Charles Berkelhammer

Azathioprine in refractory sprue

We report a patient with life-threatening refractory sprue who was dependent on high doses of corticosteroids to prevent severe diarrhea, malabsorption, and villous atrophy. Azathioprine allowed tapering of corticosteroids to lower doses, while maintaining remission in histology and in objective measures of malabsorption. Immunosuppressive therapy, however, is not without risks, particularly in patients with associated hypoglobulinemia.

Minocycline-induced hepatitis with autoimmune features and neutropenia.

Minocycline can cause various types of hepatotoxicity. We report an 18-year-old male who developed a delayed onset of minocycline-induced cholestatic hepatitis with autoimmune features and neutropenia. He responded to withdrawal of the drug and a short course of corticosteroids. If minocycline is to be administered, then periodic monitoring for hepatoxicity is recommended.

Gastric inlet patch containing submucosally infiltrating adenocarcinoma.

We describe a patient with an unusual segment of ectopic gastric mucosa in the proximal esophagus. The gastric heterotopia was circumferential and unusually long at 7 cm. It contained benign rugal-type folds, a stricture at the mid-portion of the gastric inlet patch was lined by normal antral-type gastric mucosa but harbored submucosally infiltrating adenocarcinoma. There was no evidence of Helicobacter pylori infection by biopsy or serologic screening. Malignancy, including submucosally infiltrating adenocarcinoma, should be considered in patients with strictures involving ectopic gastric mucosa in the proximal esophagus.

Intestinal Behçet's disease: Maintenance of remission with adalimumab monotherapy

To the Editor: Naganuma et al1 recently published their experience with infliximab for induction and maintenance of remission in 6 patients with intestinal Behçet’s disease (BD). Other reports have also shown the efficacy of infliximab in inducing remission in intestinal BD.2–7 However, many of these patients were receiving co-therapies. It is possible that alternate antitumor necrosis factor (antiTNF) agents may have different efficacy, just as etanercept has not been shown to be efficacious in Crohn’s disease. Therefore, the response of BD to other anti-TNF agents given as monotherapy would be of interest. We describe a patient with steroid-dependent immunosuppressive-refractory intestinal BD who has maintained complete remission on adalimumab monotherapy. A 30-year-old Caucasian female was diagnosed with BD according to the International Study Group criteria based on her long history of recurrent painful oral and genital ulcers, arthralgias, and papulopustular skin lesions. She had required intermittent courses of corticosteroids in the past. She presented with severe abdominal pain, diarrhea, and passage of blood per rectum. Sedimentation rate and C-reactive protein were significantly elevated. Colonoscopy revealed 6 deep punched-out ulcers in the cecum and ascending colon (Fig. 1a,b). The terminal ileum was normal. Biopsies revealed nonspecific chronic inflammation without granulomas. Upper endoscopy was normal, other than a 2-cm aphthous ulceration in the buccal mucosa (Fig. 2). A diagnosis of intestinal Behçet’s disease was made and she was started on prednisone 60 mg daily. Azathioprine 200 mg daily was added for several months to achieve therapeutic 6-thioguanine levels, yet she remained corticosteroid-dependent. Infliximab 5 mg/kg was added at 0, 2, and 6 weeks, and then every 8 weeks thereaf-

Plasma exchange for dramatic gestational hyperlipidemic pancreatitis

We describe the response to plasma exchange in a woman with extreme gestational hyperlipidemia and severe pancreatitis. Her serum triglyceride reached an astounding level of 21,300 mg/dl-among the highest concentrations ever recorded. Two consecutive plasma exchanges led to a remarkable reduction in triglyceride levels of 73% and 82%, respectively. Plasma viscosity decreased by 50% after the first plasma exchange. This was associated with an equally dramatic and unexpectedly rapid resolution of severe pancreatitis. Plasma exchange can rapidly and safely resolve extreme hyperlipidemia and be associated with prompt resolution of pancreatitis in women with severe gestational hyperlipidemic pancreatitis.

