Porokeratosis 

Updated: Sep 24, 2018
Author: Amarateedha Prak LeCourt, MD; Chief Editor: William D James, MD 

Overview

Background

Porokeratosis is a clonal disorder of keratinization characterized by one or more atrophic patches surrounded by a clinically and histologically distinctive hyperkeratotic ridgelike border called the cornoid lamella. Historically, porokeratosis is a misnomer that was erroneously coined on the assumptions that cornoid lamellae emerged from pores of the sweat glands.[1] Multiple clinical variants of porokeratosis are recognized. Malignancies, typically squamous cell carcinomas, may develop within lesions of porokeratosis.

The most common forms of porokeratosis are as follows:

  • Classic porokeratosis of Mibelli (PM) [2]
  • Disseminated superficial actinic porokeratosis (DSAP) and its nonactinic variant disseminated superficial porokeratosis (DSP)
  • Linear porokeratosis
  • Porokeratosis palmaris et plantaris disseminata (PPPD)
  • Punctate porokeratosis, which might represent a variant of PPPD [3]

A patient may develop more than one type of porokeratosis simultaneously or consecutively.[2]

Less commonly reported clinical entities that share the histopathologic characteristic of cornoid lamellation include the following:

  • Porokeratosis ptychotropica, a verrucous variant localized to the buttocks [4]
  • Porokeratoma, also referred to as porokeratotic acanthoma, an entity arising as a solitary keratotic or verrucous nodule with prominent multiple and confluent cornoid lamellae [5]
  • Porokeratotic adnexal ostial nevus (PAON), a rare congenital disorder of keratinization with eccrine and hair follicle involvement: This name was proposed to incorporate porokeratotic eccrine ostial and dermal duct nevus (PEODDN) and porokeratotic eccrine and hair follicle nevus (PEHFN). [6]
  • Pruritic papular porokeratosis, in which intensely pruritic papules and plaques arise fairly abruptly in a patient with or without preexisting DSP [7, 8]
  • Pigmented porokeratosis: A case published in 2016 showed a new possible variant of porokeratosis. Biopsies showed prominent melanocytic hyperplasia in 8 of 31 patients studied. The case represents a distinct variant of porokeratosis; biopsies were performed to clinically exclude melanoma. An erroneous diagnosis of melanoma in situ can be avoided with increased recognition of this entity. [9]
  • Punctate follicular porokeratosis: This has been described in two separate reports, which supports the contention that this is a unique form rather than just a variation in histology. In both cases, the cornoid lamellae originated exclusively from hair follicles with no associated annular plaque. Diagnosis relies heavily on proper histopathologic sampling, and the rarity of this variant could be explained by the low prevalence of this condition in the population or perhaps low biopsy rate of lesions that appear to represent a localized form of keratosis pilaris to physicians. [10]

Pathophysiology

Clonal proliferation of atypical keratinocytes showing abnormal terminal keratinocyte differentiation leads to the formation of the cornoid lamella. Cornoid lamellation is typically seen in porokeratosis, where it corresponds to the threadlike scale present at the lesional border.[1] This expands peripherally and forms the raised boundary between abnormal and normal keratinocytes. The atypical keratinocytes show abnormal differentiation but do not show an increased rate of proliferation.[11, 12]

It is not known what triggers this process, and more than one causative factor may be involved. Several risk factors for the development of porokeratosis have been identified, including genetic inheritance, ultraviolet radiation, and immunosuppression.

Inherited or sporadic genetic defects, possibly creating a change in immune function and/or keratinocyte function, are thought to be responsible for several forms of porokeratosis. Familial cases of all forms of porokeratosis have been reported and appear to have an autosomal dominant inheritance pattern with incomplete penetrance. Several chromosomal loci have been identified for disseminated superficial actinic porokeratosis (DSAP), disseminated superficial porokeratosis (DSP), and porokeratosis palmaris et plantaris disseminata (PPPD).[13, 14, 15, 16, 17, 18, 19] The focal variants of porokeratosis (porokeratosis of Mibelli [PM] and linear porokeratosis) may occur through mosaicism, in which somatic mutations cause focal loss of heterozygosity.[20] Genetic mutations in the SART3 and MVK genes have been found in DSAP pedigrees.

A somatic mutation in the GJB2 mutation associated with keratosis-ichthyosis-deafness syndrome was found to cause porokeratotic eccrine ostial and dermal duct nevus.[21]

Natural or artificial ultraviolet radiation, electron beam therapy, and extensive radiation therapy are well-established trigger factors for DSAP and PM. Sun exposure in genetically susceptible individuals is thought to cause DSAP, although the sparing of facial skin in most patients is unexplained.

