PACHYONYCHIA CONGENITA
Clients with this condition seek attention for nail management
CONGENITAL ORIGIN
Pachyonychia congenita (PC) is a rare condition in which the nails are thickened and discoloured at birth.
It is a keratin disorder (see *Notes to assist the reader, at the end of this article).
“Keratins are the major structural proteins of the epidermis and associated appendages and the nail, hair follicle, palm, sole and tongue are the main sites of constitutive K6, K16 and K17 expression” (Bowden, 1995)
“Mutations in keratins, the epithelial-specific intermediate filament proteins, result in aberrant cytoskeletal networks which present clinically as a variety of epithelial fragility phenotypes”
(Smith et al, 2005).
Two types have been recognised: the Jadassohn–Lewandowsky form (PC-1) and the Jackson–Lawler form (PC-2).
In PC-1 the nail dystrophy is accompanied by focal palmoplantar keratoderma and hyperkeratosis of the lingual and/or buccal mucosal tissues. The epithelia affected in P. congenita PC-1 express the keratin pair K6a and K16, and the condition is caused by dominant-negative mutations in these genes (Bowden et al, 1995; McLean et al, 1995).
The PC-2 variant is caused by mutations in keratins K6b and K17 (McLean et al, 1995; Smith et al, 1998). Here, the nail dystrophy is accompanied by mild palmoplantar keratoderma and multiple pilosebaceous cysts caused by hyperkeratosis of the opening (infundibulum) of the hair follicle and accompanying sebaceous gland. Exactly how these keratin mutations lead to hyperkeratosis of the nail is not well understood, but fragility of the underlying nailbed keratinocytes presumably leads to release of cytokines and other inflammatory products which act upon the cells of the germinal matrix and produce overgrowth of the nail (Stoof et al, 1994; De Berker et al, 2000; Irwin et al, 2003).
DIFFERENTIAL DIAGNOSIS OF PC
There are many reasons that nails are thickened to the extent of needing our management. Certain congenital conditions occur in which the nails are thickened and discoloured from birth. Nails suffer their own specific dystrophies and are sometimes affected by systemic disorders such as lupus, psoriasis, lymphatic and respiratory illnesses. Because of the conditions under which they are obliged to work they are subjected to accidental trauma and repetitive intermittent stress (exacerbated by the presence of any biomechanical lesions), and that makes them susceptible to infection by dermatophytic fungi and yeasts. The nail plates also thicken naturally with advanced age.
Traumatic injury is the origin of the onychogryphotic nail and the ostler’s nail. Less obvious is the thickening caused by constant attrition of the involuted nail plate where the lateral nail borders cause persistent stimulation/inflammation of the nail structures. Repeated loss due to trauma eventually leads to coarser, thicker nail plates. The nail of the hyperextended hallux interacts with the interior toe box surface, and the short shoe will repeatedly push the nail body back onto the germinal matrix, causing hypertrophy of the nail. Retracted lesser digits suffer the repetitive stress of apical loading and react to the same nail matrix stimulation/inflammation, again resulting in thickening of the plate. Rotated lesser digits give rise to asymmetrical nail/ground contact, rotating the nail plate and stimulating the germinal matrix.
Repetitive trauma produces thickening of the nail plate.
In contrast, Pachyonychia congenita is present at birth. The nail plate is hypertrophic, dense and hard, but not unduly brittle. The sterile matrix is affected, creating a hyperkeratotic layer that raises and thickens the nail plate. Afflicted nails often adopt a tubular configuration.
MANAGEMENT
The nails require reduction to normal length per nipper and nail drill. It may also be possible to thin the nail plate slightly to reduce the overall vertical height of the nail and prevent further thickening due to repetitive trauma. There is no reason to trespass beneath the nailplate in order to remove hyperkeratotic tissue. This would open the area to infection and the pre-existing state would only recur.
OUTLOOK
The identification of mutations in cases of P. congenita is necessary for future development of gene-specific and/or mutation-specific therapies (Liao et al, 2007)
REFERENCES
· Bowden PE, Haley JL, Kansky A, Rothnagel JA, Jones DO, Turner RJ. Mutation of a type II keratin gene (K6a) in pachyonychia congenita. Nat Genet. 1995;10:363–365.
· De Berker D, Wojnarowska F, Sviland L, Westgate GE, Dawber RP, Leigh IM. Keratin expression in the normal nail unit: markers of regional differentiation. Br. J. Dermatol. 2000;142:89–96
· Irwin WH, McLean WHI and Epithelial Genetics Group 2003 Genetic disorders of palm, skin and nail. J Anat. January; 202(1): 133–142.
· Liao H, Sayers JM, Wilson NJ, Irvine AD, Mellerio JE, Baselga E, Bayliss SJ, Uliana V, Fimiani M, Lane EB, McLean WH, Leachman SA, Smith FJ., A spectrum of mutations in keratins K6a, K16 and K17 causing pachyonychia congenita. Epithelial Genetics Group, Human Genetics Unit, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.; [Epub ahead of print] J Dermatol Sci. 2007 Aug 23
· McLean WHI, Rugg EL, Lunny DP, Morley SM, Lane EB, Swensson O, et al. Keratin 16 and keratin 17 mutations cause pachyonychia congenita. Nature Genet. 1995;9:273–278.
· Smith FJD, Jonkman MF, Van Goor H, Coleman C, Covello SP, Uitto J, et al. A mutation in human keratin K6b produces a phenocopy of the K17 disorder pachyonychia congenita type 2. Human Mol. Genet. 1998;7:1143–1148
· Smith FJ, Liao H, Cassidy AJ, Stewart A, Hamill KJ, Wood P, Joval I, van Steensel MA, Björck E, Callif-Daley F, Pals G, Collins P, Leachman SA, Munro CS, McLean WH. The genetic basis of pachyonychia congenita J Investig Dermatol Symp Proc. 2005 Oct;10(1):21-30
· Stoof, TJ.;Boorsma, DM.; Nickoloff, BJ. Keratinocytes and immunological cytokines. In: Leigh IM, Lane EB, Watt FM. , editors. The Keratinocyte Handbook. Cambridge: Cambridge University Press; 1994. pp. 365–399.
*Notes to assist the reader: In an animal cell, the cytoskeleton helps to maintain the shape of the cell, but its primary importance is in the internal movement and spatial arrangement of the components within the cell. The cytoskeleton is an organised network of three primary protein (keratin) filaments: microtubules, microfilaments and intermediate fibres. In cases of Pachyonychia congenita, within the epithelial cells there are family-shared gene mutations in the keratin proteins of which the intermediate fibres are constructed. For further explanation the reader is referred to the animal cell animation on:
http://www.cellsalive.com/cells/cell_model.htm
Pachyonychia congenita
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