Dermatology

Palmoplantar Keratodermas

Are You Confident of the Diagnosis?

Palmoplantar keratodermas (hereby referred to as PPKs) represent a large, varied group of syndromes that are vastly different with respect to symptoms and clinical presentation. Please refer to Table I for syndrome names, synonyms. Images for the syndromes discussed are cited in the Evidence section at the end of the chapter. The acquired PPKs will not be extensively covered in this chapter but should be mentioned. The acquired PPKs are as follows: Keratoderma climactericum, arsenical keratosis, aquagenic PPK, malignancy-associated PPK, malnutrition-associated PPK and drug-induced keratoderma.

Primary Feature: SkinPrimary Feature: Other
Disorder Synonyms PPK Column* ICD-9 Selected Epidemiologic Features Genetic Cause Syndromic Associations Distinguishing features Age of onset (for disorder manifistation) Erythema Transgrediens Other Epidermal Features** Systemic Features*** Relevant Pathology Differenctial Diagnosis Systemic Options Additional Specialists Needed
Acrokeratoelastoidosis Collagenous plaques of hands and feet, PPK type III, Focal Acralhyperkeratosis, Keratoelastoidosis marginalis, Acrokeratoelastoidosis of Costa   757.4 Prevelent in African female population <20 2p25-p12   Nodular and yellow with hyperkeratotic surfaces on the marginal borders of hands and/or feet Adolescence No No No No Cup shaped epidermal dell overlying a dermis with elastorrhexis, collegen degeneration, dilation of papillary blood vessels, hypopigmentation of basal layer Other PPKs, Xanthomata, Focal Acral Hyperkeratosis, Solar Elastosis skin biopsy none
Bart-Pumphrey syndrome Knuckle pads, leukonychia, and sensorineural deafness 757.4 Most prevalent in Northern European Ancestry Cx26 (GJB2) Hearing impairment Stippled or pitted hyperkeratosis of the knuckle pads, Leukonychia Early Childhood No No M E Massive orthokeratotic hyperkeratosis without parakeratosis, hypergranulosis, acanthosis and papillomatosis epidermal gap junctions appear normal on electron microscopy Vohwinkel Syndrome   Audiologist
Cantu syndrome Hyperkeratosis-hyperpigmentation syndrome, Hypertrichotic Osteochondrodysplasia   757.4   unknown Macrosomia at birth, osteochondroplasia, cardiomegaly, gingival hyperplasia Distinct PPK characteristics were not available for Cantu Syndrome other than deep creases on the soles of feet. Early Childhood No No No D, O, H   hypertrichosis universalis, x-linked congenital generalized hypertrichosis Draw Liver panel for elevated Alkaline Phosphate levels, x-rays of limbs, EKG Dentist, Orthopedist, Cardiologist  
Cardiofaciocutaneous syndrome CFC Syndrome   757.4   KRAS, FRAF, MEK1, MEK2 Heart defect, sparse hair, distinctive facial features Hyperkeratotic skin lesion, ichthyosis-like condition Birth No Yes H, I H, N, V   Noonan Syndrome, Costello Syndrome EKG Cardiologist, Neurologist, Opthalmologist  
Carvajal syndrome     757.4 Increased in Ecuadorian population Desmoplakin Heart Disease (dilated cardiomiopathy-left ventricular), Woolly hair Striate PPK over pressure areas of palms and soles Birth No No H, F H   Naxos Disease EKG Cardiologist  
CEDNIK syndrome Cerebral dygenesis, neuropathy, ichthyosis and keratoderma   757.4   SNAP29 Microcephaly and facial dysmorphism, Roving eye movement, poor head and trunk control Ichtyosis, generalized scaling, PPK reported but not described Early Childhood No No I N, V Clear vesicles in the spinous, granular, and stratum corneum layers, with retained glucosylceramides, suggesting abnormal lamellargranule maturation ARC syndrome, MEDNIK Syndrome, Sjogren-Larsson Syndrome, Chanarin-Dorman disease, trichothiodystrophy, Gaucher disease Electron microscopy analysis, brain MRI Neurologist, Opthalmologist
