Saturday, 4 December 2010

Linear porokeratosis

Linear porokeratosis has been classified as an epidermal naevus but it is still clinically and histopathologically indistinguishable from the lesions of generalized porokeratosis (disorder of keratinization). Linear porokeratosis probably reflects mosaicism for a gene responsible for generalized porokeratosis (autosomal dominant, but CAP syndrome “craniosynostosis – anal anomalies – porokeratosis” appears to segregate as autosomal recessive trait). This mosaicism can be explained by loss of heterozygosity for this dominant gene. Accordingly, an individual with inherited generalized porokeratosis undergoes a somatic mutation affecting the normal allele resulting in clonal loss of heterozygosity. The resultant line has ‘double the dose’ of porokeratosis. Skin cancers in porokeratosis are particularly associated with the linear variant. Overexpression of p53 [tumour suppressor protein (coded for by 17p)] has been reported in linear porokeratosis and in a superimposed squamous cell carcinoma. Many of topical agents, such as imiquimod 5% cream, an immune response modifier that induces cytokines such as interferon-alfa, used in the treatment cause initial inflammation which is followed by resolution.

Linear porokeratosis, with its ‘double the dose’ of porokeratosis, contrasts with the background skin, with its ‘one dose’ porokeratosis. Thus patients with linear porokeratosis can later develop disseminated superficial actinic porokeratosis (DSAP), the commonest presentation of porokeratoses, and children or siblings of patients with DSAP can have linear porokeratosis. Having said so, linear porokeratosis usually occurs sporadically and even many patients with generalised porokeratosis itself have no family history. Linear porokeratosis can exacerbate during episodes of liver failure, and improve following transplantation (unlike generalized porokeratosis that can be provoked by immune suppression).

Almost all epidermal naevi follow the pattern of lines documented by Blaschko from drawings of epidermal naevi. The pattern is attributed to the lines of migration and proliferation of epidermal cells during embryogenesis. The lines do not correspond to any known nervous, vascular or lymphatic structures. The bands of abnormal skin represent clones of cells carrying a mutation in a gene expressed in the skin. Mosaicism impact on the phenotype relates to the proportion of cells that harbour the mutation and their distribution. Mosaic describes an art form in which pictures are produced by joining together tiny pieces of different coloured stone or glass. The term is used in genetics to describe individuals composed of cells of different genotypes, such as patients with Turner syndrome who have both 45, XO and 46, XX cells. The pattern may vary according to cell type and timing of mosaicism. In the skin, genetic mosaicism classically appears as Blaschko's lines.

It should be noted that the term "porokeratosis" was first used by Vittorio Mibelli, Italian dermatologist, in 1893. Porokeratoses are characterised by presence of abnormal (disordered metabolism/increased cell kinetics) clone of keratinocytes showing varying degrees of dysplasia with gradual centrifugal migration of this clone resulting in a keratotic lesion that can progress to overt cutaneous neoplasm. The term “porokeratosis” is a misnomer, as porokeratosis has nothing to do with pores of sweat glands. Actually the lesions may or may not involve the eccrine sweat duct. The characteristic histopathology is seen in the edge of the lesion. The stratum corneum is hyperkeratotic, and at the raised border a column of poorly staining parakeratotic stratum corneum cells, the cornoid lamella, is seen running through the surrounding normal-staining cells. There is hypogranulosis beneath the cornoid lamella. Cornoid lamellae may also been seen in other conditions such as common warts (distinguished by presence of koilocytes), actinic keratosis (distinguished by presence of cytologic atypia) and some ichthyoses.

1 comment:

  1. Note that:

    1) 17p refers to the short (petit) arm of the 17th human chromosome. By the way, q indicates the long arm of a human chromosome simply because q is the next letter to p in the alphabet.

    2) Linear porokeratosis versus hypertrophic scar. In linear porokeratosis, the annular plaque is interrupted as the lesion is disposed in a linear fashion along a Blaschko’s line. There is a fine keratotic wall and sometimes also a furrow. Hypertrophic scar is a firm, pink or red plaque that usually shows signs of regression after a few months. The diagnosis is usually simple if there is a history of trauma or an inflammatory skin lesion.

    3) Many of topical agents, such as cryotherapy, imiquimod 5% cream, 5-fluorouracil, vitamin D analogues and topical retinoid, used in the treatment of linear porokeratosis cause initial inflammation which is followed by resolution and actually symptoms may not justify oral retinoid use, that may even worsen it!


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Main Works of Reference List (The first eight are my top favourites)

  • British National Formulary
  • British National Formulary for Children
  • Guidelines (BAD - BASHH - BHIVA - Uroweb)
  • Oxford Handbook of Genitourinary Medicine, HIV, and Sexual Health
  • Oxford Handbook of Medical Dermatology
  • Rook's Textbook of Dermatology
  • Simple Skin Surgery
  • Weedon's Skin Pathology
  • A Concise Atlas of Dermatopathology (P Mckee)
  • Andrews' Diseases of the Skin
  • Andrology (Nieschlag E FRCP, Behre M and Nieschlag S)
  • Bailey and Love's Short Practice of Surgery
  • Davidson's Essentials of Medicine
  • Davidson's Principles and Practice of Medicine
  • Fitzpatrick's Colour Atlas and Synopsis of Clinical Dermatology (Klaus Wolff FRCP and Richard Allen Johnson)
  • Fitzpatrick’s Dermatology in General Medicine
  • Ganong's Review of Medical Physiology
  • Gray's Anatomy
  • Hamilton Bailey's Demonstrations of Physical Signs in Clinical Surgery
  • Hutchison's Clinical Methods
  • Lever's Histopathology of the Skin
  • Lever's Histopathology of the Skin (Atlas and Synopsis)
  • Macleod's Clinical Examination
  • Martindale: The Complete Drug Reference
  • Oxford Handbook of Clinical Examination and Practical Skills
  • Oxford Textbook of Medicine
  • Practical Dermatopathology (R Rapini)
  • Sexually Transmitted Diseases (Holmes K et al)
  • Statistics in Clinical Practice (D Coggon FRCP)
  • Stockley's Drug Interactions
  • Treatment of Skin Disease: Comprehensive Therapeutic Strategies
  • Yen & Jaffe's Reproductive Endocrinology