Differential Diagnosis of Palmoplantar Keratoderma

Introduction

Palmoplantar Keratoderma (PPK) refers to thickening of the stratum corneum of the palms and soles. It may be inherited (genetic genodermatosis) or acquired (secondary to systemic disease, infection, drugs, or dermatoses). Recognition of the pattern (diffuse, focal, punctate), presence of transgrediens (extension beyond palms/soles), and associated systemic features is essential for diagnosis and management.

37.1 Classification by Pattern

Pattern	Description	Examples
Diffuse	Uniform, continuous thickening of entire palm/sole	Unna-Thost, Vörner, Mal de Meleda
Focal (Nummular/Striate)	Localized plaques at pressure points or linear keratoses	Focal non-epidermolytic PPK, Striate PPK
Punctate	Multiple small, discrete keratotic papules	Punctate PPK Type I, Arsenical keratoses

37.2 Inherited Palmoplantar Keratoderma

37.2.1 Diffuse PPK

Unna-Thost (Non-Epidermolytic PPK)

Inheritance: Autosomal Dominant. KRT1 or KRT9 mutations.
Clinical Features:
- Diffuse, waxy, yellow keratoderma of palms and soles.
- Well-demarcated at margins.
- Hyperhidrosis (excessive sweating) common → Malodor.
- May be transgredient (extending onto dorsum).
Histology: Orthokeratotic hyperkeratosis WITHOUT epidermolysis.

Vörner (Epidermolytic PPK)

Inheritance: Autosomal Dominant. KRT9 mutation.
Clinical Features: Similar to Unna-Thost clinically.
Histology: Epidermolytic hyperkeratosis (vacuolization of granular layer).
Differential from Unna-Thost: Only distinguishable histologically.

Mal de Meleda

Inheritance: Autosomal Recessive. SLURP1 gene.
Clinical Features:
- Diffuse, thick keratoderma.
- Transgrediens: Extends onto dorsal hands and feet.
- Hyperhidrosis, Malodor.
- Perioral erythema.
- Pseudoainhum (constricting bands around digits).
Geographic: Originally described in island of Meleda (Croatia).

37.2.2 Focal PPK

Focal Non-Epidermolytic PPK (Wachters)

Keratotic plaques at pressure points (metatarsal heads, heels).
Painful, often interfere with walking.

Striate PPK (Brunauer-Fuhs-Siemens)

Inheritance: Autosomal Dominant. DSG1 (Desmoglein 1) or DSP mutations.
Clinical Features:
- Linear keratoses along flexure lines of fingers and toes.
- Extends onto palms in linear pattern.
Association: DSG1 mutations also cause Focal non-epidermolytic PPK.

37.2.3 Punctate PPK

Punctate PPK Type I (Buschke-Fischer-Brauer)

Inheritance: Autosomal Dominant. AAGAB gene.
Clinical Features:
- Multiple, discrete, keratotic papules on palms and soles.
- Appear in teens or young adulthood.
- May be painful when walking.

Spiny Keratoderma (Music Box Spine Keratoderma)

Multiple tiny spiny projections on palms.

37.2.4 PPK with Significant Systemic Associations

[!CAUTION] Recognize syndromic PPK early for screening and surveillance.

Syndrome	PPK Type	Associated Features	Gene
Howel-Evans Syndrome (Tylosis)	Diffuse	Esophageal Carcinoma (very high risk)	RHBDF2 (iRhom2)
Papillon-Lefèvre Syndrome	Diffuse + Transgrediens	Severe Periodontitis, Premature loss of deciduous AND permanent teeth	CTSC (Cathepsin C)
Vohwinkel Syndrome	Honeycomb pattern	Sensorineural Deafness, Pseudoainhum (constricting bands → autoamputation)	GJB2 (Connexin 26)
Olmsted Syndrome	Diffuse + Mutilating	Periorificial keratotic plaques, Alopecia, Nail changes	TRPV3
Clouston Syndrome (Hidrotic ED)	Focal	Nail dystrophy, Sparse hair, Normal teeth and sweating	GJB6 (Connexin 30)

37.3 Acquired Palmoplantar Keratoderma

Acquired PPK is secondary to an underlying condition and develops later in life.