Clouston Syndrome Hidrotic ectodermal dysplasia, HED   757.4 Most common in French-Canadian Population Cx26 (13q11), Cx30 Nail dystrophy, sparse hair/alopecia PPK with transgradiens Birth No Yes H, N No Cytoplasmic accumulation when quickly expressed in cultured keratinocytes--complete loss of gap junction function Pachyonychia Congenita   none
Congenital ichthyosiform erythoderma CIE, IECN1, NCIE, Ichthyosiform erythroderma Brocq congenital non-bullous form, Non bullous congenital ichthyosiform erythroderma 1   757.1   TGM1, Ichthyin (5q33.3),ALOXE3,ALOXE12B,ABHD5 Thick collodion membrane with erythroderma at birth. Lifelong erythroderma, scaling Variable palmoplantar involvement Birth Yes No I No moderate hyperkeratosis, normal/slightly thickened granular cell layer, mild acanthosis, and varibale parakeratosis Lamellar Ichthyosis, Sjogren-Larsson Syndrome skin biopsy none
Dyskeratosis congenita DKC, Dyskeratosis congenita, Scoggins type   757.4 Most common in men TINF2,TERT Leukoplakia, nail dystrophy, susceptible to malignancy, continuous lacrimation Reticulated hyperpigmentation Early Childhood Yes No M, N C, G, V Atrophy of the epidermis with pigment laden macrophages present in the upper dermis Fanconi's Anemia, Naegeli-Franceshetti -Jadassohn Syndrome, GVHD skin biopsy Hematologist/Oncologist, Gastroenterologist, Ophthalmologist
Ectodermal dysplasia with skin fragility McGrath Syndrome   757.3   PKP1 Diffuse blistering, dystrophic nails, sparse hair Trauma-induced skin fragility and tearing, painful craking , hyperkeratosis of soles and palms, Birth Yes No H, N, B, S No Thickening of the epidermis and extensive widening of keratinocyte intercellular spaces, extending from the first suprabasal layer upwards. Loss of keratinocyte-keratinocyte adhesion and desmosomes in the lower suprabasallayers were small and reduced in numbers     none
Epidermolysis bullosa simplex Dowling-Meara with mottled pigmentation, Weber-Cockayne, Non-Herlitz junctional, Koebner type, EBS   757.4   K5, K14 Oral blisters, recurrent blistering following minor physical trauma Palmoplantar Bullous vesicles, patchy hyperkeratosis Birth-Early Childhood No No M, B No Disintegration of the basal and suprabasilar cells, intralepidermal blistering with evidence of cytolysis of the basal keratinocytes. Pemphigus Neonatorum   Podiatrist
Epidermolytic PPK (EPPK) Vorner type, Keratoderma, Hyperkeratosis, Localized Epidermolytic Keratosis, Keratosis of Griether, Palmaris et plantaris familiaris tylosis   757.4   K9, K1 Chilhood blistering may occur Lateral thick, yellow hyperkeratosis, border is erythematous Early Childhood Yes No B No Epidermolytic hyperkeratosis, thickened stratum corneum, keratinocytes of the granular layer and upper spinous layers had a vacuolated appearance with abnormally shaped keratohyalin granules. Maleda type, NEPPK, other PPKs skin biopsy none
Familial pityriasis rubra pilaris pityriasis rubra pilaris, PRP   696.4   unknown (K1)   Orange/red waxy PPKs, follicular papules on erythematous base Early Childhood Yes No No No Papillomatosis and widened intercellular spaces betweek keratinocytes, thickened stratum corneum with focal areas of parakeratosis and thickened granual layer. Mild lymphocytic inflammatory infiltrate surrounded vessels in the papillary dermis. Ichthiosiform dermatoses   none
Focal Acral Hyperkeratosis FAH       2p25-p12 Nail dystrophy yellowish-flesh colored, polygonal,hyperkeratotic palmoplantar papules and plaques symmetrically clustered Adolescence No No N No orthohyperkeratotosis, moderate acanthosis and hypergranulation. No evidence of elastorrhexis. AKE, Verruca plana, PPPK skin biopsy  
