Disseminated Superficial Actinic Porokeratosis Research Articles

Malignant Transformation in a Genitocrural Porokeratosis : A Case Report

Porokeratosis is a rare heterogenous group of keratinization disorder with an unclear pathogenesis, and has varied clinical presentations. It may present with annular papules or plaques with central atrophy and clinically and histologically distinct ridge-like border called 'cornoid lamella'. Common variants include porokeratosis of Mibelli (PM), disseminated superficial actinic porokeratosis (DSAP), linear porokeratosis, punctate porokeratosis and porokeratosis palmaris et plantaris disseminata (PPPD). Here we report the case of a 79 year old female, who developed malignancy of porokeratosis over the groin region which had been mismanaged as eczema for many months and has been eventually diagnosed as Squamous cell carcinoma.

Disseminated superficial actinic porokeratosis in an elderly patient undergoing androgen deprivation therapy for advanced prostate cancer: exploring the potential association

Porokeratosis is a group of chronic dermatoses characterized by the presence of cornoid lamellae. Disseminated superficial actinic porokeratosis (DSAP) is a common subtype, presenting as multiple small annular scaly lesions primarily in sun-exposed areas. While previous studies have documented DSAP in prostate cancer patients, the association with androgen deprivation therapy (ADT) has not been reported. In this report, we describe an elderly patient with advanced prostate cancer, who developed DSAP subsequent to undergoing ADT. We present the clinical, dermoscopic, and histopathological evaluations, and discuss the potential role of ADT in the pathogenesis of DSAP.

A Case of Disseminated Superficial Actinic Porokeratosis (DSAP) Following Ultraviolet Light Therapy for Palmoplantar Pustulosis

A Case of Disseminated Superficial Actinic Porokeratosis (DSAP) Following Ultraviolet Light Therapy for Palmoplantar Pustulosis

Disseminated superficial porokeratosis: Impact on quality of life

Disseminated superficial actinic porokeratosis (DSAP) is typically progressive and lifelong,1-3 but little data are available regarding the impact of DSAP on quality of life (QoL). We sought to identify the overall impairment of QoL in patients with DSAP, assess correlations in QoL impairment, and measure the impact of treatment on QoL.

Grenz ray therapy in disseminated superficial actinic porokeratosis: A case series of 17 patients

The treatments available for disseminated superficial actinic porokeratosis (DSAP) have been limited and have variable efficacy. We report the largest case series to date of the use of Grenz ray therapy in 17 patients with DSAP. There was at least 50% improvement in DSAP lesions in all cases. Erythema, itching and burning were common side effects of Grenz ray therapy. We believe that Grenz ray therapy may be an effective treatment option for patients with DSAP.

Circumferential volumetric modulated arc radiotherapy of the lower legs–a technique described in a case of disseminated superficial actinic porokeratosis

A case of a fit 65-year-old male with a long history of recalcitrant Disseminated Superficial Actinic Porokeratosis (DSAP) treated with Volumetric Modulated Arc Radiotherapy (VMAT) is presented. The whole circumference of both lower legs from knees to ankles were simultaneously treated to 43.2 Gray (Gy) in 24 fractions, one fraction short of the prescription dose of 45 Gy in 25 fractions. There was in-field clearance of DSAP at ten weeks. This is the first publication of circumferential VMAT treatment of the skin of the lower legs. More follow up is required to see the durability of control of DSAP, and more research is needed to test the generalisability of this technique.

Dermoscopy of porokeratosis: results from a multicentre study of the International Dermoscopy Society.