Immunosuppression associated with porokeratosis may be secondary to a disease process or medications. Diseases reported in association with porokeratosis include HIV infection,[22] diabetes mellitus,[23] liver disease,[24] and hematologic or solid organ malignancy.[25, 26] Immunomodulating drugs used to treat autoimmune diseases or to prevent organ transplant rejection may also trigger porokeratosis.[27, 28, 29, 30, 31, 32, 33, 34, 35] Localized cutaneous immunosuppression due to long-term application of a potent topical steroid was reported to induce PM.[36] The incidence of porokeratosis in organ transplant recipients has been reported to be anywhere from 1-11%.[28, 31]

Immunosuppression may induce new lesions or cause preexisting lesions to flare. New lesions of porokeratosis have occurred as quickly as 4 months after initiation of immunosuppressive therapy, or as long as 14 years[31, 33] and may resolve following cessation of immunosuppressive therapy.[34, 35]

Trauma, such as a burn, may also trigger porokeratosis.[37]

Etiology

Risk factors for porokeratosis include genetic inheritance, ultraviolet light exposure, and immunosuppression. One study found that approximately 10% of patients who had undergone renal transplantation developed porokeratosis.[28]

Classic porokeratosis (Mibelli)

Autosomal dominant inheritance and immunosuppression are the usual causes. Porokeratosis of Mibelli (PM) has been seen following radiation therapy, at burn wounds, and at hemodialysis sites.

Disseminated superficial (actinic) porokeratosis

Sun exposure and/or artificial ultraviolet radiation exposure in a patient who is genetically predisposed causes disseminated superficial actinic porokeratosis (DSAP). Exacerbations have been reported following prolonged sun exposure, repeated tanning bed exposure, electron beam radiation therapy, and therapeutic phototherapy or photochemotherapy for psoriasis. Drug-induced photosensitivity may play a role. Protection from ultraviolet radiation may lead to spontaneous resolution. Additionally, immunosuppression predisposes patients to both DSAP and nonactinic disseminated superficial porokeratosis (DSP).

Linear porokeratosis

No definite inheritance pattern has been established. Loss of heterozygosity has been proposed as a genetic mechanism and may explain the higher risk of malignant degeneration seen in linear porokeratosis in comparison to other forms of porokeratosis.

Porokeratosis palmaris et plantaris disseminata

Familial porokeratosis palmaris et plantaris disseminata (PPPD) is transmitted in an autosomal dominant mode with variable penetrance. Acquired PPPD may be caused by immunosuppression, or it may be a cutaneous marker of internal malignancy.

Punctate porokeratosis

This condition has no unique inheritance pattern and is usually associated with other forms of porokeratosis.

Hyperkeratotic porokeratosis

A case report on hyperkeratotic porokeratosis describes hepatitis C virus (HCV) infection as a link between the immunosuppressed state and development of acquired porokeratosis. A rare case of a hyperkeratotic variant has been described in a patient with known HIV and HCV infections and a coexisting therapy-related immunosuppressed state.[38]

Epidemiology

Frequency

Disseminated superficial actinic porokeratosis (DSAP) and porokeratosis of Mibelli (PM) are the most commonly seen variants. The other forms of porokeratosis are rare.

Race

Porokeratosis most commonly occurs in fair-skinned individuals. Porokeratosis is rare in darker-skinned populations.

Sex

PM and porokeratosis palmaris et plantaris disseminata (PPPD) affect men twice as often as women.

DSAP is twice as likely to develop in women compared with men.[33]

Linear porokeratosis is seen with equal incidence in men and women.

Age

PPPD and linear porokeratosis may be seen at any age, from birth to adulthood.

PM usually develops in childhood.

Disseminated superficial porokeratosis (DSP) generally develops in the third or fourth decade of life.

Prognosis

The prognosis is generally excellent. This is especially true for disseminated superficial porokeratosis (DSP).

Large lesions of porokeratosis, linear porokeratosis, or porokeratosis in an immunocompromised patients should be monitored carefully for the development of cutaneous malignancies within the porokeratosis lesions. Malignant transformation can occur in about 7.5% of patients.[39, 40, 41] Lesions that are large, long-standing, or linear have the greatest risk of developing an associated malignancy.[42] Chromosomal instability and reduced immune surveillance with overexpression of p53 are hypothesized to play a role in the development of cutaneous malignancies within porokeratosis.[43, 44, 45, 46, 47]

Porokeratosis of Mibelli (PM) circumferentially involving the digits may induce pseudoainhum. Most lesions are asymptomatic. Ulcerative lesions have been described. Giant PM in a facial or acral location may cause destruction of underlying soft tissue or pseudoainhum with amputation.[48]

Very rarely, porokeratosis-associated squamous cell carcinomas may metastasize and cause death.[49, 50]

Patient Education

Patients must practice strict sun precautions. These measures include wearing protective clothing; applying sunblock; avoiding exposure to midday sunlight; and discontinuing exposure to artificial ultraviolet light, such as tanning beds and therapeutic phototherapy.

