Interstitial lung disease following FOLFOX + FOLFIRI and bevacizumab therapy associated with leucovorin: A case report.

Chemotherapy-induced interstitial lung disease in colorectal cancer patients is rare but represents a life-threatening adverse reaction. We report here a case of interstitial lung disease following chemotherapy for metastatic colorectal cancer and the interesting results of the drug-induced lymphocyte stimulation test and leukocyte migration test. After chemotherapy with oxaliplatin plus infusional 5-fluorouracil and leucovorin (FOLFOX) plus bevacizumab followed by irinotecan plus infusional 5-fluorouracil and leucovorin (FOLFIRI), the patient was hospitalized with fever and chills. Laboratory data showed neutropenia and eosinophilia. Computed tomography revealed ground-glass opacities in both lungs; therefore, we diagnosed chemotherapy-induced interstitial lung disease. Steroid therapy was effective. We suspected irinotecan to be the etiological drug for interstitial lung disease in this patient because interstitial lung disease developed after switching the regimen from FOLFOX to FOLFIRI. However, drug-induced lymphocyte stimulation test and leukocyte migration test results were positive for only leucovorin and negative for irinotecan and 5-fluorouracil. This is the first case to show positive results on the drug-induced lymphocyte stimulation test and leukocyte migration test for only leucovorin and negative results for antineoplastic drugs. Our findings suggest that all drugs included in chemotherapy regimens have the potential to induce interstitial lung disease, and if rechallenge chemotherapy is considered, the drug-induced lymphocyte stimulation test and leukocyte migration test are expected to be useful for determining the drug that needs to be excluded.

Vildagliptin-induced acute lung injury: a case report.

BACKGROUND: Dipeptidyl peptidase-4 inhibitors are a class of oral hypoglycemic drugs and are used widely to treat type 2 diabetes mellitus in many countries. Adverse effects include nasopharyngitis, headache, elevated serum pancreatic enzymes, and gastrointestinal symptoms. In addition, a few cases of interstitial pneumonia associated with their use have been reported in the Japanese literature. Here we describe a patient who developed drug-induced acute lung injury shortly after the administration of the dipeptidyl peptidase-4 inhibitor vildagliptin. CASE PRESENTATION: A 38-year-old Japanese woman with diabetes mellitus developed acute respiratory failure 1 day after administration of vildagliptin. Chest computed tomography revealed nonsegmental ground-glass opacities in her lungs. There was no evidence of bacterial pneumonia or any other cause of her respiratory manifestations. After discontinuation of vildagliptin, she recovered fully from her respiratory disorder. She received insulin therapy for her diabetes mellitus, and her subsequent clinical course has been uneventful. CONCLUSIONS: The period of drug exposure in previously reported cases of patients with drug-induced interstitial pneumonia caused by dipeptidyl peptidase-4 inhibitor varied from several days to over 6 months. In the present case, our patient developed interstitial pneumonia only 1 day after the administration of vildagliptin. The precise mechanism of her vildagliptin-induced lung injury remains uncertain, but physicians should consider that dipeptidyl peptidase-4 inhibitor-induced lung injury, although rare, may appear acutely, even within days after administration of this drug.

Examination of patients suspected as having hypersensitivity to iodinated contrast media with leukocyte migration test.

In vivo tests may be used for the diagnosis of allergy to iodinated contrast media (ICM); however, the tests do not provide definitive diagnosis and are associated with risks for patients. Diagnoses based on in vitro tests are limited, and there are almost no relevant studies. Herein, the authors examined involvement of allergic reaction from a multilateral standpoint in 39 patients suspected of having ICM allergies using leukocyte migration test (LMT). The positive rate of LMT was 44%. A comparison with the positive rate of LMT in drugs other than ICM (74%) indicated 30% difference, which was significantly low value, suggesting that there is poor involvement of these drugs in the allergic reaction. In LMT positives, 76% of hypersensitivity reactions were skin rash mainly erythema, and 18% was anaphylactic reactions. Cases considered as non-immediate hypersensitivity accounted for about 4 times as many as immediate-type hypersensitivity. In examination of relevancy between a history of drugs or food allergies, the incidence of ICM allergies was 35%. There is a high possibility that these adverse reactions were caused by pseudoallergy to drug. It was suggested that most hypersensitivity reactions were skin rash related to non-immediate hypersensitivity, and approximately 20% of the reaction was immediate anaphylactic reaction. Therefore attention should be paid not only to immediate-type hypersensitivity but also delayed reactions. Moreover, it was considered that patients with past history of drug or food allergies have a high potential for manifestation of the reactions.

Study on patients who underwent suspected diagnosis of allergy to amide-type local anesthetic agents by the leukocyte migration test.

BACKGROUND: There are problems in diagnosis of allergy to amide-type local anesthetic agents (ALAs), because definitive diagnosis is not obtained by in vivo tests, which are used for the diagnosis. Consequently, patients may be exposed to risk. There are few diagnoses based on in vitro tests, and there are almost no relevant studies. METHODS: Authors examined involvement of allergic reaction using the leukocyte migration test (LMT) through multiple standpoints in 43 patients who underwent suspected diagnosis of allergy to ALAs. RESULTS: Rate of LMT-positives was 54%, and especially the positive rate of lidocaine hydrochloride preparations was significantly high. In 15 positives to lidocaine hydrochloride preparations, all cases were indicated as positive in a test with drugs containing antiseptic agent, but only 3 cases were indicated as positive in a test with lidocaine hydrochloride alone. In addition, test with paraben was conducted in 4 cases; 2 cases were confirmed as positive. In relevance of histories of drug or food allergies, development rates of ALAs-allergies were the highest in both allergies, and were 35% and 13%, respectively. CONCLUSIONS: There is a high possibility that these adverse reactions were caused by pseudoallergy to drug. Even by allergic reactions, it was assumed that 80% of them might be caused by antiseptic agents such as paraben. In addition, it was suggested that ALAs, especially lidocaine hydrochloride preparations have high antigenicity (sensitizing property). Furthermore, it was considered that patients with past history of drug or food allergies have a high potential for manifestation of the reactions.

Cervical reflex induced by click stimuli in cats.

We studied click-evoked potentials in the anterior horn of the spinal cord in 17 cats. A concentric needle electrode was inserted into the anterior horn of the spinal cord at levels C3-C6. Potentials evoked with 105 dB SPL clicks were recorded with a peak latency of 4.89-5.10 ms only at the C3 level. These responses were observed 45-60 dB SPL above the auditory brainstem response (ABR) threshold, and no potentials were evoked by stimulation of the contralateral ear. Average was performed 100 times with changes in stimulation frequency of 1-20 Hz. The amplitude of the potentials decreased with increasing stimulus frequency, but there were no changes in ABRs. The responses disappeared after destruction of the medial vestibulospinal tract at the obex level, but ABRs were still recorded. The spinal nucleus of the accessory nerves was located in the anterior horn of the spinal cord at levels C1-C6, and the sternocleidomastoid muscle motoneurons were found at levels C1-C3. The click-evoked potentials recorded in this study reflect responses of the spinal nucleus of accessory nerves through the vestibulospinal tract to click stimulation. The responses have the same characteristics as vestibular-evoked myogenic potentials that can be recorded using surface electrodes over the sternoclei-domastoid muscles of humans.