P7668Development of a standardized experimental itch model in humans

Martin Metz, MD, Department of Dermatology, Charit�e - Universit€atsmedizinBerlin, Berlin, Germany; Daniel Redoules, PhD, Skin Research Center, PierreFabre Dermo Cosmetic, Toulouse, France; Joachim Fluhr, MD, Department ofDermatology, Charit�e e Universit€atsmedizin Berlin, Berlin, Germany; MarcusMaurer, MD, Department of Dermatology, Charit�e e Universit€atsmedizin Berlin,Berlin, Germany; Tomasz Hawro, MD, Department of Dermatology, Charit�e -Universit€atsmedizin Berlin, Berlin, Germany; Val�erie Mengeaud, PhD, SkinResearch Center, Pierre Fabre Dermo Cosmetic, Toulouse, France

Chronic pruritus is a major symptom in many dermatologic diseases and canseverely impact quality of life. Thus, there is a huge medical need for novel andeffective topical and systemic itch therapies. Experimental models of induced itch inhumans can help in the development and validation of potential new substances. Tothis end, we first noninvasively assessed various parameters after skin provocationwith histamine, cowhage (Mucuna pruriens) spicules or negative controls. Toassess effects of the respective provocations, we employed volumetry, thermog-raphy and erythema as parameters of inflammation, transepidermal water loss as ameasure of barrier function, and specific itch parameters such as itch intensity anditch duration using a visual analogue scale (VAS). Overall, 20 healthy volunteers werechallenged with histamine, cowhage spicules, or saline on 1 arm and subsequentlyat various time points on the other arm. In contrast to histamine, cowhage-inducedpruritus was not associated with a significant induction of skin inflammation asmeasured by volumetry or thermography, and only a slight increase of erythema hasbeen observed. However, the mean itch intensity over time and the maximum itchintensity of cowhage were at least comparable to histamine. Interestingly, itchintensity varied depending on the time point of the second contralateralprovocation. Based on these findings, we standardized the test set up and aimedto validate the experimental itch model in a double-blind, randomized therapeuticapplication of polidocanol 3% solution vs. placebo in 45 healthy volunteers. Here,we detected a significant reduction of maximum itch intensity (31.6 6 4.8 vs. 21.26 3.5 [VAS]; P\.05) and mean itch intensity over time (254.6 6 56.7 vs. 111.0 620.4 [AUC of VAS]; P\.05) in polidocanol 3% treated skin as compared to placebocontrol. The present study describes the development of a standardized model ofexperimental non-histamine-mediated pruritus in healthy volunteers. We confirmedthe validity of the cowhage-induced itch model in a randomized, placebo-controlledstudy, showing a significant antipruritic effect of 3% polidocanol vs. placebo.

AB42

d (50%) by Pierre Fabre Derm-Cosmetique.

Sponsore

P7834DRESS syndrome caused by telaprevir: A case report

Alicia Gonz�alez Quesada, Dermatology Department of University Hospital‘‘Dr. Negr�ın,’’ Las Palmas de Gran Canaria, Spain; Carolina Medina Gil,Dermatology Department of University Hospital ‘‘Dr. Negr�ın,’’ Las Palmas deGran Canaria, Spain; Elena Castro Gonz�alez, Dermatology Department ofUniversity Hospital ‘‘Dr. Negr�ın,’’ Las Palmas de Gran Canaria, Spain; IldefonsoQui~nones, Gatroenterology Department of University Hospital ‘‘Dr. Negr�ın,’’ LasPalmas de Gran Canaria, Spain; Irene Casta~no Gonz�alez, DermatologyDepartment of University Hospital ‘‘Dr. Negr�ın,’’ Las Palmas de Gran Canaria,Spain; Jaime Vilar Alejo, Dermatology Department of University Hospital‘‘Dr. Negr�ın,’’ Las Palmas de Gran Canaria, Spain

