Australasian Journal of Dermatology

(2003)

44

,

281–283

Correspondence: Dr Rodney Sinclair, Department of Medicine(Dermatology), St Vincent’s Hospital Melbourne, PO Box 2900,Fitzroy, Vic. 3065, Australia. Email: sinclair@svhm.org.au

Shannon Harrison, MB BS. Rodney Sinclair, FACD.Submitted 10 October 2002; accepted 26 June 2003.

CASE REPORT

Porokeratosis of Mibelli: Successful treatment with topical 5% imiquimod cream

Shannon Harrison and Rodney Sinclair

Department of Medicine (Dermatology), St Vincent’s Hospital Melbourne, Victoria, Australia

INTRODUCTION

Porokeratosis of Mibelli is a disorder of epidermal keratiniz-ation.

1

The lesions are premalignant; however, the risk ofmalignant transformation remains unknown. A number oftreatments have been advocated for localized porokeratosisof Mibelli, including surgical excision,

2

curettage andelectrocautery and cryotherapy.

2

However, none of thesetherapies is universally successful and each may result inscarring. Recurrence can occur with any therapeuticmodality. Imiquimod is an immune response modifier and,because of its influence on immunity and cytokine produc-tion,

3

recent cases of its successful use in the treatment ofsuperficial basal cell carcinoma (BCC)

4

and Bowen’s

disease

5

have been reported. Topical 5% imiquimod creammay also provide an effective option in the treatment ofporokeratosis of Mibelli.

CASE REPORT

A

77-year-old

woman

presented

with

a

solitary,

oval

area7–8 cm in diameter on her left shin with an irregular, raised,keratotic border and central atrophy (Fig. 1). It had beenpresent

for

approximately

6 years.

It

was

neither

pruriticnor tender. Histological examination of a directed punchbiopsy from the edge revealed a cornoid lamella. Previoustreatment with curettage and electrocautery 3 years ago wasunsuccessful. She was immunocompetent and had nohistory of radiation therapy. No family member had similarlesions.

Given the site and size of the lesion, surgical excision wasnot practical. Topical 5% 5-fluorouracil was tried with dailyapplication under occlusion until a strong inflammatoryreaction was achieved. After 8 weeks of treatment, 30% of thecircumference of the lesion of porokeratosis had resolved,but the other 70% remained. Limited cryotherapy was triedto a test area (15 s

�

1 freeze–thaw cycle), but was unsuc-cessful. After several months of observation with no furtherimprovement in the lesion, imiquimod cream was applied tothe entire lesion once daily 3 days a week without occlusion.The patient was aware that, at this time, there were nopublished reports of topical imiquimod cream being used forthe treatment of porokeratosis of Mibelli. After 6 weeks oftreatment, an area of inflammation with erythema andinduration had replaced the existing area of porokeratosisand the topical 5% imiquimod cream was ceased. A 3-mmpunch biopsy was taken of the inflamed treated areaincluding the hyperkeratotic edge and revealed mildcompact hyperkeratosis and significant lichenoid inflam-mation. On review 6 weeks later there had been completeresolution of the inflammation and the lesion had clinicallycompletely resolved. There was no scarring evident (Fig. 2).Three months later, the healed site, previously recordedphotographically, was rebiopsied. As the lesion had com-pletely resolved, it was not possible to do a targeted biopsy ofthe lesion edge to assess for a cornoid lamella, and histo-logical examination of the 3-mm punch biopsy of the

SUMMARY

A 77-year-old woman with a large porokeratosis ofMibelli on the left shin was successfully treated withtopical 5% imiquimod cream applied to the entirelesion once daily without occlusion three times aweek. A strong inflammatory reaction was achieved in6 weeks of treatment. The lesion had been present forapproximately 6 years and prior treatments includedcurettage and electrocautery, cryotherapy and topical5-fluorouracil under occlusion. At the end of treatmentwith topical 5% imiquimod cream, punch biopsy wasnegative for porokeratosis. The lesion healed withoutscarring. At 24-month follow up there had been no signof clinical recurrence.

