Background

This group of disorders known as palmar plantar keratodermas (PPK) are characterized by diffuse or localized hyperkeratosis of the palms and soles with additional skin abnormalities. Clinically three patterns have been identified: diffuse over the palm and sole, focal with large keratin masses at points of friction, and punctate with tiny drops of keratin on the palmoplantar surface. In addition, cases associated with oral, hair, nail, dental, auditory, or neuronal abnormalities have been termed palmoplantar ectodermal dysplasia (PED). In addition to the inherited disorders, several disorders may have an associated keratodermas. Some are genodermatoses such as ichthyosis syndromes.

OUTLINE

Disease Associations
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Treatment
Commonly Used Terms
Internet Links

 

DISEASE ASSOCIATIONS	CHARACTERIZATION
Acquired Keratodermas	Genodermatoses Associated
AIDS Arsenic Callus Climacteric Corns Eczema Human papillomavirus Keratoderma blenorrhagicum Lichen planus Norwegian scabies Paraneoplastic keratoderma Psoriasis Reiter's syndrome Secondary syphilis Tinea pedis Sezary's syndrome Tuberculosis verrucosa cutis	Basal cell nevus syndrome Congenital bullous ichthyosiform erythroderma Darier's disease Epidermodysplasia verruciformis Epidermolysis bullosa simplex Ichthyosis vulgaris Lamellar ichthyosis Pityriasis rubra pilaris

Congenital Keratodermas Without Associated Manifestations

Diffuse

Name	Additional Names	Manifestations
Diffuse epidermolytic PPK	Vorner's epidermolytic PPK	AD Well demarcated symmetrical thickening of the plams and soles with dirty appearance Epideromlysis on biopsy
Diffuse nonepidermolytic PPK	Unna-Thost disease	AD Waxy involvement of plams and soles No epidermolysis
Erythrokeratoderma variabils	Progressive symmetric erythrokeratoderma, keratosis palmoplantaris transgrediens et progrediens	AD Sharply outlined geographic areas not limited to palms and soles
PPK of Sybert	Greither's PPK	AD Glove and stocking distribution

Focal

Name	Additional Names	Manifestations
Striate PPK	Brunaauer-Fuhs-Siemens type, Wachters PPK	AD Striate linear callouses usually on soles and palms

Punctate

Name	Additional Names	Manifestations
Keratosis punctata palmaris et plantaris	Buschke-Fischer-Brauer disease	AD Develops between 12-30 yrs. Multiple punctate keratosis
Spiny keratoderma	Punctate keratoderma	AD 12-50 yrs Multiple tiny keratotic plugs mimicking spines
Focal acral hyperkeratosis	Degenerative collagenous plaques of the hands	AD Late onset Oval or polygonal crateriform papules

PPK wth Associated Manifestations (Palmoplantar Ectodermal Dysplasias-PED)

PED Type	Name	Manifestations
I	Pachyonychia congenita (Jadassohn-Lewandowsky syndrome)	AD Plantar calluses with sparing of non-weight bearing digits Upward angulation of the distal end of nails with subungual hyperkeratosis giving a "door-wedge" appearance Epidermolysis
	Focal palmoplantar keratoderma with oral mucosa hyperkeratosis	AD Clinical overlap with PED I with no nail changes Oral hyperkeratosis esp. in labial attached gingiva
II	Pachyonychia congenita type II (Jackson-Sertoli syndrome)	AD Limited focal plantar keratoderma Nail changes like PED I
III	PPK associated with esophageal carcinoma (Tylosis)	AD Keratoderma over pressure points, sparing of non-weight bearing areas Palms usually spared Nails normal Oral leukokeratosis 10-90% risk of esophageal CA
IV	Papillon-Lefevre syndrome	AR Focal with punctiform accentuation of palmoplantar surfaces with accentuation of creases May spread to elbows and knees Deafness, calcification of dura
V	Oculocutaneous tyrosinemia (Richner-Hanhart syndrome)	AR Painful circumscribed callosities on pressure points Photophobia and corneal erosions Treat with low tyrosine and phenylalanine diet
VI	Olmsted syndrome (Mutilating PPK with periorificial keratotic plaques)	AD? Diffuse multilating PPK with flexion deformity of the digits Progressive perioral, perianal, and perineal hyperkeratotic plaques Corneal scarring
VII	Vohwinkel's syndrome (Keratoderma herditaria multilans)	AD Honeycombed PPK Flexion contractures Spread to extensor surfaces Nail dystrophy
VIII	Mal de Meleda (Mutilating PPK of the Gamborg-Nielsen type)	AR Diffuse and symmetric PPK spreading to the dorsa in glove and stocking distribution Constricting bands with autoamputation of digits
IX	Huriez Syndrome	AD Diffuse symmetric PPK with fingers having a pseudosclerodermatous appearance
X	Hidrotic ectodermal dysplasia (Fischer-Jacobsen-Clousten syndrome)	AD Diffuse keratoderma,progressive with age, preservation of dermatoglyphics Oral leukokeratosis Structural hair defects Ocular and skeletal abnormalities
XI	Congenital Poikiloderma with traumatic bulla formation, anhidrosis, and keratoderma (Naegeli-Franceschetti-Jadassohn syndrome)	AD Reticulate pigmentation around neck and axilla Diffuse keratoderma with punctiform and linear accentuations Normal hair, nail changes Tooth enamel defects Hypohidrosis/anhidrosis
XII	Acrokeratotic poikiloderma	AD Hyperpigmentation about 12 years age Cobblestoned keratoderma with spread to dorsa of hands and feet Poikiloderma Acral bullae and acral lichenoid keratoses
XIII	Dermatopathic pigmentosa reticularis	AD Reticulate hyperpigmentation with truncal accentuation PPK with punctiform accentuation Atrophic erythematous macules over joints Ainhum Severe periodontal disease Onychodystrophy
XIV	Woolly hair and endomyocardial fibrodysplasia	AR PPK over pressure points Acanthosis nigricans Woolly hair over scalp with short scanty eyebrows, eyelashes, beard, pubic hair Endomyocardial fibrodysplasia with venticular tachycardia and right ventricular dilatation
XV	PPK with sensorineural deafness (Bart-Pumphrey syndrome)	AD Sensorineural deafness Extensive focal PPK may extend to Achilles' tendon
XVI	Keratitis-Ichthyosis-Deafness syndrome (KID syndrome)	AR Erythroderma well demarcated serpiginous outline Diffuse keratoderma with reticulate surface Keratoconjunctivitis
XVII	Corneodermatosseous Syndrome	AD Corneal dystrophy Diffuse PPK Distal onycholysis Short stature and brachydactyly
XVIII	PPK and spastic paraplegia (Charcot-Marie-Tooth disease)	AD or X linked Dominant Thick focal keratoderma Pes cavus, frontal balding, spastic paraplegia and mental retardation Muscular atrophy Nail dystrophy
XIX	Eyelid cysts, PPK, hypodontia, and hypotrichosis (Schopf-Schulz-Passarge syndrome)	AR PPK with fragile nails Sparse hair with eyelid cysts Facial telangiectasia Loss of teach Multiple squamous cell carcinomas in areas of keratoderma
XX	Cardiofaciocutaneous syndrome	AR High boxy craniofacial appearance Motor and growth retardation Congenital cardiac defects Alopecia Dystrophic nails and teeth

