P486A PATIENT WITH XERODERMA PIGMENTOSUM TREATED WITH IMIQIMOD 5%CREAMKim Lapiere, MD, University Hospital Antwerp, Edegem, Belgium, Tamar Nijsten, MD,University Hospital Antwerp, Edegem, Belgium, Sarah Caers, University Hospital Ant-werp, Edegem, Belgium, Julien Lambert, MD, PhD, University Hospital Antwerp, Edegem,Belgium

Xeroderma pigmentosum (XP) is a rare autosomal recessive disease which affects theDNA repair system. Xeroderma pigmentosum is categorized in 7 complementationgroups (A to G), with a defect in the nucleotide excision repair and 1 variant type, witha defect in the post-replication repair. Therefore, patients with XP are unable to normallyrepair UV-induced DNA damage in keratinocytes which results in increased pigmentationand early development of actinic keratosis, nonmelanoma skin cancer and melanoma. Theprevalence of skin cancer is 1000-fold increased, with very early onset.

Both avoidance of ultraviolet (UV) exposure and aggressive treatment of precursor lesionsare pivotal in the therapy of XP. Nevertheless, XP patients develop multiple tumors thatmay be treated with surgical excision, cryotherapy or electrodesiccation and curettage.Oral retinoids has partial chemopreventive effects in these high-risk patients. Imiquimodis an immune-response modifier with antiviral effects that are mediated by INF-fN.Recently, it has also been suggested that imiquimod is effective in the treatment of skincancers such as actinic keratosis, BCC and SCC in situ.

We present a 28-year-old male diagnosed with variant type XP which is confined to hisface. Although he restricted UV exposure, used topical and systemic retinoids and wasfollowed up intensively, he developed more than 25 facial squamous cell carcinomas andbasal cell carcinomas during the past 8 years. These lesions were treated with eithersurgical excision or Mohs surgery. Imiquimod 5% cream was commenced on the face ofthis patient. After applying imiquimod three times weekly for 2 months, we discontinuedtherapy because of excellent results. The skin was remarkably softer and smoother, andall suspicious lesions cleared. One month after discontinuation, lesions reoccured andimiquimod three times a week was restarted. Imiquimod 5% cream was up to nowtolerated very well, except for the first two weeks of therapy with marked erythema,slight scaling and edema.

In conclusion, imiquimod 5% cream can be useful in the management of XP. In this case,imiquimod improved the appearance of the skin, was effective in clearing suspiciouslesions and prevented further surgical interventions during the last 6 months.

Disclosure not available at press time.

P487BASAL CELL CARCINOMA OF THE NIPPLE AND AREOLA: A CASE REPORT ANDREVIEW OF THE LITERATURENathan Rosen, MD, McGill University, Montreal, QC, Canada, Channy Muhn, MD, McGillUniversity, Montreal, QC, Canada, Steven Bernstein, MD, Universite de Montreal, Mon-treal, QC, Canada

Background: Basal cell carcinoma (BCC) occurring on sun shielded sites, especially thenipple and areola, is a very rare event. Twenty cases of BCC of the nipple have beenreported in the English language literature, with only 6 of these cases occurring inwomen.

Methods and Results: We report the 7th case of the BCC of the female nipple and areolacomplex, treated with Mohs surgery and sentinel lymph node biopsy, and review theliterature on this uncommon tumor.

Conclusion: Basal Cell carcinoma of the nipple is an extremely rare tumor with unclearetiology. These tumors can be aggressive, as evidenced by metastatic spread to theaxillary lymph nodes in three previously described cases. With detailed reporting ofdiagnosis, treatment, and follow up of these patients, we may gain an understanding ofthe pathogenesis, as well as the best method of control for these unusual tumors.

Disclosure not available at press time.

