Proton pump inhibitor-responsive oesophageal eosinophilia correlates with downregulation of eotaxin-3 and Th2 cytokines overexpression.

BACKGROUND: The molecular basis and effects of proton pump inhibitor (PPI) therapy on PPI-responsive oesophageal eosinophilia (PPI-REE) and eosinophilic oesophagitis (EoE) remain unknown. AIM: To compare symptom-histological and cytokine gene expression in PPI-REE and EoE patients, at baseline and after specific treatment. METHODS: In consecutive adult patients with an EoE phenotype (dysphagia/food impaction, typical endoscopic findings and > 15 eos/HPF), gene expression of eotaxin-3, IL-13, and IL-5 were determined in distal and proximal oesophagus, at baseline and after omeprazole 40 mg b.d. for 8 weeks. PPI-REE was defined by clinicohistological response. PPI nonresponders (EoE) were offered treatment with topical steroids. RESULTS: Fifty three patients were re-evaluated on PPI therapy. 23 patients (43%) had PPI-REE and 30 patients (57%) had EoE. At baseline, eotaxin-3/IL-13/IL-5 gene expression was indistinguishable between EoE and PPI-REE, excepting increased IL-5 expression in proximal oesophagus (12.54 vs. 57, P = 0.029). PPI therapy significantly decreased eotaxin-3/IL-13 in PPI-REE, at both oesophageal sites (P ≤ 0.008), and IL-5 in distal (P = 0.016), but not in proximal oesophagus. Patients with steroid-responsive EoE also showed a significant decrease in eotaxin-3/IL-5 expression at both oesophageal sites. In EoE patients, initial PPI trial significantly decreased distal oesophageal eosinophilia (63.78 to 41.79 eos/HPF, P = 0.025) and led to symptom remission in 16%, but did not influence Th2 markers. CONCLUSIONS: Baseline cytokine gene expression in PPI-REE was nearly indistinguishable from EoE. PPI therapy significantly downregulated oesophageal eotaxin-3/Th2-cytokine gene expression in PPI-REE, similarly to that seen in steroid-responsive EoE. A subset of EoE patients showed clinicohistological improvement on PPI therapy.

Síndrome de obstrucción de intestino distal: una complicación digestiva de la fibrosis quística / Distal intestinal obstruction syndrome: a digestive complication of Cystic Fibrosis

Los pacientes con Fibrosis Quística (FQ) pueden desarrollar complicaciones gastrointestinales y pancreáticas que aumentan la morbimortalidad, derivadas de la alteración básica secretora producida por la proteína anómala o Regulador de la Conductancia Transmembrana de la Fibrosis Quística (CFTR), que condiciona un defecto en el transporte extracelular de los iones Cl- y aumento de la reabsorción de Na+ a través de las membranas apicales celulares.Las manifestaciones clínicas del Síndrome de Obstrucción del Intestino Distal (SOID) son episodios recurrentes de obstrucción intestinal completa o parcial, secundaria a la impactación de material fecal en el íleon terminal, ciego y colon ascendente.Varios factores han sido implicados en la patogénesis: motilidad intestinal anormal, desarrollo de insuficiencia pancreática, suplementos inadecuados de enzimas pancreáticos y deshidratación.La prevalencia de SOID en pacientes FQ es del 15 por ciento y algunas veces es el único síntoma de presentación de la enfermedad. En menores de 5 años la prevalencia es del 2 por ciento y asciende al 30 por ciento en adultos.El diagnóstico es clínico y radiológico. El manejo médico inicial incluye hidratación adecuada, reajuste de dosis de suplementos de enzimas pancreáticos y fibra dietética y, si no hay respuesta, laxantes y lavado intestinal con solución electrolítica isosmolar, no absorbible. El tratamiento quirúrgico está limitado a la obstrucción completa. Comunicamos dos casos clínicos, ambos con obstrucción parcial e insuficiencia pancreática, de 7 y 23 años (AU)

Relationship between the presenting symptoms and age at diagnosis in alcoholic and nonalcoholic chronic pancreatitis: analysis of 164 patients.

OBJECTIVE: To study the different forms of presentation, patient age, delay in diagnosis and incidence of calculi in alcoholic and nonalcoholic chronic pancreatitis. METHODS: We have studied 130 men and 34 women diagnosed as having chronic pancreatitis on the basis of clinical criteria and morphological and/or functional tests. RESULTS: Alcohol was the most common cause of chronic pancreatitis in men (89.1%) existing a significant difference with respect to women (p < 0.05). The mean age of the patients with alcoholic chronic pancreatitis was 45.6 +/- 11.3 years and that of patients presenting nonalcoholic chronic pancreatitis was 54.5 +/- 11.5 years (p < 0.01), the latter showing a bimodal distribution. The ages of the patients in whom the presenting symptom was abdominal pain and acute inflammatory episodes were 43.9 +/- 12.8 and 45.3 +/- 13.5 years, respectively, significantly lower (p < 0.05) than the age of patients in whom presentation was signaled by the onset of diabetes or diarrhea (53.1 +/- 11.2 and 61.2 +/- 12.9 years, respectively). Statistically significant differences existed in the delay in diagnosis when comparing the patients before and after 1985 (12.3 +/- 14.5 years, range 0 to 50 years, versus 0.42 +/- 0.9 years, range 0 to 5 years; p = 0.005). At diagnosis, 14.3% of the patients whose presenting symptom was acute pancreatitis had pancreatic calculi, versus 42.2% of those who reported abdominal pain as the first indication. CONCLUSIONS: Alcoholic chronic pancreatitis predominates in men. Nonalcoholic chronic pancreatitis presents two peaks of prevalence. A substantial number of patients may remain pain-free up to diagnosis. Calculi are not uncommon during the initial period of chronic pancreatitis when pain is the presenting symptom, either in the form of isolated episodes of abdominal pain or attacks of acute pancreatitis.