Dermatologic adverse events (AEs) are an existing concern during hepatitis C virus(HCV) and its classic treatment (peginterferon/ribavirin). New direct-actingantivirals (telaprevir/boceprevir) have led to significant improvements in sustainedvirologic response rates, but have showed to an increase in dermatologic AEscompared to peginterferon/ribavirin alone. In telaprevir trials, approximately half oftreated patients had rash. More than 90% of these events were mild/moderate and inthe majority of cases, progression to a more severe grade did not occur. In a smallnumber of cases (6%), rash led to telaprevir discontinuation, whereupon symptomscommonly resolved. A few cases were classified as severe cutaneous adversereaction (SCAR), also referred to as serious skin reactions, a group of rare conditionsthat are potentially life-threatening (drug rash with eosinophilia and systemicsymptoms [DRESS], StevenseJohnson syndrome, and toxic epidermal necrolysis). Itis therefore important to distinguish between telaprevir related dermatitis andSCAR. We report a case of DRESS caused by telaprevir, a specific inhibitor of HCVserine protease. The patient is a 52-year-old woman with chronic genotype 1hepatitis C for 5 years of evolution that had been treated with classic drug withoutresponse. She received telaprevir in combination with pegylated interferon alfa-2aand ribavirin and, 11 weeks later, she developed a generalized pruritic maculopap-ular exanthema with malaise, fever, facial edema and lymph node swelling. A bloodtest revealed eosinophils 650/uL (normal,\500uL), hemoglobin 7.7 g/dL (normal,12-17 g/dL), creatininte 1.04 mg/dL (normal, 0.4-0.95), alanine aminotransferase 35U/L (normal, \32 U/L), and glutamyl transferase 157 U/L (normal, \36 U/L).Histologic examination of a cutaneous biopsy was consistent with a drug rashreaction. Telaprevir was stopped and continued with peginterferon/ribavirin. Shewas treated with topical and oral steroids. Cutaneous and systemic symptomsimproved in 2 weeks and disappeared completely in a month. Telaprevir wasconsidered the culprit drug. The majority of cutaneous AEs occurring withtelaprevir can be classified as a less, although we must to check the rare signs ofmore serious reactions.

cial support: None identified.

Commer

J AM ACAD DERMATOL

P7624Drug-induced lichen planus pemphigoides

Andr�e Laureano, MD, Department of Dermatology and Venereology, Hospital deCurry Cabral, Lisboa, Portugal; Gabriela Marques Pinto, MD, Department ofDermatology and Venereology, Hospital de Curry Cabral, Lisboa, Portugal; JorgeCardoso, MD, Department of Dermatology and Venereology, Hospital de CurryCabral, Lisboa, Portugal

Introduction: Lichen planus pemphigoides (LPP) is a rare autoimmune diseasecharacterized by the concomitant presence of subepidermal bullae and lichenplanus lesions.

Clinical Report: A 44-year-old woman presented with a 2-month history ofpruriginous papules on her trunk and extremities followed, 6 weeks later, bybullous lesions on her legs. Physical examination revealed multiple violaceous,poligonal, flat papules on the trunk and limbs, and tense blisters within the papulesand normal skin on the legs. There was a temporal relationship with the beginningof oral therapy with gestodene and ethinilestradiol caused by amenorrhea andelevated levels of beta-esthradiol. Histhology of a lichenoid papule showedorthokeratotic hyperkeratosis, hypergranulosis and slight acanthosis in theepidermis, destruction of the dermoepidermal junction with a dermal inflammatoryinfiltrate of lymphocytes. Histhology of a bullous lesion showed a subepidermalbulla with a dermal inflammatory infiltrate composed predominantly of eosinophils.In addition, direct immunofluorescence of perilesional skin showed a linear band ofC3 at the dermoepidermal junction. A diagnosis of LPP was confirmed with hightiters of ELISA bullous pemphigoid antigen 180. Subsequently, hormonal therapywas discontinued and oral prednisolone (40 mg/daily) was initiated. After 4 weeksthe pruritus had disappeared and there was no recurrence of new lesions. The doseof prednisolone was tapered gradually. ELISA repeated after 6 and 12 monthsshowed a marked decrease in circulating BP180 autoantibodies. This correspondedwith her clinical improvement.

