• Many porokeratoses (PKs) are explained by alterations (germinal and/or somatic) in the mevalonate pathway (cholesterol/isoprenoid biosynthesis) with an effect on keratinocyte homeostasis/differentiation. Pietkiewicz 2023 , Kostopoulos-Kanitakis 2025

• In PSDA/DSAP , mutations in MVK (and others of the mevalonate axis) were identified in families and sporadic cases. Zhang 2012

• Genomic studies have broadened the spectrum of genes involved in the pathway (e.g., MVK/PMVK/MVD ) and support the concept of PQ as a mevalonate genodermatosis . Zhang 2015 , Wang 2016

• In linear porokeratosis and some segmental forms, a “second-hit” model (postzygotic mosaicism) is supported by a germinal predisposition for mevalonate. Atzmony 2019 , Jägle 2021

• UV radiation and immunomodulation /immunosuppression act as clinical triggers or amplifiers . Zhang 2012 , Kostopoulos-Kanitakis 2025

• There is a spectrum of drug-induced porokeratosis (multifactorial mechanism), systematically described in the literature. Lu 2021

• Elementary injury
  • Annular papule/plaque or polycyclic with raised keratotic border (“collarette”/crest) and atrophic or hyperpigmented center, sometimes with itching or burning (more frequent in DSAP). Vargas-Mora 2020, Kostopoulos-Kanitakis 2025
• Affected areas (by subtype)
  • DSAP/PSDA: limbs in sun-exposed areas (forearms, legs), outbreaks/accentuation with UV. Zhang 2012, Tan 2025
  • Mibelli: traditional localized, plates with a thicker edge. Vargas-Mora 2020
  • Linear: distribution linear/blaschkoid, often from childhood; increased attention due to cancer risk. Atzmony 2019, Sasson 1996
  • PPPD: palms/soles with scattered lesions; variants have been described with loss of heterozygosity on affected skin. Jägle 2021
  • Ptychotropica: region genitogluteal/intergluteal, verrucous/pruritic plaques; rare and evolving entity. Yeo 2013
• prototypical picture
  • Course chronic, with new lesions in outbreaks or slow peripheral expansion; in DSAP there may be a “field” of multiple small lesions. Vargas-Mora 2020, Tan 2025
• Useful clinical findings
  • El borders (crest) is the best site to confirm with dermatoscopy/biopsy, as it correlates histologically with the cornoid lamella. Pietkiewicz 2023, Vargas-Mora 2020
• Evolution
  • potential of malignant transformation (especially CEC/CBC) in subgroups; requires long-term surveillance. INCI 2023, Sasson 1996
• Atypical forms (practical examples)
  • Giant/extensive plates, segmental, multiple lamellae (ptychotropica), or presentation favored by immunosuppression o drugs. Yeo 2013, Lu 2021, Kostopoulos-Kanitakis 2025

• Tinea corporis: scaly active edge, KOH/PAS positive; not typical cornoid lamella. Vargas-Mora 2020

• Annular granuloma: rings without a prominent keratotic ridge; distinct dermatoscopy; histology is of the granulomatous type. Vargas-Mora 2020

• Actinic keratosis/Bowen's disease: lesions associated with sun exposure, but with diffuse epidermal dysplasia; PQ usually has a focal cornoid lamella and annular clinical presentation. Kostopoulos-Kanitakis 2025

• Annular psoriasis/nummular eczema: morphology and distribution can be confusing; histology does not show a cornoid lamella. Vargas -Mora 2020

• Annular lichen planus: violaceous border, Wickham; typical lichenoid histology. Vargas -Mora 2020

• Histological pattern
  • Keratinization disorder with cornoid lamella as a cardinal finding. Kostopoulos-Kanitakis 2025
• Key findings
  • Parakeratosis column (lamela), with hypogranulosis/absence of granular layer underlying and dyskeratotic keratinocytes; variable superficial dermal infiltrate. Vargas-Mora 2020, Kostopoulos-Kanitakis 2025
  • En ptychotropica have been described multiple cornoid lamellae and verrucous architecture, which can be confused with other anogenital dermatoses.
• Special stains / IF / IHQ
  • Habitually not necessary to diagnose PQ if the biopsy captures the border. Vargas-Mora 2020
  • PAS/GMS They can be useful if the clinical differential includes dermatophytesIHQ reserves the right to evaluate tumor transformation if there is clinical suspicion. Vargas-Mora 2020
• Molecular tests (when they do provide information)
  • Panel/NGS of mevalonate pathway genes (e.g., MVK/PMVK/MVD) can support diagnosis, genetic counseling, and targeted therapies (at centers with availability). Zhang 2012, Zhang 2015, Pietkiewicz 2023

• Actinic keratosis/Bowen: more extensive dysplasia; PQ shows focal “columnar” cornoid lamella. Kostopoulos-Kanitakis 2025

• Wart/condyloma: koilocytic changes; distinct pattern.

