Efalizumab, a human monoclonal anti-CD11a antibody, in the treatment of moderate to severe Crohn's Disease: an open-label pilot study.

BACKGROUND AND AIMS: Efalizumab is a monoclonal antibody targeting CD11a, an adhesion molecule involved in the activation and trafficking of T-lymphocytes. This agent has proven efficacy in the treatment of psoriasis. We performed an open-label study to evaluate the efficacy and safety of efalizumab in Crohn's disease (CD). METHODS: Fifteen subjects with moderate to severe CD (Crohn's Disease Activity Index [CDAI] score 220-450) and who were refractory or intolerant to standard therapy, received a weekly 1 mg/kg subcutaneous injection of efalizumab for 8 weeks. The primary endpoint was clinical response (decrease in the CDAI score of at least 70 points) at week 8. Secondary endpoints included change in mean CDAI scores, the proportion of subjects who achieved clinical remission (CDAI score ≤ 150), change in the Inflammatory Bowel Disease Questionnaire (IBDQ) scores, and report of adverse events. RESULTS: At 8 weeks, ten (67%) subjects had clinical response and six (40%) were in remission. The mean baseline and week 8 CDAI scores were 300 and 167 respectively (P < 0.001). Mean IBDQ scores at baseline and week 8 were 124 and 168 respectively (P < 0.001). One subject with Crohn's colitis had pre- and post-treatment colonoscopy that demonstrated mucosal healing. No serious adverse events occurred. CONCLUSIONS: Efalizumab induced a clinical response in the majority of subjects with moderate to severe CD in this small, open-label pilot study. There were no serious adverse events reported during this short-term trial.

Clinical recognition of Al type amyloidosis of the luminal gastrointestinal tract.

BACKGROUND & AIMS: Amyloidosis is characterized by the pathologic deposition of specific proteins throughout the body. Gastrointestinal involvement with amyloid associated with plasma cell dyscrasias (AL type amyloidosis) is common, but systematic description of the condition is lacking. The aim of this investigation was to characterize the clinical presentation, endoscopic findings, and histopathologic correlates in a series of patients with systemic AL amyloidosis of the luminal gastrointestinal tract. METHODS: Eligible patients were identified by interrogating the histopathology database of our institution during a 14-year time period. Medical record, histopathologic, and laboratory data were collected, analyzed, and correlated with endoscopic findings. RESULTS: Nineteen patients with systemic AL amyloidosis of the luminal gastrointestinal tract were identified. Gastrointestinal symptoms or signs related to amyloid involvement were noted in 95% of patients; abdominal pain, change in bowel habits, overt gastrointestinal bleeding, and complaints related to altered motility were the predominant presentations. Endoscopic abnormalities were found in nearly three fourths of patients, including ulcerations and submucosal hematomas. When gastrointestinal bleeding was the presenting symptom, submucosal hematomas were a common finding during endoscopic evaluation. CONCLUSIONS: AL type amyloidosis of the luminal gastrointestinal tract is a rare disease that presents with common, nonspecific complaints. The endoscopic detection of a submucosal hematoma in the setting of gastrointestinal bleeding in patients with plasma cell dyscrasias should raise suspicion for the disease.

Reactive hemophagocytic syndrome complicating the treatment of inflammatory bowel disease.

BACKGROUND AND AIMS: Reactive hemophagocytic syndrome (RHS) is a rare disease in which inappropriately activated macrophages consume bone marrow-derived cells. Most cases are associated with infection in the setting of immunodeficiency. The widespread use of immunosuppressive therapy in the treatment of inflammatory bowel disease (IBD) places patients with Crohn's disease and ulcerative colitis at risk of this complication. No concerted effort has been made to alert gastroenterologists of this condition, and treatment recommendations are lacking. The aims of this study were to describe the clinical and laboratory features of RHS associated with IBD and to review diagnostic criteria, treatment options, and pathogenesis. MATERIALS AND METHODS: Clinical and laboratory data were pooled from the clinical practice of the investigators and from published cases. Descriptive statistics were performed. RESULTS AND CONCLUSIONS: Seven cases of RHS complicating the treatment of IBD were identified. All patients were on immunosuppressive therapy, with nearly half taking >1 agent. All patients presented with fever, leukopenia, anemia, and hyperferritinemia. Infection by a member of the herpesvirus family or an intracellular pathogen precipitated RHS in 6 of 7 patients. The mortality rate was 29%. The diagnosis of RHS should be considered in patients with IBD taking immunosuppressive therapy who present with fever and cytopenia. Evaluation should begin with a serum ferritin. In patients with a serum ferritin > or =10,000 ng/mL, a bone marrow biopsy should be performed to confirm hemophagocytosis. If the initial evaluation is negative, then clinical suspicion should be maintained until the episode resolves.