7th June 2025

Inherited Skin Diseases

Palmoplantar keratoderma (PPK)

Keratoderma: marked thickening in the epidermal skin layer.

Palmoplantar: refers to the skin on the palms and sole which are most affected by the disease

Aetiology

Hereditary PPK is caused by a mutation in the genes that either code a protein in the keratin
Can manifest as a sole dermatological disease, i.e. non syndromic or along with extra cutaneous manifestations, i.e. syndromic-i.e. in relation to an inflammatory skin condition (e.g. eczema or psoriasis), systemic inflammatory disease, internal cancers etc.
Inheritance:
- Autosomal dominant, recessive or X linked.
- Mitochondrial inheritance has also been reported.

Subtypes

Diffuse keratoderma
- Affects the palms and soles
Focal keratoderma
- Mainly involves the pressure areas.
Punctate-type keratoderma
- Causes bumps on the palms and soles.

Diagnosis

History and examination

Careful history regarding onset of symptoms (e.g. infancy or childhood), a positive family history of parents’ consanguinity may support the diagnosis
Examination should include the entire skin surface, nails, hair and mucous membranes. E.g. diffuse/focal/punctate/striate
- Distribution:
  - Presence or absence of extension to the dorsal area of palms and soles, around the digits
- Morphology:
  - Presence of hyperkeratosis which presents as waxy and compact areas with fissures associated with erythema and desquamation
- Extracutaneous findings (e.g. ocular keratitis, hearing loss, cardiac abnormalities and internal malignancies)
Histopathology:
- Mainly shows hyperkeratosis and acanthosis. The presence of epidermolysis is important to note as it differentiates epidermolytic-PPK from non-epidermolytic-PPK Image Source: Wikimedia Commons (2017). Palmoplanta Keratoderma, Licensed under a creative commons licence. Available for free at: https://en.wikipedia.org/wiki/Palmoplantar_keratoderma (Accessed 22 May 2025).

Management

Medical Management

Emollients
Keratolytic agents: e.g. salicylic acid
Topical /oral retinoids
Topical vitamin D ointment (calcipotriol)

Surgical Management

Specialized hand surgery if pseudoainhum (constricting rings) develop around digits.

Complications

Transgrediens- lesions extend beyond palm and sole
Mutilating: constrictive bands around the digits

Ichthyosis

Ichthyosis is derived from the Greek work Ichthyosis which means ‘fish’ denoting the presence of fishy like scales on the skin

Aetiology

Loss of function of the gene filaggrin gene function encoding for the protein filaggrin (FLG).
- It is essential in formation of keratohyalin granules which are found in the granular layer of epidermis.
- It is responsible for aggregating keratin filaments which covalently cross link and bind them together to form a condensed skin barrier.
The loss of the gene function results in the disruption in its barrier function as well as reduction/loss of the moisturizing function of the epidermal layer (Xerosis).
Excessive scaling forms as a result of the inability of the skin cells to remain hydrated as they move up through the epidermis.
As a compensatory repair mechanism, hyperkeratosis results.

Epidemiology

Ichthyosis vulgaris is the most common inherited type of ichthyosis.
Relatively common. Incidence in the British population is around 1/80-1/250.

Inheritance

Autosomal semi-dominant condition
- Individuals who inherit two alleles of the gene are much more severely affected than individuals who inherit a single allele.

Diagnosis

Diagnosis of ichthyosis is usually clinical diagnosis, based on history and examination findings.

History

Onset after birth/early childhood
Possible improvement with age, warm weather
Family history
Associated atopic diseases

Examination

Distribution
- Most commonly in the trunk and extensor extremities. Usually spares the skin folds (e.g. neck, axilla, elbow and knee crease)
Morphology:
- Scales: White/Grey fine scales
- Palmar hyper linearity: Pronunciation of major fissures as well as fissures on thenar eminence. Increase in minor fissures.
- Keratosis pilaris: Rough, small bumps on the surface of the skin.
For associated diseases Image Source: Wikimedia Commons (2017). Ichthyosis, Licensed under a creative commons licence. Available for free at: https://en.wikipedia.org/wiki/Ichthyosis#/media/File:Ichthyosis_(1).jpg (Accessed 22 May 2025).
Corneal affection
Atopic diseases

Histopathology

Clinical diagnosis is usually sufficient
Biopsy is usually taken from the extensor part of the arm/shin and shows a markedly reduced/absent granular layer in the epidermis. Electron microscopy shows abnormal keratohyalin granules.