Key words: 5-fluorouracil, cornoid lamella, immunemodulation, malignant transformation.

282 S Harrison and R Sinclair

previously

affected

area

showed

no

characteristic

changesof porokeratosis and was reported as normal skin. After24 months of follow up, no clinical recurrence of the lesionhas been observed.

DISCUSSION

Malignant neoplasms, including squamous cell carcinoma,

6,7

Bowen’s disease

8

and BCC,

9

have been noted to arise inlesions of porokeratosis of Mibelli. Reports of the frequencyof malignant transformation in lesions of porokeratosis varyfrom 7.5%

9

to 11.6%.

10

However, this may be overestimated asa result of publication bias, because malignant transform-ation may be more likely to be reported.

Given the association of malignant transformation inlesions of porokeratosis and the potential difficulties oftreating such a lesion were it to arise, the decision to treatwas made. A variety of treatments have been suggested forthe eradication of porokeratosis, including surgical exci-sion,

2

keratolytics,

2

long 585-nm pulsed dye laser,

11

carbondioxide laser

12

and cryotherapy.

2

Topical 5-fluorouracil,

13,14

etretinate

6

and diamond-fraise dermabrasion

15

have alsobeen used.

Surgical excision definitively eradicates an isolated lesionof porokeratosis, but has potential technical difficultiesdepending on the site and size of the lesion. In our case,surgical excision was not favoured as a spilt skin graft wouldhave been required for wound closure.

Imiquimod is an immune response modifier approved forthe topical treatment of perianal and external genital warts.

3

Because of its influence on immunity and cytokine pro-duction, imiquimod cream may be a potential alternativetherapy in the treatment of skin neoplasms, infections andother skin diseases.

16

Rationale for its use in this case wasprovided by recent reports of successful treatment of

superficial BCC

4

and Bowen’s disease

5

with topical 5%imiquimod cream.

Using topical 5% imiquimod cream, in a dosing scheduleof once daily three times per week without occlusion, theauthors achieved the clinical and histological resolution of alarge lesion of porokeratosis of Mibelli on the leg withoutscarring or other sequelae. Reports of topical agents such as5% 5-fluorouracil

13,14

and 5% imiquimod

17

being successfulin the treatment of porokeratosis of Mibelli have beenpublished. Recently, topical 5% imiquimod applied oncedaily for 5 days per week with occlusion for 5 weeks, wasused to clear a 3-cm diameter lesion on the leg after topical5% imiquimod alone without occlusion applied once dailyfor 5 days per week for 3 months had failed to improve thelesion.

17

Successful resolution of a lesion of porokeratosis ofMibelli

on

the

dorsum

of

the

right

thumb

with

topical5-fluorouracil has been reported, but also necessitatedocclusion with a bandage or petrolatum.

14

In these cases,both topical treatments were applied continuously to thelesion until a strong reactive inflammation was achieved.

In this case, a lower dosing frequency of topical 5%imiquimod cream without occlusion achieved resolution ofthe lesion of porokeratosis. Biopsy of the inflamed lesionupon cessation of the 5% imiquimod treatment revealedlichenoid inflammatory changes in the absence of a cornoidlamella. These changes may have been attributable to theporokeratosis itself or may have been a manifestation of theimmune-mediated resolution of the porokeratosis of Mibellias a result of the 5% imiquimod treatment. Since treating ourpatient, further cases of successful treatment with topical 5%imiquimod cream of BCC

18,19

and actinic cheilitis

20

have beenreported. Topical 5% imiquimod cream in the treatment ofporokeratosis of Mibelli is promising, but formal clinicaltrials to evaluate the efficacy and appropriate dose arerequired.

Figure 1

Lesion of porokeratosis of Mibelli on the left shin.

Figure 2

Complete resolution of the lesion 6 weeks after topical 5%imiquimod treatment was ceased.

Imiquimod for treatment of porokeratosis 283

ACKNOWLEDGEMENTS

The authors would like to thank Rebecca Davies, KathyTeagno and the photography services of the Skin and CancerFoundation in Victoria for reproducing the photographs.

