Elevated Blood Eosinophil Count Research Articles

Hypersensitivity Reactions to Chemotherapy Agents in Patients Receiving Chemoimmunotherapy With High-Dose Interleukin 2

Treatment with the immune system modulator interleukin 2 (IL-2) can result in a number of immunologic abnormalities ranging from suppression of delayed-type hypersensitivity responses and neutrophil activity to autoimmune thyroiditis and hypersensitivity reactions against iodine-containing radiographic contrast media. There are a number of published reports of chemoimmunotherapy using IL-2 in combination with various chemotherapeutic agents to treat patients with certain cancers, but none have described hypersensitivity responses to the chemotherapeutic agents given. In the early stages of an ongoing clinical trial of the efficacy of combination chemoimmunotherapy for the treatment of patients with metastatic melanoma, we discovered that a number of the patients experienced unexpected hypersensitivity reactions after receiving chemotherapy. We therefore decided to examine these hypersensitivity reactions in detail. During the period of March 1993 through February 1994, 31 patients with metastatic melanoma were treated either by chemotherapy (dacarbazine, cisplatin, and tamoxifen) or by chemoimmunotherapy (the same drug regimen plus interferon alfa and high-dose IL-2). Twelve patients were treated in a non-randomized pilot study, with six receiving chemotherapy and six receiving chemoimmunotherapy. The six patients who received chemotherapy also received carmustine (BCNU). Nineteen subsequent patients were treated in a prospective, randomized study to compare the two therapeutic approaches. In total, 15 of the 31 patients were treated by chemotherapy alone, and 16 were treated by combination chemoimmunotherapy. Overall, the patients in the two groups were balanced in terms of age, sex, and stage of disease. Ten of 16 chemoimmunotherapy patients exhibited type I hypersensitivity reactions during chemotherapy administration, ranging from pruritus, erythema, and edema to hypotension with hemodynamic instability that required pressor therapy. None of the 15 patients on the chemotherapy regimen exhibited hypersensitivity reactions. All patients in the chemoimmunotherapy group gained weight and had elevated white blood cell and eosinophil counts during chemotherapy; these effects were more prominent in those with hypersensitivity reactions. Hypersensitivity reactions occurred within several hours after chemotherapy administration in patients who had previously received one to two cycles of high-dose IL-2, suggesting that prior IL-2 therapy sensitized patients to cisplatin or dacarbazine. This is the first report of IL-2-induced hypersensitivity to chemotherapy agents.

Eosinophil cationic protein in sera of patients with atopic dermatitis

Patients with atopic dermatitis frequently show elevated blood eosinophil counts, and eosinophil-derived major basic protein has been demonstrated in the eczematous skin from patients with atopic dermatitis. To evaluate further the role of eosinophils in the pathogenesis of atopic dermatitis, the concentration of eosinophil cationic protein was measured in serum samples of 42 patients with moderate to severe disease. The results were compared with those obtained in 32 patients with psoriasis with (n = 9) or without (n = 23) a history of inhalant allergy, 12 patients with a history of pseudoallergic reactions to acetylsalicylic acid, 14 patients with a history of inhalant allergy, and 31 nonatopic healthy control subjects. Eosinophil cationic protein levels were significantly increased in the serum of patients with atopic dermatitis (p less than or equal to 0.005) and patients with a history of pseudoallergic reactions to acetylsalicylic acid (p less than or equal to 0.01). There was no significant difference between eosinophil cationic protein levels in patients with psoriasis or a history of inhalant allergy and in control subjects. Moreover, eosinophil cationic protein levels did not differ significantly in psoriasis patients with or without inhalant allergy. These studies support the concept of an active participation of eosinophils in atopic dermatitis and point to a possible role for eosinophils in pseudoallergy.

