CHAPTER 6

KERATOSES（角化症）

 

A.   Epidermis

The outermost skin layer that protects man from his environment.  Its own uppermost layer is the stratum corneum（角層）. The cornifying squamous epithelium is an ectodermal structure.

1.    Morphology: The epidermis consists of several layers

 a.  Basal cell layer (stratum basale)（基底層）

 b.  Spinous or prickle cell layer (stratum spinosum)（有棘層）

 c.  Granular layer (stratum granulosum)（顆粒層）

 d.  Stratum corneum（角層）

2.    Epidermopoiesis: The human epidermis is protected only by corneocytes that are continually shed and renewed.

 a.  Compartment of proliferation.  This includes the basal cell layer and, where the epidermis is acanthotic, also the lower spinous layer.

 b.  Compartment of differentiation.  This includes the upper spinous layer, the granular layer, and the cornified layer.

3.    Function

 a.  The principal function of the epidermis is protection.  The stratum corneum protects the body against excessive water and heat loss.

 b.  The surface of the stratum corneum is covered by a film of lipids.  Sebaceous lipids make up more than 90% of extractable lipids.  Less than 10% are derived from the epidermis itself (epidermal lipids).

 c.  The epidermal lipids, mainly ceramides, are responsible for the water binding capacity and the smoothness of the stratum corneum

 d.  The epidermal surface is acid, with a pH of approximately 5.5-5.7.  The acid mantle of the epidermis is probably of importance in protecting against bacterial infections.

 

B.   Disturbances of Keratinization

1.    The causes of keratinization disturbances are generally unknown.

2.    They are genetically determined in many cases known as genodermatoses(遺伝性皮膚疾患).

3.    Keratoses are sometimes acquired, e.g., drug reactions, or they may be a sign of a different primary disease.

4.    A thickening of the stratum corneum, i.e., hyperkeratosis(過角化), can basically result from either of two processes.

 a.  Epidermopoiesis: proliferation hyperkeratosis (e.g., psoriasis (乾癬), pityriasis rubra pilaris(毛孔性紅色粃糠疹)).

 b.  Retention Hyperkeratosis: the desquamation process is impaired and too few corneocytes are shed at the skin surface (e.g., ichthyosis vulgaris).

Keratoses are differentiated according to the sites they affect:

 a.  Diffuse Keratoses (ichthyoses)

 b.  Palmoplantar keratoses

 c.  Follicular keratoses

 d.  Circumscribed keratoses unrelated to the follicles

 

I. Diffuse Keratoses（汎発性角化症）

Consist of forms of ichthyosis that can be differentiated on the basis of clinical, genetic, histopathological, ultrastructural, and in some cases biochemical characteristics.

Abnormal keratinization involves the entire skin.

A.   Ichthyosis Vulgaris Group（尋常性魚鱗癬グループ）

1.    Ichthyosis Vulgaris（尋常性魚鱗癬）

 a.  Definition:

・ A hereditary condition of varying severity with generalized abnormal keratinization, marked by dry scales adhering firmly to the skin.

 b.  Occurrence:

・ Relatively common, with a morbidity of 1:1000.

・ Starts toward the end of the first year of life and progresses until puberty, after which it tends to regress. 

 c.  Inheritance:

・ Autosomal dominant

 d.  Pathogenesis:

・ A diminished shedding of corneocytes; retention hyperkeratosis; the basic defect seems to be in the formation of keratohyalin (formation of too little or of abnormal keratohyalin).

 e.  Clinical Findings:

     Symmetrical changes on the extensor surfaces of the limbs and the entire trunk, particularly the lower part.

1)   Ichthyosis Simplex

2)   Ichthyosis Vulgaris

3)   Ichthyosis Nigricans

4)   Ichthyosis Serpentina

 f.   Symptoms:

・ Mild pruritus, the dryness of the skin, reduced production of sweat and sebum.

 g.  Associated Disorders:

・ Atopic eczema (in up to 50% of patients)

 h.  Histopathology:

・ Orthohyperkeratosis with absent granular layer.

 i.   Course:

・ Develop in the first 3 years of life.

