0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
The Cutting Edge |

Treatment of Porokeratosis of Mibelli With Ingenol Mebutate A Possible New Therapeutic Option FREE

Sabrina Kindem, MD1; Carlos Serra-Guillén, MD1; Guillermo Sorní, MD1; Carlos Guillén, MD1; Onofre Sanmartín, MD1
[+] Author Affiliations
1Department of Dermatology, Instituto Valenciano de Oncologia, Valencia, Spain
JAMA Dermatol. 2015;151(1):85-86. doi:10.1001/jamadermatol.2014.2697.
Text Size: A A A
Published online

REPORT OF A CASE

A woman in her 50s presented with an 8-year history of an annular plaque in the left perioral area. Physical examination showed a thick hyperkeratotic annular plaque with elevated edges and an atrophic center (Figure 1). Histopathologic examination of the lesion revealed a cornoid lamella, an underlying epidermis devoid of a granular layer, and a lymphocytic infiltration in the upper dermis. The clinical and histopathologic features were consistent with a diagnosis of porokeratosis of Mibelli.

Place holder to copy figure label and caption
Figure 1.
Clinical Image Acquired Before Treatment With Ingenol Mebutate Showing Hypopigmentation

Thick hyperkeratotic annular plaque with elevated edges and an atrophic center.

Graphic Jump Location

The patient had received diverse consecutive treatments since 2008, including photodynamic therapy with aminolevulinic acid, electrocoagulation, an 8-week course of fluorouracil cream, topical treatment with the 2-compound formulation betamethasone (50 μg/g) and calcipotriol (0.5 mg/g), carbon dioxide laser, and 2 courses of imiquimod, 5%, for 6 weeks. None of the treatments had been successful. Significant hypopigmentation, possibly triggered by the strong inflammatory response, was observed in the lesion after treatment with fluorouracil cream. This hypopigmentation remained unchanged at last follow-up. The patient was also treated with pulsed-dye laser in 2012 and with diclofenac sodium, 3%, gel applied twice daily for 3 months in 2013. Neither of these treatments achieved partial or total remission of the lesion.

THERAPEUTIC CHALLENGE

Multiple treatments have been described for porokeratosis of Mibelli, but the results have frequently been disappointing. Treatment should be individualized, with consideration of cosmetic and functional impact and patient preferences. The possibility of malignant transformation must also be taken into account.

Multiple topical treatments, including corticosteroids, retinoids, fluorouracil, diclofenac, imiquimod, calcipotriol, keratolytics, and emollients have been used, with variable results.1,2 In a recent report, cantharidin, 0.7%, was used successfully in 2 patients.3 In another recent publication, topical tacrolimus was reported to have been used for linear porokeratosis.4 Other, more aggressive, treatments have also been used, including surgical excision, fractional photothermolysis, dermabrasion, cryotherapy, and oral retinoids.1,5,6

Because treatment can cause scarring and pain, asymptomatic lesions are often managed conservatively with sun protection, emollients, and monitoring for signs of malignant degeneration. Our patient was a woman who had a single lesion without indication of malignant transformation on the face, where cosmetic results were very important. The treatment therefore had to be nonscarring and safe.

SOLUTION

The patient was treated with 2 courses of ingenol mebutate, 0.015%, topical gel applied once daily for 3 consecutive days. The courses were separated by a month. The lesion showed slight inflammation for a week after both treatment courses.

Three weeks after completion of the second course, the lesion had partially cleared, and the clinical and cosmetic results were highly satisfactory (Figure 2). The lesion exhibited central atrophy and hypopigmentation, possibly due in part to the typical central atrophy of porokeratosis of Mibelli and to the multiple previous treatments. The hypopigmentation was most striking after treatment with fluorouracil cream. Treatment with ingenol mebutate resolved the hyperkeratotic annular plaque but had no noticeable effect on the atrophy or hypopigmentation.

Place holder to copy figure label and caption
Figure 2.
Clinical Image Acquired After 2 Courses of Ingenol Mebutate Treatment

Ingenol mebutate, 0.015%, was applied once daily for 3 days; the courses were separated by a month; hyperkeratotic annular plaque has resolved, leaving residual atrophy and hypopigmentation identical to that present before treatment.

Graphic Jump Location

At the 4-month follow-up visit, there were no signs of recurrence. The patient was very satisfied, and she was completely free of pain throughout the treatment course.

DISCUSSION

Porokeratosis is a primary disorder of epidermal keratinization, characterized by annular plaques with an atrophic center and hyperkeratotic edges. The disorder encompasses a group of diseases with diverse phenotypic expressions of the same genetic defect that is mainly inherited in an autosomal dominant form. Although the pathogenesis remains unclear, porokeratosis is thought to result from clonal proliferation of genetically abnormal epidermal keratinocytes that form the cornoid lamella seen on histologic analysis. Other histologic characteristics are loss of the granular layer at the base of the cornoid lamella, dilated superficial plexus capillaries, and a nonspecific superficial chronic infiltrate.

Our patient had classic porokeratosis of Mibelli. Porokeratosis lesions can affect any part of the skin but are more common on the trunk and extremities. They are generally asymptomatic. Skin biopsy and histologic examination are essential for diagnosis. Porokeratosis has oncogenic potential, with malignant transformation occurring in approximately 7% of patients. Squamous cell carcinoma is the most commonly associated tumor. Treatment should therefore preferably target the inhibition and differentiation of keratinocytes, with minimal disfiguration, discomfort, and recurrence.

