P6532Diffuse cutaneous Langerhans cell histiocytosis: Multitherapy resistantwith response to acitretin and treatment with isotretinoin

Blake Sampson, University of Washington School of Medicine, Seattle, WA,United States; Galina Stetsenko, MD, University of Washington DermatologyDivision, Seattle, WA, United States; Kyle Garton, MD, PhD, University ofWashington Dermatology Division, Seattle, WA, United States

Langerhans cell histiocytosis (LCH) is a rare disease characterized by proliferation ofCD1a+/S100+ cells. It is typically seen in children involving single or multiple organsystems, most commonly bone, liver, lung, mucosa, lymph nodes, and skin. Whilecutaneous manifestations are a common presenting feature, a disease confined tothe skin is exceedingly rare, especially of adult onset. We present a unique case oftreatment resistant adult onset LCH confined to the skin of a 58-year-old otherwisehealthy man with a demonstrable response to Soriatane (acitretin) and partialresponse to isotretinoin. Patient presented originally with nonpruritic erythematouspapules and nodules on his legs and torso, which spontaneously resolved overseveral months without treatment. Subsequently, nodules have recurred, but weremore numerous, pruritic, and diffusely involved extremities, head, neck, and torso.Initial biopsy showed diffuse dermal infiltrate suspicious for interstitial granulomaannulare, with negative fungal and AFB stains. Repeat biopsy demonstrated S100+,CD1a+ cells consistent with LCH. The patient had normal laboratory studies andperipheral blood flow cytometry showed no abnormal T- or B-cell populations. CT,PET, and MRI studies were notable for diffuse cutaneous involvement with noevidence of extracutaneous manifestations. Treatments have included mthotrexate+ NB-UVB, Humira, and prednisone. These treatments had either minimal diseaseresponse or intolerable side effects. Patient has also received cycles of cytarabineand topical nitrogen mustard, but treatment with these agents was again eitherintolerable or ineffective, respectively. Treatment with acitretin has resulted in mostsignificant improvement, with near complete clearance of lesions, however, was nottolerated because of leg and joint pain. Currently patient is showing a partialresponse to treatment with low dose isotretinoin, with no significant side effects. Toour knowledge, this is the second reported response to acitretin, and only the thirdreported treatment with isotretinoin. Systemic retinoids have an immunomodula-tory effect on Langerhans cells and are proving beneficial in the treatment ofcutaneous LCH, particularly in refractory cases.

AB48

cial support: None identified.

Commer

P6710Digital dermatofibroma: Common lesion, uncommon site

Renuga Ramesh Raghavendran, MBBS, Royal Cornwall Hospital, Truro, UnitedKingdom; Robert Jenkins, Royal Cornwall Hospital, Truro, United Kingdom

Background: Dermatofibroma (DF) is a common tumor of the skin presenting as afirm nodule, which often extends into superficial subcutaneous tissue. It is alsoknown as cutaneous fibrous histiocytoma (CFH). It may occur anywhere in the bodybut has a predilection for the limbs, shoulders, and pelvic girdles. Presentation onthe digits is uncommon and there are very few cases reported in the literature. Wepresent a rare case of digital dermatofibroma.

Case report: A 66-year-old woman presented to the general practitioner (GP) with aslow growing warty lesion on her left ring finger. It was initially treated with topicalsalicylic acid and had become friable and bleeding on contact. It was then curettedby the GP and the histology revealed a spindle cell tumor, whichwas keeping inwiththe diagnosis of cellular dermatofibroma. After a few months, she presented to thedermatologists with a thick keratinized plaque on the same site. The lesion wasexcised to rule out malignancy. The histology of the excision biopsy showedmarkedhyperkeratosis of the squamous epithelium. Deep to that was a nodular proliferationof spindle cells similar to the previous curette biopsy. There was no significant atypiaand the features were consistent with a cellular dermatofibroma and the lesionappeared to be completely removed.

Discussion: DFs are one of the most common mesenchymal tumors of the skin.Histologically, DFs are unencapsulated, well circumscribed tumors located in thereticular dermis with occasional extension into the superficial subcutis alonginterlobular septae. They are primarily composed of short spindle-shaped andstellate cells, sometimes with a mixture of giant cells, foamy macrophages, andplasma cells. Other tumors that present as firm, circumscribed nodules on the digitsthat enter the histopathologic differential diagnosis with DF include perineurioma,superficial acral fibromyxoma (SAF), acral dermatofibrosarcoma protuberans(ADFSP), and acral fibrokeratoma (AFK). Because DFs can resemble several entities,including leiomyosarcoma and ADFSP, a lack of familiarity with the occurrence of DFon the digits may result in more aggressive treatment than otherwise necessary. DFshould be in the differential diagnosis of circumscribed, firm nodules presenting onthe digits.

cial support: None identified.

Commer

J AM ACAD DERMATOL

P6674Economic burden of hidradenitis suppurativa after a single surgicalintervention: Assessment of unmet needs using a retrospective claims-based analysis

Gregor Jemec, Department of Dermatology, Roskilde Hospital, Health SciencesFaculty, University of Copenhagen, Roskilde, Denmark; Annie Gu�erin, AnalysisGroup, Inc, Boston, MA, United States; Martin Okun, Global PharmaceuticalResearch and Development, Abbott Laboratories, Abbott Park, IL, United States;Michael Kaminsky, Analysis Group, Inc, Boston, MA, United States; MuraliSundaram, Global Health Economics and Outcomes Research, AbbottLaboratories, Abbott Park, IL, United States

Objective: Hidradenitis suppurativa (HS) is a chronic inflammatory disease primarilyaffecting the axillae, perineum, and inframammary regions. HS affects approximately1% to4%of theUSpopulation. Surgery is one of the commonlyused treatments forHSpatientswith progressive disease, even though recurrences can be seen after surgeryin up to 50% of patients. Repeated treatments are more difficult and substantiallyincrease health care resource utilization and costs. The aim of the study is to estimatethe economic burden associated with unmet treatment needs in HS patients.