The diagnosis of porokeratosis can be challenging, and knowledge about its dermoscopic features is limited. To describe the dermoscopic features of porokeratosis of Mibelli and disseminated superficial actinic porokeratosis (DSAP) and the frequency of these features in a larger case series. The interobserver concordance was also assessed. In this retrospective cohort study, members of the International Dermoscopy Society contributed macroscopic and dermoscopic images of histopathologically verified cases of porokeratosis of Mibelli or DSAP. Three observers independently reviewed the collected images to identify the presence of predefined dermoscopic features. Following this, a consensus meeting was held to agree upon which dermoscopic features were present in each lesion. In total, 78 clinical and dermoscopic images of porokeratoses were collected. The most common dermoscopic feature was keratin rim, which was present in 74 lesions (92.3%). The most common vascular structures were dotted or glomerular vessels which were present in almost half of the cases (48.7%). Other relatively frequent dermoscopic findings were as follows: non-peripheral scales (44.9%), grey-brown dots or pigmentation along the keratin rim (38.5%), and light-brown pigmentation within the keratin rim (33.3%). Shiny white structures and blood spots or erosions along the keratin rim were findings never before described in porokeratosis and were detected in 16.7% and 17.9% of the lesions, respectively. Dermoscopic findings in porokeratosis of Mibelli and DSAP were similar except for fewer blood spots or erosions along the keratin rim and more light-brown pigmentation within the keratin rim in DSAP. The interobserver concordance ranged from 0.44 (moderate) to 0.84 (almost perfect). The dermoscopic hallmark of porokeratosis is the keratin rim, a finding also allowing for almost perfect interobserver agreement. Pigmentation or erosions along the keratin rim, vascular structures, as well as scales, pigmentation or shiny white structures within the keratin rim are additional dermoscopic clues.

The Malignancy Potential of Porokeratosis: A Single-Center Retrospective Study.

BackgroundPorokeratosis (PK) is a rare group of keratinization disorders. While the overall prognosis of PK is favorable, malignant transformation of PK to skin cancer has been reported in 6.9% to 11.6% of the cases. Prior estimates of malignant transformation of PK have been based on reviews of published cases, which introduces possible publication bias. We aim to eliminate this potential bias and quantify the characteristics, risk factors, and malignancy potential of PK.MethodologyA single-center retrospective chart review of patients with a diagnosis of PK was conducted.ResultsIn this study, 6.4% to 16.4% of histologically confirmed PK lesions demonstrated malignant transformation. A higher proportion of disseminated superficial actinic porokeratosis (DSAP) cases (as high as 29.3%) showed malignant transformation compared to PK of Mibelli (as high as 6.0%). Out of the two cases of linear PK, both demonstrated malignant transformation.ConclusionsIn summary, PKs are at risk for malignant transformation, and patients with DSAP and linear PK, in particular, should receive more long-term surveillance. Limitations of this study include the inability to control for confounding factors due to the retrospective nature and the small size of our cohort.

Disseminated superficial actinic porokeratosis in a patient with generalized vitiligo: A case report

Disseminated superficial actinic porokeratosis (DSAP) is the most common type of porokeratosis, occurring mainly on sun-exposed skin. Chronic sun exposure is one of the main risk factors, in addition to genetic susceptibility. Most published data concerning the relationship between vitiligo and its predisposition to nonmelanoma skin cancer suggests that patients with vitiligo show the same or even a lower incidence than other populations. Herein, we report a case of disseminated superficial actinic porokeratosis occurring in vitiligo in which chronic sun exposure was the main risk factor

A case series of disseminated porokeratosis

Porokeratosis is an autosomal dominant disorder of epidermal keratinization resulting from abnormal expansion of latent clones following chronic ultraviolet exposure or immunosuppression. Various clinical and morphological variants of porokeratosis are present, among which disseminated superficial actinic porokeratosis (DSAP) is the most common subtype located predominantly on the sun exposed areas, whereas disseminated superficial porokeratosis (DSP) is present both on the sun exposed and sun protected areas including oral mucosa and genitalia. Porokeratosis is characterized clinically by annular plaques with atrophic center and thready border and histologically by the presence of cornoid lamella. DSAP may be missed because of its inconspicuous nature in dark skinned individuals and may sometimes be mistaken for actinic keratoses in sun-damaged skin. Here, we report a case series of five patients with disseminated porokeratosis with varied presentations.

