Textbook of Pediatric Dermatology Arun C Inamadar, Aparna Palit, S Sacchidanand, S Ragunatha
Abdominal pain 508
Absidia 182
Acanthosis nigricans 520
Achromic nevus 381
Acne 318
clinical features 319
differential diagnosis 320
treatment 320
variants 321
acne conglobata 322
acne excoriee 322, 527, 551
acne fulminans 322, 551
acne keloidalis 295
acne neonatorum 20
drug-induced 322
gram-negative folliculitis 322
hyperandrogenism 322
neonatal, infantile and juvenile 321
steatocystoma multiplex 322
sweat-retention syndrome 324
Acrocyanosis 18
Acrodermaitis enteropathica 581
Acrokeratoelastoidosis of Costa 53
Acrometageria 88
Actinic keratoses 462
Acute febrile neutrophilic dermatosis 438
associations 439
clinical features 438
differential diagnosis 439
etiology 438
histopathology 439
pathogenesis 438
treatment 439
Acute hemorrhagic edema of infancy 154
Acute skin failure 560, 562
Addison's disease 518
Adenoma sebaceum 77
Adrenal gland disorders 518
Adrenogenital syndrome 519
Adrenoleukodystrophy 380
AEC syndrome 39
African eyeworm infection 192
Alkaptonuria (ochronosis) 73
Allergic contact dermatitis 108, 118
clinical features 108
management 109
Alopecia areata 282
clinical features 283
course and prognosis 284
diagnosis 283
differential diagnosis 283
etiopathogenesis 282
management 284
anthralin 285
corticosteroid 284
immunotherapy 285
minoxidil 285
PUVA 285
Alopecia mucinosa 295
Ambras syndrome 296
Amebiasis 189
Amino acid disorders 346
Amino acid metabolism disorders 72
Amniotic band syndrome 21
Amyloidosis 533
heredo-familial systemic 534
primary systemic 534
secondary systemic 534
Anagen effluvium 281
Analgan tattoo 272
Anatomy of nail 308
Ancylostomiasis 195
Anderson-Fabry disease 508
Androgen excess disorders 519
Androgenetic alopecia 285
Angioblastoma 413
Angioedema 508, 566
Angiogenesis 416
Angiokeratomas 422
Anhidrosis 326
Animal and human bites 218
Ankylogossia 273
Annular eryhthemas 404
annular erythema of infancy 405
erythema annulare centrifugum 404
erythema chronicum migrans 405
differential diagnosis 405
Anogenital warts 142
Anonychia/micronychia 310
Anorexia nervosa and bulimia 527
Antihistamines 105
Apert's syndrome 552
Aphthous ulcers 509
Aplasia cutis 279
congenita 21
Aplastic nevus 279
bromhidrosis 329
chromhidrosis 329
glands 328
miliaria 329
nevus 455
tumours 457
Appendageal tumors 457
with eccrine differentiation
benign neoplasms 457
cyst 457
hamartoma 457
syrongoma 457
with follicular differentiation
benign neoplasm 458
cysts 458
hamartoma 458
with sebaceous differentiation 459
cysts 459
hamartomas 459
Appendages 8
apocrine glands 9
dermis 9
dermo-epidermal junction 9
eccrine glands 9
formation 5
hair 8
nail 8
sebaceous glands 9
Arachnida 216
Arteriovenous malformations 419
Arthropod-borne infections 213
Arthropods 206
Ash-leaf spots 78
Aspergillosis 181
Asteatotic eczema 111
Asymmetric periflexural exanthem 153
Ataxia telangiectasia 57
Atopic dermatitis 98, 344, 543
complications 101
diagnostic features 99
key steps 100
laboratory investigations 101
differential diagnosis 101
etiopathogenesis 98
management 102
complementary treatments 106
general measures 102
specific measures 102
systemic therapy 105
natural history and prognosis 101
prevalence and incedence 98
Atopic diathesis 516
Atopic winter feet 116
Atrichia 278
Autoimmune polyglandular syndromes 521
Autosensitization dermatitis 109
Autosomal disorders 89
Autosomal mutations 521
Axillary freckling 76
α1 antitrypsin deficiency panniculitis 449
Bacille Calmette Guerin 243
Bacterial vaginosis 227
Basal cell nevus 458
syndrome 530
Basal layer 6
Basaloid follicular hamartoma 458
Batner's itch 201
Beau's lines 308
Behcect's syndrome 269
Becker's nevus 378
Bed bugs 215
Behcet's disease 515, 537
clinical features 538
diagnosis 538
differential diagnosis 538
epidemiology 537
etiology 537
histopathology 538
treatment 539
Benign cephalic histocytosis 468
Benign epithelial tumors 454
Benign neoplasm 21
Bilateral acoustic schwannoma 77
Bilharziasis 200
Blastomycosis 180
Bleaching 299, 391
Blinding filariasis 191
Blister beetle dermatitis 215
Blistering diseases 508
Blistering distal dactylitis 125
Bloch-Sulzberger disease
clinical features 39
diagnosis 40
differential diagnosis 40
genetics 39
investigations 40
management 41
Bloom syndrome 67
Blue rubber bleb nevus 508
syndrome 424
Body dysmorphic disorder dysmorphophobia 527
Bohn's nodules 271
Bourneville's disease 77
Bowen's keratoses 462
Branchial clefts and sinuses 21
Bromoderma 447
Bronchogenic cysts 21
Bullous disorders 531
Bullous ichthyosiform erythroderma 343
Bullous pemphigoid
cicatricial 366
gestationis 367
localized vulvar 366
Buschke-Ollendorff syndrome 83
Butterflies 215
C2 deficiency 59
Café au lait spots 76, 374
Calabar swellings 192
Calcifying panniculitis 513
Calcineurin inhibitors 103
Camisa's syndrome 52
Candidiasis 23, 271
Capillary malformations of the skin
clinical features 416
diagnosis 418
management 418
pathogenesis 417
Carbuncles 124
Carcinoid syndrome 516
Cardiac diseases and skin 514
Cardiff's tropical disease 201
Carney complex 57
Celiac disease 510
Cellulitis 124
buccal 125
perianal 125
periorbital and orbital 125
Centipedes 217
Cercarial dermatitis 201
Chanarin-Dorfman syndrome 48
Chédiac Higashi syndrome 59, 302, 383
Chickenpox (Varicella)
clinical features 133
epidemiology 133
laboratory investigations 134
pathogenesis 133
prognosis 134
varicella vaccine 134
varicellazoster immunoglobulin 134
Child syndrome 49
Childhood melanoma 377
Childhood psoriasis
clinical features 334
differential diagnosis 339
etiology 334
forms of psoriasis 335
eczema/psoriasis overlap 338
erythrodermic 337
flexural 337
guttate 336
nail involvement 338
plaque 335
psoriatic diaper rashes 338
pustular 337
histopathology 334
pathogenesis 334
treatment 339
phototherapy 339
removal of triggering factors 339
systemic therapy 340
topical therapy 339
Chilopoda 217
Chlamydial infection 226
Christ-Siemens-Touraine syndrome 36
Chromoblastomycosis 179
Chromosomal disorders 29, 88, 521
Chromosome instability syndromes 67
Chronic complications
arsenic toxicity 530
bullous disease 368
granulomatous disease 60
mucocutaneous candidiasis 58
Churg-Strauss syndrome 503
alopecia 293
keratoderma 52
pemphigoid 531
Clam Diggois itch 201
Claw hand 259
Clouston's syndrome 38
Clubbing 314, 515, 531
Coastal erysipelas 191
Coccidioidomycosis 181
Cockayne syndrome 69
Cold nodular panniculitis 449
Coleoptera (beetles) 215
Collagen vascular disease 508, 531
Collodion body 46
Comedo nevus 455
Common warts 141
Complement deficiency disorders 59
Condylomata acuminata 142
Congenital complications
adrenal hyperplasia 519
candidiasis 343
diffuse alopecia 278
inherited disorders 515
localized alopecia 279
melanocytic nevus 279
syphilis 25
telangiectatic erythema 67
Connective tissue disorder 80, 270
Conradi-Hünermann-Happle syndrome 48
Contiguous gene syndromes 29
Corals 218
Corticosteroids 103, 105
Cosmetic camouflage 391
Cowden syndrome 80, 530
Cradle cap 109
Cranial meningocele 279
Craw-craw 191
Creeping eruption 197
Cryofibrinogenemia 505
Cryoglobulinemia 504
Cryptococcosis 181
Cutaneous diseases
candidiasis 174
ischemia 531
larva migrans 197
mastocytosis 468
classification 469
clinical features 469
diagnosis 471
differential diagnosis 472
epidemiology 469
mosaicism 29
paraneoplastic syndromes 531
signs of cardiac diseses 514
tuberculosis 238
dermatology complications 243
erythema nodosum 242
lichen scrofulosorum 242
lupus vulgaris 239
miliary tuberculosis of the skin 239
scrofuloderma 240
secondary cutaneous 239
tuberculids 242
tuberculosis verrucosa cutis 241
tuberculous chancre 239
hyperplastica 84
laxa 81, 88
marmorata 19
telangiectatica congenita 422
Cyanosis 514
Cyclosporine 105
Cystic fibrosis 516
Cysticercosis 202
Cysts of epidermal origin 456
Cytomegalovirus infections 138
Daily hair count 281
Darier's disease 271
De Sanctis-Cacchione syndrome 69
DeBarsy syndrome 88
Dego's syndrome 50
Delusions of parasitosis 527
Demodex folliculitis 531
Dermal leishmanoid 188
artefacta 528
herpetiformis 367
venenata 117
Dermatofibrosis lenticularis disseminata 83