Consideration for vitamin D3 supplementation should be made given the need for careful sun avoidance and protection.

Patients must periodically examine their skin for lesions suggestive of malignancy. A qualified physician should promptly evaluate any change in a porokeratosis lesion.

Family members should be examined for porokeratosis if familial porokeratosis is suspected.

 

Presentation

History

Classic porokeratosis (Mibelli)

Porokeratosis of Mibelli (PM) is the second most common form of porokeratosis, accounting for about a third of reported cases.[51] It is seen in men more than twice as often as women and may first appear in childhood or young adulthood. PM initially appears as a small, asymptomatic, or slightly pruritic lesion develops that slowly expands over a period of years. Less commonly, lesions may develop during adulthood and enlarge rapidly, usually in the clinical setting of immunosuppression. Occasionally, patients have a history of an antecedent trauma, such as a burn wound.

Most PM lesions reach several centimeters in diameter, although “giant porokeratosis” lesions might grow to 10 cm or 20 cm.[52] Classically, PM lesions are located on an extremities, although they may occur anywhere, including the palms, soles, genitalia, or mucous membranes.[51, 53, 54] The center of the lesion may be slightly hypopigmented or hyperpigmented, minimally scaly, slightly atrophic, and hairless. Occasionally lesions may be confluent thick hyperkeratotic or verrucous plaques.[55, 56]

Disseminated superficial (actinic) porokeratosis

Disseminated superficial (actinic) porokeratosis (DSAP) is the most common form of porokeratosis, and may account for almost half of all cases.[51] Patients develop a few to several dozen tan, annular macules with raised peripheral ridges, developing predominantly on the distal extensor surfaces of the legs and the arms. Palms and soles are spared, and facial lesions may be seen in less than 15% of patients. Hyperkeratotic variants have been described.[57] The lesions are usually asymptomatic, but they may itch or sting slightly.[57] Extensive exposure to natural or artificial ultraviolet radiation may trigger or worsen DSAP.

The cornoid lamellae may be stained and accentuated by sunless tanning lotions containing dihydroxyacetone.

Patients are typically women in their third or fourth decade of life, with a history of ultraviolet light exposure. Patients may have a history of phototherapy for psoriasis. There is frequently a family history of DSAP, especially in other females in the family.

Lesions of disseminated superficial porokeratosis (non-actinic) appear very similar except in a generalized distribution. Patients with DSP may be more likely to be immunosuppressed and to be less likely to have worsening with sun exposure than patients with DSAP.[58]

Linear porokeratosis

Linear porokeratosis lesions typically develop during infancy or early childhood and may represent a segmental form of disseminated superficial porokeratosis (DSP).[20, 59] Females are slightly more likely to be affected than males.[31] Lesions arise usually as unilateral reddish brown patches or linear keratotic papules and plaques that are typically distributed along the lines of Blaschko, suggesting cutaneous mosaicism. Less commonly, patients may have bilateral involvement with a generalized or systematized forms.

All cases of linear porokeratosis have a higher risk of malignant degeneration than other forms of porokeratosis, possibly because of the allelic loss hypothesized to be at fault for the formation of the lesions.

Porokeratosis palmaris et plantaris disseminata

Small, relatively uniform lesions first develop in adolescence or early adulthood on the palms and the soles. They may then spread in a more generalized distribution, occasionally along lines of Blaschko. The lesions are usually asymptomatic, but they may itch or be tender to palpation and plantar lesions may cause discomfort with walking. Disseminated areas of involvement may include the mucosal membranes, where they occur as multiple small, depressed, opalescent rings with hyperemic borders.[60] Males are affected twice as often as females.