Double stenting to prevent airway compression in proximal malignant esophageal strictures

TO THE EDITOR: Acute airway obstruction causing respiratory stridor and death has been reported after placement of esophageal stents in the proximal one third of the esophagus (1–3). Double stenting of the esophagus and airway has been described (3–6), but emphasis has not been placed on the role of airway stents in preventing acute asphyxiation by release of expandable metallic stents in the proximal esophagus. This may occur in patients who have malignancy encroaching the lumens of both the esophagus and the tracheobronchial tree. We describe the placement of an airway stent before expandable esophageal stent placement in a patient in whom release of an expandable esophageal stent would have otherwise led to potentially life-threatening airway obstruction. A 52-yr-old male smoker underwent total right pneumonectomy for squamous cell carcinoma of the right lung, followed by postoperative chemoradiation. Mediastinal recurrence developed, which was treated with additional chemoradiation. He subsequently complained of hemoptysis, dyspnea, and dysphagia. Bronchoscopy demonstrated invasion and compression of the left main stem bronchus at the carina. This was treated by laser therapy. A bronchoesophageal fistula developed. Esophagram and endoscopy showed extrinsic compression on the proximal esophagus and an esophagobronchial fistula. CT scan showed compression of the remaining left mainstream bronchus by a mediastinal mass (Fig. 1). This mass was also compressing the esophageal lumen. A coated nitinol airway stent (Ultraflex, Microinvasive, Watertown, MA) was placed while the patient was under general anesthesia to stabilize the trachea and bronchus at the site of the fistula and extrinsic compression. This was followed by placement of a nitinol-coated esophageal stent (Ultraflex, Boston Scientific, Natick, MA) (Fig. 2). The double stent placement was uneventful. The patient’s respiratory status, dysphagia, and bronchoesophageal fistula remained palliated for the patient’s remaining 1.5 months of survival. Malignancies involving the proximal one third of the esophagus can be associated with concurrent infiltration Figure 1. Bleeding duodenal diverticulum.

Azathioprine-induced hypersensitivity hepatitis: tolerance to 6-mercaptopurine.