Pulmonary Involvement in the Eosinophilia-Myalgia Syndrome

We describe the cases of three women with pulmonary involvement in the eosinophilia-myalgia syndrome. The illness was characterized by elevated peripheral blood eosinophil counts, myalgias, fatigue, and dyspnea. Two of three patients had bilateral infiltrates on chest roentgenograms. All three had markedly decreased carbon monoxide diffusing capacities and pulmonary hypertension. High-dose prednisone therapy provided only partial resolution of the pulmonary symptoms. Open lung biopsy specimens showed chronic interstitial and perivascular infiltrates in two of the patients and moderate fibrointimal hyperplasia of pulmonary vasculature in the third. High-dose prednisone therapy prior to the biopsies may have modified the original histologic features.

Toxicity after Self-Poisoning by Ingestion of Potassium Chloroplatinite

A 31 year-old man ingested 10 mL of a photographic toning solution containing 600 mg of potassium chloroplatinite in a suicide attempt. Subsequent toxic effects included acute oliguric renal failure, metabolic acidosis, fever, muscle cramps, gastroenteritis and rhabdomyolysis. Laboratory abnormalities included mildly elevated liver enzymes and elevated peripheral blood neutrophil and eosinophil counts. All symptoms and signs of toxicity resolved over a six day hospital stay with supportive medical management only; thereafter he was lost to medical follow-up. A spot serum platinum concentration was 245 mcg/dL and a spot urine platinum concentration was 4200 mcg/L.

Blood and graft eosinophilia as predictors of rejection in human liver transplantation.

This study attempts to define the relationship of blood and graft eosinophilia to acute hepatic allograft rejection. Sixty liver transplant patients were studied for the first 30 days postoperatively, with daily serum bilirubin and liver enzyme levels, white blood cell counts and differential counts, and biweekly core liver biopsies. Graft eosinophilia was established if 7% or greater of the cells infiltrating the portal triads were eosinophils. Blood eosinophilia is an absolute eosinophil count greater than 500 cells/mm3 occurring on any of the 5 days preceding the day of rejection. Acute rejection was diagnosed when 2 days of hepatic allograft dysfunction occurred with histologic evidence of rejection. The 2nd day of dysfunction with appropriate histologic findings was arbitrarily chosen as the day of rejection. Graft eosinophilia predicted rejection with 92% sensitivity and 98% specificity. Blood eosinophilia occurred on the average on the day of rejection and on the 2 preceding days, while graft eosinophilia occurred on the day of rejection and on 1 preceding day. Blood eosinophilia followed by graft eosinophilia specifically occurred in cases of rejection. Blood eosinophilia not followed by graft eosinophilia was not associated with rejection. Following treatment of rejection with high-dose corticosteroids, blood and graft eosinophil counts decreased markedly. In summary: (1) graft eosinophilia is very sensitive and specific for acute hepatic allograft rejection; (2) blood eosinophilia closely precedes and parallels graft eosinophilia specifically during acute hepatic allograft rejection; and (3) elevated blood and graft eosinophil counts are markedly reduced following treatment of rejection with high-dose corticosteroids.

Bronchocentric granulomatosis

The clinical and morphologic features in 15 patients with bronchocentric granulomatosis were reviewed. Patients were divided into two groups on the basis of the morphologic findings. Group I consisted of five patients with necrotizing granulomas containing abundant eosinophils in the areas of necrosis. Three of these patients were asthmatic, two had elevated blood eosinophil counts, and in one there were fungal hyphae within necrotizing granulomas. In another case a sputum culture was positive for Aspergillus. The findings in these cases support the contention that some bronchocentric granulomas associated with tissue eosinophilia may represent a hypersensitivity reaction to inhaled Aspergillus. Group II included 10 patients with bronchocentric granulomas showing many polymorphonuclear cells but few eosinophils. None of these 10 had asthma, and blood eosinophilia was found in only one patient. The etiology and pathogenesis of these bronchocentric granulomas is unclear. The differences in morphology and clinical symptomatology between the two groups suggest that these lesions may arise from more than one etiologic agent and pathogenetic mechanism. Follow-up information was available for 11 individuals. Corticosteroids were given to four patients and lesions were resected from five patients. Neither recurrence of bronchocentric granulomas nor death due to them was reported.