Punctate porokeratosis

Punctate porokeratosis presents as multiple, asymptomatic, tiny, hyperkeratotic papules with thin, raised margins developing on the palms and the soles during adulthood. Some authors consider this to be a forme fruste of porokeratosis palmaris et plantaris disseminata (PPPD), rather than a separate entity.[61]

Other variants

Porokeratosis ptychotropica presents with inflammatory keratotic plaques with histopathologic foci of cornoid lamellae on the buttocks or genitals, and may be mistaken for psoriasis.[62, 63]

Follicular porokeratosis is described as an eruptive papular porokeratosis in the setting of DSP. Porokeratosis may occur syndromically with craniosynostosis and anal anomalies (CAP syndrome).[64]

Porokeratotic adnexal osteal nevus is the name proposed to incorporate porokeratotic eccrine ostial and dermal duct nevus (PEODDN) and porokeratotic eccrine and hair follicle nevus (PEHFN). It is considered a congenital lesion, usually developing during infancy or childhood. Lesions consist of hyperkeratotic papules and plaques, and occasionally punctate pits filled with a comedolike keratin plug. It develops typically on the distal extremities, although proximal extremities, trunk, and face may be involved. During the neonatal period, the lesions may initially appear as erosions. Lesions are often aligned along the lines of Blaschko and may extend into nailbeds. See the image below.

A young boy with a linear lesion of porokeratotic A young boy with a linear lesion of porokeratotic eccrine ostial and dermal duct nevus extending onto the nailbed, causing pterygium formation.

Physical Examination

Classic porokeratosis (Mibelli)

The lesion develops as a small, light brown, keratotic papule that slowly expands to form an irregularly shaped, annular plaque with a raised, ridgelike border. This border may be hypertrophic or verrucous and may be greater than 1 mm in height. A thin furrow is typically seen in the center of the ridge, causing a Great Wall of China effect. The lesion is slightly hypopigmented or hyperpigmented, minimally scaly, slightly atrophic, hairless, and anhidrotic. The size may vary from a few millimeters to several centimeters.

Lesions may be found anywhere, including the mucous membranes, although they most commonly occur on the extremities. Generally, few lesions are observed. Porokeratosis ptychotropica is a verrucous variant that is localized to the buttocks and clinically resembles psoriasis. Note the image below.

Porokeratosis of Mibelli on the lower leg in a ren Porokeratosis of Mibelli on the lower leg in a renal transplant recipient.

Disseminated superficial (actinic) porokeratosis

Dozens of small, indistinct, light brown patches with a threadlike border are seen on the extensor surfaces of the arms and the legs.

Facial lesions are seen in approximately 15% of patients. Nonactinic disseminated superficial porokeratosis (DSP) has a generalized distribution, sparing the palms and the soles. Bullous and pruritic variants have been described. Note the images below.

Disseminated superficial actinic porokeratosis on Disseminated superficial actinic porokeratosis on the lower legs of a female patient.
A 42-year-old woman with multiple lesions on the p A 42-year-old woman with multiple lesions on the pretibial aspects of the legs.

Linear porokeratosis

Grouped, linearly arranged, annular papules and plaques with the characteristic raised peripheral ridge are seen unilaterally on an extremity, the trunk, and/or the head and neck area. The lesions commonly follow a dermatomal or blaschkoid distribution, and they may arise initially as reddish-brown patches.

Multiple linear groups may be seen in one patient. They may be seen in association with other forms of porokeratosis. Individual lesions within the linear grouping have a well-developed border, often with a central furrow similar to that seen in classic porokeratosis of Mibelli (PM).

Clinical changes consistent with the development of a basal or squamous cell carcinoma are more common in linear porokeratosis than in other forms of porokeratosis.

Porokeratosis palmaris et plantaris disseminata

The lesions are small, superficial, relatively uniform, with a slightly hyperpigmented, atrophic center and a minimally raised peripheral ridge. Mucosal lesions are small, annular or serpiginous, and pale. Squamous cell carcinoma has been reported to develop within lesions of porokeratosis palmaris et plantaris disseminata (PPPD).

Punctate porokeratosis

Dozens of discrete or grouped seedlike hyperkeratotic lesions with characteristic thin, raised ridgelike margins develop on the palms and the soles. Patients usually have other forms of porokeratosis as well, most commonly the linear or Mibelli types. Punctate porokeratosis may be clinically and histologically indistinguishable from punctate porokeratotic keratoderma, which is considered to be a cutaneous sign of an internal malignancy.

Punctate follicular porokeratosis

Follicular involvement is contiguous with an annular cornoid lamella. It can have the appearance of multiple static perifollicular punctate keratotic lesions that occur in a patch distant from the usual location of keratosis pilaris on the lateral upper arms or anterior lateral thighs.[10]

Other variants

Porokeratosis ptychotropica presents with multiple plaques involving the medial buttocks and gluteal cleft, clinically resembling psoriasis.

