TNF-238A promoter polymorphism contributes to susceptibility to ankylosing spondylitis in HLA-B27 negative patients.

OBJECTIVE: To investigate the relative contribution of MHC loci in their susceptibility to primary ankylosing spondylitis (AS) in HLA-B27 negative patients and to compare the clinical features and genetic factors with those of HLA-B27 positive AS. METHODS: DNA from patients with B27 negative primary AS (n = 28), B27 positive primary AS (n = 77), and matched healthy controls (B27-, n = 100; B27+, n = 70) were analyzed to investigate whether HLA genes determine the disease susceptibility, or whether other closely linked loci might play a role in disease development. HLA typing was carried out by serology and PCR/SSP (HLA-B, -DR), MICA-TM polymorphism in the transmembrane region by radioactive PCR, and tumor necrosis factor-alpha (TNF-alpha) promoter polymorphism at positions -238 and -308 by PCR-RFLP. RESULTS: Subtle clinical differences were found for primary AS, the B27 negative patients being less frequently complicated by acute anterior uveitis and more associated with peripheral arthritis than B27 positive. Differences were found in the distribution of TNF-alpha -238 genotypes among patients with primary AS (B27- vs B27+). The TNF-alpha -238(A) polymorphism was present in 50% of the B27 negative patients carrying the -238 G/A and A/A genotypes and was significantly increased compared with B27 positive AS (odds ratio 4.3) and with the B27 negative control group (OR 5.9). The TNF-alpha genotypes were equally prevalent in B27 positive AS and healthy matched B27 positive controls. No significant HLA and MICA typing differences were found between the populations under study. CONCLUSION: Our results indicate that the polymorphism variation in the TNF-alpha promoter -238.2(A) influences disease susceptibility in B27 negative primary AS but had no effect in our B27 positive AS population.

[Atypical manifestations of Whipple's disease]. / Manifestaciones atípicas de la enfermedad de Whipple.

We report 2 new cases of Whipple's disease (WD) with especial characteristics. In one case, an asymptomatic leukocytosis was the first manifestation, and after therapy the patient developed a gastric adenocarcinoma. In the second, the clinic suspect we led to try antibiotic treatment in absent of histological manifestations. The clinical, analytical and histological characteristics of both patients are described. We propose that WD should be listed in the differential diagnosis of unknown leukocytosis. Moreover, we indicate the possibility to try empirical antibiotic therapy in long-term cases without histological confirmation. Finally, we suggest a possible role of WD in the development of cancer.

Mecanismos del dolor en la artrosis

El dolor es el síntoma más relevante en esta enfermedad. La presencia de dolor en la artrosis se relaciona con la incapacidad y es también un factor de riesgo en el deterioro de una articulación artrósica y en la necesidad de artroplastia. Por ello, conocer los mecanismos de este síntoma podría ser un objetivo básico en el control de la afección articular degenerativa. (AU)

Manifestaciones atípicas de la enfermedad de Whipple / Atipic manifestations of Whipple's disease

Presentamos 2 casos de enfermedad de Whipple (EW) de larga evolución con características especiales. En un caso, la presentación inicial fue una leucocitosis asintomática, hecho que no hemos encontrado publicado previamente, y que en su evolución desarrolló un adenocarcinoma gástrico. En el 2° caso, la sospecha clínica nos llevó a realizar tratamiento antibiótico empírico pese a la negatividad de los hallazgos histológicos. Se describen las características clínicas, analíticas e histológicas de ambos pacientes. Proponemos incluir a la EW dentro del diagnóstico diferencial de las leucocitosis de origen desconocido. Señalamos además la posibilidad de realizar tratamiento antibiótico empírico en aquellos casos de larga evolución con deterioro progresivo, aún sin confirmación histólogica. Finalmente planteamos que la cronicidad del proceso pueda influir en el desarrollo de neoplasias. (AU)

[Silent axial arthropathy in inflammatory bowel disease. Clinical, radiological and genetic characteristics]. / Artropatía axial silente en la enfermedad inflamatoria intestinal. Características clínicas, radiológicas y genéticas.

OBJECTIVES: To evaluate the prevalence, clinical and radiological characteristics, association with HLA B27 in a subgroup of patients with inflammatory bowel disease (IBD) and subclinical sacroileitis. The sensitivity of the diagnostic criteria for spondyloarthropathy in this group of patients is evaluated. MATERIALS AND METHODS: All patients with inflammatory bowel disease attending an outpatient gastroenterology unit from January 1994 to June 1994 were recruited. A total of 62 patients with IBD and without clinical evidence of axial involvement were included in the study. The demographic, clinical, and radiological characteristics were collected. The radiological examination included PA and lateral views for the dorso-lumbar, and three views (Ferguson, right and left oblique views) for the sacroiliac joints. Films were interpreted by three independent readers. The HLA B27 allele distribution was analyzed in the 62 patients and in 80 healthy controls. The modified New York criteria, Amor criteria, and European Spondyloarthropathy Study Group criteria were evaluated. Patients were prospectively followed for two years with the same initial protocol. The statistical management of data was performed with the information program SPSS/PC. RESULTS: Fifteen cases of silent sacroileitis were detected, and most of them were grade 2 unilateral sacroileitis. There was no correlation between sacroileitis and IBP type, extradigestive symptoms, disease duration, sex, or peripheral arthritis. The frequency of HLA B27 in the sacroileitis group was 20% (p < 0.05). During the two-year follow-up period none of these cases has changed from diagnostic category. The sensitivity of diagnostic the criteria for spondyloarthropathy was low in these patients (40%-53%). CONCLUSIONS: A high frequency of asymptomatic sacroileitis in patients with IBD was detected. We propose the term Silent Axial Arthropathy to define this category of patients and, as with other authors, we consider this is a third form of rheumatic syndrome in IBD, different from the classical forms of peripheral arthritis and ankylosing spondylitis.

Diaphysitis in tumoral calcinosis syndrome.

Diaphysitis is uncommon in children. We describe a case of diaphyseal inflammation in several bones with high levels of phosphorus in an 8-year-old boy who later developed subcutaneous masses of tumoral calcinosis. This report serves as a review of this puzzling problem in clinical diagnosis.