Antineoplastic Agents ; therapeutic use ; Autoimmune Diseases ; pathology ; Benzamides ; Cell Differentiation ; Cell Movement ; Cell Survival ; Eosinophilia ; chemically induced ; pathology ; Eosinophils ; cytology ; physiology ; Helminthiasis ; pathology ; Humans ; Hypereosinophilic Syndrome ; drug therapy ; pathology ; Hypersensitivity ; pathology ; Imatinib Mesylate ; Piperazines ; therapeutic use ; Pyrimidines ; therapeutic use

An 82-yr-old man was presented with fever and cough accompanied by generalized erythematous rash. He had taken mexiletine for 5 months, as he had been diagnosed with dilated cardiomyopathy and ventricular arrhythmia. Laboratory studies showed peripheral blood eosinophilia and elevated liver transaminase levels. Chest radiographs showed multiple nodular consolidations in both lungs. Biopsies of the lung and skin lesions revealed eosinophilic infiltration. After a thorough review of his medication history, mexiletine was suspected as the etiologic agent. After discontinuing the mexiletine and starting oral prednisolone, the patient improved, and the skin and lung lesions disappeared. Subsequently, mexiletine was confirmed as the causative agent based on a positive patch test. Drug-induced hypersensitivity syndrome is a severe adverse reaction to drugs and results from treatment with anticonvulsants, allopurinol, sulfonamides, and many other drugs. Several cases of mexiletine-induced hypersensitivity syndrome have been reported in older Japanese males with manifestation of fever, rash, peripheral blood eosinophilia, liver dysfunction without other organ involvement. Here, we report a case of mexiletine-induced hypersensitivity syndrome which presented as eosinophilic pneumonia in a Korean male.
Aged, 80 and over ; Anti-Arrhythmia Agents/*adverse effects ; Arrhythmias, Cardiac/drug therapy ; Cardiomyopathy, Dilated/drug therapy ; Drug Hypersensitivity/*diagnosis/etiology ; Exanthema/pathology ; Humans ; Lung/pathology/radiography ; Male ; Mexiletine/*adverse effects ; Pulmonary Eosinophilia/*chemically induced/*diagnosis ; Syndrome ; Tomography, X-Ray Computed

OBJECTIVETo investigate the method of development of allergic airway disease model in mice.

METHODSTen BALB/c mice were devided into the model group and the control group. Each group contained 5 mice. Ovalbumin (OVA) was used as allergen. OVA was emulsified with aluminum hydroxide and injected intraperitoneally for sensitization. Afterwards the mice from model group were challenged with aerosolized 5% OVA and subsequently instilled with OVA intranasally. For the blank control group the mice were sensitized and challenged with phosphate buffer saline (PBS). After final challenge, the nasal symptoms were scored, and mice were sacrificed for evaluation of eosinophilia of nasal septum, peribronchial inflammation and goblet cell hyperplasia. Mice serum was collected for measurement of OVA-specific IgE concentration, and levels of IL-4 and IL-5 from bronchoalveolar fluids were also tested.

RESULTSCompared with blank control mice, mice from model group displayed typical sneezing and nasal scratching symptoms. The histopathological changes, such as eosinophilia of nasal septum mucosa, infiltration of peribronchial inflammatory cells and hyperplasia of goblet cells were successfully induced by OVA sensitization and challenge. Moreover, mice in model group showed higher level of OVA-specific IgE in serum and IL-4 and IL-5 cytokines in bronchoalveolar fluids[mice from model group: IgE (1237.00 ± 153.20) pg/ml, IL-4 (46.50 ± 10.15) pg/ml, IL-5 (50.81 ± 11.41) pg/ml; mice from control group: IgE (191.90 ± 43.20) pg/ml, IL-4 (7.96 ± 1.80) pg/ml, IL-5 (7.53 ± 2.23) pg/ml;t value were 6.569, 3.738 and 3.724, respectively, all P < 0.05].

CONCLUSIONThe method using OVA as allergen could effectively develop a mouse model of allergic airway disease which could be used for pathogenesis study and drug effect evaluation.

Allergens ; Animals ; Bronchoalveolar Lavage Fluid ; chemistry ; Disease Models, Animal ; Eosinophilia ; pathology ; Immunoglobulin E ; blood ; Interleukin-4 ; metabolism ; Interleukin-5 ; metabolism ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; pharmacology ; Rhinitis, Allergic ; Rhinitis, Allergic, Perennial ; chemically induced ; pathology

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome reflects a serious hypersensitivity reaction to drugs, characterized by skin rash, fever, lymph node enlargement, and internal organ involvement. So far, numerous drugs such as sulfonamides, phenobarbital, sulfasalazine, carbamazepine, and phenytoin have been reported to cause the DRESS syndrome. We report a case in a 29-yr-old female patient who had been on celecoxib and anti-tuberculosis drugs for one month to treat knee joint pain and pulmonary tuberculosis. Our patient's clinical manifestations included fever, lymphadenopathy, rash, hypereosinophilia, and visceral involvement (hepatitis and pneumonitis). During the corticosteroid administration for DRESS syndrome, swallowing difficulty with profound muscle weakness had developed. Our patient was diagnosed as DRESS syndrome with eosinophilic polymyositis by a histopathologic study. After complete resolution of all symptoms, patch tests were positive for both celecoxib and ethambutol. Although further investigations might be needed to confirm the causality, celecoxib and ethambutol can be added to the list of drugs as having the possibility of DRESS syndrome.
Adult ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Antitubercular Agents/adverse effects ; Arthritis/complications/*drug therapy ; Drug Eruptions/*etiology/pathology ; Eosinophilia/*chemically induced/pathology ; Ethambutol/*adverse effects ; Female ; Humans ; Myositis/chemically induced/pathology ; Pyrazoles/*adverse effects ; Sulfonamides/*adverse effects ; Syndrome ; Tuberculosis, Pulmonary/complications/*drug therapy

Hepatitis A virus (HAV) infections occur predominantly in children, and are usually self-limiting. However, 75-95% of the infections in adults are symptomatic (mostly with jaundice), with the illness symptoms usually persisting for a few weeks. Atypical manifestations include relapsing hepatitis, prolonged cholestasis, and complications involving renal injury. Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a severe, drug-induced hypersensitivity reaction characterized by skin rash, fever, lymph-node enlargement, and internal organ involvement. We describe a 22-year-old male who presented with acute kidney injury and was diagnosed with prolonged cholestatic hepatitis A. The patient also developed DRESS syndrome due to antibiotic and/or antiviral treatment. To our knowledge, this is the first report of histopathologically confirmed DRESS syndrome due to antibiotic and/or antiviral treatment following HAV infection with cholestatic features and renal injury.
Acute Kidney Injury/diagnosis ; Anti-Bacterial Agents/*adverse effects/therapeutic use ; Cefotaxime/adverse effects/therapeutic use ; Cholestasis/complications/*diagnosis ; Cytomegalovirus/genetics ; Cytomegalovirus Infections/drug therapy/virology ; DNA, Viral/analysis ; Eosinophilia/etiology ; Exanthema/*chemically induced/pathology ; Ganciclovir/therapeutic use ; Hepatitis A/complications/*diagnosis/drug therapy ; Humans ; Hydrocortisone/therapeutic use ; Immunoglobulins/therapeutic use ; Male ; Syndrome ; Young Adult