Celiac disease serology in dermatitis herpetiformis: which is the best option for detecting gluten sensitivity? / Serología de enfermedad celíaca en dermatitis herpetiforme. ¿Cuál es la mejor opción para detectar sensibilidad al gluten?

Background: Dermatitis herpetiformis (DH), a wellestablished gluten-sensitive skin disorder presenting variable degrees of enteropathy, constitutes a very useful model in order to assess the utility of the celiac disease (CD)-related serology in patients with mild intestinal damage. Objective: Our aim was to explore comparatively the performance of a panel of CD-related serologic tests in patients with DH. Methods: We assessed a series of 18 consecutive patients with skin biopsy proven DH presenting the overall spectrum of intestinal damage ranging from normal mucosa (n=6) to total villous atrophy (TVA) (n=6) through partial villous atrophy (PVA) (n=6). Sera were obtained from all patients while consuming a gluten containing diet. Serologic tests were antiendomysial, anti-tissue transglutaminase and antigliadin antibodies, and newly developed tests detecting both antibody isotypes (IgA and IgG) against deamidated synthetic gliadin-derivedpeptides (a-GDP). Results: Serologic tests had a variable behaviour depending on the degree of enteropathy. While the majority of tests detected patients with TVA, only 50% of those with normal histology had positive assays. Patients with PVA had discordant results. Classical CD-specific tests were positive in only some patients with mild damage while all of them were identified by a single assay detecting both isotypes of a-GDP. Conclusion: The detection of a-GDP antibodies was the most reliable tool in order to identify gluten sensitivity in DH patients presenting a wide range of intestinal damage. Further studies should explore if these findings can be extrapolated to patients with CDhaving mild enteropathy.

Introducción: la dermatitis herpetiformis (DH), una lesión dermatológica consecuencia de sensibilidad al gluten y asociada a grados variables de enteropatía, constituye un modelo muy útil con el objeto de evaluar la eficacia de la serología de la enfermedad celíaca(EC) en pacientes con daño intestinal leve. Objetivo: explorar comparativamente la utilidad de una serie de anticuerpos empleados en EC en pacientes con DH. Métodos: analizamos una serie de 18 pacientes consecutivos con diagnóstico de DH por biopsia de piel que presentaban el más amplio espectro de daño intestinal variando desde una mucosa normal (n=6) a la atrofia vellosa total (AVT) (n=6) y pasando por atrofia vellosaparcial (AVP) (n=6). Se obtuvo plasma de todos los pacientes mientras consumían gluten. Las pruebas serológicas empleadas fueron anticuerpos antiendomisio, anti-transglutaminasa y atigliadina, y unas pruebas recientemente desarrolladas que detectan anticuerpos IgA e IgG dirigidos contra péptidos sintéticos deamidados derivados de la gliadina (a-GDP). Resultados: las diferentes pruebas tuvieron un comportamiento variable dependiendo del grado de lesión intestinal. Mientras que la mayoría de las pruebas detectaron a todos los pacientes con AVT, sólo el 50% de aquellos con histologíanormal tuvieron resultados positivos. Los pacientes con AVP tuvieron resultados discordantes. Así las pruebas clásicas fueron positivas en sólo algunos pacientescon daño leve, mientras que todos ellos fueron positivos a una prueba para detectar ambos isotipos del a-GDP. Conclusión: la determinación de anticuerpos a-GDP fue la herramienta más confiable con el objeto de identificar serológicamente la sensibilidad al gluten en pacientes con DH que presentan variables grados de daño intestinal. Otros estudios deberían explorar si estos hallazgos podrían ser extrapolados a pacientes conEC con enteropatía de grado leve.

Clinical characteristics and long-term outcome of patients with refractory sprue diagnosed at a single institution / Características clínicas y evolución a largo plazo de una serie de pacientes con sprue refractario diagnosticados en una sola institución

BACKGROUND: Refractory sprue (RS) is a rare and severe celiac-like enteropathy not responding to a strict gluten-free diet. Although prognosis is generally poor, little is known about the long-term outcome of patients. AIM: to report baseline characteristics and long-term outcome of a series of patients diagnosed and treated in a single institution. MATERIALS: We report a retrospective cohort of 25 consecutive patients (15 females; mean age 46 yr; range 28-71) diagnosed with RS based on the presence of a non-responsive celiac-like enteropathy. All patients were intensively treated with a gluten-free diet, steroids, nutritional support and immunosupression. RESULTS: Clinical and biological characteristics of patients suggest that, at least, 24 patients had clear evidences of celiac disease. HLA DQ2/DQ8 genes were present in all the 24 patients typed and autoimmune enteropathy was excluded in all. According to the genotyping, 12 patients had a polyclonal lymphocyte population (RS type I) and 13 exhibited monoclonal TCR-gamma gene rearrangements (RS type II). Sixteen patients had evidence of ulcerative jejunitis (UJ) (7 in RS type I and 9 in type II). Overall median follow-up time after diagnosis of RS was 29 mo/patient (range 7 to 204) (45 mo for type I and 24 mo for type II). Overall mortality was 48% (12 patients), 6 in each type. Eight patients with UJ (50%), 3 with lymphoma (two T-cell and one B-cell type) and 4 (44%) without ulcers died during follow-up. The causes of death were sepsis in the context of a progressive deterioration but without overt malignancies (n=5), vascular causes (n=3) and severe malnutrition (n=1). Three- and 5-yr survival rate after diagnosis of RS for the overall population was 60% and 56%. There was no differences between type I (67%, 58%) and type II RS patients (54% for both periods). Patients with UJ had lower but non-significant 3- and 5-yr survival rates (56% and 50%, respectively) compared with patients without ulcers...

