Basic Science

bullous pemphigoidx

bullous pemphigoid antigen-1, 230 kDd; bullous pemphigoid antigen-2, 180 kDa

cicatricial pemphigoid

bullous pemphigoid antigen-2

EBA

a chain of type VII collagen (290 kDa)

EB, dystrophic

type VII collagen

EB, generalized atrophic benign

bullous pemphigoid antigen-2, laminin

EB, junctional-pyloric atresia

integrin a6 b4

EB, junctional-lethal

laminin 5 a₃, b₃, g₂

EB simplex recessive with muscular dystrophy

plectin

EB simplex recessive-Koebner

keratin 14

EB, simplex

keratins 5, 14

EBA

type VII collagen (anchoring fibrils)

herpes gestationis

bullous pemphigoid antigen-2

ichthyosis vulgaris

profilaggrin?

lamellar ichthyosis

keratinocyte-specific transglutaminase

pemphigus foliaceus

desmoglein-1 (a cadherin) 160 kd

pemphigus vulgaris

desmoglein-3 (a cadherin) 130 kd

dysplastic nevus s., xeroderma pigmentosa

 

Ehlers-Danlos type VI, erythrokeratoderma viriabilis, erythrokeratoderma with ataxia

 

Chediak-Higashi s. (CHS), EB-junctional-Herlitz (LAMB3, LAMC2), familial cold urticaria, PCT, porphyria variegata (PPOX), Vohwinkel s. (LOR)

 

acrokeratoelastoidosis, kappa light chain, elastin molecule

 

Carney/LAMB/NAME s. (2p16)

 

Cockayne s.-XP-B (ERCC3), EB-pyloric atresia (ITGA6), Ehlers-Danlos IV (COL3A1) (2q31), lamellar ichthyosis, Waardenburg’s s. type I (2q35,), Waardenburg’s s. type III (2q35 PAX-3), wrinkly skin s. (WSS, 2q32), xeroderma pigmentosum-complement group B (ERCC3, XPB) (2q21)

 

EB-dystrophic dominant (3p21.3, COL3A1), EB-pretibial type (3p21.3), EB-Bart type (3p21.3), Hailey-Hailey d. (3q21-q24), Marfan s. type II (3p25-p24.2), Muir-Torre s. (3p21.3), von Hippel-Lindau s. (3p26-p25), Waardenburg’s s. type II (3p14.1-p12.3, MITF), XP-C (3p25, XPC)

 

Hailey-Hailey d.

 

chondrodysplasia punctata (4p16-p14), Ellis-van Creveld s. (4p16)

 

piebaldism (C-KIT), sclerotylosis

 

Gardner’s s. (APC)

 

HLA-A,B,C,DR,DP,DQ,E,F,G, C3 and C4, b2 microglobulin, TNF-a and b

 

hemochromatosis

 

Ehlers-Danlos type IV (arthrochalasis multiplex congenita), pro alpha 2 (I) gene

 

arginosuccinic aciduria

 

EEC s. (7q11.2-q21.3), Ehlers-Danlos s. type VII (7q22.1)

 

Rothmund-Thomson s.

 

Pfeiffer s. (8p12-p11.2), Werner s. (8p12-11.2, WER)

 

EB-Ogna (8q24), EB-muscular dystrophy (8q24, PLEC)

 

hereditary coproporphyria

 

albinism 3 (TRP1), blue rubber bleb nevus s. (TIE2), melanoma (9p21, CDKN2), trichoepithelioma-familial

 

basal cell nevus s. (9q22.3, PTC), Ehlers-Danlos I, II (COL5A1), familial keratoacanthomas, hypomelanosis of Ito (9q33-qter), nail-patella s., tuberous sclerosis 1 (TSC1), XP-A (XPAC)

 

Refsum’s d. (10pter-p11.2)

 

Apert’s s. (10q26), congenital erythropoietic porphyria (10q25.2-q26.3), Cowden d. (PTEN, MMAC1), EB-junctional-GAB (10q24.3, BPAG2), Hermansky-Pudlak (HPS)

 

acute intermittent porphyria, EB-dystrophic

 

