Difonzo, Elisa Margherita

Giannotti, Benvenuto

Pimpinelli, Nicola

Vanzi, L.

English

Difonzo, ELISA MARGHERITA

Florence Research

The treatment of basal cell carcinomas in a patient with xerodermapigmentosum with a combination of imiquimod 5% cream and oralacitretinB. Giannotti, L. Vanzi, E. M. Difonzo and N. PimpinelliDipartimento Scienze Dermatologiche, Via degli Alfani, Firenze, ItalySummary Xeroderma pigmentosum (XP) is a rare autosomal recessive photosensitive disorder,which results in multiple face, neck and head basal cell carcinomas (BCCs), squamouscell carcinomas and melanomas. A 15-year-old boy with XP presented with multiplefacial BCCs previously treated by surgical excision. Standard BCC treatments such assurgery are not ideal for patients with several facial BCCs because of the risk ofscarring, and the patient refused further surgery. As an alternative, three times weeklyapplication of imiquimod 5% cream in combination with oral acitretin (20 mg daily)was prescribed for 4–6 weeks. No adverse events were reported during treatment andall tumours had resolved at the 6-month follow up visit, highlighting the therapeuticpotential of imiquimod 5% cream.IntroductionXeroderma pigmentosum (XP) is an autosomal recessivephotosensitive disorder with an extremely high inci-dence of ultraviolet (UV)-related skin cancers. It isassociated with impaired ability to repair UV-inducedDNA damage.1,2 It reportedly effects 1 in 250 000people in Europe and the USA, while its prevalence inJapan has been documented as 1 in 40 000.2Clinical management of XP-related skin disordersconsist of early diagnosis followed by a rigorousprogramme of sun protection, including avoidance ofunnecessary UV exposure, wearing UV-blocking clo-thing and use of sun blocks on the skin.2 Failure inearly management of this condition generally resultsin basal cell carcinoma (BCC), squamous cell carci-noma (SCC) and malignant melanomas. Other com-plications of XP include ocular abnormalities.3 Thecarcinomas may be treated by surgery, curettage andelectrodesiccation, cryosurgery, Mohs’ micrographicsurgery, CO2 laser treatment or topical 5-fluoroura-cil.4–6 These methods, although effective on isolatedcarcinomas, are not ideal for treating multipletumours, primarily because of a higher risk of causingdisfiguring scarring.We report a novel method of treating multiplecarcinomas in XP patients with the immune responsemodifier, imiquimod 5% cream. Imiquimod, a recom-mended treatment option for anogenital warts, has beenshown to be effective in treating many other skindisorders, such as human papilloma virus-associatedwarts and skin carcinomas including BCCs.7–10Case reportA 15-year-old boy presented with XP with associatedmultiple BCCs and SCCs on his face. The first appear-ance of tumours was initially reported at the age of 3years, and the number and size progressively increasedwith advancing age. Previous treatment for thesetumours was surgical excision.During physical examination, multiple freckles anddry, atrophic skin were observed on light-exposedsurfaces. Conjunctivitis and ectropion were also evident.Many keratocanthomas and angiokeratomas wereobserved on the trunk and upper and lower extremities.The 11 tumours (3–6 mm in diameter) proposed fortreatment were located on the face. Some nodules hadsuperficial ulcerations, and others were covered byCorrespondence: Dr B. Giannotti, Dipartimento Scienze Dermatologiche,via degli Alfani 37, 50121 Firenze, Italy.Accepted for publication 21 July 2003Clinical and Experimental Dermatology • Concise report 2003 Blackwell Publishing Ltd • Clinical and Experimental Dermatology, 28 (Suppl. 