Cholesterol partially rescues the inhibition effect of pravastatin on keratinocytes proliferation by regulating cell cycle relative proteins through AKT and ERK pathway.

Mevalonate pathway plays a key role in skin physiological process in human. Recently, it has been reported that mutation of some genes in the mevalonate pathway cause disseminated superficial actinic porokeratosis (DSAP). But the pathogenesis is still unknown. Pravastatin (PRA), one of HMG-CoA reductase (HMGCR) inhibitors, has been found to inhibit cells proliferation, including keratinocytes (KCs). In this study, we use PRA to block the mevalonate pathway in KCs with or without the down-stream intermediate products replenishment. The results demonstrated that PRA strongly inhibited proliferation of KCs and caused the G0 /G1 arrest. When some down-stream intermediate products were added, only cholesterol (CH) could partially rescue the inhibition effect of PRA on KCs proliferation, but not other products, such as mevalonic acid, farnesyl pyrophosphate or geranylgeranyl pyrophosphate. Mechanistic analysis revealed that PRA down-regulated expression of cyclin B1, but up-regulated cyclin E and p21 expression. And PRA increased the phosphorylation level of Protein Kinase B (AKT) but decreased the phosphorylation level of Extracellular Signal Regulated Kinase (ERK1/2). CH could attenuate the elevated cyclin E and activated AKT induced by PRA. These results indicated that CH could rescue the proliferation inhibition of KCs caused by PRA, which laid a foundation for elucidating the pathogenesis of DSAP clearly.

868 Pathogenesis based therapy improves cutaneous abnormalities in porokeratosis- A pilot study

Porokeratosis is a heterogenous group of keratinization disorders associated with mevalonate pathway gene mutations. Treatments options for the disease are few and often ineffective. On the basis of the possible pathogenic role of pathway end-product deficiency (cholesterol) and accumulation of toxic precursors, we studied the efficacy of topical lovastatin/cholesterol in different variants of porokeratosis. We recruited 1 patient with disseminated superficial actinic porokeratosis (DSAP), 2 patients with porokeratosis palmaris et plantaris disseminate (PPPD) and 2 patients with linear porokeratosis (LP).

Disseminated Superficial Actinic Porokeratosis in the Elderly: A Case Report

Abstract Currently, most authors believe that disseminated superficial actinic porokeratosis (DSAP) is an inherited or acquired dermatologic disorder of keratinization that occurs in genetically predisposed individuals after adequate exposure to ultraviolet (UV) rays, or immunosuppression. Lesions in DSAP start in sun-exposed areas most commonly in the third or fourth decade of life. The lesions are pink to brownish papules and plaques with a raised scaling ridge, histologically seen as a column of parakeratotic keratinocytes, the cornoid lamella. DSAP is not only the most common, but also the most often overlooked form of porokeratosis (P). Here we present a 77-year-old male with DSAP, who sporadically developed initial skin lesions at the age of 67, at the time when his personal and medical history were significantly long for chronic intensive sun exposure and type 1 insulin dependent diabetes mellitus. We established the diagnosis of DSAP based on personal and medical history, clinical presentation, auxiliary methods such as dermoscopy, and confirmed with pathohistological findings. We advised the patient to avoid sun exposure and to apply photo-protective sunscreens, emollients and keratolytics. After five years of monitoring his changes, we continue to control his lesions for any possible alteration. Although mutations in several genes and data on sun exposure may be responsible for the onset of the disease, most cases of DSPA occur sporadically and without involving the facial skin, as in our case. Lesions usually begin in the third or fourth decade of life. In the elderly, an additional trigger may be present, such as e.g. age-related decreased immune competence. Diabetes mellitus may also be associated with immunodeficiency in the elderly. Recently, DSPA has been a special subtype of DSPA in the elderly. Malignant alteration can occur in DSPA, most commonly in lesions that are long lasting, large, in the elderly, or in lesions in immunocompromised individuals. In conclusion, this is the case of a 77-year-old male person, who sporadically developed the so-called subtype DSPA in the elderly. In addition to UV radiation, the relevant suggestive trigger factors were the immunosuppressive effects of diabetes mellitus and chronological aging.

