Are You Confident of the Diagnosis?
Porokeratois and variants typically appear as single or multiple lesions that are usually asymptomatic, although occasionally pruritus is reported. Often patients are troubled by the cosmesis of these lesions. Individual characteristics of variants are discussed below.
Desseminated Superficial Actinic Porokeratosis (DSAP)
What you should be alert for in the history
This most common variant presents as small asymptomatic, occasionally pruritic, red scaly lesions that do not resolve with the use of a moistiurizer. Sometimes patients report a family member with similar lesions.
Characteristic findings on physical examination
On physical examination, there are multiple 2-7-mm thin, flesh colored to pink or red papules with a rim of scale (Figure 1). They can expand, leaving central atrophy. They can be widespread but are often on the lower extremities of women. The actinic variant only affects sun-exposed areas. Generalized lesions in sun exposed and non-sun–exposed sites have been referred to as superficial disseminated porokeratosis.
Lesions become more prominent in the summer months. Lesions can be inherited in an autosomal dominant fashion; however, most cases are sporadic, appearing in the 3rd to 4th decade
Diagnosis can be assisted with the use of dermoscopy to identify the single or double (tram) track at the periphery.
The differential includes actinic keratosis, Bowens disease, stucco keratoses, annular lichen planus, granuloma annulare and dermatitis if the lesions lack the typical border
Porokeratosis of Mibelli (PM)
What you should be alert for in the history
These lesions begin as a small, brown to flesh-colored papules that expand over years to form an annular hyperkeratotic plaque (Figure 2). They can occur anywhere but are most often on the lower extremities. They present during infancy or childhood, affecting more boys than girls. Occasionally, patients report a prior type of cutaneous trauma.
Characteristic findings on physical examination
Typically the border is raised and sharply demarcated with a longitudinal furrow. The central part of the lesion appears as one of the following: normal, hypo-, hyperpigmented, atrophic, or anhidrotic. They can be inherited in an autosomal dominant fashion but may also appear sporadically. There is a risk of malignant transformation so treatment is recommended.
Characteristic findings on physical examination
This is one of the more rare variants. These lesions appear as classic porokeratosis; however, they follow the lines of Blaschko. Lesions are most commonly found on the extremities (distal > proximal) (Figure 3). They can occur on the trunk, often in a zosteriform distribution. They usually appear during infancy or childhood but can develop later in life.
The differential includes inflammatory linear epidermal nevus, incontinentia pigmenti and linear lichen planus.
Porokeratosis Palmaris et Plantaris Disseminate (PPPD)
What you should be alert for in the history
The lesions also appear similar to classic prokeratosis but are smaller with a less pronounced border, often mimicking the spines of a music box. PPPD appears during childhood and adolescence and is two times more common in males than in females. It is inherited in an autosomal dominant fashion.
Lesions often begin on the palms and soles but progressively spread to the trunk and extremities, even the mucous membranes. They are not limited to sun-exposed skin. 25%percent of patients report pain in the plantar lesions.
Typically this variant is treatment resistant.
What you should be alert for in te history
This is the most difficult category to diagnose, due to the size of the lesions. Lesions appear during/after adolescence with 1-2mm keratotis papules with a raised rim on the palms and/or soles.
Expected results of diagnostic studies
A skin biopsy may be necessary to confirm the diagnosis with microscopic visualization of the coronoid lamella, which represents a thin column of tightly packed parakeratotic cells extending from an epidermal invagination through the stratum corneum (Figure 4). Typically, below the coronoid lamella is either an absent or attenuated granular layer.
The coronoid lamella clinically corresponds to the raised hyperkeratotic border. It can also be seen in actinic keratoses as well as verruca vulgaris. It can be applicable to all variants but since the punctate is the most difficult to diagnose it is very important to consider with this variant.
The differentlal includes punctate keratoderma, Darier’s disease, Cowden’s disease and arsenical keratoses. Confirmation via biopsy with visualization of the characteristic coronoid lamella
Who is at Risk for Developing this Disease?