Focal palmoplantar and gingival keratosis Keratosis, focal palmoplantar and gingival   757.4   unknown Thickened fingernails, follicular keratosis, papillated leukokeratosis in the regions of the attached gingiva Hyperkeratosis on weight-bearing areas, trauma related hyperkeratosis of the palms, Adolescence No No M, N, F D Paranuclear bodies have been identified in Keratinocytes of the spinous and granular cell layers which have been characterized as condensations of tonofilaments none   Dentist
Haim-Munk syndrome PPK with periodontitis, arachnodactyly, acro-osteolysis, Cochin Jewish Disorder, HMS, Keratosis palmoplantaris with periodontopathia and onychogryposis   757.4 Jewish populations Cathepsin C Pes planus, onychogryphosis, peridontitis, arachnodactyly Scaly, circumscribed, erythematous patches on the elbows, knees, forearms, shins, and dorsum of the hands Early Childhood Yes Yes M D, O Hyperkeratosis scattered areas of acanthosis and parakeratosis. Slight inflammation around the blood vessels in theh upper part of the dermis. Mild atrophy on sweat glands. Papillon-Lefevre syndrome, HOPP syndrome X-rays Dentist, Orthopedist
Harlequin ichthyosis Harlequin Baby, Harlequin fetus, Ichthyosis congenita gravior   757.1 Found in inbred families ABCA12 Premature birth, eversion of eyelids and lips, underdeveloped ears and nasal cartilage Taut, armor-like skin Birth Yes Yes I, H O Defective lipid secretion of LG lipid contents, ABCA12 protein is restricted to the LGs in the cytoplasm of epidermal keratinocytes and fuses with the cell membrane to secrete the lipid content to the extracellular space of the stratum corneum. none Sepsis workup Orthopedist
HOPP syndrome hypotrichosis, acro-osteolysis/onychogryphosis, palmoplantar keratoderma and periodonitis   757.4   Cathepsin C Dystrophic nails, Alopecia, decreased bone density PPK- unspecified, psoriasis-like lesions Early Childhood Yes No H, N D, O Orthohyperkeratosis, hyperplasia, hyperparakeratosos, absent granular layer, elongated dermal papillae, perivascular lymphocytic infiltrate of the upper dermis Papillon-Lefevre syndrome, Haim Munk Syndrome   Dentist
Howel-Evans Syndrome Tylosis-esophageal carcinoma, non-epidermolytic PPK with carcinoma of the esophagus, Keratosis Palmaris et Plantaris with Esophageal cancer, TOC   757.4   TOC, 17q25 Associated with Esophageal carcinoma, Esophageal leukoplakia, follicular keratosis Frictional hyperkeratosis (trauma), focal, thickened skin Adolescence No No F, M C, G Gross acanthosis, hyperkeratosis (sans parakeratosis) and hypergranulosis. none   Oncologist, Gastroenterologist
Huriez syndrome PPK with scleroatrophy, TYS, Sclerotylosis, Scleroatrophic and Keratotic Dermatosis of the Limbs   757.4   unknown (4q23) Atrophic fibrosis of the limbs, hypoplasia of nails,higher risk for skin and bowel cancer, anhidrosis thickening of palms, yellow-grey, dry, scaly, hyperkeratotic palms, malignant degeneration of affected skin Birth Yes No N, S G Absence of epidermal Langerhans cells, marked acanthosis, hypergranulosis, orthokeratotic hyperkeratosis, thickened collagen bundles Marjolin Ulcer, Palmoplantar hyperkeratosis with squamous cell carcinoma Skin Biopsy Gastroenterologist
Hystrix-like ichthyosis-deafness syndrome HID syndrome, Ichthyosis Hystrix-like with deafness   757.1   GJB2 Deafness, Ichthyosis, scarring alopecia, prone to bacterial and mycotic skin infections, mild impact on palms and soles Diffuse spikey hyperkeratosis, erythematous patches Birth Yes No H, N, I E Excess formation of mucous-containing granules, reductions of tonofilaments KID Syndrome, Lamellar Ichthyosis, Clouston syndrome   Audiologist