1), 33–35 33haemorrhagic crusts (Fig. 1a). In addition, Fig. 1(b,c)show multiple lesions on the right side of the face andabove the right eyebrow, respectively. Only three ofthese tumours were biopsied (one was a BCC and twowere SCCs), although physical and radiological exam-inations excluded lymphadenopathy and metastaticinvolvement, respectively. The patient and his parentsrefused surgery as a treatment option for all of thetumours proposed for treatment. As an alternative, acombination of oral acitretin (20 mg daily) and topicallyapplied imiquimod 5% cream was prescribed.The patient was instructed to apply imiquimod 5%cream three times a week for 4–6 weeks to two tumoursat a time. The total duration of treatment depended onthe rate at which the tumours resolved. Followingtreatment the tumours were confirmed as clinicallyclear (Fig. 2a). Perioral tumours located on the delicateskin around the mouth also completely cleared(Fig. 2b,c). Tumours located on the right side of theface (Fig. 2d) and above the right eyebrow (Fig. 2e)were confirmed to be clinically clear following treat-ment. During the course of treatment, the patient didnot report any adverse events, although mild localerythema was observed during application of imiquimod5% cream. All the tumours were completely cleared atthe 6-month follow-up visit. The patient continues to beseen every 4 weeks for clinical follow-up and there hasbeen no recurrence of the tumours.DiscussionXeroderma pigmentation (XP) involves DNA repair andreplication deficiencies that predispose homozygousindividuals to a 1000-fold increase in melanoma andnonmelanoma skin cancers.11 The high incidence oftumours that develop in sun-exposed areas of the skin ofpatients with XP (> 4000 times the incidence in thegeneral population) has implicated the role of unre-paired UV-induced DNA lesions in skin carcinogene-sis.12 This hereditary condition has been found to beassociated with mutations occurring within the tumoursuppressor genes p53 and patched (PTCH).13 Within XPpatients, PTCH mutations represent an earlier event inBCC development than p53 alterations.14Clinical management of carcinomas associated withXP consists of early diagnosis followed by a rigorousprogramme of sun protection. Despite extensive precau-tionary measures, it is inevitable that sufferers of XP willexperience some cutaneous malignancies. However, theprophylactic usage of oral retinoids, topical retinoids,(a) (b) (c)Figure 1 (a) Multiple basal and squamous carcinomas on the face of an XP patient before treatment; (b) multiple lesions on the righthand side of the face; (c) basal cell carcinoma lesion located above the right eyebrow.(a) (b) (c)(e)(d)Figure 2 (a) Four to 6 weeks after treat-ment with imiquimod 5% cream, lesionson the face appear clinically clear andthere is significant improvement andclearance of perioral lesions locatedaround the mouth (b, c). (d) Lesions on theright hand side of the face successfullycleared following treatment. (e) Clearanceof the BCC lesions above the righteyebrow.Treatment of BCCs in an XP patient with imiquimod 5% cream and oral acitretin • B. Giannotti et al.34  2003 Blackwell Publishing Ltd • Clinical and Experimental Dermatology, 28 (Suppl. 1), 33–35local injection of interferon and the external use ofprokaryotic DNA repair enzymes may slow down theonset of skin cancers.2,15 Conventional methods oftreating BCC, e.g. surgery, cryotherapy and electrodes-iccation may also be employed in XP-associatedtumours.16 These treatments, although effective in theshort term, may be associated with recurrence andscarring and may not be feasible for multiple tumours.In addition to these conventional treatment modalities,a recent study by Yarosh et al. demonstrated thattopical application of DNA repair enzymes (endonuc-lease V) to sun-damaged skin of patients with XPlowered the rate of development of skin cancers,including BCCs, during a year of treatment.17The introduction of imiquimod 5% cream as atreatment for anogenital warts7 has resulted inresearchers identifying its potential use in treating bothviral and nonviral skin conditions, including skintumours such as BCC, even where these occur in thespectrum of hereditary conditions such as Gorlin’ssyndrome.10,18–21 These findings, together with itssuccessful use in treating facial BCCs in XP patients,highlights the therapeutic potential of imiquimod 5%cream for cutaneous oncological conditions.References1 Stary A, Sarasin A. The genetics of the hereditary