CLINICAL CASE
Stevens-Johnson syndrome from tetrazepam
I. Sánchez, J. L. García-Abujeta, L. Fernández*, F. Rodríguez, D. Quiñones, S. Duque*, R. López and J. Jerez
Allergy Section. "Marqués de Valdecilla" Hospital. Santander. *Allergy Section. "Sierrallana" Hospital. Torrelavega. Spain.
SUMMARY
We present a case of a patient showing a cutaneous and systemic affectation compatible with the Stevens-Johnson syndrome due to the intake of tetrazepam as a muscular relaxant. The symptoms remitted after the suspension of the involved medicines and after treatment with systemic corticoids. Months later, a study with patch tests, with the standard battery and the medicines that she took (indapamide, tetrazepam, acetyl salicylic acid, botriozolam and levomepromazine) was carried out. She presented positivity to tetrazepam at 48 and 96 hours. The oral provocations with the other medicines, which she consumed, were negative. The study of cross reactivity with other benzodiazepines was negative.
In the medical literature, different cutaneous affectations regarding benzodiazepine use (generalised drug eruptions, contact dermatitis, erythema multiforme,...) have been described byt non Stevens-Johnson syndrome. The patch tests are useful in the diagnosis of this type of cutaneous reactions, avoiding in this way the achievement of oral provocations, with the potential risk for the patient that they imply. The absence of cross-reactions with other substances of the same group has to be pointed out, even with those with which keeps great structural similarity as the diazepam. In spite of the absence of cross reactions with the rest of benzodiazepines, faced with the seriousness of the case presented, it is advised to the patient to avoid this type of medicines.
Key words: Stevens-Johnson syndrome. Tetrazepam. Benzodiazepines. Medicines. Lack of cross-reactivity.
Allergol et Immunopathol 1998;26:55-7.
INTRODUCTION
Stevens-Johnson syndrome secondary to drugs is uncommon but not rare. Sulphonamides, anticonvulsants and penicillins commonly cause this pathology, but there are not mentions in the literature about Stevens-Johnson syndrome due to benzodiazepines and few from erythema multiforme.
CASE REPORT
A 65 year-old housewife with history of arterial hypertension controlled with indapamide (Tertensif®) started treatment for lumbar arthralgia with tetrazepam (Myolastam®) 50 mg x 2 daily. She occasionally took acetyl-salicylic acid (Aspirin®), botrizolam (Sintonal®) and levomepromazine (Sinogan®).
Seven days after the prescription of tetrazepam she developed pruritus of the hands, feet and scalp followed by itchy erythematous, edematous papules and plaques, some with a purpuric center and target-shaped, affecting the face, trunk and limbs, involved about 30-40% of body surface area.
The patient was hospitalised, and three days after she presented general malaise with ocular and genitourinary itchy mucosal erosions. She did not have fever, but liver enzymes tests were abnormal (GPT 67 u/l, GGT 100 u/l). The rest of laboratory tests results such as serum chemistries, urinary and blood test were normal. When she stopped all medications the process disappeared within 2 months of being treated with systemic corticosteriods.
Patch test was performed 6 months after the lesions disappeared, with the standard series and Myolastan® (tetrazepam), Tertensif® (indapamide), Aspirin® (AAS), Sintonal® (botrizolam) and Sinogan® (levomepromazine), using crushed tablets at 20% in petrolatum, was positive only to tetrazepam (++) at 48 and 96 hours. The same substances were negative in 20 controls. Then, we performed testing with bromazepam, chlorazepate, diazepam, flurazepam, ketazolam, alprazolam, lorazepam, lormetazepam, triazolam and midazolam. All of them were negative at 48 and 96 hours. Oral challenge with Aspirin®, Sinogan® and Tertensif® were negative.
DISCUSSION
Adverse reactions to benzodiazepines are common and well known. Generally consist of neurological, gastrointestinal, salivary and renal alterations. Cutaneous reactions are rare but these are likely to be allergic (1). Have been reported fixed drug reactions (2, 3), generalised drug eruptions (4-8), contact dermatitis (9), photo-onycholysis (10), leukocytoclastic vasculitis (11), and erythema multiforme (8), but Stevens-Johnson syndrome has not previously been described.
Patch tests confirm the diagnosis in most of these cutaneous reactions, and can avoid rechanllenge in benzodiazepines-induce drug reactions, but their sensitivity is not 100% (12).
Diazepam shows great structural homology with tetrazepam, but cross-reactivity between tetrazepam and others benzodiazepines was not observed in our patient. Although, she previously never used tetrazepam, occasionally had taken other benzodiazepine: botrizolam and this may explain the sensitisation. Oral challenge test was not performed due to positive patch test and process severity.
Since there are not clinical data about cross-reactivity reactions to different benzodiazepines, avoidance of all of them by patients with proved allergy to any benzodiazepine, is justified.
RESUMEN
Presentamos el caso de un paciente con un cuadro cutáneo y de afectación general compatible con un síndrome de Stevens-Johnson en relación con la ingesta de tetrazepam como relajante muscular. El cuadro remitió tras la suspensión de los medicamentos implicados y tratamiento con corticoides sistémicos. Meses después se realizó estudio con tests epicutáneos con la batería estándar y los medicamentos que tomaba: indapamida, tetrazepam, ácido acetil salicílico, botriozolam y levomepromazina. Presentó positividad a tetrazepam a las 48 y 96 horas. Las provocaciones orales con los otros medicamentos que consumía fueron negativas. El estudio de reactividad cruzada con otras benzodiazepinas fue negativo.
Se han descrito en la literatura médica diferentes cuadros cutáneos en relación con el uso de benzodiazepinas (exantemas generalizados, dermatitis de contacto, eritema multiforme,...) pero no síndrome de Stevens-Johnson. Los tests epicutáneos son útiles en el diagnóstico de este tipo de cuadros, evitando así la realización de provocaciones orales, con el riesgo potencial para el paciente que implican. Destaca la ausencia de reacciones cruzadas con otras sustancias del mismo grupo, incluso con aquéllas con las que guarda gran similitud estructural como el diazepam. A pesar de la ausencia de reacciones cruzadas con el resto de benzodiazepinas, ante la gravedad del cuadro presentado, se recomienda al paciente evitar este tipo de medicamentos.
Palabras clave: Síndrome de Stevens-Johnson. Tetrazepam. Benzodiacepinas. Medicamentos. Ausencia de reactividad cruzada.
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| Correspondence: Inmaculada Sánchez Sección de Alergología Hospital "Marqués de Valdecilla" Avda. Valdecilla, s/n. 39008 Santander. Spain |