Keratisis-ichthyosis-deafness syndrome KID syndrome, Erythrokeratodermia progressiva Burns   757.1   GJB2 Deafness, Ichthyosis, erythroderma, alopecia, declining vision, susceptibility to Squamous cell carcinoma Severe affect on palms and soles, prone to skin infection Birth Yes No H, I E, V Excess formation of mucous-containing granules, reductions of tonofilaments Desmons or Senter Syndrome, HID syndrome, Clouston Syndrome   Opthalmologist, Audiologist
Keratoderma climactericum Haxthausen's disease   701.1 Menopausal women unknown   Keratotic lesions on plantar pressure points, minimal hand involvement Acquired               Allergist (for diagnostic testing)  
Kindler syndrome Poikiloderma, hereditary acrokeratotic, bullous acrokeratotic poikiloderma of kindler and weary, poikiloderma congenital with bullae weary type   757.4 Found mostly in Caucasian poplulation FERMT1,KIND1 Dental overbite, reticulate erythema, bleeding gums Thick, wrinikled skin and blistering of hands and feet, keratotic papules on hands, feet, elbows, and knees Early Childhood Yes No M, B D Hyperkeratosis, focal parakeratosis and acanthosis of the epidermis with loss of polarity of the basal layer. Rothmund-Thomson syndrome, Dystrophyic Epidermolysis Bullosa, Bloom Syndrome   Dentist
KLICK syndrome Keratosis linearis with ichthyosis congenital and slerosing keratoderma   757.4   POMP   PPK with pseudoainhum and a sclerosing flexion deformity of the fingers, noninflamed keratotoic striae on wrists, armfolds, and backs of the knees Birth No No I No Abnormal keratohyaline granules with enlarged and rounded shape in keratinocytes. Hyperkeratosis with a small number of parakeratotic cells. Normal granular layer. Vohwinkel, KID syndrome   none
Lamellar ichthyosis Non-bullous congenital ichthyosiform erythoderma, L1, Ichthyosis congenita type 2, Non-erythrodermic autosomal recessive lamellar ichthyosis   757.1   TGM1,ABCA12. P450 Alopecia, Collodion menbrane at birth Brown plate-like scales with raised borders, palmoplantar hyperkeratosis Birth Yes No I, H No Acanthosis, hyperkeratotic layer of cornified cells. The granular cells are small cytoplasmic vacuoles. Many melanin granules in basal cells HID syndrome, CIE Sepsis workup none
Meleda type Mal de Meleda, MDM, Meleda Disease, Keratosis Palmoplantaris Transgradiens of Siemens   757.4 Inhabitants of the island of Mljet off the Dalmation Coast SLURP-1, Ly-6/uPar (8q24.3) Secondary fungal or bacterial infections, lesions on hands, elbows, and knees, hyperhidrosis Palmoplantar thickening with erythematous border, cracked/waxy keratodermas Birth-Early Childhood Yes Yes S No Hyperkeratosis, hypergranulosis, Acanthosis, and chronic inflammatory dermal infiltrate Vohwinkel, EPPK, NEPPK   none
Naegeli-Franceshetti-Jadassohn syndrome Dermatopathia pigmentosa reticularis, NFJ syndrome, NFJS   757.4   K14 Discomfort in heat (diminished sweat gland function) Palmoplantar hypohidrosis and hyperkeratosis, blistering, poor teeth, linear punctate keratoses, reticular cutaneous pigmentation Early Childhood No No B, S D Increased for increased apoptotic activity in the basal cell layer Dyskeratosis Congenita, Incontinentia pigmenti, Dermatopathia pigmentosa reticularis Eccrine testing Dentist
Naxos disease Diffuse PPK with woolly hair and arrhythmogenic cardiomyopathy, Mal De Naxos, Keratosis palmoplantaris with arrhythmogenic cardiomyopathy   757.4 Mediterranean decent Plakoglobin (17q21) cardiac abnormality (right ventricular) Woolly hair, hyperkeratosis, hypergranulosis, and acanthosis (PPK) Birth-Adolescence Yes No H H Compact hyperkeratotsis, hypergranulosis, and acanthosis, subepidermal vessels were dilated , mild mononuclear cell infiltrate Ebstein anomaly, Carvajal syndrome, other PPKs EKG Cardiologist