Patients with porokeratotic adnexal ostial nevus develop hyperkeratotic papules and plaques, and occasionally punctate pits filled with a comedolike keratin plug. The lesions are typically on the extremities and occasionally the trunk and/or face. If present at birth, they may present as erosions that evolve into darker brown, well-marginated linear plaques. Pterygium formation can occur if lesions extend into the nail bed. Lesions are often distributed along the lines of Blaschko.

Rare case reports of porokeratotic adnexal ostial nevus (PAON) describe other findings, including psoriasis, focal anhidrosis, developmental delay, seizures, scoliosis, hemiparesis, polyneuropathy, hyperthyroidism, hearing loss, and breast hypoplasia. Squamous cell carcinoma has been reported to develop within well-established lesions. Additionally, late-onset lesions developing during adulthood may be clinically indistinguishable from PPPD.[65]

Complications

The most important complication to watch for is the development of cutaneous malignancy. Functional impairment due to involvement of critical anatomical locations may develop. Prophylactic excision could be considered in appropriate situations.

 

DDx

Diagnostic Considerations

Dermoscopy shows a "white track" structure at the periphery of the lesion, corresponding to the cornoid lamella. Occasionally the white track may be a double white track, with brownish discoloration within the furrow, especially in larger lesions such as porokeratosis of Mibelli (PM). The center may show a white homogeneous area, corresponding to an atrophic epithelium. Red dots, globules, and lines corresponding to enlarged capillary vessels that can be seen through the atrophic epithelium.[66]

The dermatoscopic features of the cornoid lamella can be accentuated using marker ink. This also highlights the presence of hair follicles and acrosyringia, some with keratotic plugs.[67]

In terms of modalities to visualize a cornoid lamellae, incisional biopsy perpendicular to the border is preferred over punch biopsy as one may lose the coronoid lamellae during processing of the punch biopsy specimen.[1]

However, a 2016 article illustrates a new biopsy technique that allows for proper orientation of the specimen during processing of PM. The authors propose a three-step technique: (1) draw a line perpendicular to the rim of the lesions, (2) then perform a punch centered at the intersection of the drawn line and coronoid lamellae, (3) then section along the perpendicular line. The laboratory acquisition should mention transection, and the cut sides should be placed down when processed.[68]

Differential Diagnoses

 

Workup

Laboratory Studies

Generally, no laboratory studies are required. Screening for diseases causing immunosuppression (eg, HIV, hematologic malignancies) and/or renal failure is appropriate when new lesions of classic porokeratosis of Mibelli (PM) or disseminated superficial porokeratosis (DSP) are seen or when sudden exacerbation of any form of porokeratosis develops.

Histologic Findings

The cornoid lamella is the histopathologic hallmark of all forms of porokeratosis. It is essential that a biopsy specimen be taken from the peripheral, raised, hyperkeratotic ridge to demonstrate this finding.

The cornoid lamella consists of a thin column of tightly packed parakeratotic cells within a keratin-filled epidermal invagination. The parakeratotic column extends at an angle away from the center of the lesion and develops from the interfollicular epidermis, but it may involve the ostia of hair follicles or sweat ducts. Within the parakeratotic column, the horny cells appear homogeneous and possess deeply basophilic pyknotic nuclei. In the epidermis beneath the parakeratotic column, the keratinocytes are irregularly arranged and have pyknotic nuclei with perinuclear edema. No granular layer is seen within the parakeratotic column, while the keratin-filled invagination of the epidermis has a well-developed granular layer.

The papillary dermis beneath the cornoid lamella contains a moderately dense, lymphocytic infiltrate and dilated capillaries. Dermal amyloid deposits have been described in some cases of disseminated superficial actinic porokeratosis (DSAP). They have also been described in the intertriginous portion of porokeratosis ptychotropica, suggesting a role for friction in pathogenesis of this variant of PM.[62]

Specimens taken from the center of the lesion show atrophy, with areas of liquefaction degeneration in the basal layer, colloid-body formation, and flattening of rete ridges. The dermis may be edematous or fibrotic with telangiectasia. Amyloid deposition may be seen in the papillary dermis, both centrally and beneath the cornoid lamellae. The cornoid lamella is prominent in PM but less distinct in DSAP, DSP, and porokeratosis palmaris et plantaris disseminata (PPPD). At the ultrastructural level, vacuolization of keratinocytes, clumping of keratin filaments, and a paucity of lamellar bodies are found. Intercellular lamellar sheets are incompletely formed and may be responsible for defective desquamation.