Dermatological diseases 270
delusional symptoms 525
emergencies 560
non-disease 527
Dermatopathia pigmentosa reticularis 378
Dermatophytids 172
Dermatophytoses 166
Dermographism 401
Dermoid cyst 21, 456
Desmoplastic trichoepithelioma 458
Diabetes mellitus 519
Diabetic bullae 520
Diabetic dermopathy 519
Diaper dermatitis
clinical features 107
diagnosis 107
differential diagnosis 107
management 107
Diarrhea and malabsorption 509
Diethyltoluamide 206
Diffuse cutaneous mastocytosis 345, 471, 567
Diffuse maculopapular truncal eruption 146
Diffuse palmoplantar keratoderma 51
Digital verrucous fibroangioma 415
Diplopoda 217
Diptera 212
Dirofilariasis 199
Discoid eczema 111
Diseases of the nail bed 310
Disinfection 11
Dissecting cellulitis of the scalp 295
Dominant character 28
Down's syndrome 89
Dracontiasis 194
Dracunculiasis 194
Dragon worm 194
Duhring's disease 367
Dyschondroplasia with hemangioma 424
Dyshidrosis 114
Dyshidrotic eczema 114
Dyskeratosis congenita 39, 271
Dyspeptic erythema 17
Dysphagia 508
Dystrophic epidermolysis bullosa 462
Early onset alopecia 277
apocrine gland tumors 330
bromhidrosis 328
gland formation 5
nevus 455
sweat glands 323
Echinococcosis 201
Echinoderms 218
Ecthyma gangrenosum 124
Ectodermal dysplasia 36, 313
ectrodactyly-ectodermal 38
hidrotic ectodermal 38
X-linked hypohidrotic/anhidrotic 36
Eczema 106, 311
classification 106
herpeticum 131
EEC syndrome 38
Ehlers-Danlos syndrome 84, 515
Elejalde syndrome 303
Elephantiasis neurofibromatosa 76
Embryonic skin
fetal transition 2
second trimester 4
third trimester 4
Emollients 11, 103
Encephaloceles 279
Encephalofacial angiomatosis 422
Enterobiasis 195
Eosinophilic granuloma 464
Epidemic hysteria syndrome 527
Epidermis 6
cyst (sebaceous cyst) 456, 458
nevus 454
nevus syndrome 456
Epidermodysplasia verruciformis 144, 462
Epidermolysis bullosa 30, 312
complications 35
differential diagnosis 35
dystrophic epidermolysis bullosa 33
DEB with AD inheritance 33
DEB with AR inheritance 33
epidermolysis bullosa simplex 30
EBS with mottled pigmentation 32
EBS with muscular dystrophy 32
EBS-Dowling-Meara (Herpetiformis) 32
EBS-Köebner 31
EBS-ogna 32
EBS-superficialis 32
EBS-Weber-Cockayne 31
epidermolysis bullosa acquisita 369
investigations 35
junctional epidermolysis bullosa 32
JEB-Herlitz 32
JEB-non-Herlitz 32
JEB-pyloric atresia 32
management 35
Epidermolytic hyperkeratosis 44
Epiloia 77
Epithelioid cell 460
Epstein's pearls 20, 271
Epstein-barr virus 136
Eruptive pseudoangiomatosis 155
Eruptive vellus hair cysts 301
Erysipelas 125
Erythema 514
gyratum repens 532
infectiosum 145
multiforme 132
neonatorum allergicum 17
nodosum 242, 447, 509
toxicum neonatorum 17
Erythroderma 341
approach to a child 346
causes and clinical features
infectious 342
metabolic and nutritional disorders 346
epidemiology 341
management 346
Erythrodermic psoriasis 345
Erythrokeratoderma 49
En cocardes of Degos 50
variabilis 50
Essential fatty acid deficiency 346
Exanthem subitum 136, 152
Expressivity 28
Fabry's disease 514, 515
Factitious cheilitis 529
Factitious skin disease 528
Faun tail deformity 298
Fibromatoses 445
Fibrotic plaque/nodules 78
Fibrous papule 458
Fifth disease 145
Filiform warts 142
Finger tip unit 103
First disease 150
Flat warts (verruca plana) 142
Fleas 214
Fluid and electrolyte replacement 564
Fluoroderma 447
Flushing 514, 530
Focal palmoplantar keratoderma
association with other disorders 53
marginal popular 53
punctate 53
striate 53
watchers 53
with oral leukokeratosis 53
Foc-Fordyce disease 329
Folliculitis 124
decalvans 294
Fong's syndrome 514
Foot drop 260
Fordyce's spots 271, 459
Forefoot eczema 116
Foreign body reactions
clinical features 444
carbon 445
immunization granulomas 445
mercury 445
silica 445
tattoos 445
diagnosis 444
pathology 444
Frechles (ephelides) 373
Frictional llichenoid eruption 354
Fugitive swellings 192
Fungal infection 166
deep 176
opportunistic 181
subcutaneous 176
superficial 166
Furuncles 124
Gardner syndrome 80, 530
Gastrointestinal bleeding 508
Generalized elastolysis 81
Genetic counseling 29
Genetically determined syndromes 530
Genodermatoses 29, 312
Genotype 28
Geographic tongue 274
German measles 152
Gianotti-Crosti syndrome 156, 353
Gingivostomatitis 130
Glandular fever 137
Glomangiomas 415
Glomangiomatosis 415
Glomuvenous malformations 419
Glossitis 274
Gnathostomiasis 199
Gonadal dysgenesis 89
Gonorrhea 226
Gorham's disease 425
Gottron's syndrome 50
Graft-versus-host disease 354, 539
acute 540
chronic 541
Gram-negative folliculitis 551
Granular cell tumor 461
Granular layer 7
Granuloma 509
clinical features 436
differential diagnosis 436
epidemiology 436
etiology 436
histopathology 436
prognosis 437
treatment 437
faciale 437
clinical features 438
differential diagnosis 438
etiology 437
histopathology 438
treatment 438
Granulosis rubra nasi 328
Greither's syndrome 52
Griscelli syndrome 302
Grönblad-Strandberg syndrome 80
Guinea worm 194
density 276
development 276
disorders 277
distribution 276
formation 5
growth rate 276
hair cycle
anagen 276
catagen 277
telogen 277
neonatal hair 277
structure 276
types 276
Hair color disoders 302
altered pigmentation 304
diffuse hypopigmentation 302
acquired reversible diffuse 304
primary diffuse 302
localized hypopigmentation 304
Hair follicle nevus 458
Hair pluck test (trichogram) 281
Hair pull test 281
Hair shaft disorders 288
abnormalities with increased fragility
Menkes’ kinky hair syndrome 290
monilethrix 288
pili bifurcati 290
pili torti (twisted hair) 289
pseudomoniletrix 288
trichorrhexis invaginata 289
trichorrhexis nodosa 288
trichothiodystrophy 290
abnormalities without increased hair fragility 291
acquired progressive kinking of the hair 292
felted hair syndrome 292
fragilitas crinium 291
pili annulati 291
uncombable hair syndrome 292
woolly hair 291
Hairy leucoplakia 272
Hairy tongue 274
Hallermann Streiff syndrome 280
Halogenodermas 446
Hamartoma 457
Hand-foot-mouth disease 147
Hand-Schüller-Christian syndrome 464
Harlequin color change 18
Harlequin ichthyosis 344
Hartnup disease 74
Hashimoto-Pitzker syndrome 465
Hay-Wells syndrome 39
Heck’s disease 144
Helminthic infections 191
Hemangioma-hemorrhage syndrome 414
Hemangiopericytoma 415
Hemiptera 215
Hemizygous 28
Henoch-Schonlein purpura 503
Hereditary disorders
angioedema 403
benign intraepithelial dyskeratosis 271
disorders of keratinization 41
metabolic disorders 72
pigmentary disorders 54
Hermansky-Pudlak syndrome 55
genitalis 131
simplex virus infection
clinical features 130
epidemiology 130
laboratory investigations 132
prognosis 133
treatment 132
virus infection 228
zoster 531
zoster (shingles) infection 134
clinical features 135
epidemiology 134
laboratory investigations 135
prognosis 136
treatment 136
Herpetic eye infection 131
Heterogeneity 28
Heterotopic meningeal or brain tissue 279
Heterozygosity 28
Hidradenitis suppurativa 329
pathogenesis 300
treatment 300
Histiocytoses 464
class I
clinical features 464
course and prognosis 466
differential diagnosis 466
investigations 465
pathogenesis 464
treatment 466
class II 466
class III 468
Histoplasmosis 181
HIV infection 229
clinical events 230
diagnosis in children 229
management 231
Homocystinuria 73
Homozygosity 28
Horny layer 8
Human immunodeficiency virus infection 24
Human papilloma virus infection 141, 228
clinical features 141
differential diagnosis 142
epidemiology 141
laboratory investigations 142
pathogenesis 141
prognosis 144
treatment 142
ablative therapies 143
HPV vaccine 144
systemic treatments 143
topical therapy 143
Huriez syndrome 52
Hutchinson-Gilford syndrome 87
Hybrid cyst 458
Hydatid disease 201
Hydatidosis 201
aestivale 397
cavacciniforme 397
Hymenoptera 214
Hyperandrogenism 551
Hyperhidrosis 323, 324, 529
Hyperimmunoglobulin E syndrome 61
Hyperpigmentation 57, 373
acquired 379
at birth 373
post inflammatory 380
Hyperpituitarism 518
Hyperplasia 457, 459
Hypersensitivity reactions 118
Hypertrichosis 296
drug induced 297
Gambras syndrome 296
lanuginose 296
prepubertal 296
primary 296
X-linked dominant 296
due to local heat and cutaneous hyperemia 299