Risk varies based on the type of the lesions and the characterists are described above. Patients often report a positive family history. Some patients on immunosuppressive medications (for example: etanercept, adalimumab, combination of methylprednisone, hydroxychloroquine and sulfasalazine) can present with the disease and there can be resolution with discontinuation of the suspected medication.
What is the Cause of the Disease?
The etiology is unknown but it is thought to be a disorder of keratinization. The most accepted theory is that the lesions are the results of an abnormal expansion of a mutant epidermal clone. The coronoid lamella is the border between the normal and mutant clone of cells.
Other contributing factors include a immunologic response with a dermal lymphocytic infiltrate and DNA ploidy within the keratinocytes. In addition, a tumor suppression protein, p53, has been reported to be overexpressed within the coronoid lamella.
Triggering factors include jultraviolet (UV exposure or immunosuppression.)
Systemic Implications and Complications
Malignant transformation has been reported in all of the variants except the punctate form. This is typically squamous cell carcinoma. It is more likely in older patients with lesions of longstanding duration as well as linear variants.
DSAP has the lowest rate of malignant change. Squamous cell carcinoma appears as a papule or plaque within the original lesion causing asymmetry. Rarely, metastatic disease has been reported from the squamous cell carcinoma from one of the porokeratotic lesions.
5-fluorouracil (5-FU): dosages include (daily in combination with 5-aminolevulinic acid (ALA); daily in combination with daily salycylic acid under occlusion, daily x 3 weeks, three times a day x 8-10 days)
Retinoids: (topical tretinoin twice a day then taper; daily x 8-10 weeks tapering to 2x/week, daily of 0.1% gel x 4 months)
Imiquimod 5%: (twice a day for 16 weeks along with topical 5-FU every morning; 5x/week for 6 weeks, daily 3x/week for 6 weeks)
Topical corticosteroids: (for example halobetasol 0.05% twice daily)
Vitamin D analogs: (calcipotriol, daily x 6-8week and tacalcitol, 2.0g lotion applied daily)
Diclofenac sodium 3% gel: twice a day x 3-6 months
Photodynamic therapy: Methyl aminolevulinate (MAL:the methyl ester of ALA, it is a prodrug and more lipophilic) applied under occlusion for 3 hours then exposed to 9 minutes of red light; ALA applied for 2 hours then exposed to blue light for 16min 40sec along with daily application with 5-FU
(Etretinate: has been the most widely reported oral retinoid; however, it is no longer available.)
Cryotherapy: (frozen for 30 seconds after the keratotic borders were removed conically by sharp dissection; 20 second freeze thaw-cycle every 6 months over 6 years)
Carbon dioxide (CO2) laser: energy density 100-150J until dermal tissue appeared
Q-switched ruby laser (QSRL), 694nm: Three treatments at an energy level of 5J; 4.3j/cm2 with a 6.5mm spot size
Neodymium-yttrium-alumninum-garnet (Nd:YAG) laser, 532nm: 4mm spot size, 1,5 J/cm2 fluence, 2.5 pulses/sec, treatment for at least 5 months
Fractional photothermolysis: Three treatment sessions at 4-week intervals using 1550-nm erbium doped fiber fractional photothermolysis, 10 passes to achieve a final treatment density of 2500 microthermal treatment zones
Grenz rays; 2GY rays daily for 5 days
Dermabrasion: Spot using a 6/18mm diamond fraise attached to an acrotorque hand engine rotating at 20,000 rpm abraided until the sebaceous glands are identified
Optimal Therapeutic Approach for this Disease
It is essential to educate the patients and emphasize that regular dermatologic follow-up is necessary to monitor for malignant transformation within the lesions. Sun protection both with topical preparations as well as clothing should be discussed and encouraged.
Obtain a family history of any members with any similar lesions. Explain the natural course of the lesions and that most of them can be relatively difficult to treat. Many successful modalities have only been reported anecdotally in individual cases.
Treatment is based on the type and extent of disease as well as patient expectations. Complete eradication can be difficult as it is essential to destroy the abnormal clone of keratinocytes. Any raised areas or ulcers within a porokeratotic lesion warrant a biopsy. The most significant concern is malignant transformation, therefore, close clinical follow-up is recommended.
