First case of skin allergy to pregabalin with positive patch test reaction

Abstract

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...

Pregabalin-induced delayed cutaneous hypersensitivity reaction occurring after 40 days of use: a case report

“…Our case had the longest time interval between initiating pregabalin and the onset of the hypersensitivity reaction, and the largest skin area of involvement compared with other cases. [5][6][7][8][9][10][11][12] These findings in our case were attributed to pregabalin and confirmed by a drug provocation test. Gabapentinoids are first-line drugs for treating HZ neuralgia.…”

“…4 Reported cases of cutaneous hypersensitivity reactions caused by pregabalin generally occur within 2 weeks of initiating medication. [5][6][7][8][9][10][11][12] We report a rare case of a delayed cutaneous hypersensitivity reaction caused by pregabalin, which was confirmed by a drug provocation test. An elderly patient with severe herpes zoster (HZ) neuralgia developed maculopapular drug eruption covering 80% to 90% of the total body surface area after 40 days of combined multidrug analgesia.…”

“…To the best of our knowledge, eight cases of cutaneous hypersensitivity reactions caused by pregabalin have been reported. [5][6][7][8][9][10][11][12] Three of Figure 3. Timeline of the patient's medications.…”

A case of pregabalin‐induced drug eruptions accompanied by extremely high serum thymus and activation‐regulated chemokine levels

“…Drug eruptions induced by pregabalin are rare, and we only found 5 other cases reported in English, 4,5 one of which only showed eosinophilia. The patient's serum TARC and IgE levels were extremely high during her condition and did not normalize even after she was successfully treated.…”

Maculopapular rash to S‐carboxymethylcysteine‐lysine (carbocisteine)

“…We delayed the allergy work‐up to prevent false‐positive results from skin hyperreactivity. As in other published cases 5 and to obtain better results, we performed patch tests in the affected skin area but they were all negative.…”