Ingenol mebutate, also known as ingenol 3-angelate, is an extract from the sap of the noninvasive weed Euphorbia peplus. It is formulated as a propyl alcohol–based gel for topical use and is approved for the treatment of actinic keratosis.7 The gel is available in 2 concentrations: 0.015% for treatment of the face and scalp and 0.05% for treatment of other parts of the body. The recommended treatment is once-daily application for 3 consecutive days. The direct effect of the drug, along with local production of inflammatory cytokines, is initial lesion ablation characterized by rapid disruption of the plasma membrane and subsequent mitochondrial swelling followed by cell death via primary necrosis. The second phase is marked by an acute inflammatory response due to neutrophil infiltration. Additionally, ingenol mebutate is a protein kinase C pathway activator and promotes caspase apoptosis, p53 stability, and phosphorylation of signaling molecules.

Treatments that target keratinocyte inhibition and differentiation (eg, ingenol mebutate) could be successful in porokeratosis of Mibelli, where there is a clonal proliferation of genetically abnormal epidermal keratinocytes. Although further studies are required to prove its effectiveness, ingenol mebutate appears to be a promising treatment for single lesions of porokeratosis of Mibelli.

ARTICLE INFORMATION

Accepted for Publication: August 1, 2014.

Corresponding Author: Sabrina Kindem, MD, Department of Dermatology, Instituto Valenciano de Oncologia, C/ Profesor Beltrán Baguena 4, 46009 Valencia, Spain (sabrinakindemgomez@gmail.com).

Published Online: November 19, 2014. doi:10.1001/jamadermatol.2014.2697.

Conflict of Interest Disclosures: None reported.

REFERENCES

Skupsky  H, Skupsky  J, Goldenberg  G.  Disseminated superficial actinic porokeratosis: a treatment review. J Dermatolog Treat. 2012;23(1):52-56.
PubMed   |  Link to Article
Riad  H, Mansour  K, Sada  HA, Shaika  SA, Ansari  HA, Mohannadi  HA.  Disseminated superficial actinic porokeratosis on the face treated with imiquimod 5% cream. Case Rep Dermatol. 2013;5(3):283-289.
PubMed   |  Link to Article
Levitt  JO, Keeley  BR, Phelps  RG.  Treatment of porokeratosis of Mibelli with cantharidin. J Am Acad Dermatol. 2013;69(5):e254-e255.
PubMed   |  Link to Article
Parks  AC, Conner  KJ, Armstrong  CA.  Long-term clearance of linear porokeratosis with tacrolimus, 0.1%, ointment. JAMA Dermatol. 2014;150(2):194-196.
PubMed   |  Link to Article
Curkova  AK, Hegyi  J, Kozub  P, Szep  Z, D’Erme  AM, Simaljakova  M.  A case of linear porokeratosis treated with photodynamic therapy with confocal microscopy surveillance. Dermatol Ther. 2014;27(3):144-147.
PubMed   |  Link to Article
Rosenblum  J, Roenigk  HH  Jr.  Erbium laser for the treatment of disseminated superficial actinic porokeratosis: a case report. Dermatol Surg. 2013;39(10):1543-1545.
PubMed
Gupta  AK, Paquet  M.  Ingenol mebutate: a promising treatment for actinic keratoses and nonmelanoma skin cancers. J Cutan Med Surg. 2013;17(3):173-179.
PubMed

Figures

Place holder to copy figure label and caption
Figure 1.
Clinical Image Acquired Before Treatment With Ingenol Mebutate Showing Hypopigmentation

Thick hyperkeratotic annular plaque with elevated edges and an atrophic center.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Clinical Image Acquired After 2 Courses of Ingenol Mebutate Treatment

Ingenol mebutate, 0.015%, was applied once daily for 3 days; the courses were separated by a month; hyperkeratotic annular plaque has resolved, leaving residual atrophy and hypopigmentation identical to that present before treatment.

Graphic Jump Location

Tables

References

Skupsky  H, Skupsky  J, Goldenberg  G.  Disseminated superficial actinic porokeratosis: a treatment review. J Dermatolog Treat. 2012;23(1):52-56.
PubMed   |  Link to Article
Riad  H, Mansour  K, Sada  HA, Shaika  SA, Ansari  HA, Mohannadi  HA.  Disseminated superficial actinic porokeratosis on the face treated with imiquimod 5% cream. Case Rep Dermatol. 2013;5(3):283-289.
PubMed   |  Link to Article
Levitt  JO, Keeley  BR, Phelps  RG.  Treatment of porokeratosis of Mibelli with cantharidin. J Am Acad Dermatol. 2013;69(5):e254-e255.
PubMed   |  Link to Article
Parks  AC, Conner  KJ, Armstrong  CA.  Long-term clearance of linear porokeratosis with tacrolimus, 0.1%, ointment. JAMA Dermatol. 2014;150(2):194-196.
PubMed   |  Link to Article
Curkova  AK, Hegyi  J, Kozub  P, Szep  Z, D’Erme  AM, Simaljakova  M.  A case of linear porokeratosis treated with photodynamic therapy with confocal microscopy surveillance. Dermatol Ther. 2014;27(3):144-147.
PubMed   |  Link to Article
Rosenblum  J, Roenigk  HH  Jr.  Erbium laser for the treatment of disseminated superficial actinic porokeratosis: a case report. Dermatol Surg. 2013;39(10):1543-1545.
PubMed
Gupta  AK, Paquet  M.  Ingenol mebutate: a promising treatment for actinic keratoses and nonmelanoma skin cancers. J Cutan Med Surg. 2013;17(3):173-179.
PubMed

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

1,566 Views
0 Citations
×

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
Jobs