Variable hematologic presentation of autoimmune gastritis: age-related progression from iron deficiency to cobalamin depletion.

Iron deficiency is a known complication of achlorhydria and may precede the development of pernicious anemia. Among 160 patients with autoimmune gastritis identified by hypergastrinemia and strongly positive antiparietal antibodies, we explored the overlap between 83 subjects presenting with iron deficiency anemia (IDA), 48 with normocytic indices, and 29 with macrocytic anemia. Compared with macrocytic patients, patients with IDA were 21 years younger (41 +/- 15 years versus 62 +/- 15 years) and mostly women. All groups had a high prevalence of thyroid disease (20%) and diabetes (8%) suggestive of the autoimmune polyendocrine syndrome. Stratification by age cohorts from younger than 20 years to older than 60 years showed a regular and progressive increase in mean corpuscular volume (MCV) from 68 +/- 9 to 95 +/- 16 fl, serum ferritin levels from 4 +/- 2 to 37 +/- 41 microg/L, gastrin level from 166 +/- 118 to 382 +/- 299 pM/L (349 +/- 247 to 800 +/- 627 pg/mL), and a decrease in cobalamin level from 392 +/- 179 to 108 +/- 65 pg/mL. The prevalence of Helicobacter pylori infection was 87.5% at age younger than 20 years, 47% at age 20 to 40 years, 37.5% at 41 to 60 years, and 12.5% at age older than 60 years. These findings challenge the common notion that pernicious anemia is a disease of the elderly and imply a disease starting many years before the establishment of clinical cobalamin deficiency, by an autoimmune process likely triggered by H pylori.

Transient severe eosinophilia precipitating massive venous thrombosis in a patient with hereditary thrombophilia.

We describe a patient homozygous for both the prothrombin G20210A and methylenetetrahydrofolate reductase C667T mutations who was symptom-free for 40 years and developed near-catastrophic thrombotic complications following transient, severe eosinophilia. This course of events raises the possibility of an increased risk of thrombosis associated with transient eosinophilia in the presence of hereditary thrombophilia and supports the concept of multifactorial etiology of venous thrombosis. Our experience suggests that in patients with severe eosinophilia, evaluation for known causes of hereditary or acquired thrombophilia may be useful for identifying subjects at increased risk of thrombosis.

Emergency treatment of life-threatening intrathecal methotrexate overdose.

A male 34-year-old patient with aggressive diffuse malignant lymphoma was hospitalized for treatment. Because of high likelihood of CNS involvement, intrathecal methotrexate (MTX) 15 mg was administered with hydrocortisone 100mg. Shortly after the intrathecal injection the patient became agitated, and complained of severe low back pain and 2h later he became confused and developed generalized seizures. At this stage, it was realized that the dose contained 1200 mg of MTX (80-fold overdose). The patient developed ARDS and was comatose; he was intubated and transferred to ICU. The patient was immediately treated with intravenous leucovorin 1200 mg, and 15 mg every 6h, thereafter, for 72 h. In addition, CSF exchange with warm normal saline was initiated via intrathecal catheter, and a total of 200 ml of CSF were replaced during 48 h. Finally, at the end of the exchange 2 mg of leucovorin with 2 mg of dexamethasone were administered intrathecally. MTX levels in CSF 7h post-injection were 770 microM, and increased to 1250 microM 2h later. Thereafter, the levels in CSF declined, and 48 h post-injection were 47 microM. The plasma levels of MTX 7h post-injection were 10 microM, and declined to 0.7 microM at 68 h. The patient regained consciousness and underwent successful weaning from ventilator after tracheostomy. The highest reported intrathecal dose after which the patient survived was 625 mg. Due to the rarity of reported cases, there are no clear guidelines for treatment of massive intrathecal overdose. There is a controversy regarding the toxicity of intrathecal injection of leucovorin. We propose CSF exchange and intravenous leucovorin as the mainstay of treatment.