For pruritic lesions, a class 1 or 2 topical corticosteroid is typically effective at reducing that symptom.For more disseminated lesions, topical preparations can be considered; however, often only a partial response is achieved.
Topical 5-fluorouracil causes an inflammatory response due to the hyperproliferative characteristics of the lesions. A similar response has also been seen with systemic 5-FU. It has been reported for the treatment of all variants.
The inflammatory response is essential, so treatment must continue until this is achieved. Increased penetration is possible with occlusion and/or the use of a topical retinoid. Recurences are common with discontinuation.
Imiquimod induce cytokines, which stimulate Th-1 cells resulting in an increased immune response. Oftentimes the use of occlusion with this medication improves the efficacy of treatment with imiquimod. Case reports reveal that occlusion increases the effectiveness of this topical preparation. It has been reported effective with the treatment of PM.
Topical vitamin D-3 preparations (calcipotriol and tacalcitol) regulate keratoinocyte differentiation, but there is a risk of elevated serum calcium levels. Reports show this to be effective in the treatment of DSAP.
Diclofenac is a nonsteroidal antiinflammatory drug with cyclooxygenase (COX) inhibitor activity. It is suggested that there is inhibition of the arachnidonic acid metabolism thereby reducing tumorigenic effects of its metabolites.
Retinoids decrease abnormal keratinization and are thought to decrease the probaility of malignant transformation. Oral retinoids should be considered in those patients who are immunosupressed and at an increased risk of malignant transformation. A combination of topical 5-fluorouracil and isotretinoin has been reported effective for both PPPD and DSAP.
Photodynamic therapy selectively destructs atypical keratinocytes. Those keratinocytes preferentially accumulate a topical photosensitizer, which then generates a cytotoxic reactive oxygen species when exposed to light.
There are multiple photosensitizers; however, it has been suggested that MAL is more effective than 5-aminolevulinic because of its high lipophilicity, allowing it to penetrate deeper. Methyl aminolevulinate has been reported effective with DSAP and linear porokeratosis.
For discrete lesions, cryosurgery is the most common modality; however, this can be painful and cause scarring. When ineffective, electrodessication and curretage are the next step in the destructive modality.
The following lasers have been described in the treatment of these lesions; however, variable results are reported. They include the CO2, 585nm flashed lamp pumped pulsed dye, Q-switched ruby laser, frequency doubled Nd:Yag.
Interestingly, the CO2 laser has been able to irradicate these lesions; however, significant scarring and hyperpigmentation is a concern. The QSRL is typically used to treat pigmented lesions but when used in porokeratosis it causes selective thermolysis and the irradiation induces thermal denaturation on the basal layer theerby minimizing scaring and hyperpigmentation.
Patients must minimize irradiation exposure and must be closely monitored for signs of malignant transformation.
Occasionally these lesions have been reported following transplantation or immunosuppression, such as renal transplantation, esophageal cancer, colon cancer, and myelodysplastic syndrome. Some reports have suggested that development of DSAP could be considered a paraneoplastic syndrome.
In the reports fDSAP, the cutaneous disease has been seen prior to the malignancy diagnosis. In many of these cancer diagnoses there is involvement of the p53 pathway. P53 gene products are also thought to be expressed under or near the coronoid lamella
Some variants can be seen with other types of porokeratsis lesions in the same patient, however this is rare and thought to be secondary to loss of heterogeneity.
Unusual Clinical Scenarios to Consider in Patient Management
When either new lesions appear or there is worsening of withstanding lesions, an immunosuppresion work-up is advisable. Possibilities include HIV, hematologic malignancies, and/or renal failure.
What is the Evidence?
Dereli, T, Ozyurt, S, Osturk, G. “Porokeratosis of Mibelli: Successful treatment with cryosurgery”. J Dermatol. vol. 31. 2004. pp. 223-7. (A report of eight patients with a total of 20 lesions treated with 30 second cycles of cryotherapy followed by a sharp dissection of the lesion border. A majority of the lesions resolved after one treatment with only two requiring an additional session.)
Skupsky, H, Skupsky, J, Goldenberg, G. “Disseminated superficial actinic porokeratosis: A treatment review”. J Dermatolog Treat. 2010. pp. 1-5. (A comprehensive review of treatments, including the level of evidence of each therapeutic modality.)