OTHER VARIANTS AND ASSOCIATIONS

VARIANT	CHARACTERIZATION
AQUAGENIC
Aquagenic palmoplantar keratoderma Albert C. Yan, etal.	J Am Acad Dermatol 2001;44:696-9. Abstract quote Aquagenic palmoplantar keratoderma is an acquired condition characterized by burning and edema limited to the hands after brief immersion in water. The 3 patients described possess a striking similarity to those with transient reactive papulotranslucent acrokeratoderma. All 3 patients manifested the “hand-in-the-bucket” sign, having presented to a physician with a hand immersed in a bucket of water to more promptly demonstrate the physical findings. Aluminum chloride hexahydrate represents a potentially valuable therapeutic option for this unusual condition. In 1996 English and McCollough described two sisters with an unusual acquired condition characterized by burning and edema affecting the palms after brief immersion in water. They coined the term transient reactive papulotranslucent acrokeratoderma to describe their two patients. No successful treatment modalities were described. We describe 3 additional patients with very similar clinical findings to those seen by English and McCollough. All 3 patients were young women who presented with an acquired condition characterized by burning and edema affecting primarily the palms and, in one case, the soles after exposure to water. Our patients responded to topical therapeutic interventions. Because of distinct differences between hereditary papulotranslucent acrokeratoderma and those features seen in these patients, we believe the term aquagenic palmoplantar keratoderma more accurately reflects the clinical features of this condition
CLIMACTERIC
Keratoderma climactericum (Haxthausen's disease): clinical signs, laboratory findings and etretinate treatment in 10 patients. Deschamps P, Leroy D, Pedailles S, Mandard JC.	Dermatologica 1986;172(5):258-62 Abstract quote 10 cases of keratoderma climactericum are reported. This keratosis of the palms and soles appears late in women of menopausal age. The keratotic lesions first develop at the plantar pressure points, making walking troublesome. Involvement of the hands remains discrete. Examination for contact allergy, fungal tests, vitamin A serum levels, and sex hormones were negative or normal in all the 10 patients. Microscopy revealed a lichenified eczema with evidence of mechanical irritation. Etretinate (0.78 mg/kg/day) brought about partial or total remission of the hyperkeratosis. Pain on walking disappeared in all the patients.