Introducción: El sprue refractario (SR) es una rara y severa entidad consistente en una enteropatía tipo celíaca que no responde a una estricta dieta libre degluten. Aún cuando el pronóstico es generalmente pobre, poco es conocido acerca de la evolución de lospacientes a largo plazo. Objetivo: reportar las característicasclínicas y la evolución a largo plazo de una serie de pacientes diagnosticados y tratados en una solainstitución. Materiales: Reportamos una cohorteretrospectiva de 25 pacientes consecutivos (15 mujeres; edad media 46 años; rango 28-71) diagnosticadoscomo SR sobre la base de una enteropatía tipo celíaca que no respondió a la dieta libre de gluten. Todos los pacientes recibieron un tratamiento intensivo consistenteen dieta libre de gluten, alimentación enteral o parenteral, corticosteroides e inmunosupresión. Resultados: Los elementos clínicos y biológicos sugierenque 24 pacientes exhibían claras evidencias de enfermedadcelíaca. Los genes HLA DQ2/DQ8 estuvieron presentes en los 24 pacientes estudiados y se excluyó laenteropatía autoinmune en todos los casos. De acuerdo al genotipo, 12 pacientes presentaron una poblaciónlinfocitaria intraepitelial policlonal (SR tipo I) y 13 exhibieron un rearreglo genético monoclonal del TCR-γ (SR tipo II). Dieciséis pacientes presentaron evidencias de yeyunitis ulcerativa (YU) (7 en SR tipo I y 9 enel tipo II). El tiempo promedio de seguimiento luego del diagnóstico de SR fue 29 meses/paciente (rango 7 -204) (45 y 24 meses para tipo I y tipo II, respectivamente). La mortalidad global fue del 48% (12 pacientes),6 en cada tipo de SR. Ocho pacientes con YU (50%) murieron durante el seguimiento, 3 con linfoma(dos de células T y uno de células B) y cuatro(44%) individuos sin úlceras también fallecieron. Lascausas de muerte fueron vasculares (n=3), sepsis en elmarco de deterioro progresivo sin desarrollo de malignidad(n=5) y desnutrición progresiva (n=1)...

Impaired monocyte function in patients succesfully treated for Wipple's disease

Peripheral blood mononuclear cells (monocytes) from patients with Whipple's disease in long-term remission were tested for their ability to handle intracellular microorganisms. Phagocytosis and lysis of Candida tropicalis by monocytes of patients (n=12) andcontrols (n=8) were quantified after 30 min of incubation. Phagocytosis was similar in both groups but intracellular Killing of Candida tropicalis was significativily lower in patients (p<0.001). We concluded that our study showed an in vitro defect in the intracellular Killing function of monocytes in subjects in remission many years after diagnosis of Whipple's disease. The defective function did not seem to be related to relapse or to the susceptibility to other infections.

Abnormal colonic transit time in untreated celiac sprue

Motility disorders of the digestive tract have long been implicated in the pathophysiology of diarrhea in patients with celiac sprue. However, the contribution of the colon to the intestinal transit of celiac sprue has not been reported. Our aim was to determine whether sprue alters gut transit and whether differences in the clinical status of the disease influences colonic transit. We prospectively studied 25 patients with untreated celiac sprue, 15 treated patients and 15 healthy controls. Oro-cecal transit time, measured by the lactulose breath H2 test, was significantly delayed in untreated patients compared with treated patients and controls (p<0.001 and p<0.01 respectively). The delayed transit through the stomach and small bowel was not related to the presence of the steatorrhea. Transit of radiopaque makers, a measure of total colonic tansit, was significantly faster in untreated patients (p<0.05). The major finding was that this abnormal colonic behavior was principally due to a subpopulation of untreated patients with very fast transit times (<18 hours). A weakly significant inverse correlation between transit and fecal weight (r:-0.55, p<0.01), and between transit and steatorrhea (r:-0.38, p<0.05), was observed. We confirm previous descriptions of delayed oro-cecal transit time in untreated patients, and also provide the first evidence that disordered colonic transit contributes to the pathophysiology of the diarrhea in sprue.