Marshall Sparberg

Efficacy and safety of tacrolimus in refractory ulcerative colitis and Crohn's disease: A single-center experience

Background: The published experience regarding the use of tacrolimus in Crohns disease (CD) and ulcerative colitis (UC) refractory to more commonly used medical therapy has been fairly limited. Our objective was to describe our experience with its use in a cohort of patients which, to our knowledge, represents the largest North American cohort described to date. Methods: This was a retrospective, single‐center chart analysis. Patients were identified by compiling all hospital discharges with principle diagnoses of ICD‐9 codes for 555.0‐555.9 (regional enteritis) and 556.0‐556.9 (ulcerative colitis) from January 1, 2000, to October 31, 2005, and then cross‐referencing the electronic charts for tacrolimus serum concentrations ordered during this time period. Additional patients were identified through verbal communication with participating clinicians. Information abstracted included proportion with clinical response and remission (using a modified disease activity index), ability to wean from steroids, need for surgery / time to surgery, and side‐effect profile. Results: In all, 32 UC patients and 15 CD patients were identified. The mean disease duration was: UC 81 months (range, 1 month to 37 years), CD 100 months (range, 1 month to 35 years). The disease distribution for UC was: pancolitis 12 (37.5%), extensive colitis 6 (18.8%), left‐sided 11 (34.4%), and proctitis 3(9.4%). For CD this was: TI 2 (13.3%), small bowel 2 (13.3%), colonic 3 (20.7%), ileocolonic 7(46.7%), and perianal 1 (6.7%). The duration of tacrolimus treatment for UC was mean, 29 weeks. For CD it was mean, 9.9 weeks. In all, 30/32 UC and 7/15 CD patients were on steroids; 4/30 UC and 0/7 CD patients were able to subsequently wean off steroids. In all, 12/32 UC patients proceeded to colectomy. Mean time to colectomy was 28 weeks and 6/15 CD patients proceeded to a resective surgery. The mean time to surgery was 22 weeks. In all, 22/32 UC patients achieved a clinical response; 3/32 achieved remission and 8/15 CD patients achieved a clinical response; 1/15 achieved remission. Adverse reactions were generally mild. In 6 patients the drug had to be discontinued because of an adverse reaction. There were no opportunistic infections identified, no cases of renal insufficiency related to drug administration, and no deaths while on the medicine. Conclusions: Our experience with tacrolimus in UC and CD indicates that it is safe and relatively well tolerated, although its clinical efficacy is quite variable. More prospective studies assessing its use are necessary.

A study of potential hepatotoxicity of etretinate used in the treatment of psoriasis

Etretinate was used to treat twenty patients who had severe, disabling psoriasis and an increased risk of liver damage. Potential hepatotoxicity was evaluated by obtaining liver biopsies prior to starting therapy and after a 6-month course on a dosage of 0.75 mg/kg/day. In comparing pretreatment biopsies to posttreatment biopsies, five of twenty patients demonstrated a morphologic change in their liver. Three showed progressive fatty metamorphosis, and two showed liver cell necrosis and progressive fibrosis. One of these was due to heavy alcohol intake. Based on our 6-month evaluation, etretinate does not produce a consistent toxic effect on the liver.

Serial liver biopsies in psoriatic patients receiving long‐term etretinate

Twenty psoriatic patients treated with etretinate have been followed in a prospective study of liver biopsies. Twelve patients were followed up for 3 years, with four liver biopsies each. No significant damage to the liver was found during etretinate therapy. Etretinate may be stored in the fatty tissues of the liver or other body areas for prolonged periods.

Ultrastructural survey and tissue analysis of human livers after a 6-month course of etretinate

A prospective study of the histology and ultrastructure of liver biopsies and analysis of liver tissue for retinoid was performed in twenty psoriasis patients treated with etretinate for 6 months. Nonspecific ultrastructural changes were noted in several liver specimens. Etretinate was detected in all samples. We find no significant hepatotoxicity after a 6 month course of etretinate. Body fat is probably a more important site than the liver for storage of etretinate.

Cecal diverticulitis in young patients

Of the patients with cecal diverticulitis, 24 to 50% are below the age of 30, and such cases are usually misdiagnosed preoperatively as appendicitis. Two young patients with cecal diverticulitis were diagnosed preoperatively by barium enemas. The barium enemas correctly identified the extent of the disease. Treatment was tailored to the clinical and roentgenographic findings with both patients requiring elective colon resections.

Urological Complications of Regional Enteritis

Urological complications of regional enteritis occur frequently and may be clinically unsuspected. Radiographic findings include nephrolithiasis, characteristic stricture of the ureter, panvesiculitis, and enterovesical fistula. Less specific findings include renal amyloidosis and retroperitoneal abscesses. Mucosal nodularity of the bladder dome, even without gastrointestinal symptoms, should raise the possibility of regional enteritis. On the other hand, occult ureteral stenosis in patients with known regional enteritis may be present. For this reason, it is recommended that routine and periodic excretory urograms be a central part of the evaluation of the patient with regional enteritis.

Right subhepatic abscesses detected by technetium liver scans

A focal defect at the inferior margin of the right lobe of the liver was found in two patients with subhepatic abscesses. This defect must be differentiated from the porta hepatis and the gallbladder fossa. When technetium liver scans are obtained in patients with suspect abdominal abscesses, the inferior margin of the right lobe of the liver should be carefully scrutinized so that right subhepatic abscesses will not be overlooked.

Pituitary-Adrenal Suppression Following Intrarectal Administration of Dexamethasone-21-Phosphate

Summary An oral dose of 1 mg of dexamethasone or 2 mg of dexamethasone-21-phosphate as a retention enema given at 8:00 AM produced significant suppression of the 3:00 PM serum 17-hydroxycorticosteroids. The probability of the long term intrarectal administration of soluble corticosteroids producing pituitary-adrenal suppression is discussed.