Pattern of food‐induced anaphylaxis in children of an Asian community

a tricyclic antidepressant. In week 4 of the treatment with phenytoin, the patient developed in 24±48 h fever of 398C combined with generalized erythematous skin rash. The other systemic and neurologic probes were normal. The blood cell count showed leukocytosis with eosinophilia (16 500 leukocytes/mm, 12% eosinophils), and the coagulation study, biochemical and hepatic pro®le, hemocultures, coprocultures, and urocultures then done, as well as the chest radiography, were normal. Computed tomography of the skull described the continuity to a parietal level without any other important alteration. With the clinical suspicion that there was an adverse reaction to medication, the phenytoin and the tricyclic antidepressant were stopped. During the following week, the patient continued to show fever and eosinophilia, and the skin rash became desquamative. The clinical situation worsened gradually and between days 8 and 10 after stopping the phenytoin, she showed acute hepatic failure with high cytolysis and cholestasis (glucose 57 mg/dl, SGOT 1535 U/l, SGPT 497 U/l, gamma GT 1055 U/l, alkaline phosphatase 662 U/l, cholesterol 110 mg/dl, total bilirubin 17.5 mg/dl, LDH 2862 U/l, albumin 1.7 g/dl), linked to severe coagulopathy (prothrombin Ac. 21%, APTT 53/29). The analysis then done did not reveal any indication of a possible cause, and the abdominal echography showed only a spleen slightly increased in size. In the following days, the patient developed acute renal failure and pancytopenia with severe neutropenia (2400 leukocytes/mm with 190 neutrophils, 10 000 blood platelets/mm, hemoglobin 8.9 g/dl). The patient died 15 days after stopping the phenytoin. The autopsy showed submassive hepatic necrosis linked to splenomegaly, and moderate in ̄ammatory in®ltrated vascular congestion of the skin. The anatomopathologic diagnosis was phenytoin hypersensitivity syndrome. Phenytoin is an anticonvulsant affecting hepatic metabolism. Among its more frequent side-effects are gastric intolerance, skin rash, and gingival hyperplasia. Less frequently, cases of hypersensitivity syndrome to DFH have been described. This syndrome with anticonvulsants was ®rst described in 1950 by Chaiken et al. (1); they called it dilantin hypersensitivity syndrome. Later, cases involving carbamacepine, primidone, and phenobarbital were described. The hypersensitivity syndrome to phenytoin is of low incidence (1/1000±10 000 treated with DFH), and it usually appears between weeks 1 and 4 of treatment. Risk factors have not been clearly identi®ed when they appeared and their origin is not dose dependent. Skin signs were the most common in the syndrome in the study by Silverman (2). Fever, lymphadenopathies, and megalies are common, as well as leukocytosis and eosinophilia. Aplastic marrow and hepatic affectation are less common. Those rare signs appear late during the development of the syndrome, and most of the patients who develop them have previous skin alterations. The pathogenic mechanism of this syndrome has not been established. Most of the facts suggest a hypersensitivity phenomenon, although idiosyncratic and toxic mechanisms with enzymatic induction of Cp 450 and the production of intermediary metabolites have also been involved. These metabolites are potentially cytotoxic, and they can alter the lymphocytic function, increasing the hepatocellular necrosis and lymphadenopathies, as described by Haword et al. (3). The diagnosis of this syndrome is clinical and analytic. Studies of lymphocytic stimulation and the patch test can indicate the therapeutic option of withdrawal of DFH, although the patient's condition can alter. This emphasizes the danger of a premature diagnosis. Steroids are usually used during the treatment, although their indexing is not well established and does not alter the mortality rate. However, they are effective in the skin symptoms and can shorten their course. Excessive medication taken with DFH can worsen the prognosis. Dreifuss et al. (4) have shown cross-reactivity with other anticonvulsants and interaction with antidepressants. The mortality rate in this syndrome rises to 30±40% if hepatic damage occurs. Mullick (5), in a clinical pathologic study, has reported 20 cases of hepatic injury associated with diphenylhydantoin; the mortality rate without hepatic affectation was 10%. Our patient showed hypersensitivity syndrome to DFH after 4 weeks of treatment. She developed fever, desquamative erythema, and eosinophilia linked to aplastic marrow and severe hepatic failure, which caused her death.