2.    X-Chromosomal Recessive Ichthyosis（伴性遺伝性魚鱗癬）

 a.  Definition:

・ A form of ichthyosis which clinically resembles ichthyosis vulgaris.

 b.  Occurrence:

・ Rare, confined to males.

 c.  Inheritance:

・ X-chromosomal recessive.

 d.  Pathogenesis:

・ A retention hyperkeratosis.  Reduced arylsulfate E and steroid sulfatase activities in the epidermis.

 e.  Clinical Findings:

・ The extensor surfaces of the extremities and the lower parts of the trunk, especially the abdomen.

 f.   Histopathology:

・ The interfollicular orthohyperkeratotic stratum corneum is of approximately ten times the normal thickness.

・ In contrast to ichthyosis vulgaris, the stratum granulosum is normal, as are all other parts of the epidermis.

 g.  Course:

     Be present at birth and always appear in infancy.

3.    Refsum's Syndrome（レフザム症候群）

 a.  Occurrence:

・ Very rare, begins in early childhood.

 b.  Pathogenesis:

1)   Caused by a congenital enzyme abnormality, which is transmitted as an autosomal-recessive trait.

2)   A defective enzyme (phytanic acid-hydroxylase) prevents the normal metabolism of ingested phytanic acid, a branched-chain fatty acid (tetramethylhexadecanoic acid).

3)   This results in the accumulation of phytanic acid           (normally only traces are present in the lipid fractions of many organs).

4)   Phytanic acid is a degradation product of phytol, an alcohol which is bound to pyrrol ring IV of chlorophyll and is ingested with the diet.

 c.  Clinical Findings:

1)   The condition is marked by pathological changes in the skin, eyes, and nerves.  Skin changes in the form of mild ichthyosis vulgaris have been described in 54% of the cases.

2)   Systemic findings include night blindness and other visual disorders associated with atypical retinitis pigmentosa, sensorineural hearing loss (ranging from approximately 50-60% to total), chronic progressive polyneuritis with paralysis of the distal extremities, joint dysplasia, and cerebellar signs such as ataxia.

4.    Ichthyosis Congenita Gravis

 a.  Synonyms:  Harlequin fetus（道化師様魚鱗癬）

 b.  Occurrence:

・ Exceedingly rare, probably transmitted as an autosomal recessive trait.

 c.  Pathogenesis:

1)   The lethal genotype of abnormal keratinization, probably involving the formation of β-keratin in place of the normal α-keratin.

2)   β-Keratin is a normal constituent of bird feathers and reptilian skin.

 d.  Clinical Findings:

・ Born prematurely with grotesque malformations including amor-like thickening of the skin containing deep fissures, contractures, and ectropion of the eyelids and the oral and genital mucous membranes.

5.    Ichthyosis Congenita Mitis and Tarda

Synonyms.  Non-bullous Congenital Ichthyosiform Erythroderma（非水疱型先天性魚鱗癬様紅皮症）

 a.  Definition:

・ Abnormal keratinization of varying severity transmitted as an autosomal recessive trait.

 b.  Occurrence:

・ The conditions are very rare.

 c.  Pathogenesis:

1)   Greatly increased epidermal proliferation, and very rapid passage of the keratinocytes through the epidermis.

2)   A proliferation hyperkeratosis

 d.  Clinical Findings:

     The condition varies in severity and on this basis may be described as ichthyosis congenita mitis, tarda, or larvata.  The fish-scale-type abnormal keratinization birth but in certain milder forms it manifests itself only in the first months of life.

 e.  Histopathology:

1)   The epidermis shows an irregular acanthosis and the stratum granulosum is thickened.

2)   The stratum corneum is massively orthohyperkeratotic with up to 100 layers of cells in place of the normal 15-20.

6.    Lamellar Ichthyosis（葉状魚鱗癬）

 a.  Definition:

・ A form of ichthyosis congenita.

 b.  Occurrence:

・ Very rare.  There are two forms: one transmitted as an autosomal recessive, the other as an autosomal dominant trait.

 c.  Clinical Findings:

1)   Different degrees of severity have been described.

2)   Neonates may show diffuse reddening and lamellar scaling.

3)   Sometimes an infant is born covered with a yellow-brown, creased, dry, film-like membrane reminiscent of a collodion film or parchment.

 

B.   Ichthyosis Hystrix Group（豪猪皮状魚鱗癬）

Definition

・  Applied to all ichthyoses characterized by the most severe, verrucous, porcupine-like, black-brown, hyperkeratotic ridges.

