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| ORIGINAL ARTICLE |
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| Year : 2000 | Volume
: 66
| Issue : 3 | Page : 132-135 |
Evaluation of patch test in identification of causative agent in drug rashes due to antiepileptics
Maneesha Vatve, Kumar Vinod Sharma, IMS Sawhney, K
,
Correspondence Address:
Maneesha Vatve
PMID: 20877054
Patch test was evaluated for the identification of causative agent in cutaneous eruptions due to antiepileptics. Patch tests were carried out in twenty patients and ten controls with carbamazepine, phenytoin sodium, phenobarbitone and sodium valproate. Sodium valproate was found tobe irritant in 1 and 5% concentration and further dilution is recommended for patch testing. Patch test was positive in 14 (70%) patients and in 7 with suspected drug alone, and remaining 7 were positive with more than one antiepileptic drug. We recommended patch test for identification of causative drug in rashes due to antiepileptics.
Keywords: Antiepileptic drugs, Carbamazepine, Patch test, Phenobarbitone, Phenytoin sodium, Sodium valporate
How to cite this article:
Vatve M, Sharma KV, Sawhney I, K. Evaluation of patch test in identification of causative agent in drug rashes due to antiepileptics. Indian J Dermatol Venereol Leprol 2000;66:132-5 |
How to cite this URL:
Vatve M, Sharma KV, Sawhney I, K. Evaluation of patch test in identification of causative agent in drug rashes due to antiepileptics. Indian J Dermatol Venereol Leprol [serial online] 2000 [cited 2013 Jun 19];66:132-5. Available from: http://www.ijdvl.com/text.asp?2000/66/3/132/4896 |
| Introduction | |  |
Antiepileptics are essential drugs for the treatment of seizures. [1] Development of drug hypersensitivity is one of the major complication of their usage. Antiepileptics are blamed for 20% of all drug rashes and are commonly incriminated drugs in severe cutaneous adverse reactions (SCAR) like Stevens-Johnson syndrome More Details (SJS) or toxic epidermal necrolysis (TEN). The overall prevalence of rash is 2-3% due to antiepileptic drugs in epilepsy patients. [2]
Patch testing on the other hand is widely used, noninvasive test in the field of contact dermatitis. Its use in the diagnosis of drug reactions is under evaluation. Initial reports confirmed its reliability in diagnosis of fixed drug reactions and also in reactions due to sulphonamides,penicillin and antiepileptics. [3],[4],[5] However, there are no systematic studies in this field. In the present study we evaluated patch test in identifying the causative drug in rashes due to antiepileptic drugs.
| Materials and Methods | | |
Twenty consecutive patients on antiepileptic drugs attending Dermatology and Neurology out patient department of Postgraduate Institute of Medical Education and Research, Chandigarh, India, who presented with cutaneous hypersensitivity, irrespective of age and sex were included in the study. Hypersensitivity syndrome was defined as a delayed onset skin rash with or without fever,lymphadenopathy, hepatitis, renal involvement and haematological abnormalities. To avoid misdiagnosis Naranjo's algorithm was used. [6] only patients with definite or probable rash were included in the study. Clinical classification of drug reactions into erythema multiforme, SJS or TEN was made based on the criteria laid down by Bastuji-Garin et al. [7] Relevant investigations and Paul Bunnel test were done in all patients.
Patients suspected to have viral exanthem and autoimmune disorders like systemic lupus erythematous (SLE) were excluded from the study.
Ten age and sex matched epileptics on antiepileptic drugs but without any adverse reaction (present or past) acted as controls.