• Verrucous epidermal nevus: hyperkeratosis/acanthosis without a typical cornoid lamella. Vargas-Mora 2020

• There are no specific diagnostic laboratory tests for porokeratosis. Vargas-Mora 2020

• In extensive/atypical or recent-onset pemphigus cystic fibrosis (PCF), it is reasonable to document associated factors such as UV exposure , immunosuppression , and transplantation , and to review temporally related medications . Kostopoulos-Kanitakis 2025 , Lu 2021

• Biopsy:
  • Preferred biopsy type
    • Punch (4–6 mm) or incisional taking the hyperkeratotic border and the adjacent center (the cornoid lamella is usually at the edge). Vargas-Mora 2020
    • In a single small lesion with suspected cancer: excisional with narrow diagnostic/therapeutic margins depending on location. Sasson 1996
  • Decision-making considerations
    • Avoid sampling only the atrophic centerbecause the lamella can be lost. Vargas-Mora 2020
    • If there ulceration/rapid growthSample that area + edge to rule out CEC/CBC. INCI 2023, Novice 2021
  • Contraindications
    • No specifics beyond the general ones of the procedure (anticoagulation, local infection, etc.).
  • Fixing/Shipping
    • Formalin  to 10%

In PQs, the evidence is heterogeneous (many case reports/series). Prioritize: photoprotection , field control , subtype-targeted treatment , and oncological surveillance . Weidner 2017 , Tan 2025 , La 2024

• First line (practice)
  • Strict photoprotection + self-assessment education (especially DSAP). Tan 2025
  • Mevalonate-targeted therapy (statin ± cholesterol topicals):
    • DSAP: randomized clinical trial showed improvement with Topical lovastatin 2% (with or without 2% cholesterol), with no clear differences from adding cholesterol. Saint Lucia 2023
    • Previous series supported lovastatin/cholesterol as targeted therapy in variants (DSAP, PPPD, linear). Atzmony 2020
  • Limited injuries: Cryotherapy, laser o targeted ablation Depending on availability/experience, with variable results. Weidner 2017, Tan 2025
• Second and third line (according to subtype and tolerance)
  • Topical or systemic retinoids (field), 5-fluorouracil, imiquimod, vitamin D analogues, photodynamic therapy, CO₂/Er:YAG laseramong others (mostly low-to-moderate and variable evidence). Weidner 2017, First, Tan 2025
  • DSAP: This systematic review summarizes multiple options, but highlights the scarcity of trials high quality. Tan 2025
  • Ptychotropica: randomized (split-body) trial showed efficacy of topical simvastatin with or without cholesterol versus placebo in symptomatic/lesional control. Chen 2025
• General care and safety
  • Topical irritants (5-FU/imiquimod/retinoids): monitor irritant dermatitis, erosions and adhesion. Weidner 2017
  • Systemic retinoids: standard precautions (teratogenicity, lipid/hepatotoxicity) when considered. First
  • Topical statins: in trials/series it was reported good tolerance and absence of serious events, although there may be local discomfort or minor events. Saint Lucia 2023, Farmhouse 2023
• Contraindications (indicative)
  • Systemic retinoids: contraindication in pregnancy (and planning) and caution due to hepatic/lipid comorbidities. First
  • Imiquimod/5-FU: Caution in severe dermatitis/extensive erosions; individualize by location and tolerance. Weidner 2017

• Ulcer, bleeding, new pain, rapid growth, nodule , or marked change within a PQ lesion → immediate biopsy to rule out CSC/CBC. Inc. 2023 , Novice 2021

• Linear PC , large or long-standing lesions : increased surveillance due to oncological risk. Sasson 1996 , Novice 2021

• PQ that appears or worsens with immunosuppression or after starting a drug : reassess exposure and comorbidities. Lu 2021 , Kostopoulos-Kanitakis 2025

