Anticarbamazepine antibody induced by carbamazepine in a patient with severe serum sickness.

Abstract

Anticarbamazepine antibody was detected in a patient who had clinical signs of serum sickness induced by carbamazepine. Skin rash, fever, oedema, and lymphadenopathy are classic signs of severe adverse reaction, but although immunological hypersensitivity is thought to be a contributory factor, the presence of anticarbamazepine antibody has not previously been reported to our knowledge.Carbamazepine is widely used in the treatment of various forms of epileptic disorders.' 2 Although different side effects have been reported, skin rash is the most common adverse reaction. Exfoliative dermatitis, urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome, and a reaction similar to systemic lupus erythematosus have been reported.2 3 In some cases the skin rash is part of a severe illness affecting several organs, and immunological hypersensitivity is thought to contribute to the skin reaction.3 4 So far, however, we know of no report of the presence of anticarbamazepine antibody in any patient with severe skin reactions.We present a patient with the typical clinical manifestations of serum sickness, fever, eruption with oedema (particularly around the face and neck), and lymphadenopathy. The laboratory findings showed a decrease in complement C4 and an increase in C3a and C4a activity. Anticarbamazepine antibody was detected in the serum using an enzyme linked immunosorbent assay (ELISA). Methods BALB/C mice were given carbamazepine (1 g/kg) orally, and bled six hours later. The serum was used as the antigen.The anticarbamazepine antibody of serum from the patient was analysed by ELISA, a procedure that has been described elsewhere.5 Briefly, the mouse serum diluted (1:100) with 10 mM carbonate buffer was added to 96 well polyvinylchloride microtitre plates, and left for two hours at room temperature. The nonbinding sites were blocked with phosphate buffered saline containing 0 05% Tween 20 and 2% ovalbumin. Diluted human serum was added to the wells and incubated for one hour at 4°C. After three washings, 100 >t of appropriately diluted horseradish peroxidase conjugated goat antimouse Ig antiserum was added to each well. The plates were then incubated for one hour at 4°C and washed three times, and 200 tl of freshly prepared substrate solution containing 0-05% o-phenylendiamine and 0 0075% hydrogen peroxide in McIlvain buffer, pH 6-0, was added to each well. After 30 minutes of incubation at room temperature, absorbance was read at 405 nm with a Titertek Multiskan plate reader.Case report An 8 year old girl was admitted with fever and skin rash. Thirty seven days before admission carbamazepine 200 mg (10 mg/kg) had been prescribed because of a complex partial seizure. Twenty seven days before admission the first skin rash had appeared on her cheeks, but this disappeared within a few days. Twenty three days before admission, the dose of carbamazepine had been increased to 300 mg. The day before admission she had again developed maculopapular erythema on her face and neck, this time accompanied by fever...

Patch testing in cutaneous reactions caused by carbamazepine

“…In vitro lymphocyte proliferation induced by carbamazepine was found by Zakrzewska & Ivanyi (19) in all 9 patients with histories of rashes caused by the drug, but not in 33 control subjects. Single cases of positive patch test reactions with carbamazepine have been published by other authors (10,(20)(21)(22). The test substance used has varied from 1% carbamazepine (mostly in pet.)…”

“…The laboratory findings may include an abnormality in liver function tests (GOT, GPT) and an increase in the number of eosinophilic granulocytes or an appearance of reactive lymphocytes in the peripheral blood. This syndrome has been described as "serum-sickness-like reaction" (10,11) and "pseudolymphoma syndrome" (11,12). Carbamazepine can also cause fixed drug eruptions and erythema multiforme reactions as well as exfoliative dermatitis (erythrodermas).…”

Immunosuppressive Factors Detected during Convalescence in a Patient with Severe Serum Sickness Induced by Carbamazepine

“…Some of these cases were induced by drugs. Here we report further details of a patient described previously, who showed fever, skin rash, facial edema, lymphadeno pathy and hypergammaglobulinemia [6]. We have consid ered this to be a case of severe serum sickness induced by CBZ, and have documented the presence of anti-CBZ an tibody and CBZ-specific T cells [6].…”

“…Patients Patient AM, a 5-year-old girl, has already been reported [6], She showed fever, skin rash, generalized lymphadenopathy, hepatosplcnomegaly, hypocomplementcmia and polyclonal hypergamma-globulincmia. The clinical manifestations were compatible with severe se rum sickness (type III allergy) induced by CBZ, since anti-CBZ IgG antibody was detected in the serum.…”

Severe Adverse Reaction to Carbamazepine: Significance of Humoral and Cellular Reactions to the Drug

“…Side effects induced by carbamazepine are not uncommon and include rash, fever, hematological, gastrointestinal, cardiovascular, neurological symptoms and disturbances of liver and renal function (2). Although these side effects are usually mild and disappear rapidly after carbamazepine discontinuation, severe serum sickness has been reported in some cases (5). The typical clinical manifestations including fever, skin rash, petechial bleeding and lymphadenopathy were regarded as indicative of a type 111 hypersensitivity reaction (6).…”