Patch test was done in all patients and controls after informed consent. Patch test was carried out with 10% and 5% concentration of phenytoin (Sisco Research Lab.Pvt.Ltd. Mumbai),10% and 5% Phenobarbitone (Biodeal Laboratories Pvt. Ltd.Calcutta), 10% and 5% sodium valproate (Reckitt & Colman India Ltd., Calcutta) in petrolatum. Close patch testing was done with patches made from 5 x 5cm micropore (3M) hypoallergenic tape and reading were taken at 48 and 72hours. A positive reading was graded as recommended by the International Contact Dermatitis Research Group. [8] Patients were tested after the reaction had subsided and they were off oral corticosteroids for more than 3weeks. As patients and controls initially developed irritant reaction with 10% and 5% sodium valproate, its concentration was reduced to 1%.
| Results | | |
Age of the patients varied from 4-83 years (mean 28.55 years). There were 13 males and 7 females. Antiepileptics were advocated in 13 patients for epilepsy, in 3 with brain tumours, 2 with peripheral neuropathy and one each with dental neuralgia and manic depressive psychosis. The incubation period varied between 9 to 42 days (mean 22days). Twelve out of 20 patients had definite drug reaction and 8 had probable reaction according to Naranjo's algorithm. Carbamazepine was the commonest drug (25%) followed by phenytoin (20%) phenobarbitone in 1.0% and 6 patients (30%) were receiving both phenytoin and carbamazepine.
Maculopapular (MP) rash was the commonest clinical pattern seen in 13 (65%) patients followed by TEN in 3 (15%), erythroderma in 2 (10%), SJS in 1(5%) and SJS-TEN overlap in 1 patient (5%). Associated abnormalities in laboratory parameters were present in 9 (45%) patients including elevated liver enzymes in 7 (35%), leucocytosis in 5 (35%), albuminuria in 2 (10%) and hyperbilirubinemia in 1 (5%) patient. No patient had abnormal circulating lymphocytes and Paul Bunnel test was negative in all patients.
| Patch test results | | |
Irritant reaction to valproate was noted in 75% patients and 50% controls with both 5% and 1% concentration and it was therefore excluded from further analysis. Patch test positivity were same to both 5% and 10% concentration of phenytoin, phenobarbitone and carbamazepine in all patients and controls. The results of patch test with antiepileptics are summarised in [Table - 1]. Two patients who had rash due to carbamazepine developed generalized eruption following patch test.
Fourteen of the 20 (70%) patients tested positive to causative drugs of which 7 (35%) each, had positive reaction to one and more than one drug. Patch . test positivity was recorded in 9(45%) patients with phenobarbitone. None of the controls was patch test positive to antiepileptics tested.
Out of the 7 patients who had positive patch test to the suspected drugs alone, 6 had maculopapular rash and 1 had TEN. Of the 7 patients who showed cross reactivity, 4 patients showed cross reactivity between phenytoin and carbamazpine and one each between phenytoin. One patient who had erythroderma tested positive to all 3 drugs. Three patients had false positive reaction as they tolerated the drug to which they showed cross reactivity on patch test.
| Discussion | | |
Idiosyncratic reaction is one of the common side effects of antiepileptic drugs and requires stoppage of the drug in 15% patients. [9] In India, antiepileptic drugs account for 4.5-9.25% of all drug reactions [10],[11] though Western studies incriminate anticonvulsants in 20% of all drug reactions. [2]
As expected maculopapular rash was the commonest clinical manifestation [12] but significant number of our patients 7 out of 20 (35%) had severe cutaneous adverse reaction (SCAR). This could be due to the fact that our institiute being a tertiary care centre many severe reactions are referred for management.
Puig et al [13] proposed that patch test positivity depends on type of eruption, with maximum positive reactions seen in maculopapular rash and erythroderma. Recently patch test has yielded positive results in TEN too. [14] In our study, patients with maculopapular rash, TEN and erythroderma gave positive patch tests. Though most workers have reported positive patch test with carbamazepine alone, [11],[12],[13],[14],[15],[16] we have for the first time tested a series of 4 antiepileptic drugs and found equal number of positive to phenytoin and carbamazepine. Patch test positivity was found to be 70% which is comparable to other studies where patch test positivity vary from 24-100%. [17] Despite the possibility of a generalised flare up of rash following patch test in a small proportion of patients, patch test is ethically more accepTable than oral rechallenge, the significant cross reactivity (35%) between antiepileptics is probably due to their structural homology.