 

PATHOGENESIS	CHARACTERIZATION
Olmsted Syndrome Report of a Case With Study of the Cellular Proliferation in Keratoderma Luis Requena, M.D.; Felix Manzarbeitia, M.D.; Carmen Moreno, M.D.; Maria Jose Izquierdo, M.D.; Maria Antonia Pastor, M.D.; Loreto Carrasco, M.D.; Maria Carmen Fariña, M.D.; Lucia Martín, M.D. From the Departments of Dermatology (L.R., M.J.I., M.A.P., L.C., M.C.F., L.M.) and Pathology (F.M., C.M.), Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain.	Am J Dermatopathol 2001;23:514-520 Abstract quote Olmsted syndrome is a rare disorder that consists of sharply marginated keratoderma of the palms and soles, constriction of digits and toes that may result in spontaneous amputation of the distal phalanges, hyperkeratotic plaques around the body orifices, onychodystrophy, and other less common cutaneous and extracutaneous anomalies. Although some patients had other affected family members, most cases of Olmsted syndrome seem to be of sporadic occurrence. We describe a patient with the characteristic features of Olmsted syndrome. The symptoms consisted of diffuse transgrediens palmoplantar keratoderma and keratotic plaques around the mouth and nose. Our patient also had the associated anomalies of hyperhidrosis of the palms and soles and congenital deaf-mutism. Histopathologic study of the keratoderma demonstrated epidermal hyperplasia with acanthosis, papillomatosis, and orthokeratotic hyperkeratosis. Immunohistochemical study showed more basal and suprabasal keratinocytes of the epidermis with immunoreactivity for Ki-67 marker when compared with the keratinocytes of the epidermis of the adjacent non-involved skin. These results support the notion that Olmsted syndrome is a hyperproliferative disorder of the epidermis.
The molecular basis of hereditary palmoplantar keratodermas. Kimyai-Asadi A, Kotcher LB, Jih MH. Ronald O. Perelman Department of Dermatology, The New York University School of Medicine.	J Am Acad Dermatol 2002 Sep;47(3):327-43 Abstract quote In recent years, the gene defects causing many types of hereditary palmoplantar keratoderma have been discovered. These genes encode a variety of proteins involved in the terminal differentiation of keratinocytes and the formation of the cornified cell envelope. In this article, we review the molecular defects underlying various palmoplantar keratodermas with particular attention to the role of these molecules in the terminal differentiation of palmoplantar epidermis. Of the proteins involved in keratodermas, loricrin, keratins, and desmosomal proteins provide the protein structure of the cornified cell envelope. Connexins form intercellular gap junctions, which regulate ionic calcium signals necessary for the expression of the proteins that form the cornified cell envelope. Cathepsins likely mediate enzymatic processes necessary for the formation and dissolution of the cornified cell envelope. The clinical phenotypes produced by various mutations affecting these proteins are discussed vis-a-vis data from genetic, cellular, and molecular experiments. (J Am Acad Dermatol 2002;47:327-43.) Learning objective: At the completion of this learning activity, participants should be familiar with the genetic and molecular basis of hereditary palmoplantar keratodermas. The participants should also have more knowledge about the process of epidermal differentiation and formation and dissolution of the cornified cell envelope.

 

TREATMENT	CHARACTERIZATION
GENERAL
ACITRETIN
Papillon-Lefevre syndrome: the response to Acitretin. Al-Khenaizan S. Division Of Dermatology/Department of Medicine, King Abdulaziz Medical City, King Fahad National Guard Hospital, Saudi Arabia.	Int J Dermatol 2002 Dec;41(12):938-41 Abstract quote Papillon-Lefevre syndrome is a rare autosomal recessive disease comprising palmoplantar keratoderma and periodontitis. Palmoplantar keratoderma can be severe, necessitating systemic treatment. Different systemic retinoids were found to be highly efficacious. We describe the successful use of acitretin in one patient who had severe palmoplantar keratoderma, with maintenance of the improvement using topical treatment.
DEBRIDEMENT
Effect of scalpel debridement on the pain associated with plantar hyperkeratosis. Redmond A, Allen N, Vernon W. Division of Podiatry, University of Western Sydney-Macarthur, Campbelltown, New South Wales, Australia.	J Am Podiatr Med Assoc 1999 Oct;89(10):515-9 Abstract quote Seventy-nine subjects from 14 centers in eight English National Health Service Trusts recorded their levels of preoperative and postoperative pain and perceived change in pain on 100-mm visual analog scales before and after scalpel debridement of painful plantar hyperkeratosis. A significant reduction in pain was reported following treatment, and there were highly significant differences between the preoperative and postoperative scores. There were no age- or sex-related differences in any of the preoperative, postoperative, or perceived-change scores. The objective data support the anecdotal evidence that scalpel debridement of painful plantar hyperkeratosis is immediately effective in the palliative management of such patients.
ETRETINATE
Mutilating palmoplantar keratoderma successfully treated with etretinate. Wereide K.	Acta Derm Venereol 1984;64(6):566-9 Abstract quote Three patients, a mother and her two sons, with mutilating palmoplantar keratoderma (Vohwinkel's syndrome) were successfully treated with oral etretinate (Tigason). All of them had keratotic constriction furrows of one or more digits (pseudo-ainhum) with threatening spontaneous amputation. Oral treatment with etretinate brought about disappearance of the pseudo-ainhums and normalization of the digital blood circulation. The hyperkeratotic skin became thinned and pliable with a dose-dependent trend towards redness and atrophy. Continued long term etretinate medication has made it possible for these patients to fulfill their social and occupational activities. All 3 patients had acoustic impairment of high-pitched tone perception.

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Progrediens-Progression with age.

Transgrediens-Extent of spread.

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Last Updated October 30, 2006

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