To the Editor: We describe a patient with severe azathioprine (AZA)-induced hypersensitivity hepatitis. Rechallenge with 6-mercaptopurine (6-MP) was tolerated for 6 years without hepatotoxicity. 6-Methylmercaptopurine (6-MMP) levels were markedly elevated on 6MP, yet liver biochemistries remained normal. This indicates a mechanism of hypersensitivity hepatitis that is unrelated to 6-MMP. AZA-induced hypersensitivity hepatitis may be related to AZA itself, or to its imidazole-derivative byproduct of glutathione metabolism. A 50-year-old male with steroiddependent ulcerative colitis and normal thiopurine methyltransferase (TPMT) enzyme activity (TPMP*1/TPMT*1) was initiated on AZA 50 mg/day. His only other medications were mesalamine and prednisone. Baseline liver biochemistries were normal. Four weeks after starting AZA his liver biochemistries rose dramatically to a bilirubin of 4.6 mg/dL, alanine aminotransferase (ALT) of 1077 U/L, aspartate aminotransferase (AST) of 624 U/L, and alkaline phosphatase of 361 U/L. Prothrombin time (PT) and partial thromboplastin time (PTT) were normal. Eosinophilia was not present. Extensive serologies to other causes of acute hepatitis were negative including IgM to hepatitis A, hepatitis B surface antigen and core antibody, HCV RNA to hepatitis C, IgM to Epstein–Barr virus, IgM to cytomegalovirus, antinuclear antibody, antismooth muscle antibody, antisoluble liver antigen, liverkidney microsomal antibody, antimitochondrial antibody, and perinuclear antinuclear cytoplasmic antibody. AZA was discontinued and liver biochemistries returned to normal. Desensitization to 6-MP was elected after informed consent, beginning with 12.5 mg/day with a dose escalation of 12.5 mg every 2 weeks. Liver biochemistries were carefully monitored. 6-MP was gradually increased to 100 mg per day and tolerated well. His 6-MMP levels were elevated to 15,400 pmol/8 10 erythrocytes (normal <5400 pmol/8 10 erythrocytes). The patient has remained on this dose of 6MP for 6 years. Liver biochemistries have remained normal with no signs of liver disease or portal hypertension. The incidence of AZA and 6-MP hepatotoxicity varies between 3%– 10%. Various hepatotoxicities have been described. These include elevations in liver biochemistries that may be transient and spontaneously resolving, dose-dependent elevations in liver biochemistries, hypersensitivity hepatitis, cholestatic reaction, nodular regenerative hyperplasia, and endothelial cell injury. The latter includes venoocclusive disease, peliosis hepatis, and peri-sinusoidal fibrosis. Dose-dependent elevations of liver biochemistries have a weak correlation with 6-MMP levels, but this has not been a consistent finding. In 1 study, 40% of patients with hepatotoxicity on AZA had therapeutic 6-MMP metabolites within the safe range at <5300 pmol/8 10 erythrocytes. Similarly, only 11% of patients with toxic 6-MMP levels above 5300 pmol/8 10 erythrocytes had abnormal liver function tests. The mechanism of AZA-induced hypersensitivity hepatitis is unknown. Our patient had markedly elevated 6MMP levels while on 6-MP. His liver function tests remained normal, indicating that AZA-induced hypersensitivity hepatitis is unrelated to 6-MMP. AZA is metabolized by glutathione into 6-MP plus an imidazole-derivative. AZA-induced hypersensitivity hepatitis may be related to AZA itself, or its imidazole derivative. Tolerance to 6-MP after AZAinduced hepatotoxicity has been described. In one study 12 out of 17 patients (77%) with AZA-induced hepatotoxicity tolerated 6-MP. In other smaller studies, 6-MP was tolerated in 7 of 8 (88%) and 3 of 9 (33%) patients with AZA-induced hepatotoxicity. However, many of these cases had mild hepatotoxicity, with transaminases less than 4-fold elevated. In contrast, our case had severe hypersensitivity hepatitis with jaundice and transaminases that were 20-fold elevated within 4 weeks of initiating therapy. Our patient’s tolerance to 6-MP may have been related to bypassing the production of the imidazole derivative associated with the use of AZA. Although our patient was rechallenged with desensitizing doses of 6-MP beginning with very small doses, it is unclear what role, if any, desensitization therapy played in our patient’s tolerance to 6-MP. In conclusion, patients with severe AZA-induced hypersensitivity hepatitis may tolerate 6-MP. The mechanism of AZA-induced hypersensitivity hepatitis is unrelated to 6-MMP. AZA-induced hypersensitivity hepatitis may relate to AZA itself, or its imidazole derivative. The role of desensitization therapy, if any, is unknown.

Ileocecal Intussusception of Small-bowel Lymphoma: Diagnosis by Colonoscopy

Intussusception is rare in adults. There is little information on the role of colonoscopy in colonic intussusception. We report, to our knowledge, the first adult case of small-bowel lymphoma causing ileocecal intussusception in which the diagnosis was made by colonoscopy. Colonoscopy has a useful role in the diagnosis and management of ileocecal intussusception.

Nortriptyline-induced fulminant hepatic failure.

We describe, to our knowledge, the first reported case of nortriptyline-induced fulminant hepatic failure. This tricyclic antidepressant drug was taken by a postmenopausal woman for 64 days before her presentation. The absence of fever, rash, or marked eosinophilia, the predominant zone 3 necrosis with bridging, and the latent period favor a metabolic idiosyncratic reaction. The fatal outcome underscores the importance of recognizing the association and discontinuing the offending agent.

Spontaneous multiperforation in lymphomatous colitis masquerading as Crohn's disease.

We present a case of necrotizing lymphomatous colitis--masquerading as Crohns disease--that was complicated by spontaneous multiple perforations. This potentially fatal occurrence might have been obviated by earlier immunologic diagnosis.