Netherton syndrome Comel-Netherton Syndrome, NS, Ichthyosis linearis circumflexa, Trichorrhexis invaginata, NTS   757.1 Found mostly in women SPINK5 Imbalance of immune system, alopecia, bamboo hair, short stature Ichthyotic skin, scaling,eczemous plaques Birth Yes No I, H G stratum corneum layer was replaced by parakeratotic cells, premature secretion of lamellar body contents CIE, Atopic Dermatitis, Erythrodermic psoriasis RAST test Allergist
Non-epidermolytic PPK (NEPPK) Unna-Thost type, Keratoderma   757.4   K6, K1, K7, K16 Secondary infections, nails can be stubby Erythematous, thickened palmoplantar skin, thick, yellow hyperkeratosis Birth-Early Childhood Yes No N, B No Hyperkeratosis of the stratum corneum (no epidermolysis), cells of granules characteristic of epidermolytic hyperkeratosis EPPK, Mal De Meleda, Howel-Evans Syndrome   none
Oculodentodigital dysplasia ODD syndrome, Oculodentoosseous dysplasia, ODDD, ODOD   757.4   GJA1(Cx43) Narrow nose, small teeth, syndactyly, missing toes, glaucoma, deafness, dysplastic iris, sparse hair, enamelogenesis imperfecta Folicular hyperkeratosis, scaly plaques Birth-Early Childhood No No H, N, F N, O, V, E, H Electron microspcopy conducted on hair: focal, semi-smooth ovoid dells in the beaded areas Francois dyscephalic syndrome   Neurologist, Orthopedist, Opthalmologist, Audiologist, Cardiologist
Olmsted syndrome mutilating PPK with perioficial plaques   757.4 Affects men 75% more than women K5, K14 Susceptible to infections, deafnes, hyperkeratotic nails, necrotic blisters Erythema, hyperkeratotic plaques, scaling, hyperpigmentation, yellow fissures Early Childhood Yes No B, N E Hyperkeratosis, acanthosis, and papillomatosis. Acrodermatitis Enteropathica, Vohwinkel syndrome, mucocutaneous candidiasis   Audiologist
Pachyonychia congenita Jadassohn-Lewandowsky type, Jackson-Lawler type   757.5 Increased in Slavic/Jewish populations K16, K6a thickened nails, natal teeth, hoarseness, oral leukokeratosis Painful plantar calluses Early Childhood No No H, N, B, M, S D Keratin filaments aggregate and filament structure is weakened and less resilient leading to greater trauma experienced, increased blister formation and increased callusing. Clousten syndrome, Dyskeratosis congenita, Weber-Cockayne syndrome   none
Papillon-Lefevre syndrome PPK with periodontitis, PALS, PLS, Keratosis Palmoplantaris with Periodontopathia   757.4   Cathepsin C,DPPI Loss of teeth varied palmoplantar involvement (psoriasiform scaly sin to overt hyperkeratosis), knees and elbows may also be affected Early Childhood No Yes No D, N Predominance of plasma cells in the lamina propria Maleda type, Haim-Munk Syndrome, HOPP syndrome   Neurologist, Dentist
PPK striata/areata type Striate PPK, focal non-epidermolytic PPK, Wachters type, Brunauer-Fuhs-Seimens type, Hereditary painful callosites   757.4   Dsg1, K16 Painful fissures over pressure areas, friction associated trauma, increased skin fragility Yellow linear calluses on soles and palms Childhood No Yes No No Hyperkeratosis, hypergranulosis, moderate acanthosis without inflammatory cell infiltrate in the dermis Other PPKs   none
Punctate palmoplantar keratoderma (PPPK) Keratosis punctata palmaris et plantaris, Buschke-Fischer-Brauer type   757.4   Unknown Pits with keratotic plugs on the plantar aspects of both soles and palms. Spinous keratoses on volar aspects of hands and feet Adolescence No No No No Columnar parakeratosis from the malpigian layer with little granular layer Verrucae Vulgaris   none
