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.[1] The term porokeratosis is actually a misnomer; it was erroneously coined on the assumption that the cornoid lamella emerged from pores of the sweat glands.[2] Multiple clinical variants of porokeratosis are recognized, the most common of which are the following:
A patient may develop more than one type of porokeratosis simultaneously or consecutively.[4] Malignancy (typically squamous cell carcinoma [SCC]) may develop within lesions of porokeratosis.
Less commonly reported clinical entities that share the histopathologic characteristic of cornoid lamellation include the following:
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.[2] 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 (UV) radiation, and immunosuppression.
Inherited or sporadic genetic defects, possibly affecting immune function 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 DSAP, DSP, and PPPD.[13, 14, 15, 16, 17, 18, 19] The focal variants of porokeratosis (PM and linear porokeratosis) may occur through mosaicism, in which somatic mutations cause focal loss of heterozygosity.[20]
Genetic mutations in SART3MVK genes have been found in DSAP pedigrees.[21] DSAP has been shown to originate from a postnatal keratinocyte clone with a different second-hit genetic event in the wild-type allele of the corresponding gene.[22, 23]
A somatic mutation in GJB2 associated with keratosis-ichthyosis-deafness syndrome has been found to cause porokeratotic eccrine ostial and dermal duct nevus.[24]
Natural or artificial UV 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, though the sparing of facial skin in most patients remains to be explained.
Immunosuppression associated with porokeratosis may be secondary to a disease process or medications. Diseases reported in association with porokeratosis include the following:
Immunomodulating drugs used to treat autoimmune diseases or to prevent organ transplant rejection may also trigger porokeratosis.[30, 31] Localized cutaneous immunosuppression due to long-term application of a potent topical steroid has been reported to induce PM.[32] The reported incidence of porokeratosis in organ transplant recipients has been in the range of 1-11%.[33, 34]
Immunosuppression may induce new lesions or cause preexisting lesions to flare. New lesions of porokeratosis have occurred as early as 4 months or as late as 14 years after initiation of immunosuppressive therapy,[34, 31] and they may resolve after cessation of such therapy.[35]
Trauma (eg, thermal injury) may also trigger porokeratosis.
Risk factors for porokeratosis include genetic inheritance, UV light exposure, and immunosuppression. One study found that approximately 10% of patients who had undergone renal transplantation developed porokeratosis.[33]
Autosomal dominant inheritance and immunosuppression are the usual causes of PM. This form has been seen after radiation therapy, at burn wounds, and at hemodialysis sites.
Exposure to natural or artificial UV radiation in a patient who is genetically predisposed causes 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 UV radiation may lead to spontaneous resolution. Additionally, immunosuppression predisposes patients to both DSAP and its nonactinic equivalent, DSP.
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 with other forms of porokeratosis.
Familial 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.
This condition has no unique inheritance pattern and is usually associated with other forms of porokeratosis.
Hepatitis C virus (HCV) infection has been suggested as a link between the immunosuppressed state and development of acquired porokeratosis. A case of a hyperkeratotic variant of porokeratosis was described in a patient with known HIV and HCV infections and a coexisting therapy-related immunosuppressed state.[36]
DSAP and PM are the most commonly seen forms of porokeratosis; the other forms are rare.
PPPD and linear porokeratosis may be seen at any age, from birth to adulthood. PM usually develops in childhood. DSP generally develops in the third or fourth decade of life.
PM and PPPD affect men twice as often as women. DSAP is twice as likely to develop in women as compared with men.[31] Linear porokeratosis is seen with equal frequency in men and women.
Porokeratosis most commonly occurs in lighter-skinned individuals; it is rare in darker-skinned populations.
The prognosis is generally excellent, especially for DSP.
Large lesions of porokeratosis, linear porokeratosis, or porokeratosis in an immunocompromised patient should be monitored carefully for the development of cutaneous malignancies within the lesions. Malignant transformation may occur in about 7.5% of patients.[37, 38] Lesions that are large, longstanding, or linear carry the greatest risk for the development of an associated malignancy.[39] Chromosomal instability and reduced immune surveillance with overexpression of p53 are hypothesized to play a role in the development of cutaneous malignancies within porokeratosis.[40]
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.
Very rarely, porokeratosis-associated SCC may metastasize and cause death.[41]
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.
Given the need for careful sun avoidance and protection, it is advisable to consider vitamin D3 supplementation.
Patients should periodically examine their skin for lesions suggestive of malignancy. Any change in a porokeratosis lesion should be promptly evaluated by a qualified physician.
If familial porokeratosis is suspected, family members should be examined for porokeratosis.