xero-derma pigmentosum syndrome. Biochimie 2002; 84: 49–60.2 Moriwaki S, Kraemer KH. Xeroderma pigmentosum-bridging a gap between clinic and laboratory. Photoder-matol Photoimmunol Photomed 2001; 17: 47–54.3 Kraemer KH, Lee MM, Scotto J. Xeroderma pigmentosum.Cutaneous, occular and neurologic abnormalities in 830published cases. Arch Dermatol 1987; 123: 241–50.4 Drake MLA, Ceilley RI, Cornelison RL et al. Guidelines ofcare for basal cell carcinoma. J Am Acad Dermatol 1992;26: 117–20.5 Kopera D, Cerroni L, Fink-Puches R, Kerl H. Differenttreatment modalities for the managment of a patient withthe nevoid basal cell carcinoma syndrome. J Am AcadDermatol 1996; 345: 937–9.6 Hamouda B, Jamila Z, Najet R et al. Topical 5-fluorouracilto treat multiple or unresectable facial squamous cellcarcinomas in xeroderma pigmentosum. J Am AcadDermatol 2001; 44: 1054.7 Edwards L, Ferenczy A, Eron L et al. Self-administeredtopical 5% imiquimod cream for external anogenitalwarts. Arch Dermatol 1998; 134: 25–30.8 Hengge UR, Esser S, Schultewolter T et al. Self-adminis-tered topical 5% imiquimod for the treatment of commonwarts and molluscum contagiosum. Br J Dermatol 2000;143: 1026–31.9 Schroeder TL, Sengelmann RD. Squamous cell carcinomain situ of the penis successfully treated with imiquimod 5%cream. J Am Acad Dermatol 2002; 46: 545–8.10 Beutner KR, Spruance SL, Hougham AJ et al. Therapeuticresponse of basal carcinoma to the immune responsemodifier imiquimod 5% cream. J Am Acad Dermatol 1999;41: 1002–7.11 Cleaver JE. Common pathways for ultraviolet skin car-cinogenesis in the repair and replication defective groupsof xeroderma pigmentosum. J Dermatol Sci 2000; 23:1–11.12 Stary A, Sarasin A. The genetic basis of xeroderma pig-mentosum and trichothiodystrophy syndromes. CancerSurvey 1996; 26: 155–71.13 Lacour JP. Carcinogenesis of basal cell carcinoma: gen-etics and molecular mechanisms. Br J Dermatol 2002;146 (Suppl.): 17–9.14 D’Errico M, Calcagnile A, Canzona F et al. UV mutationsignature in tumour suppressor genes involvled in skincarcinogenesis in xeroderma pigmentosum patients.Oncogene 2000; 19: 463–7.15 Somos S, Farkas B, Schneider I. Cancer protection inxeroderma pigmentosum variant (VP-V). Anticancer Res1999; 19: 2195–9.16 Nguyen TH, Ho DQ. Nonmelanoma skin cancer. CurrTreat Options Oncol 2002; 3: 193–203.17 Yarosh D, Klein J, O’Connor A, Hawk J, Rafal E, Wolf P.Effect of topically applied T4 endonuclease V in liposomeson skin cancer in xeroderma pigmentosum: a randomisedstudy. Xeroderma pigmentosum Study Group. Lancet2001; 357: 926–9.18 Tyring SK, Arany I, Stanley MA et al. A randomised,controlled, molecular study of condylomata acuminataclearance during treatment with imiquimod. J Infect Dis1998; 178: 551–5.19 Strauss RM, Doyle EL, Mohsem AH, Green ST. Successfultreatment of molluscum contagiosum with topical imiq-uimod in a severely immunocompromised HIV-positivepatient. Int J STD AIDS 2001; 12: 264–6.20 Marks R, Gebauer K, Shumack S et al. Imiquimod 5%cream in the treatment of superficial basal cell carcinoma:results of a multicentre 6 week dose-response trial. J AmAcad Dermatol 2001; 44: 807–13.21 Kagy MK, Amonette R. The use of imiquimod 5% creamfor the treatment of superficial basal cell carcinomas in abasal cell nevus syndrome patient. Dermatol Surg 2000;26: 577–8.Treatment of BCCs in an XP patient with imiquimod 5% cream and oral acitretin • B. Giannotti et al. 2003 Blackwell Publishing Ltd • Clinical and Experimental Dermatology, 28 (Suppl. 1), 33–35 35

THE TREATMENT OF BASAL CELL CARCINOMAS IN A PATIENT WITH XERODERMA PIGMENTOSUM WITH A COMBINATION OF IMIQUIMOD 5% CREAM AND ORAL ACITREIN

https://flore.unifi.it/bitstream/2158/24887/1/The%20treatment%20of%20basal%20cell%20carcinomas%20in%20a%20patient%20with%20xeroderma%20pigmentosum%20with%20a%20combination%20of%20imiquimod%205%25%20cream%20and%20oral%20acitretin.pdf

THE TREATMENT OF BASAL CELL CARCINOMAS IN A PATIENT WITH XERODERMA PIGMENTOSUM WITH A COMBINATION OF IMIQUIMOD 5% CREAM AND ORAL ACITREIN

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