Beckwith-Wiedemann s. (11pter-p15.4), XP-E (DDB)

 

albinism-tyrosinase - & + (11q14-q21, TYR), ataxia telangiectasia (11q22.3), atopy (11q12-q13), hereditary angioedema (11q11-q13.1, C1NH), Papillion-Lefevre s., porphyria-acute intermittent (11q24.1-q24.2)

 

Darier’s d. (12q23-q24.1), EB-simplex, epidermolytic hyperkeratosis, non-epidermolytic palmoplantar hyperkeratosis, ichthyosis bullosa of Siemens (12q11-q13), monilethrix (12q13), multiple lipomatosis (12q15), pachyonychia congenita (12q12-q14), white sponge nevus (12p11.2-q11)

 

XP-G (13q33, ERCC5), hidrotic ectodermal dysplasia

 

ataxia telangiectasia, heavy chain

 

lamellar ichthyosis (TGM1)

 

albinism-tyrosinase + (15q11.2-q12), Bloom’s s. (15q26.1), hypomelanosis of Ito (15q11-q13), Marfan s. (15q21.1), tyrosinemia type I (15q23-q25)

 

Rubinstein-Taybi s. (16q13.3), tuberous sclerosis-2 (TSC2)

 

cylindroma, tyrosinemia II- Richner-Hanhart s. (TAT)

 

Sjogren-Larson s. (FALDH)

 

EB-simplex, epidermolytic hyperkeratosis (generalized/palmoplantar) (17q12-q21), pachyonychia congenita, white sponge nevus, neurofibromatosis 1 (17q11.2, NF1), tylosis, EB-junctional (ITGB4)

 

hereditary multiple leiomyomata (18p11.32)

 

EB-junctional (18q11.2, LAMA3), palmoplantar keratoderma, striae, erythropoietic protoporphyria (18q21.3, FCE)

 

acanthosis nigricans, C3 deficiency, Peutz-Jeghers s. (19p13.3)

 

XP-D (19q13.2-q13.3)

 

McCune-Albright s. (20q13.2), SCID with ADA deficiency (20q13.11)

 

CR3 deficiency

 

leukocyte adhesion deficiency (21q22.3)

 

lambda light chain,

 

DiGeorge s. (22q11), neurofibromatosis II (22q12.2)

 

hypomelanosis of Ito, incontinentia pigmenti type I, Menkes s.

 

Gorlin-Goltz s. ichthyosis-recessive X-linked (Xp22.32, STS), incontinentia pigmenti-1, Kallmann s. (Xp22.3), keratosis follicularis spinulosa decalvans (Xp22.2-p22.13), ocular albinism, Partington s. (Xp22-p21), Wiskott-Aldrich s. (Xp11.23-p11.22)

 

Alport s. (Xq 22), anhidrotic ectodermal dysplasia (EDA), congenital generalized hypertrichosis, dyskeratosis congenita (Xq28), Fabry’s d. (Xq22), incontinentia pigmenti-2 (Xq28), Menkes s. (Xq12-q13)

 

acanthosis nigricans (19p), acrokeratoelastoidosis (2), acute intermittent porphyria (11), albinism 3 (TRP1) (9p), albinism-tyrosinase - & + (11q, TYR), albinism-tyrosinase + (15q), anhidrotic ectodermal dysplasia (Xq, EDA), arginosuccinic aciduria (7p), ataxia telangiectasia (14),

b2 microglobulin (6), BCC (patched), basal cell nevus s. (9q, PTC) (), Bloom’s s. (15q26.1), blue rubber bleb nevus s. (9p, TIE2) 

C3 deficiency (19p), CR3 deficiency (21), Chediak-Higashi s. (CHS) (1q42.1-42.2), Cockayne s.-XP-B (10q11, ERCC3), congenital generalized hypertrichosis (Xq), Cowden d. (10q22-q23, PTEN, MMAC1), cylindroma (16q),

Darier’s d. (12q23-24.1), dysplastic nevus s. (1)