Porokeratosis of Mibelli (PM) is the second most common form of porokeratosis, accounting for about a third of reported cases.[42] It is seen in men more than twice as often as in 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, and so-called giant porokeratosis lesions might grow to 10 or even 20 cm.[43] Classically, PM lesions are located on an extremity, though they may also occur on any part of the body, including the palms, soles, genitalia, and mucous membranes.[42] 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.[44, 45]
Disseminated superficial actinic porokeratosis (DSAP) is the most common form of porokeratosis and may account for almost half of all cases.[42] Patients develop a few to several dozen tan, annular macules with raised peripheral ridges, predominantly on the distal extensor surfaces of the legs and the arms. Palms and soles are spared, and facial lesions may be seen in fewer than 15% of patients. Hyperkeratotic variants have been described.[46] The lesions are usually asymptomatic, but they may itch or sting slightly.[46] Extensive exposure to natural or artificial ultraviolet (UV) 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 who have a history of UV 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 nonactinic disseminated superficial porokeratosis (DSP) appear very similar to those of DSAP, but their distribution is generalized. 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.[47]
Linear porokeratosis lesions typically develop during infancy or early childhood and may represent a segmental form of DSP.[20, 48] Females are slightly more likely to be affected than males are.[34] Lesions usually arise 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 form.
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.
In porokeratosis palmaris et plantaris disseminata (PPPD), 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 the 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. Males are affected twice as often as females are.
Punctate porokeratosis presents as multiple asymptomatic, tiny, hyperkeratotic papules with thin, raised margins developing on the palms and the soles during adulthood. Some authors have considered this variant to be a forme fruste of PPPD rather than a separate entity.[49]
Porokeratosis ptychotropica presents with inflammatory keratotic plaques with histopathologic foci of cornoid lamellae on the buttocks or genitals and may be mistaken for psoriasis.[50, 51]
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).[52]
Porokeratotic adnexal osteal nevus (PAON) is a term proposed for incorporating 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. PAON typically develops on the distal extremities, though the 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 nail beds (see the image below).
![]() View Image | Young boy with linear lesion of porokeratotic eccrine ostial and dermal duct nevus extending onto nail bed, causing pterygium formation. |
In PM, 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 exceed 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. It may range in size from a few millimeters to several centimeters.
Lesions may be found anywhere, including the mucous membranes, though they are most commonly located on the extremities (see the image below). Generally, few lesions are observed. Porokeratosis ptychotropica is a verrucous variant that is localized to the buttocks and clinically resembles psoriasis.
![]() View Image | Porokeratosis of Mibelli on lower leg of renal transplant recipient. |
In DSAP, dozens of small, indistinct light-brown patches with a threadlike border are seen on the extensor surfaces of the arms and the legs. (See the images below.) Facial lesions are seen in approximately 15% of patients. DSP has a generalized distribution, sparing the palms and the soles. Bullous and pruritic variants have been described.
![]() View Image | Disseminated superficial actinic porokeratosis on lower legs of female patient. |
![]() View Image | 42-year-old woman with multiple lesions on pretibial aspects of legs. |
Grouped, linearly arranged annular papules and plaques with the characteristic raised peripheral ridge are seen unilaterally on an extremity, the trunk, 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 PM.
Clinical changes consistent with the development of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) are more common in linear porokeratosis than in other forms of porokeratosis.
The lesions of PPPD are small, superficial, and relatively uniform, with a slightly hyperpigmented, atrophic center and a minimally raised peripheral ridge. Mucosal lesions are small, annular or serpiginous, and pale. SCC has been reported to develop within PPPD lesions.
In 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 linear porokeratosis or PM. Punctate porokeratosis may be clinically and histologically indistinguishable from punctate porokeratotic keratoderma, which is considered to be a cutaneous sign of an internal malignancy.
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]
Porokeratosis ptychotropica presents with multiple plaques involving the medial buttocks and gluteal cleft, clinically resembling psoriasis.
Patients with PAON develop hyperkeratotic papules and plaques and, occasionally, punctate pits filled with a comedolike keratin plug. The lesions are typically on the extremities and occasionally on the trunk 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 PAON have described other findings, including psoriasis, focal anhidrosis, developmental delay, seizures, scoliosis, hemiparesis, polyneuropathy, hyperthyroidism, hearing loss, and breast hypoplasia. SCC has been reported to develop within well-established lesions. Additionally, late-onset lesions developing during adulthood may be clinically indistinguishable from those of PPPD.[53]
The most important complication to watch for is the development of cutaneous malignancy. Functional impairment due to involvement of critical anatomic locations may develop. Prophylactic excision could be considered in appropriate situations.
Generally, no laboratory studies are required for the workup of porokeratosis. Screening for diseases causing immunosuppression (eg, HIV infection and hematologic malignancies) 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.
Dermatoscopy (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 PM. The center may show a white homogeneous area, corresponding to an atrophic epithelium. Red dots, globules, and lines corresponding to enlarged capillary vessels can be seen through the atrophic epithelium.[54]
The dermatoscopic features of the cornoid lamella can be accentuated by using marker ink. This also highlights the presence of hair follicles and acrosyringia, some with keratotic plugs.[55]
In terms of modalities for visualizing a cornoid lamella, incisional biopsy perpendicular to the border is generally preferred to punch biopsy because there is a risk that cornoid lamellae may be lost during processing of the punch biopsy specimen.[2] However, a 2016 article described a newer punch biopsy technique that enables proper orientation of the specimen during processing of PM.[56] This technique includes the following three steps:
The laboratory acquisition should mention transection, and the cut sides should be placed down when processed.