Management

General measures

Regular bathing and exfoliating

Medical Management

Emollients and moisturizers
Keratolytics e.g. salicylic acid, are proved to be superior to simple emollients as evidenced by a systemic review of randomized controlled studies.
The use of topical steroids/calcipotriene/ retinoids are not usually indicated.
Oral retinoids are used for severe cases
Management of complications
- Skin infection, allergies, overheating
- Higher incidence of atopic conditions may require specific management

Ectodermal dysplasia

Aetiology

Occurs when the ectodermal layer of the skin fails to develop
Vast group of inherited disorders
- Primarily involving defects in hair, teeth, nails or sweat glands.
- Additionally, tissues of ectodermal origin are often affected which include the ears, eyes, lips, mucous membranes of the mouth or nose and the CNS.
It is caused by a defect in the transmembrane protein ectodysplasin which is a member of the TNF related ligand proteins involved in the early epithelial-mesenchymal interaction that is essential for the regulation of the ectodermal appendage formation
They are present from birth and are non-progressive in nature.
The classification is based on the presence or absence of the four primary ectodermal dysplasia defects:
- Dental dysplasia
- Trichodysplasia (hair dysplasia)
- Onchodysplasia (nail dysplasia)
- Dyshidrosis (sweat gland dysplasia)

Diagnosis

Prenatal testing is available in some centers.
History
- Family history
- Onset of symptoms (usually at birth- recurrent unexplained fevers)
Clinical
- Depends on the organs being affected
- Sweat glands
  - Absence/reduced sweat gland production results in disrupted thermoregulation which can lead to abnormally high temperatures in children.
  - Seizures and neurological problems occur as a sequalae.
- Hair
  - Thinning and sparsity of the hair present in the scalp and body.
  - The facial, axillary and pubic hairs are usually spared.
- Nails
  - Fingernail and toenail abnormalities including thinning, ridging, discoloration, brittle nails, or absence of nails.
- Teeth
  - Disfigurement in tooth shape, including pointed/peg shaped teeth. Teeth may also be missing
- Other symptoms:
  - Skin: dryness, pigmentation, thickening leading to cracking, bleeding, and infections
  - Eyes: Keratoconjunctivitis sicca due to lack of tear production. Cataracts and visual defects can occur.
  - Mucous membranes: foul smelling nasal discharge and respiratory infections due to decreased synthesis of normal protective secretions.
  - Cleft lip/palate
Histopathology
- Skin biopsy shows reduced numbers of sweat glands

Management

Multidisciplinary approach with a team of dentists and doctors.
General
- If defective sweat gland production- affected individuals must live in cooler areas/air-conditioned houses which may be very useful in body temperature control
- Wigs may help improve the cosmetic appearance in people with affected hair
Medical
- Artificial tears may help protection from corneal damage that results from lack of tear production
- Early dental intervention is essential as some children may require dentures at an early age
Surgical
- Surgical repair of cleft lip and palate

Complications

Seizures and neurological sequalae from defective thermoregulation
Recurrent chest infections

Pachyonychia congenita

Aetiology, epidemiology, and inheritance

Rare disorder primarily affecting the keratinization in the skin and nails
Mutation in the gene sequence encoding for keratin resulting in disruption of the keratin cytoskeleton leading to the formation of weak keratin aggregates.
1000-10,000 people are affected with pachyonychia congenita worldwide
Autosomal dominant inheritance

Diagnosis

Presents usually in first few years of life and a positive family history.
Clinical manifestations.
- Predominant clinical manifestations involve a triad of hypertrophic nail dystrophy, plantar keratoderma, and severe plantar pain.
- Nail: Hyperkeratosis in the nail is usually the first manifestation. Some or all the nails can be affected. The affected nail either grows in an up-slanting way due to aggregates of keratin underneath or terminates prematurely exposing the distal nail bed.
- Plantar keratoderma: Usually starts to manifest when the child starts weight bearing and walking. Image Source: Wikimedia Commons (2021). Planter Keratoderma, Licensed under a creative commons licence. Available for free at: https://en.wikipedia.org/wiki/Keratoderma#/media/File:Planter_keratodermaC.jpg (Accessed 22 May 2025).
- Diffuse or focal hyperkeratosis happens causing severe pain.
- Other lesions:
- Oral leukokeratosis appears as grey-white patches on the oral mucosa
- Natal/Prenatal teeth
Histopathology
- Accentuated and prominent keratosis seen on biopsy from plantar keratoderma lesions. On electron microscopy- aggregates of keratin are seen in the spinous layer.

Management

Mainly focused on reducing nail and palmoplantar keratosis as well as pain management.
General
- Good oral hygiene in oral leukokeratosis
Medical
- Softening of the skin by keratolytic lesions e.g. salicylic acid, moisturizers and emollients.
- Oral retinoids
Surgical
- Filing of hyperkeratotic areas by podiatry

Complications

Plantar keratoderma associated pain-
- Chronic plantar pain may be debilitating leaving the child with severe mobility limitations affecting his daily living.
Oral Leukokeratosis
- May cause feeding difficulties in children and if severe, may cause hoarseness of voice and/or acute airway obstruction.