EB-dystrophic (COL3A1) (3p21.3), EB-dystrophic (11), EB-junctional (1q25-q31, LAMB3, LAMC2), EB-junctional-GAB (10q, BPAG2), EB-junctional (17q, ITGB4), EB-junctional (18q, LAMA3), EB-muscular dystrophy (8q, PLEC), EB-Ogna (8q), EB-pretibial type (3p21.3), EB-pyloric atresia (2q, ITGA6), EB-simplex (12q), EB-simplex (17q), Ehlers-Danlos IV (2q, COL3A1), Ehlers-Danlos I, II (9q, COL5A1), Ehlers-Danlos type IV (arthrochalasis multiplex congenita) (7), Ehlers-Danlos type VI (1p36.3-p36.2), elastin molecule (2), epidermolytic hyperkeratosis (12q), epidermolytic hyperkeratosis (generalized/palmoplantar) (17q), erythropoietic protoporphyria (18q21.3, FCE), erythrokeratoderma viriabilis (1p34-35), erythrokeratoderma with ataxia (1p34-35)

familial cold urticaria (1q), familial keratoacanthomas (9q),

Gardner’s s. (5q, APC),

Hailey-Hailey d. (3q21-24), heavy chain (14), hemochromatosis (6p), hereditary angioedema (11p, C1NH), hereditary coproporphyria (9), HLA-A,B,C,DR,DP,DQ,E,F,G, C3 & C4 (6), Hermansky-Pudlak (10q23.1-q23.3, HPS), hidrotic ectodermal dysplasia (13q), hypomelanosis of Ito (15q11-q13),

ichthyosis bullosa of Siemens (12q), incontinentia pigmenti type I (Xp11), incontinentia pigmenti-2 (Xq28), ichthyosis vulgaris (1q21,FLG),

k light chain (2),

l light chain (22), lamellar ichthyosis (2q), lamellar ichthyosis (14q, TGM1),

Marfan s. type II (3p25-p24.2), melanoma (9p, CDKN2), Menkes s. (X-MKN/ATP7A), monilethrix (12q13), Muir-Torre s. (3p21.3)

nail-patella s. (9q34.1), neurofibromatosis 1 (17q11.2, NF1), neurofibromatosis II (22), non-epidermolytic palmoplantar hyperkeratosis (12q),

ocular albinism (Xp), Osler-Rendu-Weber s. 2 (12q11-q14)

pachyonychia congenita (12q12-q14), pachyonychia congenita (17q), palmoplantar keratoderma (18q), Papillion-Lefevre s. (11q), PCT (1q), Peutz-Jeghers s. (19p13.3), piebaldism (4q12, C-KIT), porphyria variegata (1q22, PPOX), pro alpha 2 (I) gene (7), porphyria-congenital erythropoietic (10q25.2-q26.3), psoriasis susceptibility (17q)

recessive X-linked ichthyosis (Xp, STS), Rubinstein-Taybi s. (16p13.3)

sclerotylosis (4q), Sjogren-Larson s. (17p11.2, FALDH), striae (18q),

TNF-a & b (6), trichoepithelioma-familial (9p), tuberous sclerosis 1 (9q34, TSC1), tuberous sclerosis-2 (16p13.3, TSC2), tylosis (17q), tyrosinemia II [Richner-Hanhart s.] (16q, TAT),

Vohwinkel s. (1q21, LOR), von Hippel-Lindau s. (3p26-p25)

Waardenburg’s s. 1 (2q35, PAX-3), Waardenburg’s s. 2 (3p & 13q, MITF), Watson s. (17q11.2), Werner s. (8p, WER), white sponge nevus (12p11.2-q11, 17q21-q22),

xeroderma pigmentosa (1), XP-A (9q, XPAC), XP-C (3p25, XPC), XP-D (19q), XP-E (11p, DDB), XP-F (16p13.13-p13.2), XP-G (13q33, ERCC5),

I

[a1(I)]₂a2(I)

bone, skin, tendon

Ehlers-Danlos type 7A, 7B

I-trimer

[a1(I)]₃

skin, tumors

 

II

[a1(II)]₃

cartilage

 

III

[a1(III)]₃

fetal skin, blood vessels, GI tract

Ehlers-Danlos type 4

IV

[a1(IV)]₂a2(IV)

basement membrane

 