anterior cervical 297
association with nevi or tumors 298
hairy cutaneous malformations of palms and soles 298
hemihypertrophy with hypertrichosis 298
hypertrichosis cubiti 297
hypertrichosis with cranial meningoceles 298
lumbosacral hypertrichosis 298
nevoid hypertrichosis 297
posterior cervical hypertrichosis 297
scrotal hair 298
with focal facial dermaldysplasia 298
management 299
Hyperhidrosis 324
palmolantar 325
treatment 325
Hypomelanosis of Ito 382
Hypopigmentation or depigmentation 54, 380
acquiring 383
congenital 380
post inflammatory 385
Hypopituitarism 518
Hypothyroidism 517
with ectodermal dysplasias 278
with genetic disorders 279
with immunodeficiency syndromes 279
with ichthyoses 278
with premature aging syndrome 278
IBIDS syndrome 49
Ichthyosiform syndromes 47
Ichthyosis 41
and related syndromes 343
epidermolytic hyperkeratosis 44
Harlequin ichthyosis 43
ichthyosis bullosa of Siemens 45
ichthyosis hystrix 45
ichthyosis vulgaris 41
lamellar ichthyosis 43
multiple sulfatase deficiency 43
nonbullous ichthyosiform erythroderma 45
X-linked recessive ichthyosis 42
Icterus 530
Idiopathic nodular panniculitis 448
Immunobullous disorders 362
Immunodeficiency disorders 57
Immunoglobulin deficiency 61
Impetigo 122
diagnosis 123
treatment 123
bullous 122
non-bullous 122
Incontinentia pigmenti 39
Incubator 11
Infantile acne 548
clinical acne variants 551
clinical features 550
differential diagnosis 552
etiology 548
genetic 549
hormonal 548
exacerbating factors 549
cosmetics 550
diet 549
drugs 549
premenstrual flare 549
stress 550
ultraviolet radiation 549
laboratory investigations 552
management 553
alternative medicine 558
general principles 553
physical modalities 557
side effects 556
systemic treatment 555
topical treatment 554
treatment of acne scars 557
treatment of resistant/refractory cases 556
natural history 548
pathogenesis 549
Infantile erythroderma 561
Infantile hemangiona
classification 408
clinical features 409
deep infantile 410
mixed infantile 409
congenital hemangioma 411
miliary hemangiomatosis 411
PHACES syndrome 411
spinal dysraphism 411
diagnosis 410
differential diagnosis 410
etiology 408
immuno-histochemical studies 409
immunoreactivity 409
investigations 412
management 412
pathology 409
ultrastructural studies 409
Infectious eczematoid dermatitis 112
Infectious mononucleosis 137, 148
Inflammatory bowel disease 509
Ingrown nails 310
Inherited defects
connective tissue 508
DNA-repair disorders 67
vesiculo-bullous disorders 30
Inoculation HSV infection 131
Intertrigo 175
Invasive fungal dermatitis 176
Iododerma 446
Irritant reactions 117
Isolation of dermatophytes 173
Itching 510
Jadassohn-Lewandowsky syndrome 312
Jaundice 511
Jellyfish 218
Johanson-Blizzard syndrome 41
Juvenile dermatomyositis 483
clinical features
cutaneous manifestations 484
musculoskeletal manifestations 485
other systemic changes 485
diagnosis 487
epidemiology 484
etiology 483
laboratory abnormalities 486
treatment 487
Juvenile idiopathic arthritis 492
clinical features
enthesitis-related arthritis 494
oligoarthritis 493
polyarthritis 493
psoriatic arthritis 494
systemic onset JIA 493
diagnosis 494
epidemiology 493
etiology 493
treatment 494
Juvenile plantar dermatosis 116
Juvenile spring eruption 397
Juvenile xanthogranuloma 467
Kaposi's sarcoma 508
Kaposi's varicelliform eruption 567
Kaposiform hemangioendothelioma 414
Kasabach-Merritt phenomenon 568
Kasabach-Merritt syndrome 414
Katayama fever 200
Kawasaki disease 158, 500, 565
clinical features
acute febrile phase 159
convalescent 160
subacute phase 159
complications 160
diagnosis 160
etiology 158
laboratory investigations 160
pathogenesis 159
treatment 161
Keloids 462
Keratinization 4
Keratitis, ichthyosis and deafness syndrome 278
palmoplantaris transgrediens 52
with sclerotrophy 52
Keratosis pilaris atrophicans 293
atrophoderma vermiculatum 294
keratosis follicularis spinulosa 294
keratosis pilaris atrophicans faciei 294
Kid syndrome 49, 344
Kissing bugs 215
Klinefelter's syndrome 90
Klippel-Trenaunay syndrome 423
Knuckle pads 445
Koenen's tumors 78
Koganbyo 201
KOH preparation 172
Koilonychia 313
Koplik's spot 271
Lamellar ichthyosis 278, 344
Langerhans’ cells 8
Larva currens 196
Larval taeniasis 202
Latrodectism 216
Leeches (hirudinea) 217
Leiner's disease 345
Leiomyoma 461
Leishmaniasis 186
cutaneous 186
diffuse cutaneous 188
mucocutaneous 187
post-kala-azar dermal 188
visceral 188
diagnosis 188
treatment 189
Lentigines 374
Leopard syndrome 57, 515
Lepidoptera 215
Leprosy 249, 385
chemotherapy 261
classification 253
revised IAL 253
Ridley and Jopling 253
WHO 253
clinical leprosy 255
claw hand 259
foot drop 260
differential diagnosis
hypopigmented macules 260
postinflammatory hypopigmentation 261
elimination 263
epidemiology 254
etiology 250
pathogenesis 251
antigen presentation 252
expression of immune response 252
human leukocyte antigen (HLA) susceptibility 251
induction of immune response 252
reactions in leprosy 258
treatment of reactions 262
types of childhood leprosy 256
borderline tuberculoid 257
indeterminate 256
pure neuritic 258
tuberculoid 256
vaccines in leprosy 263
Lesions of the tongue 273
acquired 274
congenital 273
Letterer-Siwe diease 465
Leukonychia 311
Leukoplakia 271
Lichen planus 311, 348
lichenoid reactions 270
sclerosus atrophicus 384
scrofulosorum 242
simplex 527
simplex chronicus 114
striatus 385, 456
Lichenoid eruptions 348
lichen nitidus 349
lichen planus 348
lichen sclerosus 351
lichen striatus 350
other skin diseases 353
Gianotti-Crosti syndrome 353
lichen aureus 353
pigmented purpuric lichenoid dermatosis 353
pityriasis lichenoides 352
Linear IgA
dermatosis 531
disease of childhood 368
Lipoatrophy (lipodystrophy)
localized 450
partial 450
total 451
Lipoid proteinosis 441
clinical features 442
differential diagnosis 443
etiology 442
histology 442
pathogenesis 442
treatment 443
Loaloa filariasis 192
Localized diseases 568
alopecia 280
Löffler's syndrome 516
Loiasis 192
Loose anagen hair 287
Loricrin keratoderma 52
Loxoscelism 216
Lupus erythematosus
discoid 476
neonatal 482
subacute cutaneous 477
systemic 477
clinical features 478
diagnosis 481
epidemiology 477
etiology 477
laboratory findings 480
mucocutaneous manifestations 478
systemic manifestations 480
treatment 481
Lupus vulgaris 239
Lymphatic filariasis 193
Lymphatic malformations
classification 420
clinical features 421
diagnosis 421
management 422
pathogenesis 421
Lymphomatoid papulosis 358
Macroglossia 273
Maffucci's syndrome 424
Majocchi's granuloma 171
Mal de Meleda 52
Mal morado 191
Malignant tumors 461
Mantoux or tuberculin test 243
Marfan's syndrome 82, 515
Mastocytoma 470
Measles 150
Medina worm 194
Melagenine 391
Melanin pigmentation 372
Melanocytes 8
Melanocytic nevi 375, 460
acquired 376
congenital 375
dermal 376
Melanocytic proliferative lesions 459
Melanosis 530
Mendes da Costa syndrome 50
Meningococcemia 127
Menkes’ kinky hair syndrome 290
Merkel cells 8
Microglossia 273
Milia 16
Miliaria 18, 327
Milker's nodule 140
Millipedes 217
Miniature puberty 20
Mitochondrial inheritance 28
Mixed connective tissue disease 495
Molluscum contagiosum 138, 229
clinical features 139
laboratory investigations 139
pathogenesis 139
prognosis 140
treatment 139
Mongolism 89
Monilethrix (necklace hair) 288
Monomorphic erythematous papules 157
Montgomery's tubercles 459
Morphea 385
Moths 215
Mouth ulcers 268
Mucocutaneous candidiasis 176
Mucormycosis 182
Mucosal neuroma syndrome 520, 530
Mucous membrane infections 269
Muir-Torre syndrome 530
Multiple complications
carboxylase deficiency 346
endocrine gland dysfunctions 520
endocrine neoplasia syndrome 520
eruptive seborrheic keratosis 532
glomus tumors 415
hamartoma syndrome 80
longitudinal nail grooves 309
sulfatase deficiency 43
tumor syndromes 75
Multisystem diseases 513, 515
Münchausen's syndrome 529
Mycetoma 177
Mycoses 166
Myiasis 213
Nail artefact 529
Nail biting (onychophagia) 310
Nail changes in liver disease 511
Nail disorders 308
disease of the nail bed 310
endocrine and rheumatologic diseases 314
nail biting and onychotillomania 310