1.    Erythrodermia Ichthyosiformis Congenitalis Bullosa （水疱型先天性魚鱗癬様紅皮症）
Synonyms: Epidermolytic Hyperkeratosis, Bullous Congenital Ichthyosiform Erythroderma, Keratosis Rubra Congenita.

 a.  Definition:

・ Congenital abnormality of keratinization, with universal reddening, scaling, and sometimes vesiculation.

 b.  Occurrence:

・ Very rare, irregular transmission as an autosomal dominant trait.

 c.  Clinical Findings:

1)   Erythroderma, i.e., reddening and lamellar scaling of the entire skin is generally present at birth.

2)   Periodic eruptions of large flaccid bullae which burst under mechanical pressure, leaving erosions which ultimately heal without scarring.

3)   Diffuse keratoses on the palms and soles spread to the dorsal surfaces of the hands and feet.

4)   Ultimately the clinical picture can resemble that of ichthyosis congenita but they can be easily differentiated histologically.

 d.  Histopathology

1)   Epidermolytic hyperkeratosis with marked degeneration in the stratum granulosum (granular degeneration).

2)   Proliferation hyperkeratosis

2.    Acquired (Symptomatic) Ichthyoses（後天性魚鱗癬）

Synonym:  Symptomatic Ichthyosiform Skin Changes

 a.  Clinical Findings:

・ Often not possible clinically or histologically to distinguish these conditions from ichthyosis vulgaris.

 b.  Causes:

・ Ichthyosiform skin lesions occur:

1)   As paraneoplastic syndromes in Hodgkin's disease, mycosis fungoides, other malignant lymphomas, and visceral carcinomas

2)   As a concomitant symptom in infectious diseases, e.g., leprosy, tuberculosis, AIDS, typhoid and typhus fever

3)   In dietary and vitamin deficiencies (vitamin A deficiency, pellagra)

 

II. Palmar and Plantar Keratoses（掌蹠角化症）

Abnormal keratinization in this group of disorders affects, to varying degrees, the palms and soles.

1.    Keratosis Palmoplantaris Diffusa Circumscripta（限局性びまん性掌蹠角化症）

 a.  Clinical Findings:

・ Symmetrical and consist of diffuse thickening of the stratum corneum which is waxy and yellow with exaggerated markings and sometimes fissures.

 b.  Histopathology:

・ A massive thickening of the stratum corneum.

2.    Keratosis Palmoplantaris Transgrediens

 a.  Occurrence:

・ Keratosis palmoplantaris transgrediens transmitted as an autosomal recessive trait.

 b.  Clinical Findings:

・ Begins in infancy

3.  Syndromes with Palmoplantar Keratoses

・ Papillon-Lefevre Syndrome: Hyperkeratosis palmaris et plantaris with periodontosis.

・ Keratosis Palmoplantaris Mutilans: Keratoma hereditarium mutilans.

・ Richner-Hanhart Syndrome: Keratosis palmoplantaris circumscripta seu areata, oculocutaneous tyrosinemia.

・ Keratosis Palmoplantaris with Carcinoma of the Esophagus

 

III. Follicular Keratoses（毛孔性角化症）

The impaired keratinization is confined to the hair follicles.

1.    Keratosis Pilaris（毛孔性角化症）

Synonyms: Lichen Pilaris（毛孔性苔癬）, Keratosis Follicularis, Keratosis Suprafollicularis.

 a.  Definition:

・ Benign impairment of the keratinization of the hair follicles, the openings of which become filled with keratin plugs that are raised above the level of the skin.

 b.  Histopathology:

・ Hyperkeratosis of the follicular ostium and of the entire supraseboglandular follicular epithelium with varying degrees of inflammation.

2.    Ulerythema Ophryogenes: Keratosis pilaris rubra atrophicans faciei（眉毛瘢痕性紅斑）

 a.  Occurrence:

・ Relatively rare: irregular autosomal dominant transmission.

3.    Hyperkeratosis Follicularis et Parafollicularis in Cutem Penetrans [Kyrle 1916]（真皮貫通性毛包性毛包周囲性角質増殖症）

Synonym:  Kyrle's Disease（キルレ病）.

 a.  Definition:

1)   Usually isolated but sometimes grouped follicular papules, chiefly on the legs, with firmly inserted keratotic pegs.