• If it “looks like tinea/annular plaque,” ​​but there is a hard keratotic ridge and central atrophy , consider keratoconjunctivitis and examine the border with dermatoscopy. Vargas-Mora 2020

• Biopsies that do not include the margin are the most frequent cause of false negatives (lamella not visible). Vargas-Mora 2020

• In linear/segmental disease, consider mosaicism/second hit (impacts genetic counseling and therapeutic approach). Atzmony 2019

• Pietkiewicz P, et al. Porokeratoses—A Comprehensive Review on the Genetics and Metabolomics, Imaging Methods and Management of Common Clinical Variants. Metabolites. 2023, 13 (12): 1176. DOI: 10.3390/metabo13121176. PMID: 38132857.
  Brief summary: Comprehensive and modern review: genetics (mevalonate), imaging tools (including dermatoscopy) and management by subtypes; useful as a general map for diagnosis/therapy. Pietkiewicz 2023

• Vargas-Mora P, Morgado-Carrasco D, Fustà-Novell X. Porokeratosis: A Review of Its Pathophysiology, Clinical Manifestations, Diagnosis, and Treatment. Actas Dermosifiliogr (Engl Ed). 2020;111(7):545-560. DOI:10.1016/j.ad.2020.03.005. PMID: 32401728.
  Brief summary: Practical clinicopathological review (Spanish/English), with emphasis on variants, histological diagnosis (cornoid lamela) and traditional therapeutic options. Vargas-Mora 2020

• Kostopoulos-Kanitakis KA, Kanitakis J. Porokeratoses: an update on pathogenesis and treatment. Int J Dermatol.2025;64(1):62-71 (Epub 2024). DOI: 10.1111/ijd.17411. PMID: 39129190.
  Brief summary: Update focused on pathogenesis (mevalonate, second hit, triggers) and contemporary therapeutic approach. Kostopoulos-Kanitakis 2025

• Weidner T, Illing T, Miguel D, Elsner P. Treatment of Porokeratosis: A Systematic Review. Am J Clin Dermatol.2017;18(4):435-449. DOI: 10.1007/s40257-017-0271-3. PMID: 28283894.
  Brief summary: Systematic review of treatments (topical, systemic and procedures), highlighting the low overall quality of evidence and variability by subtype. Weidner 2017

• Y, Zhu J, Mueller SM. Conventional and Novel Treatment Strategies for Porokeratoses: A Narrative Review. J Dtsch Dermatol Ges. 2024;22(8):1073-1077. DOI: 10.1111/ddg.15436. PMID: 38961534.
  Brief summary: Narrative review focused on “classic” vs novel strategies (including mevalonate-targeted therapy), with a practical orientation. First

• Zhang SQ, et al. Exome sequencing identifies MVK mutations in disseminated superficial actinic porokeratosis. Nat Genet. 2012;44(10):1156-1160. DOI: 10.1038/ng.2409. PMID: 22983302.
  Brief summary: Key work that identifies mutations in MVK in DSAP and proposes functional mechanisms in keratinocytes and relationship with UV. Zhang 2012

• Zhang Z, et al. Genomic variations of the mevalonate pathway in porokeratosis. eLife. 2015; 4: e06322. DOI:10.7554/eLife.06322. PMID: 26202976.
  Brief summary: Expands the genetic spectrum of mevalonate in PQs; supports common molecular basis between subtypes and pathways for targeted therapies. Zhang 2015

• Wang J, et al. Loss-of-function Mutation in PMVK Causes Autosomal Dominant Disseminated Superficial Porokeratosis. SciRep. 2016; 6: 24226. DOI: 10.1038/srep24226. PMID: 27052676.
  Brief summary: Evidence of PMVK as a causal gene in disseminated forms; integrates cellular and lesion tissue observations. Wang 2016

• Atzmony L, et al. Second-Hit, Postzygotic PMVK and MVD Mutations in Linear Porokeratosis. JAMA Dermatol.2019;155(5):548-555. DOI: 10.1001/jamadermatol.2019.0016. PMID: 30942823.
  Brief summary: It establishes the model of mosaicism/second stroke in linear porokeratosis, linking it to mevalonate genes. Atzmony 2019