Maubec, E, Duvillard, P, Margulis, A, Bachollet, B, Degois, G, Avril, MF. “Common skin cancers in porokeratosis”. Br J Dermatol. vol. 152. 2005. pp. 1389-91. (A retrospective study of 11 patients with porokeraotsis with 1/3 showing multiple skin tumors.)
Vlachou, C, Kanelleas, AI, Martin-Clavijo, A, Berth-Jones, J. “Treatment of disseminated superficial actinic porokeratosis with topical diclofenac gel: A case series”. J Eur Acad Dermatol Venerol. vol. 22. 200. pp. 1343-5. (A case series of eight patients, all of whom had failed at least one other modality. Patients were treated with daily application and assessed at both 3 and 6 months. This treatment was generally well tolerated. Only one patient expressed satisfaction.)
Bohm, M, Luger, T, Bonsmann, G. “Disseminated superficial actinic porokeratosis: Treatment with topical tacalcitol”. J Am Acad Dermatol. vol. 40. 1999. pp. 479-80. (A case report of a patient with DSAP who was unresponsive to other treatment modalities including topical corticosteroids, salicylic acid, and tazorotene. She applied 0.0004% tacalcitol once daily. At 3 months the lesions had substantially faded and at 5 months they were completely resolved. She was maintained on every other day application.)
Cavicchini, S, Tourlaki, A. “Successful treatment of disseminated superficial actinic porokeratosis with methyl aminolevulinate-photodynamic therapy (letter)”. J Dermatolog Treat. vol. 17. 2006. pp. 190-1. (A case report revealing the successful treatment of DSAP using MAL-PDT showing high efficacy and a good cosmetic outcome with high patient satisfaction.)
Arun, B, Reason, J, Chalmers, R. “Disseminated superficial actinic porokeratosis treated effectively with topical imiquimod 5% cream”. Clin Exp Dermatol. 2011; Apr. pp. 1-3. (A case report describing a 68 year-old gentlemen with DSAP who applied topical imiquimod 5% five times weekly for 6 weeks. This regimen caused a dramatic inflammatory response after 4 weeks. At 8 weeks follow-up the treated areas were healed with slight scarring and erythema with no evidence of the originial lesions.)
Spencer, JM, Katz, BE. “Successful treatment of porokeratosis of Mibelli with diamond fraise dermabrasion”. Arch Dermatol. vol. 128. 1992. pp. 1187-8. (A case report of a patient with a 4-cm lesion that recently became symptomatic on her right thigh that responded well to dermabrasion without clinical recurrence.)
Lolis, MS, Marmur, ES. “Treatment of disseminated superficial actinic porokeratosis (DSAP) with the Q-switched ruby laser”. J Cosmet Laser Ther. vol. 10. 2008. pp. 124-7. (A case report of a 48-year-old woman with DSAP treated with three QSRL sessions to over 50 sites on her upper and lower extremities. The treatment was tolerated well and clinical improvement and patient satisfaction was positive at the 3-month follow-up.)
Chrastil, B, Glaich, AS, Goldberg, LH, Friedman, PM. “Fractional photothermolysis: A novel treatment for disseminated superficial actinic porokeratosis”. Arch Dermatol. vol. 143. 2007. pp. 1450-2. (A report of two patients revealing marked decrease in the size of the lesions as well as improvement of texture after 3 to 6 treatments. These results were maintained at 1 year. The treatments were tolerated well and patient satisfaction was achieved.)
Shelley, WB, Shelley, ED. “Disseminated superficial porokeratosis:rapid therapeutic response to 5-fluorouracil”. Cutis. vol. 32. 1983. pp. 39-40. (Lesions were treated with daily application of 5% 5-fluorouracil for 3 weeks when resolution was observed and maintained at 5-month follow-up.)
Kaur, S. “Co-existence of variants of porokeratosis: a case report and review of the literature”. J Dermatol. vol. 29. 2002. pp. 305(A report of a patient with linear porokeratosis since birth who then developed DSAP. This is a rare event, however. This is a review of the literature and discusses possible genetic linkage.)
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