Rapp-Hodgkin syndrome RHS   757.3   TP63 Anhidrotic ectodermal dysplasia, cleft lip/palate, syndactyly, small mouth and nose, alopecia, atretic ear canals PPK has been reported though no description has been found Birth No No H, N, S E, O, D   AEC, EEC, Hay-Wells Syndrome   Audiologist, Orthopedist, Dentist  
Refsum Syndrome (Infantile) IRD, Infantile Phytanic Acid Storage Disease   356.3   PEX1, PEX2, PEX26 Facial Dysmorphism, hearing loss, osteoporosis, hepatomegaly, mental retardation PPK has been reported though no description has been found Birth No No I N, V, H, G   Zellweger Syndrome, Adrenoleukodystrophy Blood Plasma work- elevated phytanic levels Neurologist, Opthalmologist, Cardiologist, Nutritionist  
Refsum Syndrome 1 and 2 (Adult) Refsum Disease, Phytanic acid oxidase deficiency, Heredopathia Atactica Polyneuritiformis, Hereditary Motor and sensory neuropathy IV, HMSN IV   356.3   PHYH, PAHX, PEX7 Retinitis pigmentosa, peripheral neuropathy, cerebellar ataxia, cardiac dysfunction, deafness, Ichthyosis PPK has been reported though no description has been found Adolescence-Adulthood No No I N, V, H, G   Zellweger Syndrome, Infantile Refsum Syndrome, Ichthyosis Vulgaris, Rhizomelic Chondroplasia Punctata Blood Plasma work- elevated phytanic levels Neurologist, Opthalmologist, Cardiologist, Nutritionist  
Richner-Hanhart Syndrome Tryrosinemia type II, Oculocutaneous tyrosinemia, TAT deficiency, Keratosis palmoplantaris with corneal dystrophy, Tyrosinosis Oculocutaneous type, tyrosine aminotransferase deficiency   270.2 Incestuous result TAT (chrom 16) Photophobia, dendritic keratitis, corneal ulcerations, elevated tyrosine aminotransferase Painful, hyperkeratotic, rigid palmoplantar yellow-white papules and plaques Childhood-Adolescence No No No V, G increased synthesis of tonofibrils and keratohyalin, many microtubules and tight packing of basal cells of the epithelium none Urine test- elevated hydroxyphenylpyruvic acid. Elevated serum tyrosine levels. Gastroenterologist/Nutritionist, Ophthalmologist
Schopf-Schulz-Passarge syndrome PPK with hidrocystomas, hypodontia and hypotrichosis, Eccrine tumors with extodermal dysplasia, Keratosis palmoplantaris with cystic eyelids, hypodontia, and hypotrichosis   757.4   WNT10A Hypodontia, hypotrichosis, eyelid cysts, nail fragility, susceptible for basal cell carcinoma, abnormal deciduous teeth, excessive sweating diffuse keratoderma with a well-defined border Early Childhood No No N, M, S D, E   Papillon-LeFevre Syndrome   Dentist, Opthalmologist  
Sjogren-Larsson syndrome SLS, FALDH deficiency, Fatty Aldehyde Dehydrogenase Deficiency, Ichthyosis spastic neurologic disorder and oligophrenia, Fatty alcohol: NAD+ Oxidoreductase deficiency   757.1   ALDH3A2 Spastic quadriplegia, pigmentary retinal degeneration, short stature, photophobia, dental dysplasia Hyperkeratosis and gray-brown scaling Birth Yes No I G, N, E, D Papillomatous epideris with hypergranulosis,impaired hexadecanol oxidation CIE Blood work- fatty aldehyde dehydrogenase deficiency Nutritionist, Neurologist, Opthalmologist, Dentist
Vohwinkel syndrome Mutilating PPK, Keratoderma Hereditarium, KHM, Keratoma Hereditaria Mutilans   757.4   Cx26 (GJB2),K1, Loricrin Constricting bands of the fingers and toes, hearing loss, spastic paraplegia, Ichthyosis, Acanthosis, Alopecia honeycomb or star-shape hyperkeratotic plaques on the dorsa of feet, hands, knees, and elbows--yellowish thickening on palms and soles Birth No Yes H, I E, O Hyperkeratosis, focal parakeratosis, hypergranulosis, papillomatous acanthosis. Mild perivascular mononuclear infiltrate Mal de Maleda, Bart-Pumphrey syndrome, Xanthomata, Olmstead syndrome   Audiologist, Orthopedist