Discussion: Few cases of drug-induced LPP have been reported. Although admittinga coincidence, given the clinical features and the response to withdrawal ofgestodene and ethinilestradiol, it is possible that these drugs were the cause of theLPP in our patient. As far as we know, it is the first case of such association.

cial support: None identified.

Commer

P8048Efficacy results using a novel hidradenitis suppurativa endpoint, HiSCR(hidradenitis suppurativa clinical response), from the placebo-controlledphase of a phase 2 adalimumab study

Gregor Jemec, MD, Department of Dermatology, Roskilde Hospital, HealthSciences Faculty, University of Copenhagen, Roskilde, Denmark; Jeffrey Sobell,MD, Skin Care Physicians, Chestnut Hill, MA, United States; Noah Scheinfeld, MD,Department of Dermatology, Weil Cornell Medical College Midtown West, NewYork, NY, United States; Sarika Sood, MD, AbbVie Inc, North Chicago, IL, UnitedStates; Yihua Gu, MS, AbbVie Inc, North Chicago, IL, United States

Introduction: Hidradenitis suppurativa (HS) is a chronic inflammatory skin folliculardisease with symptoms such as recurrent inflamed nodules, abscesses, and fistulas.We report efficacy results using the novel endpoint Hidradenitis SuppurativaClinical Response (HiSCR; ¼ 50% reduction from baseline in total abscess andinflammatory nodule [AN] count, with no observed increase in either abscess ordraining fistula counts) from the 16-week, double-blind, placebo (pbo)-controlledphase of a 52-week adalimumab (ADA) study.

Methods: Moderate to severe HS patients (pts) were randomized 1:1:1 (intent totreat population [ITT]) to pbo (n¼ 51), ADA 40mgevery other week, 80mg atWeek0 (W0) (eow, n¼ 52), or ADA 40 mg every week, 160 mg at W0, 80 mg at W2 (ew, n¼ 51). For pts with baseline AN count ¼ 3 and draining fistula count ¼ 20 (mITTpopulation), the following retrospective evaluations are reported for W12 andW16:percentage of pts achieving HS-Physician Global Assessment (HS-PGA)-basedClinical Response (non-responder imputation [NRI]); percentage of pts achievingHiSCR; percentage of pts achieving 50%, 75%, 100% reduction in total AN count(AN50, AN75, AN100) relative to baseline (NRI), and percent change from baselinein AN count (last observation carried forward).

Results: mITT population W12 and W16, HS-PGA-based Clinical Response rates (%)for pbo/eow/ew groups were, 4.7/6.7/25.0 (P\.05 pbo vs ew) and 2.3/6.7/20.5 (P\ .05 pbo vs ew), respectively. HiSCR response rates (%) at W12 and W16,respectively, for pbo/eow/ew groups were 16.3/35.6/59.1 (P\.05 pbo vs ew andpbo vs ewo) and 25.6/33.3/54.5 (P\.05 pbo vs ew). For pbo/eow/ew groups, pts(%) achieving specified percent reduction in AN counts at W12were 32.6/42.2/63.6(AN50); 20.9/28.9/43.2 (AN75); 4.7/6.7/22.7 (AN100); at W16, 34.9/48.9/56.8(AN50); 27.9/24.4/40.9 (AN75); 2.3/8.9/20.5 (AN100). For pbo/eow/ew groups,mean percent (%) reduction from baseline in AN count at W12 was 12.2/32.3/60.3,and at wk16, 19.8/38.8/59.7.

Conclusion: ADA efficacy was demonstrated in moderate to severe HS pts.Differences for ADA ew versus pbo in HS-PGA-based Clinical Response and HiSCRat W12 and W16 were statistically significant. Percent improvement in AN countswas greater after ADA ew treatment. HiSCR appeared more responsive to changeand better able to discriminate improvement in eow-treated pts than HS-PGA-basedClinical Response and may be a useful new tool to assess HS therapy efficacy.

d 100% by AbbVie.

Sponsore

MAY 2014