nail changes associated with chemotherapy 314
nail changes in primary cutaneous disorders 311
nail changes in systemic disorders 313
pathological changes of the nail apparatus 308
alterations in nail size 310
alterations in the nail plate 308
specific nail changes in cardiopulmonary diseases 314
traumatic nail disorders 310
Nail formation 5
Nail patella syndrome 313, 514
Napkin dermatitis 107
Nappy rash 107
Necrobiosis lipoidica diabeticorum 437, 519
Necrotizing fascitis 125
Neonatal complications
candidiasis 175
erythema 18
herpes simplex infection 567
herpetic infection 131
occipital alopecia 279
progeroid syndrome 88
pustular melanosis 17
varicella 24, 567
Neoplasia 270, 460
Netherton's syndrome 49, 344
Neural tumors 461
Neurilemmoma 461
Neurocutaneous diseases 521
Neurodermatitis 114
Neurofibroma 461
Neurofibromatoses 75, 77, 514
Neuroma 461
Neurothekoma 461
Neutral lipid storage disease 344
Neutrophilic eccrine hidradenitis 328
Nevi 513
Nevomelanocytic nevus 460
Nevus anemicus 261, 422
Nevus sebaceous 455
Nevus spilus 459
Newborn skin 6, 9
chemical 10
immunologic 10
maintenance of homeostasis 10
mechanical 9
physical 10
synthesis of essential nutrients 10
ultraviolet protection 10
Newly rediscovered viral exanthems 153
Non-bullous ichthyosiform erythroderma 343
Nonkeratinocytes 8
Nonscarring alopecia 280
Nontuberculous mycobacterial infections
classification 246
clinical features 247
complications 249
diagnosis 248
differential diagnosis 249
general characteristics 246
histopathology 248
pathogenesis 247
treatment 249
Noonan's syndrome 515
Nummular eczema 111
Nutrition deficiency disorders 572
biotin (vitamin H) 577
essential fatty acid 579
niacin (vitamin B3) 572
protein-energy malnutrition 579
pyridoxine (vitamin B6) 573
riboflavin (vitamin B2) 572
vitamin A 578
vitamin C (ascorbic acid) 575
vitamine B12 574
acquired 580
copper 583
heritable 581
Oculocutaneous albinism 55, 383
Oligoarthritis 493
Olmsted syndrome 52
Omenn's syndrome 346
Onchocerciasis 191
Onychauxis 309
Onycholysis 310
Onychomadesis 309
Onychomycosis 175
Onychophagia 528
Onychotillomania 528
Ophthalmia neonatorum 227
Oral-facial-digital syndrome 41, 514
ORF 140
Organoid nevus 455
Orooculogenito-cutaneous syndromes 508
Osmidrosis 329
Osteogenesis imperfecta 85
Oxyuriasis 195
Pachyonychia congenita 271, 312
Palmar erythema 512, 530
Palmoplantar keratoderma 50
Pancreatitis 509
Panniculitis 447
pancreatic 449
Papillon Lefevre/Haim-Munk syndrome 53
Papular purpuric gloves and socks syndrome 161
Papular urticaria 211, 544
clinical features 212
differential diagnosis 212
etiology 211
histopathology 212
treatment 212
Paracoccidioidomycosis 181
Parapsoriasis 357
Parathyroid gland disorder 518
Paronychia 175, 311
Patch testing 108
Patterns of genetic transmission 28
Pediculosis 209
clinical features 210
diagnosis 210
differential diagnosis 210
epidemiology 210
etiology 209
treatment 210
Peeling skin syndrome 54, 278
Pemphigus 362, 531
drug induced 364
foliaceous 363
IgA 364
neonatorum 365
paraneoplastic 364
vulgaris 362
Penetrance 28
Perforating disorders 513
Periderm 4
Perioral dermatitis 110
Periungual fibromas 313
Perleche 175
Peutz Jagher's syndrome 272
Phenotype 28
Phenylketonuria 72, 383
Photoallergy 397
Photosensitivity 62, 396
acquired 396
genetic 396
genodermatoses associated with 398
Phototoxicity 397
Physiological desquamation 16
Phytodermatoses 117
Phytophotodermatitis 118
Piebaldism 54, 382
Pigmentation 512
Pigmented xerodermoid 69
Pili torti 289
Pilosebaceous apparatus 5
Pimecrolimus 105
Pinworm 195
Pitted keratolysis 126
Pitting 309
Pituitary gland disorder 518
alba 113 383
rosea 354
rubra pilaris 355
simplex 261
versicolor 260
Plantar palmar fibromatosis 446
Plantar warts 142
Plexiform neurofibroma 75
Poikiloderma congenitale 71
Polyarterits nodosa 499
Polycystic ovary syndrome 519
Polymorphic light eruption 261, 396
Polyonychia 310
Polyposis 509
Polyarthritis 493
Pompholyx 114
Porphyrias 62, 508
classification 62
acute intermittent 65
chester 65
congenital erythropoietic 63
erythropoietic coproporphyria 64
erythropoietic protoporphyria 64
hepatoerythropoietic 65
hereditary coproporphyria 65
porphyria cutanea tarda 64
variegate 65
differential diagnosis 66
investigations 65
management 66
Portuguese man-of-war 218
Portwine stain 417
Post steroid nodular panniculitis 450
Post-kala-azar dermal leishmaniasis 188
Pox viruses 138
Preauricular cysts (ear pits) 457
Premature ageing syndromes 86
Premature graying 303
Prenatal diagnosis of hereditary skin disorders 29
Primary cutaneous amyloidosis 443
clinical features 444
etiology 444
histopathology 444
staining characteristics 443
treatment 444
Principles of genetics 28
Progeria 87, 515
Progressive macular hypomelanosis 384
Protein deficiency 532
Protein malnutrition 346
Protein-energy malnutrition 579
Protozoan infections 186
Prurigo 115
Pruritus 512, 531, 542
anogenital 544
cholestasis 544
chronic renal failure 544
etiology 541
hematological disorders 544
hiemalis 111
Pseudomoniletrix 288
Pseudopelade 295
Pseudoxanthoma elasticum 80, 515
Psoriasis 312
Psoriatic diaper rash 338
Psychocutaneous disorders 522
Psychogenic pruritus 529
Psychological importance of skin 525
Pulmonary arteriovenous fistula 516
Pupura fulminans 532, 566
clinical features 533
etiology 532
pathophysiology 532
treatment 533
Pustular melanosis 17
Pyoderma gangrenosum 439, 509
clinical features 440
differential diagnosis 440
etiology 439
histopathology 440
treatment 440
RAPP-Hodgkin syndrome 39
Recessive character 28
Recurrent infections 131
aphthous stomatitis 268
Refsum disease 48
Relapsing polychondritis 497
Renal disorders in children 512
Renocutaneous syndrome 513
Reticulate vascular nevus 422
Rhabdomyoma 462
Rhabdomyosarcoma 462
Rhinosporidiosis 180
Rhizomucor 182
Rhizopus 182
Richner Hanhart syndrome 73
River blindness 191
Roseola infantum 136, 152
Rothmund-Thomson syndrome 71
Rubella 152
Rubeola 150
Sacral dimple 22
Salmon patch 417
Sandworm eruption 197
Sarcoidosis 517, 534
clinical features 535
diagnosis 537
epidemiology 534
etiology 534
histopathology 535
immunology 534
specific lesions 535
angio-lupoid form 536
annular form 536
erythema nodosum 536
lupus pernio 536
maculopapular form 535
nodular form 535
papular form 535
treatment 537
unusual and atypical forms 536
eyes 536
mucosal involvement 536
nail changes 536
pulmonary involvement 536
skeletal system 536
uveo-parotid fever 536
Sawah itch 201
Scabies 206, 543
clinical features 207
diagnosis 209
differential diagnosis 208
epidemiology 207
etiology 206
treatment 209
Scalp injury 279
Scaring alopecia 293
Scarlet fever 342
Schistosomiasis 200
Schöpf-Schulz-Passarge syndrome 41
Sclerema neonatorum 568
Scleroderma 385
Scleromyxoedema 441
Scorpion 216
Scrofuloderma 240
Sea anemones 218
Sea cucumbers 218
Seatworm 195
Sebaceous gland hyperplasia 16
Sebaceous glands 318
Sebaceous nevus 279
Seborrheic dermatitis 109, 345
Secondary nodular panniculitis 449
Sedge pool itch 201
Segmental hypermelanoses 378
Self-inflicted and simulated skin disease 527
Serpent worm 194
Severe combined immunodeficiency 61
Sex-chromosomal disorder 89
Sexually transmitted diseases 220
bacterial 221
viral 228
Shagreen patches 78
Shell nails 314
Sipple syndrome 520
Sixth disease 152
Sjögren syndrome 495
clinical features 496
diagnosis 496
etiology 496
treatment 497
Sjögren-Larsson syndrome 47, 344
Skeletal muscle tumors 461
Skin atrophy/lipoatrophy 88
Skin care
premature infant 10
preventive measures 11
neonatal skin care 11
skin care at birth 11
term baby and infant 12
Skin gene therapy 90
approaches 91
candidate diseases 91
goals 90
limitations 91
target cells 90
techniques 91
Skin laxity 88
Smooth muscle hamartoma 461
Snail fever 200
Solar urticaria 397
Sowda 191
Spider nevus/angioma 511
Spiders 216
Spinal dysraphism 22
Spindle cell 460
Spinous layer 7
Spitz nevus 460
Sporadic disorder 28
Sporotrichosis 177
Staphylococcal scalded skin syndrome 126, 342
Starfish 218
Stein-Leventhal syndrome 519
Striated muscle hamartoma 461
Strongyloidiosis 196
Stunted growth 67
Sturge-Weber syndrome 422