Methods: Adult patients ($ 18 years of age) with $ 1 diagnosis for HS (ICD-9 code705.83), and $ 1 claim for a skin surgery (ie, incision and drainage, excisions, graftsandflaps, closures, and transfers)within6months after anHSdiagnosiswere selectedfrom the Ingenix Employer Solutions database (Q1 1999-Q1 2011). The followingindicators of unmet needs were observed during the 1-year period following theindex date (ie, the earliest skin surgery date): another skin surgery, an inpatient oremergency department (ED) visit with an HS diagnosis, or a diagnosis for surgerycomplications. Health care resource utilization and health care costs (US $2010;measured from a payer perspective) were observed over a 1-year period after theindex date and were compared between patients with and without surgery failureusing multivariate generalized linear regression models with a log link and a negativebinomial distribution and linearmodels, respectively.Multivariate analyses controlledfor demographics, comorbidities, and baseline health care resource utilization.

Results: Of the 2668 patients meeting the study criteria (67% female, average age 45years), 51% had $ 1 of the studied indicators of unmet needs. After multivariateadjustments, the incidence of inpatient visits was 63% higher for patients withindicators of unmet needs compared to patients without; the incidence of ED andoutpatient visits were 59% and 35% higher, respectively (all P\.001). The averagetotal health care costs were $13,235 and $8193 for patients with and withoutindicators of unmet needs, respectively. After multivariate adjustment, the differ-ence was $3109 (P\.001), which was mainly driven by the incremental inpatientcosts (difference ¼ $1958; P\.001).

Conclusion: Unmet treatment needs in HS patients represent a significant burden onpatients and payers in terms of health care resource utilization and costs.

y was funded by Abbott Laboratories.

This stud

P6607Effect of everolimus, an oral mtor inhibitor, on angiogenic biomarkers inpatients with tuberous sclerosis complex (TSC) and skin lesions

John Bissler, MD, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH,United States; David Franz, MD, Cincinnati Children’s Hospital Medical Center,Cincinnati, OH, United States; Karen Stein, MD, MPH, Novartis PharmaceuticalsCorporation, Florham Park, NJ, United States; Klemens Budde, MD, Charite-Universit€atsmedizin Berlin, Berlin, Germany; Sergiusz Jozwiak, MD, TheChildren’s Memorial Health Institute of Warsaw, Warsaw, Poland; ThomasBrechenmacher, Novartis Pharma S.A.S., Rueil-Malmaison Cedex, France

Everolimus (EVE) was assessed in the EXIST-1 (NCT00789828) and EXIST-2(NCT00790400) trials for the treatment of subependymal giant cell astrocytoma(SEGA) associated with TSC or renal angiomyolipoma (AML) associated with eitherTSC or sporadic lymphangioleiomyomatosis, respectively. For the primary end-points, SEGA and AML response rate, EVE was superior to placebo (PBO). Asecondary endpoint, skin lesion response rate (proportion of patients with $ 1 skinlesion at baseline who had a complete clinical or partial clinical response) wasgreater for EVE than for PBO in both trials (EXIST-1, 42% vs 11%; P¼.0004; EXIST-2,26% vs 0%; P ¼ .0002). This study compared the dynamic changes of solubleangiogenic biomarkers between patients of different skin lesion response status inthe EVE arms of the EXIST studies. Patients received EVE (n ¼ 78) starting at 4.5mg/m2/d (target trough, 5-15 ng/mL) or PBO (n¼ 39) in EXIST-1 and 10mg/d EVE (n¼ 79) or PBO (n ¼ 39) in EXIST-2. In EXIST-1 and -2, 30 and 25 EVE patients,respectively, had skin responses and 42 and 52 EVE patients, respectively, werenonresponders. Plasma levels of vascular endothelial growth factor (VEGF)-A and -D,placental growth factor (PLGF), soluble VEGF receptor-1 and -2 (sVEGFR1 andsVEGFR2), c-Kit, and collagen type IV (col IV) were measured at baseline and day1 of weeks 4, 12, 24, 36, and 48. Similar baseline plasma levels of biomarkers werenoted between skin lesion responders and nonresponders in both trials. Regardlessof skin lesion response, no change in any biomarker level was seen in PBO-treatedpatients. No change in PLGF, c-Kit or sVEGFR1 in EVE-treated patients in either trialwas detected. Among EVE patients, there was a 64% decrease in VEGF-D at week 24for both skin responders and nonresponders in EXIST-2 and a trend towarddecreased VEGF-D level only in skin responders in EXIST-1. VEGF-A increased inskin responders and nonresponders for both trials (at week 24: EXIST-1, 26% and43%; EXIST-2, 68% and 57%, respectively). In both skin responders and nonre-sponders, col IV levels at week 24 decreased ;45% in EXIST-2 and 32% and 24%,respectively, in EXIST-1. sVEGFR2 levels decreased ;20% at week 24 in both skinresponders and nonresponders in EXIST-1 and EXIST-2. Skin lesion responses werehigher in EVE-treated patients in both EXIST trials. Although EVEmodulated levels ofmultiple angiogenic molecules, there was no strong association between change ofangiogenic markers and skin lesion responses in either study.

d by Novartis Pharmaceuticals Corporation.

Sponsore

APRIL 2013