• Atzmony L, et al. Topical cholesterol/lovastatin for the treatment of porokeratosis: A pathogenesis-directed therapy. J Am Acad Dermatol. 2020;82(1):123-131. DOI: 10.1016/j.jaad.2019.08.043. PMID: 31449901.
  Brief summary: Clinical series that inaugurates a targeted therapeutic approach (statins + cholesterol) in different subtypes. Atzmony 2020

• Santa Lucia G, et al. Safety and Efficacy of Topical Lovastatin Plus Cholesterol Cream vs Topical Lovastatin Cream Alone for the Treatment of DSAP: A Randomized Clinical Trial. JAMA Dermatol. 2023;159(5):488-495. DOI:10.1001/jamadermatol.2023.0205. PMID: 36947042.
  Brief summary: Randomized trial in DSAP: both arms (lovastatin alone vs combination) improve; guides formulation and realistic expectations. Saint Lucia 2023

• Casale F, et al. Efficacy of Topical Cholesterol and Statin Combination Therapy in the Treatment of Porokeratosis: A Systematic Review and Meta-Analysis. J Drugs Dermatol. 2023;22(12):1160-1165. DOI: 10.36849/JDD.7775. PMID:38051843.
  Brief summary: Systematic review/meta-analysis (small samples): suggests overall benefit, but emphasizes methodological limitations. Farmhouse 2023

• Tan S, Tan E. Disseminated Superficial Actinic Porokeratosis: A Systematic Treatment Review. Am J Clin Dermatol.2025;26(1):7-21 (Epub 2024). DOI: 10.1007/s40257-024-00903-x. PMID: 39485670.
  Brief summary: Specific systematic review of DSAP: compares topical, laser and PDT; concludes lack of robust RCTs. Tan 2025

• Chen Z, et al. Safety and efficacy of topical simvastatin plus cholesterol vs simvastatin alone for porokeratosis ptychotropica: randomized split-body trial. J Am Acad Dermatol. 2025;93(4):980-987. DOI:10.1016/j.jaad.2025.04.082. PMID: 40403974.
  Brief summary: Controlled trial in ptychotropica: topical statin (with or without cholesterol) superior to placebo, with no clear differences between formulations. Chen 2025

• Lu JD, et al. Drugs associated with development of porokeratosis: A systematic review. Dermatol Ther.2021, 34 (1): e14560. DOI: 10.1111/dth.14560. PMID: 33210788.
  Brief summary: Systematic review of drug-associated porokeratosis; useful for targeted history taking and pharmacovigilance. Lu 2021

• Inci R, et al. Porokeratosis… associated with an increased risk of keratinocyte cancer and melanoma. J Eur Acad Dermatol Venereol. 2023;37(2):420-427 (Epub 2022). DOI: 10.1111/jdv.18587. PMID: 36152004.
  Brief summary: Swedish national cohort: quantifies increased risk for CEC/CBC and melanoma (high HR), supporting systematic surveillance. INCI 2023

• Novice T, Nakamura M, Helfrich Y. The Malignancy Potential of Porokeratosis: A Single-Center Retrospective Study.Cureus. 2021, 13 (2): e13083. DOI: 10.7759/cureus.13083. PMID: 33680623.
  Brief summary: Retrospective study with figures of malignant transformation by lesion/subtype; highlights close surveillance in DSAP and linear. Novice 2021

• Sasson M, Krain AD. Porokeratosis and cutaneous malignancy. A review. Dermatol Surg. 1996. DOI:10.1111/j.1524-4725.1996.tb00327.x. PMID: 8624658.
  Brief summary: Classic review of premalignant potential, risk factors (large lesions, long evolution, linear type) and need for follow-up. Sasson 1996

• Leow YH, Soon YH, Tham SN. A report of 31 cases of porokeratosis at the National Skin Centre. Ann Acad Med Singapore. 1996;25(6):837-841. PMID: 9055013.
  Brief summary: Clinical series useful for subtype distribution and therapeutic landscape prior to the “mevalonate” era; emphasizes photoprotection and surveillance. Leow 1996

• Jägle S, et al. Porokeratosis Plantaris, Palmaris et Disseminata… MVD… loss of heterozygosity. Acta Derm Venereol. 2021;101(2):adv00397. DOI: 10.2340 / 00015555-3753. PMID: 33491095.
  Brief summary: Connect PPPD and some linear forms with variants in MVD and evidence of a second blow to the skin, reinforcing the genetic-mosaic model. Jägle 2021