P488DIFFERENT DOSING REGIMENS OF IMIQUIMOD 5% CREAM CAN BE USED TOSAFELY AND EFFECTIVELY TREAT ACTINIC KERATOSISJoseph Jorizzo, MD, Wake Forest University School of Medicine, Winston-Salem, NC,United States, Mark Lebwohl, MD, Mount Sinai School of Medicine, New York, NY, UnitedStates, Stuart Salasche, MD, University of Arizona Health Sciences Center, Tucson, AZ,United States, Eggert Stockfleth, MD, Charite Hospital, Universitatshautklinik der Charite,Berlin, Germany

The immune system plays a critical role in the development and pathogenesis of actinickeratosis (AK). Imiquimod 5% cream has been shown to stimulate the cutaneous immuneresponse and to be effective for the treatment of nonmelanoma skin cancers. Data fromfive large, randomized, vehicle-controlled studies were analyzed to determine if morethan one dosing regimen could be used to effectively treat AK. Subjects applied imi-quimod 5% cream or vehicle to AK lesions located on the face or balding scalp for 16weeks. Subjects dosed 2 times per week in two studies, and 3 times per week in threestudies, one of which required a negative posttreatment biopsy. In all five studies,subjects randomized to imiquimod 5% cream had statistically significantly higher com-plete clearance rates than vehicle subjects. Combined data from the 2 times per weekstudies showed that 45% of imiquimod subjects completely cleared. In the 3 times perweek study with the biopsy requirement, almost 60% of imiquimod subjects achievedcomplete clearance, and combined data from the two remaining 3 times per week studiesshowed that 48% of imiquimod subjects completely cleared. The median percent reduc-tion in the number of AK lesions counted at baseline for imiquimod subjects was 83.3%for the 2 times per week studies; 100% for the 3 times per week biopsy study; and 86.6%for the remaining 3 times per week studies. Imiquimod 5% cream was well tolerated, andthe most common side effect was erythema. Data from several open label studies showedthat similarly high clearance rates can be achieved with even shorter dosing durations.This suggests that immune responses can vary among individuals. Together, these resultsindicate that imiquimod 5% cream can be used in several different dosing regimens totreat actinic keratosis safely and effectively.

All authors have been paid study investigators and/or consultants for 3M Pharmaceuticals.

100% is sponsored by 3M Pharmaceuticals.

P489IMIQUIMOD 5% CREAM INDUCES CELL-MEDIATED IMMUNE RESPONSEMary Owens, MD, 3M Pharmaceuticals, St. Paul, MN, United States, Ross Barnetson, MD,Royal Prince Alfred Hospital, Camperdown, Australia, Gary Halliday, PhD, Royal PrinceAlfred Hospital, Camperdown, Australia, Andrew Satchell, MBBS, Royal Prince AlfredHospital, Camperdown, Australia

Imiquimod 5% cream is a topically applied immune response modifier that has beenshown to effectively treat both basal cell carcinoma (BCC) and actinic keratosis (AK). Theexact molecular mechanism for imiquimod is not known. In order to better elucidate theimmune response to imiquimod in non-melanoma skin cancers, two phase I studies wereconducted in which immune biomarker levels were analyzed at various time points afterapplication of imiquimod 5% cream. One study included 16 evaluable subjects with atleast 1 clinically diagnosed superficial BCC tumor, while the other study included 18subjects with AK. In both studies, biopsy specimens were examined using routine andimmunohistochemical staining. Many changes in biomarker levels were observed in bothstudies, the most significant of which are presented here. In subjects with BCC that usedimiquimod, cluster determinant 4 (CD4) levels were raised by week 1 and remainedconstant. CD11c levels increased with time, while MAC387 levels were highest at week1 and declined slightly by weeks 2 and 4. Similarly, in AK subjects treated with imi-quimod, statistically significantly higher levels of CD3, CD4, CD8, CD11c, CD86/CD11c,CD68, HLA-DR, and TUNEL were observed at week 2 than at baseline. Local skin reactionsoccurred in both studies and were well tolerated. Application site reactions were themost common adverse events among imiquimod-treated subjects and occurred in 57.1%(8/14) of BCC subjects and 66.7% (8/12) AK subjects. The results of these studies areconsistent with previous data indicating that imiquimod works through the stimulation ofthe innate and adaptive immune response.

Dr. Owens is an employee of 3M Pharmaceuticals. Drs Barnetson and Halliday are paidinvestigators and/or consultants for 3M.

100% is sponsored by 3M Pharmaceuticals.

P126 J AM ACAD DERMATOL MARCH 2004