Immunohistochemical studies show that keratinocytes beneath the cornoid lamella stain in a pattern similar to that observed in squamous cell carcinomas. The parakeratosis appears to be the result of faulty maturation of keratinocytes, rather than an increased rate of proliferation.[11] Keratinocytes central to the cornoid lamella stain in a pattern identical to that of premalignant lesions, such as actinic keratosis. Keratinocytes peripheral to the cornoid lamella stain normally.

Recent studies showing reduced bleomycin hydralase expression in porokeratosis lesions support the hypothesis that the pathogenesis of porokeratosis involves a defect in the late stage of epidermal differentiation.[12]

 

Treatment

Medical Care

The approach to treatment must be individualized, based on the size of the lesion and the anatomical location, the functional and aesthetic considerations, the risk of malignancy, and the patient's preference. Protection from the sun, use of emollients, and watchful observation for signs of malignant degeneration may be all that is needed for many patients. If lesions are widespread and medical treatment is desired, several medications have potential benefit.

Topical 5-fluorouracil

Topical 5-fluorouracil can induce remission in all forms of porokeratosis.[69, 70] Treatment must be continued until a brisk inflammatory reaction is obtained. Enhancement of penetration, which heightens the response, may be achieved by occlusion or the addition of topical tretinoin, tazarotene, or salicylic acid.[71] Recurrences may be seen.

Topical vitamin D-3 analogues

Both calcipotriol and tacalcitol have been shown to be effective after 3-6 months of treatment of disseminated superficial actinic porokeratosis (DSAP).[72, 73, 74]

Immunomodulators

Topical imiquimod cream has been shown to be effective for treating classic porokeratosis of Mibelli (PM).[75, 76]

Ingenol mebutate has shown efficacy in the treatment of PM.[77]

Calcineurin inhibitors

Tacrolimus (0.1%) was shown to be effective for treating linear porokeratosis. A single case report showed complete resolution of associated pain, pruritus, and paresthesias, as well as cosmetic improvement.[78]

Topical retinoids

Topically applied retinoids (tretinoin, tazarotene) may be beneficial for improving the abnormality in keratinization that causes cornoid lamellation, thereby reducing the hyperkeratosis of the edge of the lesions. It is also thought to improve the percutaneous absorption of other topically applied medications, rendering them somewhat more effective.

Diclofenac gel

Diclofenac gel 3% (Solaraze), may be effective for DSAP.[79]

Oral retinoids

The use of oral retinoids (isotretinoin, etretinate, and acitretin) in patients who are immunosuppressed, who are at higher risk for malignant degeneration, may reduce the risk of carcinoma in porokeratotic lesions.

Oral isotretinoin at 20 mg daily combined with topical 5-fluorouracil is reported to be effective for DSAP and porokeratosis palmaris et plantaris disseminata (PPPD), but it causes burning, itching, and painful erosions.

Prior to the removal of etretinate from the US market, conflicting reports of etretinate efficacy were published. Reports of etretinate efficacy are conflicting. Etretinate at doses of 75 mg/d for 1 week followed by 50 mg/d was shown to be helpful in linear porokeratosis and symptomatic PM. Higher doses of 1 mg/kg/d were reported to exacerbate lesions of DSAP after 4-6 weeks of treatment.[80] Even when etretinate therapy is successful, relapses may occur. Digitate keratoses were reported to develop after the use of etretinate for DSAP.[81]

Acitretin, a second-generation monoaromatic retinoid that is the active metabolite of etretinate, is likely to have results similar to those of etretinate. A case of systematized linear porokeratosis with good response to acitretin has been reported.[82, 83]

Surgical Care

Surgical treatment is essential for porokeratosis lesions that have undergone malignant transformation. No studies showing the value of prophylactic nonexcisional surgical treatment in reducing the incidence of malignancy within porokeratosis have been reported. Surgical modalities other than excision may improve cosmesis and/or function but are frequently followed by relapses.

Excision is most appropriate when malignant degeneration develops.

Cryotherapy is helpful for porokeratosis lesions with minimally raised cornoid lamellae, such as disseminated superficial actinic porokeratosis (DSAP) and porokeratosis palmaris et plantaris disseminata (PPPD). It is a minimally invasive method of inducing resolution for large numbers of lesions.

Electrodesiccation and curettage can be used to treat small lesions or when cryosurgery is ineffective.