Subcutaneous infections 568
Sucking pads/calluses 19
Suction blister 19
Summer prurigo of Hutchinson 397
Sunburn 396
Surgical treatment of hemangiomatous malformations 425
Sweet syndrome 438, 532
Swellings/lumps 272
bony 272
gingival 273
salivary gland 273
soft tissue swelling 272
Swimmer's itch 201
Syphilis 221
clinical manifestations
early 221
late 223
diagnosis 224
pathology 221
stigmata 224
acquired 225
congenital 221
treatment schedules
acquired 225
congenital 225
Systemic disease 270
mycosis 180
sclerosis scleroderma 488
clinical features 489
diagnosis 491
epidemiology 489
etiology 489
investigations 491
treatment 491
classification 498
pathophysiology 498
Tacrolimus 103
Takayasu arteritis 499
Telangiectasia 530
Telangiectatic macularis eruptive perstans 471
Telogen effluvium 280
Temporal triangular alopecia 279
Third disease 152
Thread worm 195
Thyroglossal duct cysts 21
Thyroid gland disorders 517
Ticks 217
Tinea infection
capitis 168
inflammatory 169
non inflammatory 168
corporis 170
cruris 170
imbricata 170
incognita 171
mannum 171
pedis 171
unguium 171
versicolor 384
TORCH infections 23
cytomegalovirus infection 23
herpes simplex 24
rubella 23
toxoplasmosis 23
Toxic epidermal necrolysis 345
Toxic erythema of newborn 17
Toxic shock syndrome 342
Toxocariasis 198
Toxoplasmosis 190
Traction alopecia 286
Traditional exanthems 145
Transcutaneous oxygen monitors 11
Transient neonatal dermatoses 16
Transient neonatal pustular melanosis 17
Traumatic alopecia 286
Traumatic ulceration 269
Trichilemmal cyst (pilar cyst) 458
Trichilemmoma 459
Trichinosis 199
Trichodiscoma 458
Trichoepithelioma 458
Trichomonal infection 227
Trichomycosis axillaris 126
Trichopoliodystrophy 290
Trichorrhexis 289
nodosa 288
Trichothiodystrophy 72, 290
Trichotillomania 286, 527
Trimming of the hair 299
Tripe palms 532
Tropical elephantiasis 193
Tuberculids 242
Tuberous sclerosis 381, 515
complex 77, 514
Tuft of hair 22
Tufted angioma 413
Turner syndrome 89
Twenty nail dystrophy 312
Tyrosinemia 73
Ulerythema ophryogenes 294
Urticaria 400, 566
clinical features 400
cholinergic 402
cold 402
contact 403
hereditary angioedema 403
ordinary 400
physical 400
pressure 402
solar 403
vibratory 402
differential diagnosis 403
etiopathogenesis 400
laboratory investigation 403
treatment 404
Urticaria pigmentosa 380, 469
Varicella-zoster virus infections 24, 133
Vascular malformation 416
Vasculitis 509. 531
Vasculogenesis 416
Vellus hair cyst 458
Venous malformations 418, 424
clinical characteristics 418
diagnosis 418
differential diagnosis 418
management 419
pathogenesis 418
Vernix caseosa 11, 16
Verruca vulgaris 141
Vesiculobullous diseases 270
Viral exanthems 145
Visceral larva migrans 198
Vitiligo 260, 385
associations 388
classification 388
clinical manifestations 387
diagnosis and differentials 389
epidemiology 386
etiopathogenesis 386
treatment 390
phototherapy and lasers 391
surgical therapy 392
topical 390
Vohwinkel's syndrome 52
von Hipple Landau syndrome 514
von-Recklinghausen's disease 75, 514
Vulvovaginitis 175, 195
Waardenburg syndrome 54
Warts 312
Washboard nails 309
Wegener's granulomatosis 502
Werner syndrome 87, 520
Whipple's disease 510
White lesions 271
White sponge nevus 271
Wiedman-Rautenstrauch syndrome 88
Wiskott-Aldrich syndrome 62
Woolly hair 291
Wood's lamp 172
Wrinkly skin syndrome 88
Xanthoma 530
Xeroderma pigmentosum 68
Xerotic eczema 111
X-linked disorders 521
X-linked dominant conditions 280
Yellow nail syndrome 516
Zinsser-Cole-Engman syndrome 39
Ziprkowski-Margolis syndrome 383
Zygomycosis 182
Chapter Notes

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Structure and Functions of the Skin1

Chidambara Murthy S.
zoom view
Embryonic period corresponds to the age of conception until two months of estimated gestational age (EGA). Fetal period refers to the age between second month of EGA until birth. Initiation of histogenesis of all skin regions and differentiation of some of those tissues occur during embryonic period. Formation and differentiation of tissues is continuous through all the trimesters. This section describes the formation and development of skin during various phases of fetal development (Table 1.1).
During the third week after fertilization, embryo undergoes gastrulation, resulting in the formation of ectoderm, endoderm and mesoderm. Shortly ectoderm divides into neuroectoderm and presumptive epidermis. At 30 days EGA, formation of skin is evident. By about six weeks the epidermis, dermo-epidermal junction (DEJ) and dermis are well delineated with nerve and blood vessel formation. Distinction between dermis and subcutaneous tissue is seen only at places. There is no evidence of formation of appendages.
The epidermis consists of simple, flat two-layered epithelium consisting of basal and periderm cells. Both layers are filled with glycogen. Both types of cells consist of a central nucleus with sparse cytoplasmic organelles around the nucleus or at the periphery of the cell. Keratin (K) intermediate filaments K19 and K8 are present in both, while K5 and K14 are expressed by basal layers. K18, a marker for Merkel cell, is also expressed by the cells of periderm. The filaments are dispersed in the cytoplasm or assembled in small, short bundles in association with desmosomes and hemidesmosomes. Basal cells express platelet-derived growth factor. Microvilli project from the peridermal surface into the amniotic fluid. Although melanocytes are found to be dendritic by about 50 days, there is lack of evidence of melanosomes in the cytoplasm. Langerhans’ cells are recognized as early as 42 days EGA based on the presence of ATPase, HLA-DR and by their truncated or dendritic morphology. They are probably derived from the yolk sac or fetal liver with a density of about 50 cells/mm3.
Merkel cells can be recognized by 55–60 days using keratins K8, K18, K10 and K20. They are neuroendocrine cells distributed at a density of 130 cells/mm2. Merkel cells are derived from keratinocytes in situ.
The molecules and antigens characteristic of basal laminae (type IV collagen, laminin, heparan sulfate proteoglycan, nidogen/entactin) are expressed by 8 weeks. Skin-specific molecules are recognized during late first trimester. The antigens associated with the attachment structures are not recognized by light microscopy although keratinocytes have begun synthesizing them.
The dermis is highly cellular, but also contains extra cellular fibrous matrix proteins and type I, III, V and VI interstitial collagens. It consists of mesenchymal cells which are stellate and rich in glycogen. It also contains hyaluronic acid-rich proteoglycan matrix. Compact mesenchyme with a zone of sulfated proteoglycans, situated beneath the epidermis is rich in growth factors and receptors.
Elastic fibers are not detectable by light microscopy, although fibrillin and elastin can be recognized immuno-histochemically and microfibrils by electron microscopy. Fine nerve fibers, arterioles; venules and capillaries are present within compact mesenchyme and deep dermis. The large nerve trunks and vessels are located in subcutaneous tissue.
Type IV collagen is present in basement membranes around the vessels, while type III and V collagen in vascular sheets. Autonomic nerves are not recognized.
Embryonic—Fetal Transition
The skin has a mucoid quality and is prone to errors in development at this stage. Transition from embryo to fetus also heralds the formation of appendages (discussed later). The hallmark of this stage is stratification of epidermis with an additional intermediate layer. Intermediate layer expresses K5 and K14 similar to basal layer. Additionally K1 and K10 are also present. Other markers of keratinocyte differentiation like pemphigus antigen, cornified cell envelope proteins; blood group antigens and cell surface glycoproteins are also expressed. This layer also contains glycogen. Genetic diseases involving mutation of keratins can be recognized by this period. At the same time cells of the periderm increase in size and develop microvilli-covered blebs.