V

[a1(V)]₂a2(V); [a1(V)]₃

all

Ehlers-Danlos type 2

VI

a1(VI) a2(VI) a3(VI)

all

 

VII

[a1(VII)]₃

anchoring fibrils

 

VIII

[a1(VIII)]₃

endothelial cells

 

IX

a1(IX) a2(IX) a3(IX)

cartilage

 

X

[a1(X)]₃

hypertrophic cartilage

 

XI

a1(XI) a2(XI) a3(XI)

cartilage

 

XII

[a1(XII)]₃

cornea, ligaments, perichondrium, periosteum, tendons

 

XIII

[a1(XIII)]₃

all

 

XIV

[a1(XIV)]₃

cornea, skin, tendons

 

XV

unknown

basement membrane

 

XVI

[a1(XVI)]₃

cartilage, internal organs, skin

 

XVII

[a1(XVII)]₃

hemidesmosomes

 

XVIII

unknown

basement membrane

 

XIX

unknown

basement membrane

 

basic FGF, acidic FGF

macrophages, endothelial cells

angiogenesis & fibroblast proliferation

CSF-1

multiple cells

macrophage activation, granulation tissue formation

EGF

 

epidermal growth & differentiation, wound healing, keratinocyte migration via a₂ integrins

IFN-g

produced by Th1 cells

inhibits IgE synthesis, down-regulates Th2 responses

IL-1

produce by neutrophils, keratinocyte derived

express growth factors, T & B cell activation, chemotaxis, ICAM-1 induction, pyrogen

IL-1 sources

astrocytes, B-cells, corneal cells, dendritic cells, endothelial cells, fibroblasts, keratinocytes, Langerhan’s cells, macrophages, melanoma cells, mesangial cells, neutrophils, OKM 1+ LGL

 

IL-2

 

stimulates T lymphocytes

IL-3

keratinocyte derived

stimulates proliferation

IL-4

secreted by Th2 cells

synthesis of IgE, accumulation of eosinophils

IL-5

secreted by Th2 cells

synthesis of IgE, accumulation of eosinophils

IL-6

secreted by Th2 cells, keratinocyte derived

synthesis of IgE, accumulation of eosinophils

Insulin-like GF-I

fibroblasts; epidermal cells

reepithelialization and granulation tissue formation, induces TGF-a autocrine proliferation of keratinocytes

keratinocyte GF

fibroblasts

keratinocyte motility and proliferation

PDGF

platelets, macrophages, epidermal cells

fibroblast proliferation and chemoattraction, macrophage chemoattraction and activation, mediates vasoconstriction

PGE₂

produced by monocytes

inhibits Th1 cell derived IFN-g

TGF-a, heparin-binding EGF

platelets

epidermal and mesenchymal regeneration, pleiotropic cell motility and proliferation

TGF-b1 and b2

platelets, macrophages

epidermal cell motility, chemotaxis of macrophages and fibroblasts, extracellular matrix synthesis and remodeling

TGF-b3

macrophages

anti-scarring effects

TNF-a

neutrophils

expression of growth factors

ALA dehydratase

converts D-aminolevulinic acid to porphobilinogen; ALA dehydratase deficiency porphyria

cholesterol sulfate

inhibits normal desquamation of stratum corneum cells

coproporphyrinogen oxidase

converts coproporphyrinogen III oxidase to harderoporphyrinogen; hereditary coproporphyria

ferrochelatase

converts protoporphyrin to heme; erythropoietic protoporphyria

glucose-6-phosphate dehydrogenase

oxidoreductase class enzyme, first enzyme in the pentose phosphate shunt of glucose metabolism, absence may lead to increased hemolysis (e.g. for patients on dapsone)

homogentisic acid oxidase

lack leads to endogenous ochronosis (alkaptonuria)

porphobilinogen deaminase

Converts porphobilinogen to hydroxymethylbilane; acute intermittent porphyria

protoporphyrinogen oxidase

converts protoporphyrinogen oxidase to protoporphyrin IX; variegate porphyria

steroid sulfatase

converts cholesterol sulfate to cholesterol; absent in recessive X-linked ichthyosis

uroporphyrinogen decarboxylase

converts uroporphyrinogen I to coproporphyrinogen I, converts uroporphyrinogen III to 7-carboxyl porphyrinogen III; porphyria cutanea tarda, hepatoerythropoietic porphyria

uroporphyrinogen II cosynthase

converts hydroxymethylbilane to uroporphyrinogen; congenital erythropoietic porphyria

alopecia areata

DQB1*03 (DQ3), DRB1 (DR11)   severe; DRB1*0401 (DR4), DQB1*0301 (DQ7)

Behçet’s s.

