K E Y W O R D S : allergy, case report, patch tests, pregabalin, rash Pregabalin (PG) is a antiepileptic drug with a structure similar to gabapentin, providing analgesic effects in patients with neuropathic conditions. 1 CASE REPORTA 51-year-old female patient was treated with PG (Lyrica) at 25 mg/day for 3 weeks and at 75 mg/day during a fourth week. After a month of treatment, a maculopular rash developed in the nape, neck, ears, arms, knees and ankles that improved after the withdrawal of the drug and administration of deflazacort 30 mg for 5 days. A biopsy of skin lesions showed superficial perivascular lymphocytic dermatitis with some eosinophil and some lymphocyte permeation in the epidermis.Patch tests with PG (Lyrica) 5% pet. and aq., respectively, in the dorsal region of the left arm were read on day (D) 2 and D4. These remained negative; however, on D3, the patient noted a rash similar to the rash that developed when she was taking PG, particularly on the back of the right forearm. A patch test with placebo (pet.) gave negative results on D2 and D4. A subsequent patch test with PG (5% pet.) on the right forearm where the rash reappeared gave positive results in terms of a ++ reaction on D2 and a +++ reaction on D4, whereas a similar lesional patch test with PG aq. on the right forearm remained negative. The diagnosis of erythematous maculopapular rash caused by type IV hypersensitivity to PG was made. DISCUSSIONAdverse reactions to PG are usually dose-related 2 ; in our case, the rash appeared after the dose had been increased. Five cases with skin reactions that were not biopsied have been published (Supporting Information Table S1) 1-5 ; in our case, the results of the biopsy support the diagnosis of a cutaneous adverse drug reaction.It is of note that, similarly to what is seen in fixed drug eruption testing, where, commonly, patch testing gives positive results only in the area where the rash appears, owing to activation of intraepidermal CD8 + memory T cells at these sites, 6 our patient showed a clear positive reaction only on lesional skin. Lacosamide, a third-generation antiepileptic drug, may be a useful alternative to PG, 7 if tolerance is confirmed prior to prescription. CONFLICTS OF INTERESTThe authors have no conflicts of interest to report. REFERENCES 1. Smith TL, Baldwin A, Cunningham LL Jr, Cook AM. Rash associated with pregabalin use. Ann Pharmacother. 2008;42:1899-1902. 2. Bamanikar A, Dhobale S, Lokwani S. Pregabalin hypersensitivity in a patient treated for postherpetic neuralgia. Indian J Pharmacol. 2013;45: 522-523. 3. Yoshioka M, Okura R, Hino R, Nakamura M. A case of drug eruption due to pregabalin. J Clin Dermatol. 2013;67:569-572. 4. Inoue A, Sawda Y, Ohmori S, et al. Maculopapular type drug eruption caused by pregabalin: a case and literature review. Allergol Int. 2016;65: 351-352. 5. Ortega-Camarero MA, Avila R, Prados Castaño M, Piñero M, Quiralte J, Cimbollek S. Challenge-based pregabalin induced urticaria and angioedema. A case report. Allergol Immunopathol (Madr). 2012; 4...

A 77-year-old male with trigeminal neuralgia was initially treated with carbamazepine (CBZ). Three weeks later pregabalin (PG) was added to his treatment regimen as the pain persisted. However, 1 week after initiating the combination therapy (CBZ + PG), the patient developed a generalized maculopapular rash, facial edema, and fever. On physical examination a skin rash was observed and hepatomegaly and lymphadenopathy detected. Laboratory tests revealed the following measurements: leukocytes 13 100/ mm 3 , lymphocytes 3800/mm 3 , eosinophils 2900/mm 3 , aspartate aminotransferase 62 IU/L, alanine aminotransferase 101 IU/L, urea 80 mg/dL, and creatinine 1.5 mg/dL. A skin biopsy was performed which showed moderate spongiosis with few eosinophils and signs of vasculitis. GÓMEZ TORRIJOS ET AL. 405 The patient was eventually diagnosed with drug rash with eosinophilia and systemic symptoms (DRESS) syndrome and therapy with CBZ and PG was stopped. The patient recovered within 1 month, following treatment with only levocetirizine. Allergy tests were performed 1 month after his recovery. Patch tests were performed with PG (Lyrica) 5% and CBZ (Tegretol) 5% in both water and pet., with both drugs initially placed at the dorsal region of the left arm, and readings obtained on day (D) 2 and D4 ( Figure 1). Test results were positive with both drugs in aq. and pet. for readings obtained on D2 and D4 ( Figure 1A). The same tests were then repeated with these two drugs but on different arms and after a 2-week interval: PG 5% (Lyrica) at the dorsal region of the right arm and, 2 weeks later, CBZ 5% (Tegretol) at the dorsal region of the left arm. These patch tests were negative with PG ( Figure 1B) but positive with CBZ. The patient then underwent an oral challenge with PG (75 mg/d/4 d) which did not trigger a reaction. DISCUSSION Mitchell emphasized that skin hyperirritability is a serious problem in patch testing and demonstrated that, in the presence of a strong positive patch test reaction, other concomitant weak positive reactions may be false positive. 1,2 Skin hyperirritability affects the entire skin; for this reason, Bruynzeel and Maibach proposed the name EES instead of ABS. 2 Our patient has had a rash 1-2 months earlier, so he could still have some degree of skin hyperirritability. In the initial patch test, both drugs were placed very close to each other and the positive response of PG was not reproducible when re-examined separately 3,4 ; therefore, the proximity of the patch tests has likely caused this syndrome. 1,2 However, it was important to identify the drug that had triggered DRESS syndrome in our patient because PG could have been effective in treating pain; therefore, we decided to repeat the patch test with PG alone and on the contralateral arm, and demonstrated that the previous result had indeed been false-positive due to EES. 1,4 Most allergens that give false-positive results are "marginal irritants," such as nickel (1) but are usually not drugs. EES may have many causes depending on both the contac...

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