Around 80 days EGA, melanocytes are present in maximal density (3000/mm2). The number decreases towards birth. Melanosomes in these cells can be recognized by late first trimester. The knowledge about this helps in the prenatal diagnosis of tyrosinase-negative oculocutaneous albinism.
TABLE 1.1   Major events and related diseases in the embryogenesis of skin
Major events
Vital proteins involved in the embryogenesis (diseases)
Bone Morphogenetic Proteins, Engrailed-1 (Aplasia cutis)
Epidermal specification:
  • Presumptive epidermis
  • Periderm
3 wks
6 wks
Epidermal stratification:
  • Intermediate layer
8 wks
p63 (AEC, EEC)
Epidermal keratinization:
  • Follicular: Beginning
  • Interfollicular: Beginning
    (Stratum granulosum and Stratum corneum
11–15 wks
24 wks
15 wks
22–24 wks
K1, K10 (BCIE), K1, K9 (Vorner, Unna-Throst, Greither), Loricrin (NBCIE, Vohwinkle's), Transglutaminase-1(LI), Steroid sulfatase (X-linked ichthyosis), Fatty Aldehyde dehydrogenase (Sjogren-Larsson), Phytanoyl CoA Hydroxylase (Refsum disease), LEKTI (Netherton's)
Non keratinocytes:
  • Melanocytes: in epidermis Melanin
  • Transfer to keratinocytes
  • Langerhan's cells
  • Merckel cells
8 wks
12–16 wks
20 wks
6 wks
8–12 wks
c-Kit (Peibaldism), PAX-3(Waardenburg's syndrome type 1)
Cellular attachments:
  • Desmosomes
8 wks
Dermoepidermal junction
  • Basement membrane
  • All basement membrane antigens
8 wks
12 wks
K5, K14 (EB Simplex), Plectin (EB with MD), a6p4 (EB with PA), Laminin5 (Junctional EB), BPAG2 (GABEB), Collagen VII (Dystrophic EB)
  • Presumptive dermis
  • Papillary and reticular dermis
  • Elastic fibers
  • Collagen bundles
  • Cutaneous vessels and nerves:
    • Beginning
    • Angiogenesis
6–8 wks
12–15 wks
22–24 wks
12–16 wks
9 wks
20 weks-3 m postnatally
Collagen 1 (Osteogenesis Imperfecta), Fibrillin (Marfan syndrome), elastin (Cutis laxa), MRP6 (Pseudoxanthoma elasticum)
TIE2 (venous malformations), Endoglein and Activin receptor-like kinase1 (Hereditary Hemorrhagic Telangiectasia)
  • Hair (Scalp): Beginning Visible hair
  • Sebaceous gland maturation
  • Eccrine glands (palmoplantar):
    • Beginning
    • Gland and dermal duct
    • Epidermal duct
  • Apocrine glands Nail: Beginning
    Nail bed keratinization
    Complete growth of nail plate
9–12 wks
19–21 wks
13–16 wks
8–9 wks
16 wks
22 wks
24 wks
8–10 wks
11 wks
20 wks
EDA (X-linked hypohidrotic ED), MSX1 (Witkop syndrome/tooth-nail syndrome)
Lmx-1B (Nail-Patella Syndrome), K6a/K16 (PC1), K6b/K17 (PC2, Steatocystoma Multiplex)
  • Fat lobules and fibrous septa
Note: AEC-ankyloblepharon-ectodermal dysplasia-clefting, BPAG-bullous pemphigoid antigen, EB-epidermolysis bullosa, ED-ectodermal dysplasia, EDA-ectodysplasin A, EEC-ectrodactyly-ectodermaldysplasia-clefting, EGA-estimated gestational age, GABEB-generalized atrophic benign EB, K-keratin, MD-muscular dystrophy, NBCIE-non bullous congenital ichthyosiform erythroderma, PA-pyloric atresia, PC-pachyonychia congenita
By about 80 days, Langerhans’ cells are highly dendritic, begin to express CD1a at the surface and develop Birbeck granules.
Merkel cells are located along the primary epidermal ridges of palmar skin and at a maximum density of 1400 cells/mm2. They are found in association with developing hair follicles and sweat glands. They are also present in the dermis and are thought to originate from follicular or interfollicular epidermis. They may play a role in the organization of nerve fibers. Dense Core granules, characteristic marker for Merkel cells are absent.
DEJ has acquired adult features with well-developed hemidesmosomes, anchoring filaments and fibrils. Dermal and subcutaneous mesenchymal cells assume fibroblastic morphology and synthesize matrix molecules. Papillary and reticular dermis is demarcated based on increased cell density proximal to the epidermis, and larger collagen fibril diameter and fiber bundle size in reticular dermis. Adult vasculature is developed with one plexus at dermo-subcutaneous boundary and the other at the boundary between the papillary and reticular dermis interconnected by vertical plexuses. The nerve fibers are well formed. Collagen types III and V localize around vessels and nerves. Dilated channels of venous and lymphatic structures are seen in subcutaneous tissue.
Second Trimester
Important events that occur in second trimester include completion of the formation of lanugo hair, synthesis of the hair (17–19 weeks EGA), completion of nail (20–22 weeks EGA) and keratinization of interfollicular epidermis (22–24 weeks). Proliferation of basal cells results in addition of three intermediate cells which are flattened towards epidermal surface. At the end of this phase, interfollicular epidermis keratinizes. Cornified cell envelope and lamellar granules are found. Keratohyaline granules with profilaggrin and filaggrin are identified with formation of spinous layer. By 22–24 weeks EGA, cells similar to true stratum corneum and granular layers are identified.
Merkel cells at a density of 1700 Cells/mm2 and Langerhans’ cells at 200 cells/mm2 are found in the epidermis. Melanosomes are transferred to keratinocytes in the fifth month of gestation. AF-1 and AF-2 associated with anchoring fibrils are recognized at this age. By 19–21 weeks hemidesmosomes, anchoring filaments and banded anchoring fibrils are well formed. In the dermis, interwoven, fibrous connective tissue, elastin and elastic fibers similar to elastin fibers of adult skin are recognized. Fibroblasts, mast cells, macrophages and smooth cells are also present.
In the hypodermis, by about 15–16 weeks, first stage of adipose tissue formation occurs. By 18 weeks, lipid droplets appear and at 20 weeks lobules of fat are formed. By the end of this stage, well-formed fetus with hair is present.
Third Trimester
The epidermis is fully keratinized. DEJ, dermis and adnexae are fully formed. Before 26 weeks, Langerhans’ cells are localized only in the basal layer. From 27th week, they are also found in stratum spinosum. Large fat lobules are seen in hypodermis. Sweating response is limited but apocrine secretion begins. However, the structure and functions are not as matured as neonate. Babies may be born as preterm at this stage. The vasculature is less organized compared to the newborn.
Periderm is the outermost transient cellular layer shed into amniotic fluid at the end of the second trimester. It may take its origin from either the basal cells or the amnion or it itself may be the original ectoderm. It undergoes changes resulting in epidermis development (Figure 1.1), but does not undergo keratinization. It is a layer that undergoes apoptosis.
Functions of periderm:
  1. Exchange of substances between the fetus and the skin e.g. drugs.
  2. It may add (secrete) materials into the amnion.
  3. It may protect the developing epidermis.
Regionalization in Developing Skin
Regional differences as in adult skin are well documented. However, similar differences in the expression of diseases may indicate multiple biopsies for the prenatal diagnosis.
It occurs in different structures at different times of gestation. The timing appears to follow a rigidly specified program.
zoom view
FIGURE 1.1: Development of epidermis
By 10–11 weeks EGA, basal epidermal cells proliferate to form buds at specifically patterned sites. These buds grow into the dermis as hair germs and sweat ducts or fold to result in nail fold. This occurs in response to epithelial-mesenchymal interactions. Apart from this the nerves, vessels and adhesion molecules also play a role. The dermis is responsible for initiation and assembly, while epidermis determines the type of appendage.
Nail Formation
By 70 days, the boundaries of the nail folds are established by proximal, lateral and distal folds. By 90 days, the dorsal ridge is formed. The nail fold invaginates deeply into the dermis resulting in dorsal and ventral layers. The ventral fold becomes the nail matrix. Nail is the earliest structure to keratinize in utero. By 15 weeks, a fragile nail consisting of cells form nail bed and by about 19 weeks, cells from both nail bed as well as matrix form nail.
Eccrine Gland Formation
By around 10–12 weeks EGA, sweat glands are initiated on the palms and soles. Primary epidermal ridges organize from the basal layer. Mounds of mesenchyme form volar pads. These are transient and disappear by the end of first trimester. Sweat glands develop on the body late in the second trimester.
Pilosebaceous Apparatus
Formation of hair follicle begins on the head and face around 70–80 days EGA and proceeds cephalo-caudally. There are different stages of formation of hair follicle (Figure 1.2).
zoom view
FIGURE 1.2: Stages of hair formation
The induction, development, maintenance and regression in adults are dependent upon an association of follicle epithelium with dermal mesenchymal cells which form dermal papilla. Cells from the basal layer bud into the dermis to become hair germs. Condensed mesenchymal cells associate closely with the germs. Around 13–14weeks EGA, hair pegs are formed. It consists of an inner cuboidal and an outer columnar layer associated with the basal lamina surrounding the follicle and continuous with that of the interfollicular epidermis. Merkel cells are present among outer root sheath keratinocytes. Each hair peg is cylindrical and later develops into infundibulum, isthmus and bulb. Elongated core cells in the neck of the follicle continue into the epidermis, in between the basal and intermediate layers. This is the hair tract and presumptive hair canal.
