DISEASE CARD

Disease group Keratinization disorders
DISEASE NAME PALMOPLANTAR KERATODERMA
Synonymous Epidermolytic Palmoplantar Keratoderma
Estimated prevalence Unknown
OMIM 144200
Inheritance Autosomal dominant
Gene (s) KRT1 (139350), KRT9 (607606)

Definition

Palmoplantar Keratoderma (PPK) describes a group of keratinization disorders with thickening of the skin on palms and soles [1]. A broad spectrum of genetic heterogeneity has been reported, and many keratinization disorders as well as epithelial adhesion disorders share PPK as a clinical characteristic. Furthermore, acquired forms of PPK do exist. This heterogeneity inevitably results in a variety of clinical subtypes, which include epidermolytic (EPPK) and non-epidermolytic (NEPPK) forms [2, 3]. The following sections focus on the KRT1 and KRT9 based forms of PPK, since KRT9 expression is restricted to the suprabasal layers of palms and soles, where it dimerizes with KRT1 [4].

Clinical Description

Three distinct clinical phenotypes were identified in PPK: diffuse, focal and punctate. Diffuse PPK shows a uniform involvement of the palmoplantar skin. Focal PPK presents with localized areas of hyperkeratosis at pressure points and sites of recurrent friction. Punctate PPK consists of tiny hyperkeratotic papules, spicules or nodules, which can either be localized or cover the entire palmoplantar surface. Hyperkeratosis can be restricted to the palmoplantar region (nontransgradient) or spread dorsally up to the wrist (transgradient). Onset of the disease occurs usually in the first few months after birth and is fully developed at age of 3-4 years. In some cases it may occur later in childhood. In EPPK (Vorner PPK) a well-demarcated, thick, yellow hyperkeratosis covers the palms and soles. Occasionally an erythematous band is seen at the margin of the keratosis and the surface often appears uneven and verrucous. EPPK is usually nontransgradient. Clinical features of NEPPK (Unna-Thost PPK) are similar to EPPK with sometimes waxy appearance of keratosis and aberrant keratotic lesions in the dorsum of hands, feet, knees and elbows [2].

Pathogenesis

Mutations in the central regions of KRT1 and KRT9 were found with epidermolytic forms of PPK, and KRT1 mutations appear to result in less severe phenotypes [5, 6]. The central rod domains of Keratins are structurally essential for heterodimer formation, filament assembly and stability. Impairment of intermediate filament stability then leads to cytolysis. Mutations in the N-terminal variable end region V1 of KRT1 were associated with non-epidermolytic PPK [7].

Diagnosis

Differential diagnosis, solely on the phenotypical representation of a patient, is complicated due to the genetic heterogeneity of PPK. Differentiations have to be made between hereditary and acquired forms of PPK, epidermolytic and non-epidermolytic forms, diffuse, focal and punctate forms. Clinically identical forms can be distinguished histologically and ultrastructurally. Unequivocal diagnosis can be achieved by DNA sequencing of candidate genes.

Treatment

Application of keratinolytics. Salicylic acid, 50% propylene glycol in water under plastic occlusion several nights per week. Lactic acid and urea-containing creams. Mechanical debridement may also be helpful. Treatment with antifungal drugs in case of dermatophyte infections [2].

References

1
Chamcheu JC, Siddiqui IA, Syed DN, Adhami VM, Liovic M, Mukhtar H. (2011) Keratin Gene Mutations in Disorders of Human Skin and its Appendages. Arch Biochem Biophys 508:123-137.

2
Kingsbery MY. Keratosis Palmaris et Plantaris. Online information. Last updated July 8, 2013. http://emedicine.medscape.com/article/1108406-overview

3
Hamada T, Tsuruta D, Fukuda S, Ishii N, Teye K, Numata S, Dainichi T, Karashima T, Ohata C, Furumura M, Hashimoto T. (2013) How do keratinizing disorders and blistering disorders overlap? Exp Dermatol 22:83-87.

4
Moll R, Divo M, Langbein L. (2008) The human keratins: biology and pathology. Histochem Cell Biol 129:705-733.

5
Yang JM, Lee S, Kang HJ, Lee HJ, Yeo UC, Son IY, Park KB, Steinert PM, Lee ES. (1998) Mutations in the 1A rod domain segment of the keratin 9 gene in epidermolytic palmoplantar keratoderma. Acta Derm Venereol 78:412-416.

6
Gach JE, Munro CS, Lane EB, Wilson NJ, Moss C. (2005) Two families with Greither's syndrome caused by a keratin 1 mutation. J Am Acad Dermatol 53(5 Suppl 1):S225-230.

7
Kimonis V, DiGiovanna JJ, Yang JM, Doyle SZ, Bale SJ, Compton JG. (1994) A mutation in the V1 end domain of keratin 1 in non-epidermolytic palmar-plantar keratoderma. J Invest Dermatol 103:764-769.