Diamond fraise dermabrasion has been used with conflicting reports of efficacy. It was effective in improving the appearance of linear porokeratosis in one patient, but a child with a large porokeratosis of Mibelli (PM) lesion had recurrence after treatment.[84]

Various types of laser therapy have been used. A rapid recurrence reportedly followed carbon dioxide laser ablation. The 585 nm flashlamp-pumped pulsed dye laser was shown to help one patient with linear porokeratosis. Another patient with PM with an underlying hemangioma had good improvement of the hemangioma but no change in the porokeratosis after treatment. The frequency-doubled Nd:YAG laser was shown to be helpful for one patient with disseminated superficial porokeratosis (DSP). Two cases of disseminated superficial actinic porokeratosis were successfully treated with the 1927-nm thulium fiber fractional laser.[85] The Q-switched ruby laser has been reported to be effective in the treatment of DSAP and PM. Benefits of laser therapy include convenience and safety, with nearly no downtime or morbidity associated with pigment or textural changes.[85, 86, 87]

Ultrasonic surgical aspiration was shown to be effective in the treatment of vulvar porokeratosis in one patient.

Photodynamic therapy with methyl aminolevulinate has been reported to be successful for DSAP and linear porokeratosis.[88]

Long-Term Monitoring

Regularly monitoring patients for the development of malignant transformation is essential, especially in the setting of immunosuppression. Squamous cell or basal cell carcinomas can be aggressive in patients who are immunosuppressed.

 

Medication

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications. Topically applied agents that might yield improvement in some patients include topical 5-fluorouracil, topical vitamin D-3 analogues, topical immunomodulators (imiquimod), and topical retinoids.

Antineoplastics, Antimetabolite

Class Summary

These agents inhibit cell growth and proliferation.

Fluorouracil topical (Efudex, Carac, Fluoroplex)

Fluorouracil is preferentially taken up by cells that are dividing abnormally and rapidly; it interferes with DNA and RNA synthesis and leads to death of the abnormal cells. Fluorouracil 5% cream is most commonly used.; 1% cream may be used in thin-skinned areas.

Vitamins, Fat-Soluble

Class Summary

These agents regulate calcium-induced keratinocyte differentiation. Tacalcitol has been used, but it is not available in the United States.

Calcipotriene cream 0.005% (Dovonex, Calcitrene, Sorilux)

Calcipotriene cream 0.005% is a synthetic vitamin D-3 analog that regulates skin cell production and development. It is approved for the treatment of psoriasis and has been reported to be helpful in DSAP.

Retinoid-like Agents

Class Summary

These agents decrease the cohesiveness of abnormal hyperproliferative keratinocytes and may reduce the potential for malignant degeneration. They modulate keratinocyte differentiation and have been shown to reduce the risk of skin cancer formation in patients who have undergone renal transplantation.

Tretinoin topical (Retin-A, Renova, Atralin, Tretin X)

Tretinoin topical inhibits microcomedo formation and eliminates lesions. It makes keratinocytes in sebaceous follicles less adherent and easier to remove. It is used primarily to treat acne but has beneficial effects on actinic keratoses and may reduce the malignant potential of porokeratosis. Tretinoin topical is available as 0.025%, 0.05%, and 0.1% creams and 0.01% and 0.025% gels.

Isotretinoin (Amnesteem, Claravis, Myorisan, Sotrel)

Isotretinoin is an oral agent that treats serious dermatologic conditions. It is a synthetic 13-cis isomer of naturally occurring tretinoin (trans-retinoic acid). Both agents are structurally related to vitamin A. Isotretinoin decreases sebaceous gland size and sebum production. It may inhibit sebaceous gland differentiation and abnormal keratinization. It treats severe recalcitrant cystic acne and appears to help in the treatment of porokeratosis.

A US Food and Drug Administration–mandated registry is now in place for all individuals prescribing, dispensing, or taking isotretinoin. For more information on this registry, see iPLEDGE. This registry aims to further decrease the risk of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy.

Acitretin (Soriatane)

Acitretin is a second-generation monoaromatic retinoid and active metabolite of etretinate. It has demonstrated clinical effects close to those seen with etretinate. Its mechanism of action is unknown. No studies have looked at its effect on porokeratosis.

Immunomodulators

Class Summary

These agents modulate processes that promote immune reactions resulting from diverse stimuli.

Imiquimod 5% cream (Aldara, Zyclara)

Imiquimod induces the secretion of interferon-alpha and other cytokines; its mechanism of action is unknown.

Ingenol mebutate topical (Picato)

Ingenol mebutate is an extract from the sap of the noninvasive weed Euphorbia peplus. Its direct effect is related to destruction of the plasma membrane, swelling of the mitochondria, and then cell death via necrosis. It has been shown to have efficacy in the treatment of porokeratosis of Mibelli, used for 3 days for 2 cycles 1 month apart.

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

Class Summary

Nonsteroidal anti-inflammatory drugs (NSAIDs) are most commonly used for relief of mild to moderately severe pain. Although the pain-relieving effects tend to be patient-specific, ibuprofen is usually used for initial therapy.