The distal end of the hair peg flattens and the epithelial cells along this basal border elongate to form matrix. Inner root sheath and hair cone are formed. Melanocytes aggregate in the matrix and produce melanin ahead of other sites. Between 15 and 17 weeks, bulbous hair peg and bulges for arrector pili muscle, sebaceous gland and apocrine glands are formed.
Applied Importance
  1. Disorders of keratinization can be identified by using chorionic villus biopsy, amniocentesis and fetal skin biopsy at various stages of development.
  2. Density of melanocytes can be useful in early detection of tyrosinase-negative oculocutaneous albinism.
  3. Capillary malformations in hereditary hemorrhagic telangiectasia may result due to mutation in TGF-β binding protein.
The newborn skin has similar structural composition as that of adult. However, there are a few salient differences. DEJ in neonates, although complete, is flat without ridges. Dermis is also relatively immature compared to adults. Reticular dermal collagen is in smaller bundles, elastic fibers are finer, less mature and it is cellular consisting of more fibroblasts (Table 1.2). Functional, biochemical and even structural maturity may not be achieved until several years of age.
Skin is made up of epidermis and dermis (Figure 1.3) which contain epidermal appendages, blood vessels and nerves providing nutrition and integration to these tissues. Epidermis is made up of keratinocytes, Merkel cells, melanocytes and Langerhans’ cells. DEJ is a complex structure which supports epidermis and transports molecules bi-directionally. Dermis consists of mast cells, blood vessels, lymphatics and appendages.
Keratinocytes form more than 90% of the cells. Epidermis comprises of basal, spinous, granular and horny layers. Melanocytes, Merkel cells and Langerhans’ cells are present among them.
Basal Layer
It is known as stratum basale or germinativum. The basal keratinocyte is a columnar cell, which rests on basement membrane (hemidesmosome).
zoom view
FIGURE 1.3: Structure of the skin
TABLE 1.2   Structural and functional difference between adult, term and preterm infant skin
Term infant
Preterm infant
Epidermal thickness
50 μm
50 μm
27 μm
↑TEWL, Percutaneous toxicity
Barrier maturity
Attains maturity in 2–3 wks, in VLBW maturity is slow, 8 wks
↑TEWL, Percutaneous toxicity and infection
Surface area to weight ratio
Five times more than adults
Seven times more than adults
↑Percutaneous toxicity
Two-third of total insensible water loss
10–15 times greater than term infants
Fluid loss as much as 30% of body weight in 24 hrs, heat loss, ↑calorie loss (580 calories/ml)
Antimicrobial defense
impaired expression of antimicrobial cationic peptides and antibacterial acid mantle
↑Percutaneous infections
One-third of term infant
↑risk of photosensitivity
↑skin fragility and blistering
Elastin and elastic fiber
↓in papillary dermis with finer fibers
↓↓ in papillary dermis with finer fibers
↑skin fragility and blister formation (e.g. syphilis)
Brown fat
Non shivering thermogenesis
Synchronized growth phase
Synchronized growth phase, persistent lanugo hairs
Neonatal alopecia, estimation of gestational age
Sweat response
Thermal stress
Greater thermal stimulus is required
Same as that of term infant
↑insensible water loss in infants on phototherapy/under radiant warmer
Well developed
Not well developed
Thermoregulatory response (neural/endocrine)
Present but less pronounced
↑Susceptibility to cold and heat stress
Note: TEWL-transepidermal water loss, VLBW-very low birth weight, ↑- increased, ↓- decreased
It has desmosomal junctions, gap junctions, adherens junctions with other basal keratinocytes and spinous keratinocytes, and desmosomal junctions with Merkel cells. It also borders Langerhans’ cells and melanocytes. Keratins K5 and K14 are hallmarks, although K15 can be present in small amounts. This acts as a renewing source for life-time of an individual.
Spinous Layer
Stratum spinosum consists of 3 to 4 layers of more flattened cells containing large bundles of keratin filaments. In addition to the keratin filaments of basal layer, newly synthesized K1 and K10 are present. Desmosomes are prominent and shrinkage of tissue during processing gives spine-like appearance. Lamellar granules are 300–500 micrometers in diameter, membrane-bound organelles formed in the Golgi bodies. These contain carbohydrate complexed with proteins, lipids and hydrolytic enzymes. These help in barrier function.
Granular Layer
In stratum granulosum the cells are arranged in two to three layers and contain keratohyalin granules. Lamellar granules are released which fuse and aggregate with the plasma membrane in between granular and horny layers.8
Filaggrin forms in this layer and may have a role in aggregating keratin filaments. Transitional layer in between granular and horny layer comprising of cells with heavily convoluted nucleus may be present. Apoptosis is initiated in this layer.
Horny Layer
This is the outermost layer of cells comprising of dead cells. It varies form 15 layers on general skin up to hundreds of layers on palms and soles. The thickness is similar in children and adults. Within plasma membrane, a highly cross-linked structure ‘the cornified cell envelope’, formed by epidermal transglutaminase, loricrin, keratins, pancornulin and other proteins is present. Epidermal ceramides are cross-linked across the cell membrane to the envelope which may stabilize the extracellular lipid layer.
In the epidermis, Melanocytes are located in the basal layer. Each melanocyte is linked with 36 basal and spinous cells forming epidermal melanin unit (EMU). Melanocyte is a round to oval cell with refractile brown granules in the cytoplasm. Melanosomes are complex organelles and the site of melanin production. They contain tyrosinase and lysosomal enzymes. They are divided into four stages based on the pigmentation.
Langerhans’ Cells
Langerhans’ cells are regularly distributed suprabasally at a density of 460–1000 cells/mm2. They have a convoluted nucleus and the Birbeck granules. Surface markers include class I and II HLA-antigens, S-100 protein and others.
Merkel Cells
Merkel Cells these are located individually in basal layer or in larger groups as touch receptors in association with myelinated nerves in epidermis, hairs and mucosae. They contain dense core granules and simple keratins. K20 is relatively specific for these cells.
Hair follicle is divided into four segments, infundibulum, isthmus, stem and bulb (Figure 1.4). The pilosebaceous duct in the infundibulum is lined by a stratified keratinzed epithelium. The bulge is the site of expansion of outer root sheath cells and is at the insertion of the arrector pili muscle. This is the site of stem cell population of the follicle. The bulb contains the germinal cells of the follicle, melanocytes, langerhans’ cells and Merkel cells. Dermal papilla is located in the concavity of the bulb. The inner root sheath ends at the junction between the isthmus and the infundibulum. The cells of the innermost sheath synthesize trichohyalin but the outer root sheath cells do not keratinize. Fully formed hair consists of inner and outer cuticular layers, cortex and medulla. Hair provides protection, sensory perception and adds to the cosmetic appearance.
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FIGURE 1.4: Structure of the hair
Nail consists of nail matrix, nail bed, nail plate, lateral and posterior folds, lunula, cuticle and hyponychium (Figure 1.5).
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FIGURE 1.5: Structure of the nail
Nail matrix differs from epidermis and hair in producing cells that retain nuclei. Melanocytes are present in the lower two to four layers of matrix. It protects the underlying structures from physical trauma as well as infections. Nails can be used for scratching.
Eccrine Glands
They are distributed all over the body. The highest density is on the palms, soles and the forehead. The secretory coil is in the reticular dermis or subcutaneous tissue. The secretory portion consists of pyramidal, clear, dark and myoepithelial cells. Clear cells secrete water and electrolytes. The eccrine duct has two layers in the dermis. The intraepidermal portion of the duct lining is keratinized at the outermost sweat pore. The outer cells have prominent microvilli and mitochondria for reabsorption. The innermost cells form a “cuticular border” with microvilli, microfilaments and intermediate filaments. Clinically, sweating starts on 1st day after life.
Apocrine Glands
These are large, coiled tubular glands situated deep in the dermis. They occur over face, scalp, axilla and anogenital regions. Modified glands are present in eyelids (Moll's gland), ear canal and areola. It consists of secretory and myoepithelial cells. The duct contains three layers of cells.
Sebaceous Glands
They are associated with hair follicle. The density is highest over face, scalp and upper chest. Modified glands may be present in eyelids, lips, buccal mucosa, glans and prepuce. They secrete sebum which is oily.
Dermo-epidermal Junction (Figure 1.6)
This consists of dermal ridges and papillae. Electron microscopy shows lamina lucida, lamina densa, anchoring filaments, anchoring fibrils, the reticular lamina and sub-epidermal region of the papillary dermis. Hemidesmo-somes span the cytoplasm of keratinocyte and portions of lamina lucida. It includes the bullous pemphigoid antigens.
Dermis consists of papillary and reticular zones. Reticular lamina (compact zone) in superficial papillary dermis consists of fine dense collagen. In contrast, reticular dermis has elastic fibers, thicker collagen bundles and a higher density of vessels than papillary dermis. They contain fibroblasts and dermal dendrocytes. Fibroblasts are the source of the extra-cellular structural molecules of the dermis.
Skin protects against the trauma due to blunt objects. Dermis plays a major role, although stratum corneum and subcutaneous tissue also play a part.