B5, B51, B52

dermatitis herpetiformis

B8, DR3, DQw2

epidermolysis bullosa acquisita

DR2

erythema multiforme

B35, B62

erythema multiforme (herpes-associated)

DQB1*0301, DQw3, Bw62, B35, DR53, DR4

Hailey-Hailey d.

B16

herpes gestationis

DR3, DR4

lichen planus

DQw1, DR2, DR1, DR10, DRw9, Bw61/DRw9

linear IgA

B8

mycosis fungoides

DR5, DQB1*03

pemphigus foliaceus

DRB1*0102, DR1, DQw1, DR4,DQw3, DQB*0301

pemphigus vulgaris

Dw10/DR4, Dw10, DR4, DRw6, DQB1.3

pityriasis rosea

DR

psoriasis, pustular

B27

psoriasis

Cw6 (9-15x), B13, B17, Bw57

psoriatic arthritis

B27, B39, DQw3

Reiter’s s.

B27 (80%)

Sezary s.

DQB1*0502

Sjögren’s s.

DQw2, DR3

systemic lupus erythematosus

homozygous C4A+DR2, DR2, DR3

systemic sclerosis

DQA2, C4AQ0

Unna-Thost d.

12q11-13

urticaria, chronic idiopathic

DR4, DRB4 53, DQ8, DQA 3011/12

vitiligo

A30, Cw6, Cw7, DQw3, DR4, DR6

Vogt-Koyanagi-Harada s.

Dw15, DQw3, DR4, DRw53

K1

structural keratin, suprabasal epidermal keratinocytes, palmoplantar suprabasal keratinocytes; non-epidermolytic palmoplantar keratoderma, epidermolytic hyperkeratosis

K2e

epidermal granular layer

K2e

ichthyosis bullosa of Siemens

K3

cornea

K4

non-keratinizing stratified squamous epithelia; white sponge nevus

K5

basal layer “mitotic” keratinocytes; epidermolysis bullosa simplex

K6

proliferation, keratoderma (epidermolytic)

K6a

outer root sheath, hyperproliferative keratinocytes, oral epithelium; pachyonychia congenita-Jadassohn-Lewandowsky type (type 1)

K6b

nail bed, myoepithelium, inflammation

K7

transformed cells

K8

simple epithelia

K9

palmar-plantar specific protein keratoderma (nonepidermolytic)

K10

structural keratin, epidermal granular layer; epidermolytic hyperkeratosis

K11

 

K12

cornea

K13

white sponge nevus

K14

basal layer “mitotic” keratinocytes

K15

basal layer of non-keratinizing epithelia

K16

outer root sheath, hyperproliferative keratinocytes, oral epithelium; proliferation keratoderma (epidermolytic), pachyonychia congenita-Jadassohn-Lewandowsky type (type 1)

K17

nail bed, myoepithelium, inflammation; pachyonychia congenita (Jackson-Lawler-type 2), PRP

K18

simple epithelia

K19

bulge cells, simple epithelia

K20

Merkel cells

K21

intestinal epithelium

citrulline

keratotic BCC, inner root sheath, hair medulla, keratolinin

cysteine

involucrin

desmoglein 1

pemphigus foliaceous

desmoglein 3

pemphigus vulgaris

elastin

dermis; pseudoxanthoma elasticum

fibrillin

elastic microfibril of lower BMZ & dermis; Marfan’s s.

filaggrin

binds keratinocytes

histidine

filaggrin, profilaggrin

involucrin

differentiation

keratolinin

differentiation

loricrin

differentiation

profilaggrin

processed to filaggrin; absent in ichthyosis vulgaris