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. This 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, whereas 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.[50]
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 carcinoma (SCC). 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.
Studies showing reduced bleomycin hydralase expression in porokeratosis lesions have given support to the hypothesis that the pathogenesis of porokeratosis involves a defect in the late stage of epidermal differentiation.[12]
The approach to treatment must be individualized on the basis of the following factors:
For many patients, protection from the sun, use of emollients, and watchful observation for signs of malignant degeneration may be all that is needed. If lesions are widespread and medical treatment is desired, several medications have potential benefit.[57] For porokeratosis lesions that have undergone malignant transformation, surgical treatment is essential.
Topically applied agents that might yield improvement in some patients include 5-fluorouracil (5-FU), vitamin D3 analogues, immunomodulators (eg, imiquimod), statins plus cholesterol,[58] and retinoids. The use of oral retinoids (isotretinoin, etretinate, and acitretin) in immunosuppressed patients, who are at higher risk for malignant degeneration, may reduce the risk of carcinoma in porokeratotic lesions.
Topical 5-FU can induce remission in all forms of porokeratosis.[59] 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.[60] Recurrences may be seen.
Both calcipotriol and tacalcitol have been shown to be effective after 3-6 months of treatment of disseminated superficial actinic porokeratosis (DSAP).[61, 62, 63]
Topical imiquimod cream has been shown to be effective for treating classic porokeratosis of Mibelli (PM).[64, 65] Ingenol mebutate has shown efficacy in the treatment of PM.[66]
Tacrolimus (0.1%) has been shown to be effective for treating linear porokeratosis. A case report described complete resolution of associated pain, pruritus, and paresthesias, as well as cosmetic improvement.[67]
Topically applied retinoids (eg, tretinoin and tazarotene) may be beneficial for improving the abnormality in keratinization that causes cornoid lamellation, thereby reducing the hyperkeratosis of the edge of the lesions. They are also thought to improve percutaneous absorption of other topically applied medications, thereby rendering these medications somewhat more effective.
Diclofenac gel 3% may be effective for treating DSAP.[68]
Some studies have found value in topical application of a statin combined with cholesterol cream.[58] In one case series, topical lovastatin plus cholesterol yielded near-complete clearance of DSAP and moderate improvement in porokeratosis palmaris et plantaris disseminata (PPPD) and linear keratosis after 4 weeks.[69] A randomized controlled trial found this same combination to be safe and effective but noted that topical lovastatin alone appeared to be as effective as the combination.[70] An open-label split-body clinical trial reported success with a combination of simvastatin and cholesterol.[71]
The combination of oral isotretinoin 20 mg/day and topical 5-FU has been reported to be effective for DSAP and PPPD, but it causes burning, itching, and painful erosions.
Before etretinate was removed from the US market, conflicting reports of its efficacy were published. A regimen of 75 mg/day for 1 week followed by 50 mg/day was shown to be helpful for linear porokeratosis and symptomatic PM. Higher dosages of 1 mg/kg/day were reported to exacerbate DSAP lesions after 4-6 weeks of treatment.[72] Even when etretinate therapy was successful, relapses were noted. Digitate keratoses were reported to develop after the use of etretinate for DSAP.[73]
Acitretin, a second-generation monoaromatic retinoid that is the active metabolite of etretinate, appears to have results similar to those of etretinate. Cases of systematized linear porokeratosis with good response to acitretin have been reported.[74, 75]
Surgical treatment is essential for porokeratosis lesions that have undergone malignant transformation. Excision is most appropriate when malignant degeneration develops. Surgical modalities other than excision may improve cosmesis, function, or both but are frequently followed by relapses. Studies have not shown prophylactic nonexcisional surgical treatment to have value for reducing the incidence of malignancy within porokeratosis.
Cryotherapy is helpful for porokeratosis lesions with minimally raised cornoid lamellae (eg, DSAP and PPPD). It is a minimally invasive method of inducing resolution for large numbers of lesions.
Electrodesiccation and curettage can be used for treatment of small lesions or for cases where 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 PM lesion had recurrence after treatment.[76]
Reported benefits of laser therapy have included convenience and safety, with nearly no downtime or morbidity associated with pigment or textural changes.[77, 78, 79] Various types of laser therapy have been used.
Rapid recurrence was reported after 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. The frequency-doubled Nd:YAG laser was helpful for one patient with disseminated superficial porokeratosis (DSP). Two cases of DSAP were successfully treated with the 1927-nm thulium fiber fractional laser.[77] The Q-switched ruby laser was reported to be effective in the treatment of DSAP and PM.
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.[80]
Regularly monitoring patients for the development of malignant transformation is essential, especially in the setting of immunosuppression. Squamous cell carcinoma (SCC) or basal cell carcinoma (BCC) can be aggressive in patients who are immunosuppressed.
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