(1)
Department of Dermatology, University of Pennsylvania, Penn Presbyterian Medical Center Medical Arts Building, Philadelphia, PA, USA
Abstract
Keratotic diseases are clinically characterized by an accumulation of scale or hyperkeratosis. Many inherited disorders of keratin or the cornified envelope may lead to these diseases. Some diseases may be papillomatous without much clinically appreciable scaling.
Keywords
IchthyosisPalmoplantar keratodermaHyperkeratosis13.1 Ichthyoses
Note: ichthyosis = “fish-like” scaling, from root “ichthys” meaning fish
13.1.1 Retention of Keratin (Retention Hyperkeratosis)
(a)
Follicular keratoses
Treatment with keratolytics (urea, lactic acid, salicylic acid, glycolic acid), also n-acetylcysteine compounded as topical (10 % in 5 % urea)
I.
Keratosis pilaris
Folliculocentric hyperkeratosis/follicular plugging; most commonly affects upper arms, thighs, buttocks, cheeks
1.
Keratosis pilaris rubra
KP with more erythema
2.
Keratosis pilaris atrophicans (ulerythema ophryogenes)
KP with atrophy, scarring alopecia
3.
Erythromelanosis follicularis faciei et colli
KP with erythema on cheeks/neck
Note: Graham-Little syndrome
Includes LPP, KP, and axillary non-scarring alopecia
II.
Lichen spinulosus
Patch of grouped keratotic follicular papules
III.
Phrynoderma
“Toad skin,” from vitamin A deficiency
(b)
Ichthyosis vulgaris
Most common disorder of cornification, most common ichthyosis
Hyperlinear palms, sparing of flexures
FLG (filaggrin) defect; decreased profilaggrin
Strongly predisposes patients to atopy (atopic dermatitis/allergic rhinitis/asthma)
(c)
Steroid sulfatase deficiency (X-linked recessive ichthyosis)
“Dirty neck,” comma-shaped corneal opacities, cryptorchidism
Defect in cholesterol metabolism (fatty aldehyde dehydrogenase)
(d)
Axillary granular parakeratosis
Presents as scaly rash classically in axilla, but may be elsewhere
Path: unusually thickened stratum corneum with parakeratosis, retention of basophilic keratohyalin granules (?filaggrin defect?)
(e)
Acquired ichthyosis
May be associated with systemic disease: HIV (in 30%), malignancy (most common = Hodgkin’s), autoimmune connective tissue disease, sarcoidosis, mycosis fungoides, drugs (nicotinic acid, statins)
13.1.2 Hyperproliferation of Keratin (Proliferative Hyperkeratosis)
(a)
Epidermolytic ichthyosis
Aka bullous congenital ichthyosiform erythroderma (BCIE)
On path, aka epidermolytic hyperkeratosis (EHK) = hyperkeratosis with “shot out”/messy granular layer (vacuolization of cells)
Clinically, erythroderma initially; later with accentuated skin markings (corrugated appearance)
Defect = keratin 1 and 10 mutation, autosomal dominant
Can sometimes see EHK in epidermal nevi; risk for phenotypically normal individual with EHK in epidermal nevus having children with epidermolytic ichthyosis (due to mosaicism)
(b)
Ichthyosis bullosa of Siemens
Ddx BCIE, EB simplex; appears as a milder form of BCIE
Only mild blistering at birth; can develop trauma-induced blisters, then hyperkeratosis in childhood, especially over joints/flexures, but sparing palms/soles.