2)   Occur in conjunction with renal disease (dialysis patients).

 b.  Histology:

・ A follicular hyperkeratosis which penetrates via the follicular wall into the dermal connective tissue and induces foreign-body granulomas.

4.    Keratosis Follicularis
Synonyms:  Darier's Disease（ダリエー病）, Darier-White Disease, Dyskeratosis Follicularis.

a.    Definition:

1)   A rare familial abnormality of keratinization which tends to increase with advancing age.

2)   Manifests itself clinically by keratotic papules and histologically by dyskeratosis.

3)   Mutation in SERCa (savioendoplasmic reticulum Ca²⁺ ATPase) gene.

 b.  Occurrence:

・ The condition is rare; males are affected more often than females.  The disorder is transmitted as an autosomal dominant trait with varying penetrance; spontaneous mutations are not uncommon.

 c.  Clinical Findings:

・ The favored symmetrical sites subject to seborrheic dermatitis（脂漏性皮膚炎）and intertrigo（間擦疹）.

・ Individual Lesions: Conical papules, 1-3 mm in size, which are covered by a firmly adhering dirty-gray to yellowish-brown keratotic mass: keratotic papules

・ Head: Oily, foul-smelling crusts form on the scalp but there is no hair loss.

・ Palms and Soles: Interrupted ridges in the fingerprints.

・ Nails: Longitudinal splitting, onychorrhexis, thickening, or subungual keratoses.

・ Mucous Membranes: Whitish, small papules with concave tops which can even involve the esophagus.

・ Mental State: Retarded and/or abnormal behavior.  Depression and psychoses.

・ Symptoms: Severe pruritus especially from intertriginous or irritated lesions

 d.  Histopathology:

・ Dyskeratosis with suprabasal acantholysis and lacunae in the slightly acanthotic epidermis as well as hyperkeratosis and patchy parakeratosis.

・ Focal acantholytic dyskeratosis

 

IV. Circumscribed Keratoses not Restricted to the Follicles

1.    Acrokeratosis Verruciformis（疣贅状肢端角化症）

 a.  Definition:

1)   Resembling plane warts, on the backs of hands.

2)   Seen concomitantly with keratosis follicularis (Darier's disease).

 b.  Clinical Findings:

1)   The condition, which is frequently begins in adolescence and consists of plane, often polygonal papules, of the same color as the skin or slightly red or brown.

2)   A variant of keratosis follicularis

2.    Porokeratosis of Mibelli（汗孔角化症）

 a.  Definition:

・ A multifocal circumscribed impairment of epidermal differentiation in combination with parakeratosis.

 b.  Occurrence:

・ The condition is transmitted as an irregular autosomal dominant trait but may occur spontaneously.

 c.  Clinical Findings

・ Begin at any age.  The extremities and to a lesser extent the trunk, face and glans penis.

3.    Disseminated Superficial Actinic Porokeratosis（播種状表在性光線性汗孔角化症）
Synonym:  Porokeratosis superficialis disseminata actinica.

 a.  Clinical Findings:

1)  A disseminated form of porokeratosis occurring in light-exposed areas of the skin, e.g., the dorsi of the hands, extensor surfaces of the lower arms, lower legs, and the face.

2)   The lesions resemble the small lesions of porokeratosis of Mibelli, both clinically and histologically.

4.    Ichthyosis Linearis Circumflexa（曲折線状魚鱗癬）

Synonym:  Netherton's syndrome

 a.  Definition:

・ Congenital impairment of keratinization, classified between ichthyoses and erythrokeratodermas, with geographical, linear, or polycyclic brownish-red hyperkeratoses, usually associated with abnormalities of the hair.

 b.  Occurrence:

・ An autosomal recessive trait.

 c.  Clinical Findings:

・ Begins in the 1st year of life.  Diffuse reddening of the skin is followed by gyrate, annular or geographical brownish-red keratoses surrounded by double margins of scales.

 d.  Associated Findings:

・ Abnormalities of the hair including diffuse alopecia（びまん性脱毛）, trichorrhexis in vaginata (bamboo hair), trichorrhexis nodosa（結節性裂毛）, or pilitorti（捻転毛）.