REFERENCES

1. Griffiths WAD, Judge MR, Leigh IM. Disorders of keratinisation.In: Champion RH, Burton JL, Burns AD, Breathnach SM (eds).

Textbook of Dermatology

, Vol. 2, 6th edn. Oxford: BlackwellScience, 1998; 1483–588.

2. Schamroth JM, Zlotogorski A, Gilead L. Porokeratosis of Mibelli:Overview and review of the literature.

Acta Derm. Venereol.

1997;

77

: 207–13.3. Sauder DN. Immunomodulatory and pharmacologic properties

of imiquimod.

J. Am. Acad. Dermatol.

2000;

43

: S6–S11.4. Beutner KR, Geisse JK, Helman D, Fox TL, Ginkel A, Owens ML.

Therapeutic response of a basal cell carcinoma to the immuneresponse modifier imiquimod 5% cream.

J. Am. Acad. Dermatol.

1999;

41

: 1002–7.5. Mackenzie-Wood A, Kossard S, de Launey J, Wilkinson B, Owens

ML. Imiquimod 5% cream in the treatment of Bowen’s disease.

J. Am. Acad. Dermatol.

2001;

44

: 462–70.6. Scott OLS. Porokeratosis of Mibelli with squamous cell carcin-

oma.

Br. J. Dermatol.

1983;

109

(Suppl. 24): 74.7. James WD, Rodman OG. Squamous cell carcinoma arising in

porokeratosis of Mibelli.

Int. J. Dermatol.

1986;

25

: 389–91.8. Coskey RJ, Mehregen A. Bowen’s disease associated with

porokeratosis of Mibelli.

Arch. Dermatol.

1975;

111

: 1480–1.9. Otsuka F, Someya T, Ishibashi Y. Porokeratosis and malignant

skin tumors.

Cancer Res. Clin. Oncol.

1991;

117

: 55–60.

10. Sasson M, Krain AD. Porokeratosis and cutaneous malignancy.A review.

Dermatol. Surg.

1996;

22

: 339–42.11. Alster

TS,

Nanni

CA.

Successful

treatment

of

porokeratosiswith

585nm

pulsed

dye

laser

irradiation.

Cutis

1999;

63

:265–6.

12. Barnett JH. Linear porokeratosis: Treatment with the carbondioxide laser.

J. Am. Acad. Dermatol.

1986;

14

: 902–4.13. Goncalves JCA. Fluorouracil ointment treatment of porokera-

tosis of Mibelli.

Arch. Dermatol.

1973;

108

: 131–2.14. McDonald SG, Peterka ES. Porokeratosis (Mibelli): Treatment

with

topical

5-fluorouracil.

J.

Am.

Acad.

Dermatol. 1983; 8:107–10.

15. Spencer JM, Katz BE. Successful treatment of porokeratosis ofMibelli with diamond fraise dermabrasion. Arch. Dermatol.1992; 128: 1187–8.

16. Dahl MV. Imiquimod: An immune response modifier. J. Am.Acad. Dermatol. 2000; 43: S1–S5.

17. Agarwal S, Berth-Jones J. Porokeratosis of Mibelli: Successfultreatment with 5% imiquimod cream. Br. J. Dermatol. 2002; 146:338–9.

18. Sterry W, Ruzicka T, Herrera E, Takwale A, Bichel J, Andres K,Ding L, Thissen MR. Imiquimod 5% cream for the treatment ofsuperficial and nodular basal cell carcinoma: Randomizedstudies comparing low-frequency dosing with and withoutocclusion. Br. J. Dermatol. 2002; 147: 1227–36.

19. Marks R, Gebauer K, Shumack S, Amies M, Bryden J, Fox TL,Owens ML. Imiquimod 5% cream in the treatment of superficialbasal cell carcinoma: Results of a multicenter 6-week dose–response trial. J. Am. Acad. Dermatol. 2001; 44: 807–13.

20. Smith KJ, Germain M, Yeager J, Skelton H. Topical 5% imiquimodfor the therapy of actinic cheilitis. J. Am. Acad. Dermatol. 2002;47: 497–501.