Diclofenac topical (Flector Transdermal Patch, Pennsaid topical solution, Solaraze Gel)

This is one of a series of phenylacetic acids that has demonstrated anti-inflammatory and analgesic properties in pharmacological studies. It is believed to inhibit the enzyme cyclooxygenase, which is essential in the biosynthesis of prostaglandins. Diclofenac gel 3% may be effective for DSAP.

Calcineurin Inhibitors

Class Summary

These agents suppress the immune system by preventing interleukin-2 production in T cells.

Tacrolimus ointment (Protopic)

Tacrolimus is hypothesized to amplify the innate immune response in keratinocytes and prevent the proliferation of the abnormal keratinocytes, thus leading to the improvement in lesions. However, further research and controlled studies with a larger patient population and long-term follow up are needed to evaluate its true effectiveness.

 

Questions & Answers

Overview

What is porokeratosis?

What are most common forms of porokeratosis?

What are the less common forms of porokeratosis?

What is the pathophysiology of porokeratosis?

What are other trigger factors of porokeratosis?

What are the risk factors for porokeratosis?

What causes classic porokeratosis of Mibelli (PM)?

What causes disseminated superficial actinic porokeratosis (DSAP)?

What causes linear porokeratosis?

What causes porokeratosis palmaris et plantaris disseminata (PPPD)?

What causes punctate porokeratosis?

What causes hyperkeratotic porokeratosis?

What is the prevalence of porokeratosis?

What are the racial predilections of porokeratosis?

What is the sexual predilection of porokeratosis?

Which age groups have the highest prevalence of porokeratosis?

What is the prognosis of porokeratosis?

What is included in patient education about porokeratosis?

Presentation

Which clinical history findings are characteristic of classic porokeratosis of Mibelli (PM)?

Which clinical history findings are characteristic of disseminated superficial actinic porokeratosis (DSAP)?

Which clinical history findings are characteristic of disseminated superficial porokeratosis (DSP)?

Which clinical history findings are characteristic of linear porokeratosis?

Which clinical history findings are characteristic of porokeratosis palmaris et plantaris disseminata (PPPD)?

Which clinical history findings are characteristic of punctate porokeratosis?

Which clinical history findings are characteristic of less common variants of porokeratosis?

Which physical findings are characteristic of classic porokeratosis of Mibelli (PM)?

Which physical findings are characteristic of disseminated superficial actinic porokeratosis (DSAP)?

Which physical findings are characteristic of linear porokeratosis?

Which physical findings are characteristic of porokeratosis palmaris et plantaris disseminata (PPPD)?

Which physical findings are characteristic of punctate porokeratosis?

Which physical findings are characteristic of punctate follicular porokeratosis?

Which physical findings are characteristic of the less common variants of porokeratosis?

What are the possible complications of porokeratosis?

DDX

What is the role of dermoscopy in the diagnosis of porokeratosis?

Which biopsy technique should be used in the workup of porokeratosis?

What are the differential diagnoses for Porokeratosis?

Workup

What is the role of lab testing in the workup of porokeratosis?

Which histologic findings are characteristic of porokeratosis?

Treatment

How is porokeratosis treated?

What is the role of topical 5-fluorouracil in the treatment of porokeratosis?

What is the role of topical vitamin D-3 analogues in the treatment of porokeratosis?

What is the role of immunomodulators in the treatment of porokeratosis?

What is the role of calcineurin inhibitors in the treatment of porokeratosis?

What is the role of topical retinoids in the treatment of porokeratosis?

What is the role of diclofenac gel in the treatment of porokeratosis?

What is the role of oral retinoids in the treatment of porokeratosis?

What is the role of surgery in the treatment of porokeratosis?

What is the role of laser therapy in the treatment of porokeratosis?

What is included in the long-term monitoring of patients with porokeratosis?

Medications

Which medications are used for the treatment of porokeratosis?

Which medications in the drug class Calcineurin Inhibitors are used in the treatment of Porokeratosis?

Which medications in the drug class Nonsteroidal Anti-inflammatory Drugs (NSAIDs) are used in the treatment of Porokeratosis?

Which medications in the drug class Immunomodulators are used in the treatment of Porokeratosis?

Which medications in the drug class Retinoid-like Agents are used in the treatment of Porokeratosis?

Which medications in the drug class Vitamins, Fat-Soluble are used in the treatment of Porokeratosis?

Which medications in the drug class Antineoplastics, Antimetabolite are used in the treatment of Porokeratosis?