Disseminated superficial actinic porokeratosis, Bowen's disease and basal cell carcinoma. Coincidence or rare double malignant transformation?

Disseminated superficial actinic porokeratosis (DSAP) is a skin condition that consist of multiple annular, hyperkeratotic lesions. They are usually distributed bilaterally and mostly affect the extremities. DSAPs have a wider distribution than the porokeratosis of Mibelli and usually appears between the age of 40 and 50. Squamous cell carcinoma, Bowen’s disease, and basal cell carcinoma that arises in the classical type of porokeratosis of Mibelli is well-documented, but there are not many reported cases of Bowen’s disease and basal cell carcinoma arising in DSAP. We present a 77-year-old woman in whom the two– Bowen’s disease and Basal cell carcinoma develop in a histologically proven DSAP.

Disseminated superficial porokeratosis and disseminated superficial actinic porokeratosis: A case series of 39 patients

Porokeratosis is characterized by keratotic papules or plaques with a ridge-like border. Both disseminated superficial porokeratosis (DSP) and disseminated superficial actinic porokeratosis (DSAP) manifest as numerous, small, round maculopapules with thin thread-like elevated border but differ in their distribution of lesions and the association with sunlight exposure. To analyze and compare the clinical features of DSP and DSAP, we conducted this hospital-based retrospective study. A total of 39 patients were recruited, including 19 DSP patients and 20 DSAP patients. The median age of diagnosis of DSP and DSAP patients was 63 years and 59 years, respectively. A male predominance was noted in DSP, while a female predominance was noted in DSAP. Itchiness was the most common symptom in both subtypes. Commonly used treatments included corticosteroids and retinoids, both topical and oral. Among the treatments, oral retinoid, diclofenac gel, and cryotherapy showed higher rates of improvement, but none of them yielded complete remission of the skin lesions. In conclusion, DSP and DSAP showed differences in the gender predilection, and both DSP and DSAP had prolonged clinical course and generally refractory to topical or systemic treatments.

Lichenoid inflammation of DSAP lesions following treatment with durvalumab, olaparib and paclitaxel: A potential diagnostic pitfall mimicking lichenoid drug eruptions associated with PDL-1 inhibitors

Disseminated superficial actinic porokeratosis (DSAP) is an uncommon skin condition that can be inherited or may occur sporadically with multiple red-brown, thin plaques in a photodistribution. The condition more often affects middle-aged women and is often recalcitrant to therapy. In rare literature reports, systemic medications can trigger exacerbation or promote inflammation in pre-existing lesions of DSAP. We present a novel case of chemotherapy-associated DSAP inflammation in a 66-year-old woman after triple therapy with durvalumab (PD-L1 inhibitor), olaparib (PARP inhibitor) and paclitaxel, showing similarities to primary lichen planus-like eruption from immune checkpoint inhibitors.

A precancerous skin lesion that is often misdiagnosed.

Disseminated superficial actinic porokeratosis (DSAP) is a precancerous skin condition often seen by dermatologists that is characterised bymultiple annular hyperkeratotic lesions on sun-exposed areas. In Australia, DSAP is not a rare condition, possibly owing to Australia's high levels of sun exposure, and patients with DSAP often initially present to general practitioners (GPs). Alack of awareness about DSAP may result in misdiagnosis and inappropriate management of the condition. The aim of this article is to provide an overview of DSAP relevant to GPs to better facilitate diagnosis, management and referral to a dermatologist. The underlying pathophysiological mechanism of DSAP is unknown. Although there is currently no effective standardised treatment, ongoing management is warranted, given the potential for malignant transformation. Suggested strategies include frequent full skin checks, patient education about sun protection and ablative treatment (such as cryotherapy) if indicated. Suspicious lesions require excision and histopathology.

