, with a standard deviation (SD) of 21.475. Primary concerns included: having an ostomy bag, effects of medication, developing cancer, energy level, and uncertain nature of disease. Female patients scored higher on total RFIPC and on most items. Cronbachs alpha was 0.924. A good correlation was seen between two consecutive answers for 37 patients; the Spearmans coefficient was 0.842 (p < 0.001), and the intraclass correlation coefficient (ICC) was 0.775 (p < 0.001). Correlation was also found between RFIPC and both the IBDQ-32 emotional domain (0.413, p < 0.001) and anxiety scale (0.543, p < 0.001).nnnCONCLUSIONSnThe RFIPC questionnaire may be administered to Spanish patients.espanolAntecedentes y objetivos: las preocupaciones influyen en la calidad de vida de los pacientes con enfermedad inflamatoria intestinal (EII). Pretendemos identificar las preocupaciones de los pacientes con EII que atendemos en nuestra consulta y comprobar si el Rating Form of IBD Patients Concerns (RFIPC) es un cuestionario aplicable a los pacientes espanoles. Pacientes y metodos: ciento treinta y un pacientes atendidos en la consulta contestaron la version espanola del RFIPC. Se ha estudiado la fiabilidad, validez y capacidad discriminadora del cuestionario. Resultados: la puntuacion total fue 46,93 con desviacion estandar (DS) de 21,475. Las preocupaciones principales fueron: “que me coloquen una bolsa”, “reacciones a medicamentos”, “padecer cancer”, “vitalidad” y “situacion incierta de la enfermedad”. Los pacientes de sexo femenino puntuaron mas alto en el RFIPC y en la mayoria de los items. El valor alfa de Cronbach fue 0,924. Se comprobo una buena correlacion entre dos respuestas consecutivas de 37 pacientes, Spearman 0,842 (p Tambien hubo correlacion entre el RFIPC y el dominio emocional del Inflammatoy Bowel Disease Questionnarie (IBDQ) 32 0,413 (p Conclusiones: el cuestionario RFIPC puede aplicarse a los pacientes espanoles. EnglishBackground and objectives: Concerns impact the quality of life for patients with inflammatory bowel disease (IBD). We attempted to identify the concerns of IBD patients in our practice, and to assess the applicability of the Rating Form of IBD Patients Concerns (RFIPC) questionnaire to Spanish patients. Patients and methods: One hundred and thirty-one patients seen in our practice filled out the Spanish version of RFIPC. The questionnaire’s reliability, validity, and discriminating power were analyzed. Results: The total score was 46.93, with a standard deviation (SD) of 21.475. Primary concerns included: “having an ostomy bag”, “effects of medication”, “developing cancer”, “energy level”, and “uncertain nature of disease”. Female patients scored higher on total RFIPC and on most items. Cronbach’s alpha was 0.924. A good correlation was seen between two consecutive answers for 37 patients; the Spearman’s coefficient was 0.842 (p Correlation was also found between RFIPC and both the IBDQ-32 emotional domain (0.413, p Conclusions: The RFIPC questionnaire may be administered to Spanish patients.