It is known that problems with both diagnosis and prediction arise when anticonvulsant hypersensitivity occurs. Also, if a patient is treated with more than one drug it is difficult to identify the responsible drug and potential cross reactivity between the 3 major antiepileptics limits the choice for future therapy. In such a situation we find that a positive patch test with one drug and a negative test with others would be useful in deciding future therapy. Sodium valproate in 5% and 1% concentration was not suiTable for patch testing due to irritant reaction suggesting that further dilution is needed. Sodium valproate is a sodium salt of valproic acid and it is highly hygroscopic and gets converted rapidly to its acidic form which could act as an irritant. [18],[19]
| Conclusions | | |
Despite its limitations of cross reactivity, patch test is a useful tool in identifying the suspected drug causing the reaction. It has the advantage of ethical acceptance and is easy to perform.
| References | | |
| 1. | Ramsay R, Wilder Berger 3, et al. A double blind study comparing carbamazepine with phenytoin as initial seizure therapy in adults. Neurology 1983; 33: 904-910.  |
| 2. | Levantine A, Almeyda J. Drug reactions XX: Cutaneous reactions to anticonvulsants. Br J Dermatol 1972; 87: 646-649. |
| 3. | Alanko K, Stubb 5, Reitamo S. Topical provocation of FDE. Br J Dermatol 1987; 116: 561-567. |
| 4. | Houwerjil J, Gast GC, Nater GP. Patch tests in drug eruptions. Contact Dermatitis 1975; 1: 180-192. |
| 5. | Vailant L. Patch testing with carbamazepine. Reinduction of exfoliative dermatitis. Arch Dermatol 1989; 125: 299. |
| 6. | Naranjo CA, Busto U, Selhers EM, et al. A method of estimating the probability of ADRs. Clin Pharmacol Ther 1987; 30: 239-245. |
| 7. | Bastuji-Garin S, Rzany B, Stern RS, et al. Clinical classification of toxic epidermal necrolysis, Stevens - Johnson syndrome and erythema multiforme. Arch Dermatol 1993; 129:92-96. [PUBMED] |
| 8. | Cronin E. In: Textbook of Contact Dermatitis Edn II, Edinberg: Churchil Livingstone 1980; pp 6-8. |
| 9. | Bray PF. Diphenylhydantoin after 20 years. Review with reemphasis by treatment of 84 patients. 1959; 13: 151-161. |
| 10. | Kaur 5, Kumar B, Ravikiran TN, et al. A study of cutaneous drug reactions. Bull PGI 1980; 14: 73-79. |
| 11. | Mani MZ, Mathew M. Study of 218 drug eruptions. Indian J Dermatol Venereol Leprol 1983; 49: 109-117. |
| 12. | Pelekano 3, camfield B, Camfield C, et al. Allergic rash due to antiepileptic drugs. Clinical features and management. Epilepsia 1991; 32: 554-559. |
| 13. | Puig L, Nadal C, Figure s MT, et al. Cambamazepine induced drug rashes. Diagnostic value of patch test depends on clinicopathologic presentation. Contact Dermatitis 1996; 34: 435437. |
| 14. | Eberherd KC, Trautman A, Zillikens D, et al. Patch testing in an unusual case of TEN. Contact Dermatitis 1995; 33:448-449. |
| 15. | Alanko K. Patch testing in cutaneous reactions caused by carbamazepine. Contact Dermatitis 1993; 29: 254-257. [PUBMED] |
| 16. | Jones M, Fernandez HJ, Dordo 3M, et al. Epicutaneous test in carbamazepine cutaneous reactions. Dermatology 1994 ; 188 28-30. |
| 17. | Rall TW, Schleifer LS. In: Goodman & Gilmans. The Pharmacological Basis of Therapeutics, Edn 7, New York: Macmillan Publishing Co. 1985; p. 462. |
| 18. | Duke NM, Aronson JK, Dn: Side Effects of Drugs. Annual 15, Amsterdam: Elseview Science Publishers 1991, p.63. |
| 19. | Pirmohammed A, Graham A, Roberts P, et al. Carbamazepine hypersensitivity: Assessment of Clinical and in vitro chemical cross reactivity with phenytoin and carbamazepine. Br 3 Clin Pharmac 1991; 32: 741-749. |
Tables
[Table - 1]
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