What you should be alert for in the history

Questions regarding age of onset, past medical history, family information (geographic as well as medical history), erythema, involvement and inclusion of the dorsal aspects of hands and feet should be asked and considered during a clinical examination.

Characteristic findings on physical examination

Characteristic findings on physical examination are variable depending on the gene affected as well as the manifestation which varies from person to person. Please refer to the column “Distinguishing PPK features” on the accompanying table for the most common manifestations of each syndrome. PPKs are generally classified in three categories: Focal, Diffuse, and Punctate.

  • Positive gene defect results should be expected for the disorders with known genetic causation. Outcomes from other forms of testing such as blood work, urinalysis, or x-ray can be found on the “work-up and treatment” column on the accompanying table.

  • Diagnosis confirmation is gained by pathologic and/or genetic testing or by observing the natural course of the disease. Family history and examination of affected family members can be helpful. Consulting a geneticist is recommended for counseling.

Who is at Risk for Developing this Disease?

PPKs are primarily genetic and/or hereditary. The mode of inheritance can be autosomal recessive, autosomal dominant, x-linked, a combination of all three, or acquired. The mode of inheritance for all of the PPK syndromes can be found in the “notes” section on the included table.

What is the Cause of the Disease?

The cause for a PPK is highly variable. The genetic basis for many of these disorders is known. Genetic testing for those will identify a pathogenic gene defect. Please refer to the “Genetic Cause/Association” column for gene defect information for each syndrome.

Systemic Implications and Complications

Several PPKs are associated with severe systemic problems such as gastrointestinal, neurological, or cardiac involvement. Disorders with severe systemic implications whould be ruled out first. There are a few syndromes to be highlighted due to the high occurrence of associated cancer:

Howel-Evans is characterized by the onset of esophageal carcinoma. Until esophageal carcinoma develops, it is difficult to accurately diagnose this syndrome (See Figure 34, Figure 35).

Huriez Syndrome has an elevated risk of developing Squamous Cell carcinoma of the skin (See Figure 36).

KID syndrome reportedly has a susceptibility to Squamous Cell carcinoma of the skin (See Figure 37, Figure 38, Figure 39).

Olmsted Syndrome is at risk for development of Squamous Cell carcinoma in hyperkeratotic skin (See Figure 52, Figure 53).

Treatment Options

Traditional forms of treatment for PPKs include keratolytics (salicylic acid up to 25%, propylene glycol, urea 5%-10%), oral (acitretin) or topical retinoids such as adapalane, topical Vitamin D, topical steroids, tetracyclines, antibiotics (choice depending on the bacterial species and resistance pattern) or antifungals (when needed), and mechanical debridement.

Treatment should be tailored to the patient’s individual symptoms. The above treatments have been listed as successsful in certain cases. The patient should be seen in follow up as needed to ease the symptoms.

Optimal Therapeutic Approach for this Disease

It is very rare for an optimal therapeutic approach to exist for these disorders. Evidence from trials is lacking for the established treatments. Most patients require symptomatic relief as discussed in “Treatment options” above.

Treatment (cure) of the tumor/cancer in Howell Evans syndrome does not result in resolution of the PPK.

Patient Management

As noted in the “Additional Specialists Needed” column on the attached table, a helpful patient management tactic for PPKs is to be familiar with the systemic implications associated with PPKs. This will enable a physician to refer his or her patients to the correct specialist.

Unusual Clinical Scenarios to Consider in Patient Management

Manifestations of each PPK may altered by an underlying inflammatory infection, fungal, or bacterial component. Also, be aware of the possibility that a clincal presentation might be a combination of one or more individual disorders.

Blecher, SR, Kapalanga, J, Lalonde, D. "Induction of sweat glands by epidermal growth factor inmurine X-linked anhitdrotic ectodermal dysplasia". Nature Genet. vol. 345. 1990. pp. 542-4.

Clarke, A, Burn, J. "Sweat testing to identify female carriers of X linked hypohidrotic ectodermal dysplasia". J Med Genet. vol. 28. 1991. pp. 330-3.

Clarke, A. "Hypohidrotic ectodermal dysplasia". J Med Genet. vol. 24. 1987. pp. 659-63.

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