Cause	Key Features
Psoriasis	Silvery scale elsewhere, Nail changes, Family history
Eczema/Dermatitis	Pruritic, Fissured, Vesicles (pompholyx)
Pityriasis Rubra Pilaris	Orange-waxy PPK, Erythroderma with islands of sparing
Secondary Syphilis	Copper papules on palms/soles, Generalized rash, RPR+
Keratoderma Climactericum (Haxthausen)	Postmenopausal women, Heels primarily affected, Fissuring
Reactive Arthritis (Keratoderma Blennorrhagicum)	Pustular keratoderma mimicking pustular psoriasis, Arthritis, Urethritis
Arsenical Keratoses	Punctate, hard keratoses on palms/soles. Chronic arsenic exposure. Pre-malignant.
Mycosis Fungoides	Rare palmoplantar involvement
Norwegian (Crusted) Scabies	Thick crusted scale, Mites on scraping
Hypothyroidism	Diffuse dry, hyperkeratotic skin
Paraneoplastic	Associated with internal malignancy (NOT Howel-Evans specific)

37.3.1 Key Acquired Causes in Detail

Keratoderma Climactericum

Demographics: Postmenopausal women.
Distribution: Heels, Weight-bearing areas.
Features: Hyperkeratosis with painful fissures.
Associations: Obesity, Menopause.

Arsenical Keratoses

History: Chronic arsenic exposure (Well water in endemic areas, Pesticides).
Clinical Features: Small, hard, punctate keratoses on palms and soles.
Significance: Pre-malignant → Risk of SCC, BCC, Internal malignancy (Lung, Bladder).
Associated Findings: Mees' lines (nails), Raindrop pigmentation (trunk).

Keratoderma Blennorrhagicum (Reactive Arthritis)

Classic Triad of Reactive Arthritis (Reiter's): Arthritis + Urethritis + Conjunctivitis.
Skin Features: Pustular keratoderma on palms/soles. May look identical to pustular psoriasis.
Mucosal: Circinate balanitis (psoriasiform lesion on glans).

37.4 Diagnostic Algorithm

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37.5 Summary Comparison Table

Condition	Pattern	Onset	Key Association
Unna-Thost	Diffuse	Childhood	Hyperhidrosis
Vörner	Diffuse	Childhood	Epidermolytic histology
Mal de Meleda	Diffuse + Transgrediens	Childhood	Pseudoainhum
Papillon-Lefèvre	Diffuse + Transgrediens	Childhood	Periodontitis, Tooth loss
Vohwinkel	Honeycomb	Childhood	Deafness, Pseudoainhum
Howel-Evans (Tylosis)	Diffuse	Childhood	Esophageal Carcinoma
Punctate PPK	Punctate	Adolescence	Painful when walking
PRP	Orange, Waxy	Variable	Islands of sparing
Secondary Syphilis	Copper papules	Acquired	RPR+, Generalized rash
Arsenical Keratoses	Punctate	Acquired	Arsenic, Malignancy risk
Keratoderma Climactericum	Heels	Postmenopausal	Fissures

37.6 Clinical Pearls

Childhood diffuse PPK + Severe periodontitis + Early tooth loss → Papillon-Lefèvre syndrome.
Diffuse PPK + Esophageal symptoms → Howel-Evans syndrome. Screen for esophageal carcinoma (very high risk).
Honeycomb PPK + Deafness + Finger constrictions → Vohwinkel syndrome.
Orange-waxy PPK + Islands of sparing elsewhere → Pityriasis Rubra Pilaris.
Punctate keratoses + Arsenic exposure → Arsenical keratoses. Screen for internal malignancy.
Copper-colored papules on palms/soles + Generalized rash → Secondary syphilis. Order RPR.
Postmenopausal woman + Fissured heels → Keratoderma climactericum.
Acquired PPK: Always look for underlying systemic cause or associated dermatosis.