Characteristic feature = superficially denuded areas with collarette-like borders described as ‘molting’ or ‘Mauserung’, which develop due to superficial blistering and shedding of the stratum corneum
Defect in keratin 2e
(c)
Lamellar ichthyosis
May present at birth with collodion membrane
Mutation in transglutaminase-1, AR, defect in protein-lipid envelope crosslinking
(d)
Non-bullous congenital ichthyosiform erythroderma (NBCIE)
Deficiency of loricrin (same as Vohwinkel’s with ichthyosis); also can have TGase-1 defect
On a spectrum with lamellar ichthyosis
(e)
Harlequin ichthyosis (Harlequin fetus)
Autosomal recessive, ABCA12 deficiency
Ectropion, eclabium, death as neonate
(f)
Collodion baby
Taut, shiny, transparent membrane formed by thickened stratum corneum; resembles a plastic wrap
Tautness often leads to ectropion, eclabium
Seen in lamellar ichthyosis and non-bullous congenital ichythosiform erythroderma, self-healing collodion baby, more rarely in some other genodermatoses
Babies at risk for hypernatremic dehydration
(g)
White sponge nevus
White plaques of oral mucosa
Defects in keratin 4 and 13 (specific to oral keratinocytes)
13.1.3 Genodermatoses With Ichthyosis or Erythrokeratodermia
(a)
Sjögren–Larsson syndrome
Autosomal recessive, fatty aldehyde dehydrogenase deficiency
Triad of ichthyosis (like NBCIE), diplegia or quadriplegia (scissor gait), mental retardation
On eye exam: perifoveal glistening white dots
Mnemonic = “fat Swede dancing with disco ball”
(b)
Refsum disease
From defect in PHYH or PEX7
Phytanic acid oxidase deficiency → leads to accumulation of phytanic acid leading to neuropathy and ichthyosis; disease might be stalled by restricting phytanic acid in diet
Ichthyosis (can be late-onset), atypical “salt and pepper” retinitis pigmentosa, cerebellar ataxia, chronic polyneuropathy, difficulty hearing
Mnemonic = “Deaf ref (black/white like salt and pepper) stumbled over (ataxia) and broke up the PHYH/phytanic acid (fight) then checked his PEX7 (pecs)”
(c)
KID syndrome (keratitis-ichthyosis-deafness)
Autosomal dominant, connexin 26 defect, GJB2 gene (same as Vohwinkel)
Symmetric erythematous hyperkeratotic plaques (erythrokeratodermia rather than ichthyosis), usually includes face/cheeks
(d)
Erythrokeratodermia variabilis (EKV)
Disorder of cornification associated with non-inflammatory erythema
Clinical hallmark: coexistence of transient erythematous patches and more stable hyperkeratosis
The erythema may present in large geographic/figurate patches (more in childhood), while the hyperkeratosis progresses
Aka Mendes da Costa disease
Mostly from defects in connexin 31 and 30.3 (genes GJB3 and GJB4)
(e)
CHILD syndrome
Aka Congenital Hemidysplasia with Ichthyosiform erythroderma and Limb Defects
X-linked dominant, NSDHL gene
(f)
Chanarin-Dorfman syndrome
A neutral lipid storage disease
(g)
Conradi–Hünermann–Happle syndrome (X-linked dominant chondrodysplasia punctata)
Defect = emopamil binding protein (EMP); in other types of inheritance, other defects can be found: perioxisomal enzyme defect PEX7 gene (AR), and arylsulfatase E (XR)
Erythroderma and linear streaks/whorls of hyperkeratosis; may spontaneously resolve in first year of life, replaced by bands of follicular atrophoderma
Follicular atrophoderma → patchy scarring alopecia
Skeletal abnormalities (stippled epiphyses)
(h)
Netherton syndrome
Types: ichthyosis linearis circumflexa and congenital ichthyosiform erythroderma (like NBCIE, but no collodion); presents with failure to thrive
Ichthyosis linearis circumflexa = “double-edged scale”
Autosomal recessive, LEKTI (encoded by SPINK5)
Trichorrhexis invaginata (bamboo hairs) most specific, though other hair shaft abnormalities seen
Avoid giving topical tacrolimus (Protopic), because of increased systemic absorption
13.2 Palmoplantar Keratoderma (PPK)
Transgrediens = does not respect boundaries of palmar/dorsal hands
Non-transgrediens = does respect palmar/dorsal boundaries
When describing, think transgradiens vs. non-transgradiens, diffuse vs. focal vs. punctate
13.2.1 Inherited Palmoplantar Keratodermas
(a)
Non-transgradiens inherited PPK (respects boundaries, limited to palms)
I.
Unna-Thost syndrome (non-epidermolytic)
Autosomal dominant, keratin 1 defect
II.
Vörner type (epidermolytic)
Defect in keratins 1 and 9
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
