Doença imunoproliferativa do intestino delgado: estudo clínico prospectivo de casuística

Abstract

This investigation refers to a prospective clinical study that included 24 patients with immunoproliferative small intestinal disease (IPSID), who were followed up from 1988 to 2004. These patients were selected among those attended in the reference center for gastrointestinal diseases at the University Hospital, Federal University of Minas Gerais,Belo Horizonte, Brazil. The study aimed at the investigation of the clinical and laboratorial characteristics of the disease, some of its epidemiological aspects, the response to treatment, as well as the analysis of the agreement of the histopathological findings observed in the samples of the small bowel obtained by three different ways: upperdigestive endoscopy, peroral jejunal biopsy and laparotomy, in staging the IPSID. The results related to demographic dada showed mild predominance in women (54.2%); mean age of 33 ± 11.8 years and median age of 33.5 years; and moderate predominance in nonwhite(62.5%). The disease was more frequent in the lower social economic class, which includes people who live in the periphery of the cities. Using the criteria for histological staging proposed by Galian et al.92, five (20.8%) patients were in stage A; five (20.8%), in B; and 14 (58.3%), in C. The clinical manifestations were very constant, and the most frequent were: weight loss (95.8%), diarrhea (91.7%), abdominal pain (87.5%), and clubbing fingers (75.0%). The frequency of these manifestations was similar in the three stages, however they were more exuberant in the stages B and C. The hematological and biochemical exams were devoided of diagnostic value; nonetheless they correlated with thesystemic repercussion of the IPSID and proved useful in evaluating the response to the treatment. The most frequent abnormalities were: hypoalbuminemia (83.3%), anemia (62.5%), raised erythrocyte sedimentation rate (59.2%), and hypocalcemia (54.2%). Steatorrhea was observed in 77.8% of the patients, and the frequency of infections byintestinal parasites in these individuals was similar to that observed in Brazilian population, in general. Immunoelectrophoresis performed in serum allowed the identification of the á- heavy chain in four patients belonged to the stage C, and of the ã-heavy chain in sevencases distributed among the three stages. The immunohistochemical staining of the intestinal mucosa permitted the diagnosis of the á-heavy chain non-secretory form of the disease in three cases, and of the ã-heavy chain, in two cases. The endoscopic aspect of theduodenum was suggested of IPSID in 65% of the patients; nodules (45%) and shallow ulcerations (15%) were the most frequent findings. Bowel series showed alterations in all of the patients and proved to be of great value in the approach of suspect cases. Nodules (100%), thickening of the mucosa (79.2%), and irregularity in the periphery of the mucosa (41.7%) were more frequent and more evident in the stages B and C. Twenty (83.3%) patients were submitted to surgical staging. Mesenteric lymphadenopathy (90%), followed by thickening (75%) and nodules (40%) of the jejunum wall were the most common alterations observed. The histopathological aspect of the intestinal mucosa, as described by other authors, was characterized by a dense and diffused cellular infiltration, formed by lymphocytes and plasmocytes, leading to the disruption of the normal architecture of the mucosa. Atypical cells and cellular infiltration involving the different layers of the intestinal wall were characteristic of the stages B and C. Samples from the second portionof the duodenum, obtained by endoscophy, were diagnostic in 44.4% of the cases included in the stages B or C. The peroral jejunum biopsy showed to be very useful in the diagnosis of IPSID and in the evaluation of its therapeutic response. This method provided the diagnosis in 100% of the cases. The material obtained by laparotomy confirmed thediagnosis in all of the patients and was the golden standard for the histophatological staging. The agreement of the three methods used for obtaining the samples of the intestinal mucosa for histological staging of the disease was evaluated by the Kappa test. Considering the three stages together, the duodenum and the peroral jejunum biopsies showed little agreement with the results of laparotomy. Even though, good agreement between the peroral jejunum biopsy and laparotomic findings was observed when considering the stages B and C together. This result raises the question of the necessity of the surgical procedure,when the sample obtained by peroral jejunum biopsy allows the classification of the disease in any of these two stages. Four patients included in stage A were treated with tetracycline whereas the fifth one did not receive any treatment, as he evolved to death not related toIPSID. Complete reemission (CR) was observed in 66.7% of the stage A cases, while partial remission (PR) was obtained in 33.3% of these patients. Virtually, all patients included in stages B and C received cyclophosphamide, vincristine, prednisone, and adriamycin (CHOP) and/or CHOP associated with bleomycin sulfate. CR was reached in75% of the individuals included in stage B, and in 45.5% of those included in stage C; PR was observed in 9.1% of the patients belonged to stage C; and therapeutic failure occurred in 25% of the cases classified as stage B, and in 45.5% of those classified as stage C. Theoverall survival rate in five years was of 100% for stage A, 75% for stage B, and 55% for the cases included in stage C. At the end of the study 66.6% of the patients were alive. All the deaths occurred within the first 60 months of the follow up. In nine patients, the ã-heavy chain disease presented the involvement of the small bowel as the first manifestation. This frequency is higher than that referred in the literature.