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FIGURE 1.6: Dermo-epidermal junction
Stratum corneum acts as an effective physical barrier to prevent entry of toxic substances into the skin. Although the thickness and layers of stratum corneum in neonates is comparable to that of adult, it is functionally immature. Hence care should be taken during topical applications of soaps, aniline dyes, hexachlorophene, phenol and other toxic substances. Further, infants have three times more surface area per unit weight compared to adults, resulting in toxicity of topical applications.
An intact stratum corneum prevents invasion by microorganisms. Sebaceous lipids are known to have antibacterial properties. Anti Microbial Peptides (AMPs) such as defensins and cathelicidins present in the epidermis can destroy gram-positive and gram-negative organisms.
Skin plays an important role in thermoregulation by heat loss or conservation. Heat can be lost through radiation, convection, conduction and evaporation. Dermal vasculature plays an important role. In high environmental temperatures, eccrine sweating plays a role. In neonates, since the barrier function is immature, the rate of heat loss by evaporation may exceed the baby's heat production.
Protection from ultraviolet rays is provided by melanin barrier in the epidermis and a protein barrier in the stratum corneum.
Vitamin D synthesis occurs in the spinous and the basal layers, under the influence of ultraviolet rays from sunlight.
Skin acts as an immunologic organ, as it contains macrophages, Langerhans’ cells and dermal dendrocytes participating in the cell-mediated response. It also seeks to check the invading pathogens by immunologic mechanism.
A premature infant is the one who is born before 37 weeks of gestation. It also refers to infants with less than 2.5 kg of weight. Extreme prematurity refers to babies with less than 1.25 kgs of body weight. The skin of the premature infant is that of the third trimester fetus. The skin is immature in both structural and physiologic properties. The skin of a newborn infant of 26 weeks’ gestation is pink and relatively transparent; the underlying blood vessels are readily seen with moist surface. The epidermis although structurally complete, is relatively thin with only 5–6 layers of cells in stratum corneum and is poorly keratinized. Glycogen is still retained and barrier is poorly developed. Also, as the surface area per unit weight is seven times that of an adult, absorption and toxicity of topically applied medications can occur. Lack of enzymatic activities to detoxify substances, also adds to this. Nonspecific factors such as increased permeability of the skin and decreased gastric acid content of the stomach also may reduce neonatal immunity. Transepidermal water loss is also increased in preterm skin. It is inversely proportional to gestational age. There are only a few mature Melanosomes in the melanocytes. The development of DEJ is complete but flat. The papillary dermis is edematous and the bundles of collagen fibrils are smaller and more widely spaced. The dermis is about three-quarters of the thickness of adult dermis. Fine collagen fibers and small-sized collagen fiber bundles give the dermis a highly cellular and delicate appearance. Elastic fibers are tiny, sparse and immature. Lack of subcutaneous fat, poor autonomic control of cutaneous vessels and functionally reduced sweating contribute to poor thermal regulation. Premature infants have increased cutaneous gaseous exchange i.e. increased oxygen absorption and carbon dioxide evaporation.
Skin matures rapidly in preterm infants after birth. Goals of therapy include immediate access to the infants, heat retention, fluid and electrolyte balance, prevention of infection and rapid epithelial maturation. They are preferably nursed in closed incubator and kept warm. Environmental conditions in these units are potentially harmful, resulting in scarring. Cosmetically or functionally 11significant lesions may be caused by different procedures including skin stripping due to adhesive tape. Neonatal staff must be aware of this potential long-term complication.
Preventive Measures
Disinfection: Catheter-related septicemia is most commonly caused by coagulase-negative Staphylococci. To prevent this, hand washing by staff and parents must be advocated. Two consecutive10 second wipes with chlorhexidine, alcohol or povidone-iodine or a longer duration of cleaning for about 30 seconds is more effective than a single 10 second wipe.
The Incubator: Regular change of infants’ posture reduces the risk of skin erosions and bedsores. Fingers and toes must be kept visible. Catheters or needles should be secured with a transparent tape to detect extravasation. Scarring alopecia can occur after extracorporeal membrane oxygenation or hypoxaemia-hypoperfusion. Non-blanchable erythema and disruption of epidermis are early indicators of pressure sore and demands postural change.
Transcutaneous oxygen monitors: These should not be left in place for more than one hour without surveillance. Non-blanchable erythema and hyper pigmented skin craters following prolonged contact can occur. Karaya electrodes seem to be less traumatic. Placement of electrodes on the limbs may facilitate frequent auscultation.
Minimal use of tape and adhesive: Tapes and adhesives should be used on small areas of skin and removed gently with warm water soaked gauze and diluted soap but not alcohol, which may irritate. A pectin-based skin barrier may be used, when frequent application and removal of adhesives is needed.
Emollients: Emollients are safe and effective in neonatal peeling and scaling dermatitis. They decrease fragility, improve wound care and help to protect infants. Vegetable oil (e.g. olive oil), lanolin and petrolatum – based ointments reduce scaling and fissure, and enhance cutaneous hydration.
Transparent cover: Use of a transparent covering over the isolette on small premature infants may help to decrease insensible water losses.
Reduction of water loss: Water loss can be reduced by humidification of the surrounding air, use of plastic bubble blankets, heat shields or topical application of paraffin.
After birth, neonatal skin is exposed to air, temperature changes, friction, microbes etc. Maintaining skin integrity and preventing exposure to toxic substances in childhood assures healthy skin for several years ahead.
At birth, microbial colonization of skin is nil. Within a few days, aerobic flora colonizes over the groins, axillae and scalp. Coagulase-negative Staphylococci (Staphylococcus epidermidis) is the commonest followed by S. aureus. The latter is usually due to contamination by the mother or nursing staff.
Removal of Vernix Caseosa
At birth, newborn skin is coated with vernix caseosa, blood, meconium and cellular debris. Premature infants tend to have less vernix than term babies and the post mature little or none. There is considerable inter-individual variation. It is unclear whether vernix gives mechanical or microbial protection. It is wiped off with a clean towel after birth.
Washing and Bathing
A bath cleans the infant completely. It should not last for more than five minutes. Infants may be bathed immediately after birth. The water should be sterilized by boiling, but the temperature of the bath -water should not exceed 37° C. A solid or liquid soap or a syndet may be used to clean the baby. Bubbles bath used can irritate or dry the skin. Soap should be thoroughly rinsed, and the baby patted dry especially in folds.
Napkin Changes
Napkin should be changed frequently, at least at each nursing and feeding time. Baby should be washed in lukewarm water and dried thoroughly. Partial occlusive agent like mineral oil application can act as a physiological barrier. Skin should be thoroughly air-dried each time the diaper is changed. Powder may be applied in the skin folds after drying. Soaps should preferably be avoided or they should be mild. Nappies should be home 12laundered with mild detergents. Nappy pads with cotton padding are more suited.
Shampoos may be rarely used. On first signs of seborreic dermatitis, application of mineral or animal oil limits the spread.
They should be trimmed short and kept clean.
The Ears
Cotton swabs soaked in boiling water may be used without injury to the canals.
After birth, the umbilical cord dries out and falls within 5–10 days. Certain products containing eosin or other stains are applied. They act as drying agents rather than as antiseptics.
A large number of over-the-counter cosmetics for children are available in the market. In addition to the prescribed medical treatment, infants’ skin is at risk by these cosmetics.
Role of Cosmetic Products
Several types of products are used like detergents in the form of soaps or shampoos, antiseptics, emollients etc.
Detergents: Detergent is a substance capable of cleaning the skin by removing impurities like dust, greasy substances and micro-organisms. These act by reducing surface tension between water and air, creating a foaming effect. Foaming power is directly proportional to skin damage. Its usage should be followed by a thorough rinsing.
Soaps are alkalis with delipidating effect on the skin. In hard water, soaps tend to precipitate.
Syndets: These are composed of tensioactive cleansing agents with detergent quality, produce little foam and minimal irritation. They should be used with moisture as an additive.
Bubble Bath Products: Prolonged bath may irritate the genital mucosa.
Shampoos: These contain anionic tensioactive agents which ensure adequate cleansing. The pH should be equivalent to that of tears and have low ocular irritation index. Medicated shampoos containing selenium sulphide, zinc pyrithione and ketoconazole may be used for seborreic dermatitis.
Antiseptics: Risk of toxicity due to absorption is high with these topical medications, due to increased surface area, immature barrier and other factors. Biguanides and amidines are better for use in infants. Dilution, application time and rinsing conditions need to be determined since the action is time-dependent.
Emollients: Emollients can be applied on normal as well as pathologic skin and reduces imperceptible water loss.
Protective creams: Protective creams are used to reduce the risk of irritation, particularly napkin rash. These contain a fatty phase, an aqueous phase, a surfactant, zinc oxide, scents and preservatives. They can paradoxically increase occlusion and cause napkin dermatitis. Early sensitization can occur with certain preservatives.
Powders: These are used to prevent maceration over the skin folds in infants. Excessive use may cause miliaria
Role of Massage
Touch helps in growth and development of the child. Massage with oil is better than without. The oil should be smooth, of optimum viscosity, frictionless and non-occlusive. Mineral oil is one of the best ingredients. Gentle massage can be practiced from 10th day till 10th year of life. Massage given by the mother helps in developing bondage between the mother and the baby. Complete head to toe massage can be given daily.
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