Carbamazepine


Carbamazepine is a drug widely used in the treatment of epilepsy, trigeminal neuralgia and affective disorders.
 
Incidence
Cutaneous reactions: 3 to 16%.
 
Stevens-Johnson’s syndrome: 1/5000 to 1/10000.
 
Clinical manifestations
(occurring one week to 3 months (average 4 weeks) after starting therapy)
 
Carbamazepine hypersensitivity syndrome: fever + lympha-denopathy (pseudolymphoma syndrome) + generalized rash.
 
Other: serum sickness, glandular fever-like syndrome, Kawasaki-like syndrome, systemic lupus erythematosus-like syndrome, hypersensitivity vasculitis, necrotizing granulomatous vasculitis.
 
Cutaneous: macular or maculopapular rash, eczematoid dermatitis, edema of the face, hands and feet, purpura, erythroderma, urticaria, exfoliative dermatitis, erythema multiforme, toxic epidermal necrolysis.
 
Respiratory: cough, dyspnea, pneumonitis.
 
Digestive: hepatosplenomegaly, hepatitis
 
Renal: acute tubulointerstitial nephritis, hypersensitivity vasculitis.
 
Hematological: leukocytosis, eosinophilia, leukopenia, lymphopenia, agranulocytosis, aplastic anemia, thrombocytopenia.
 
E.N.T: pharyngitis.
 
Ophthalmic: conjunctivitis.
 
Diagnostic methods
Cutaneous testing.
 
Patch-tests.
 
Haye’s patch-tests chambers: carbamazepine 100%, 10%, 1% and 0.1% in pet. jelly and in acetone: positive in patients with carbamazepine hypersensitivity syndrome.
 
Lymphocyte transformation test: positive in patient with carbamazepine hypersensitivity syndrome.
 
Mechanisms
Highly reactive arene oxide or epoxide metabolites formed by cytochrome P 450, or other metabolites formed by myeloperoxidase bind to tissue macromolecules causing cell damage or act as haptens and elicit an immune response.
 
The results of the patch-tests and lymphocyte transformation tests indicate the presence of a specific T-cell reactivity.
 
Anticarbamazepine antibodies have been detected.
 
Presence of immunosuppressive cytokines, production of numerous auto-antibodies, deposits of immune complexes in the skin.
 
Management
Systemic corticosteroids are recommended in the management of carbamazepine hypersensitivity syndrome.
 
Desensitization is possible (isolated skin rash).
 
Cross-reactivity between carbamazepine, phenytoin, and phenobarbital is common.

References

  1. Morkunas A.R, Miller M.B, "Anticonvulsivant hypersensitivity syndrome", Crit. Care. Clin., 1997; 13 (4): 727-39
  2. de Vriese A.S, Philippe J, Van Renterghem D.M, de Cuyper C.A, Hindryckx P.H, Matthys E.G, Louagie A, "Carbamazepine hypersensitivity syndrome: report of 4 cases and review of the literature", Medicine (Baltimore), 1995; 74 (3): 144-51
  3. Pirmohamed M, Graham A, Roberts P, Smith D, Chadwick D, Breckenridge A.M, Park B.K, "Carbamazepine-hypersensitivity: assessment of clinical and in vitro chemical cross-reactivity with phenytoin and oxcarbazepine", Br. J. Clin. Pharmacol., 1991; 32 (6): 741-9

As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.