Effective treatment of disseminated superficial actinic porokeratosis with chemical peels – customary treatment for a rare disease

Background: Disseminated superficial actinic porokeratosis (DSAP) is a rare dermatologic disorder of the epidermis. Often misdiagnosed as chronic UV-damage or actinic keratoses, patients are treated for years with different therapeutic options with little success. Current treatment options include imiquimod, ingenol mebutate, cryosurgery, photodynamic therapy and topical or systemic therapy with retinoids. Since those approaches show only little success or come along with major side effects, therapeutic alternatives are strongly requested. Methods: We report a series of five female patients with history of DSAP that were successfully treated with chemical peels. Results: All patients suffered from the disease for 14.4 years on average and all were refractory to at least two therapeutic options, mostly imiquimod and topical tretinoin. Patients were treated with glycolic acid 50% and salicylic acid 25% in a two-layer-technique. After a mean of three cycles every 6 weeks a clear reduction in lesion was assessed by physicians. Patients were highly satisfied with outcome and rare occurrence of side effects as assessed by TSQM questionnaire. Conclusion: Chemical peels are safe and well tolerated treatment options for patients with refractory porokeratosis. As characteristic for chronic diseases, frequent repetition of treatment is needed in order to control disease activity.

Novel mutations in mevalonate kinase cause disseminated superficial actinic porokeratosis.

Disseminated superficial actinic porokeratosis (DSAP) is a rare autosomal dominant disease. In our previous research, we found that a linkage region of DSAP in a large family is located at 12q23·2-q24·1. Subsequently, the mevalonate kinase gene (MVK) was shown to be pathogenic in DSAP. To elucidate the mechanism by which MVK mutations lead to keratinocyte apoptosis and DSAP, and to report a new missense mutation, c.566 C>T (p.A189V), in MVK in a Chinese DSAP pedigree. The half-life of wild-type (WT) MVK protein and mutants was assessed using cycloheximide treatment of cells. Dimerization of MVK was analysed by coimmunoprecipitation and glutathione S transferase pull-down assay. MVK kinase activity, production of cell cholesterol, mitochondrial complex activity and apoptosis were detected, using the corresponding commercial kits, in cells overexpressing MVK WT and mutants. Mechanically, we demonstrated that both the pathogenic p.A189V mutant and a sporadic mutation p.H312R (c.935A>G), which we reported previously, have rapid degradation, decreased kinase activity and reduced production of cell cholesterol. Also, we found the p.H312R mutation confers on the MVK protein an inability to dimerize. Further, we demonstrated that the mutants are impaired in mitochondrial function and lead to increased apoptosis. Our results provide an important basis for elucidating the mechanism by which MVK missense mutations contribute to DSAP.

Clonal Expansion of Second-Hit Cells with Somatic Recombinations or C>T Transitions Form Porokeratosis in MVD or MVK Mutant Heterozygotes

Patients with disseminated superficial actinic porokeratosis (DSAP) and linear porokeratosis (LP) exhibit monoallelic germline mutations in genes encoding mevalonate pathway enzymes, such as MVD or MVK. Here, we showed that each skin lesion of DSAP exhibited an individual second hit genetic change in the wild-type allele of the corresponding gene specifically in the epidermis, indicating that a postnatal second hit triggering biallelic deficiency of the gene is required for porokeratosis to develop. Most skin lesions exhibited one of two principal second hits, either somatic homologous recombinations rendering the monoallelic mutation biallelic or C>T transition mutations in the wild-type allele. The second hits differed among DSAP lesions but were identical in those of congenital LP, suggesting that DSAP is attributable to sporadic postnatal second hits and congenital LP to a single second hit in the embryonic period. In the characteristic annular skin lesions of DSAP, the central epidermis featured mostly second hit keratinocytes, and that of the annular ring featured a mixture of such cells and naïve keratinocytes, implying that each lesion reflects the clonal expansion of single second hit keratinocytes. DSAP is therefore a benign intraepidermal neoplasia, which can be included in the genetic tumor disorders explicable by Knudson's two-hit hypothesis.