Genoderm - Disorders Of Pigmentation Flashcards
Hyperpigmentation disorders
LINEAR/BLASCHKOID
Incontinentia pigmenti
Linear and whorled naevoid hypermelanosis
RETICULATE Dyskeratosis congenita Naegeli-Franceschetti-Jadassohn syndrome + Dermatopathia pigmentosa reticularis Dowling-Degos disease Reticulate pigmentation of Kitamura
PUNCTATE
Peutz-Jeghers syndrome
Incontinentia pigmenti (linear/blaschkoid hyperpigmentation)
Multisystem ectodermal dysplasia
NEMO gene
XLD
Inherited from affected mother or de novo
Lethal in males —> miscarriage
Classically females (50% risk of inheritance)
CUTANEOUS CLINICAL FEATURES
Vesiculobullous stage I - erythematous veiscular eruption following Blaschko’s lines, can recur during febrile illness
Verrucous stage II (within a few months) - mainly on the limbs
Hyperpigmented stage III (within months) - hyperpigmented streaks and whorls along Blaschko’s lines, fades in adolescence
Hypopigmented stage IV (adolescence) - pale, hairless, atrophic linear streaks/patches lower extremities
Cicatricial Alopecia scalp
EXTRACUTANEOUS CLINICAL FEATURES
Eyes - retinal neovascularisation, retinal detachment
Teeth - delayed dentition, missing teeth, cone-shaped teeth
Nails - onychodystrophy
CNS - microcephaly, seizures, cognitive/motor impairment (though majority neurologically normal)
DDX VESICULOBULLOUS STAGE I EB Bullous impetigo HSV VZV Congenital syphilis
DDX VERRUCOUS STAGE II
Warts
Epidermal naevus syndrome
DDX HYPERPIGMENTED STAGE III
Linear and whorled naevoid hypermelanosis
DDX HYPOPIGMENTED STAGE IV
Hypomelanosis of Ito
Scarring
MX
No specific Rx
Eyes —> opthal monitoring and Rx i.e. cryotherapy, laser
Teeth —> paed orthodontist + speech therapist + nutritionist
CNS —> paed neurologist —> Brain MRI in any child with functional neuro abnormalities, retinal neovascularisation
Linear and whorled naevoid hypermelanosis (linear/blaschkoid hyperpigmentation)
Cutaneous mosaicism
reverse of hypomelanosis of Ito
Benign
Onset infancy
Hyperpigmented streaks following lines of Blaschko on trunk and limbs
Spares face, palms, soles, mucosa
No extracutaneous features
ASSOCIATED ABNORMALITIES (rare)
Cardiovascular
Neurological
MSK
Dyskeratosis congenita (reticulate hyperpigmentation)
Genetically heterogeneous - AR, AD, XLR
DKC1 gene (XLR) TERC gene (AD)
Highly variable phenotype
CUTANEOUS CLINICAL FEATURES (classic)
Reticulated grey brown skin pigmentation + telengiectasia, hypopigmentation, atrophy within pigmentation (poikiloderma) —> diffuse on neck, upper chest, proximal limbs
Nail dystrophy
Premalignant Leukoplakia of the oral mucosa —> often undergoes malignant transformation
+/- PPK
+/- hyperhidrosis
+/- friction bullae
+/- acrocyanosis
+/- thinning alopecia scalp, eyebrows, eyelashes
EXTRACUTANEOUS CLINICAL FEATURES
Haem - Fanconi’s type pancytopenia —> risk of secondary infection, haemorrhage
Eyes - blepharitis, conjunctivitis
Mild - mod mental retardation
COMPLICATIONS (Malignancy)
Bone marrow/haem
Epithelial i.e. SCC
COURSE/PROGNOSIS
Early death in 20s/30s d/t
- malignancy
- GI haemorrhage (result from pancytopaenia)
- opportunistic infection (result from pancytopaenia)
Naegeli-Franceschetti-Jadassohn syndrome + Dermatopathia pigmentosa reticularis (reticulate hyperpigmentation)
2 closely related Ectodermal dysplasia syndrome
KRT14 gene
SHARED FEATURES Reticulate skin pigmentation face, trunk PPK Complete absence of dermatoglyphics Abnormal sweating Dental anomalies Nail dystrophy Plantar bullae in early childhood
NAEGELI-FRANCESCHETTI-JADASSOHN SYNDROME cardinal features
Reticulate skin pigmentation starting in early life without preceding inflammatory stage
Hyperkeratosis palms and soles
Discomfort provoked by heat d/t diminished sweat gland function
Poor teeth
M = F
DERMATOPATHIA PIGMENTOSA RETICULARIS cardinal features
Reticulate skin hyperpigmentation
Non-scarring alopecia
Onychodystrophy
Dowling-Degos disease (reticulate hyperpigmentation)
AD with variable penetrance
KRT5 gene (flexural Dowling-Degos disease, Galli-Galli disease) POFUT1 gene (generalised Dowling-Degos disease) POGLUT1 gene (generalised Dowling-Degos disease)
Post pubertal onset
CUTANEOUS CLINICAL FEATURES
Reticulate pigmentation with FLEXURAL distribution —> progressive, disfiguring
Reticulated pigmented lesions genital and perianal
Comedo-like lesions neck
Pitted perioral acneiform scars
NO hair/nail abnormalities
CLINICAL VARIANT
Generalised Dowling-Degos disease —> hyperpigmented/erythematous macules/papules on neck, chest, abdomen
HISTOLOGICAL VARIANT
Galli-Galli disease —> same clinical features with flexural Dowling-Degos disease + acantholysis on histology
Reticulate pigmentation of Kitamura (reticulate hyperpigmentation)
AD
ADAM10 gene
Onset 1st - 2nd decade of life
CUTANEOUS CLINICAL FEATURES
Reticulate hyperpigmentation + atrophic macules dorsal hands —> gradually darken, spreading proximally on the limbs
Pits on palms and soles
Peutz-Jeghers syndrome (punctate hyperpigmentation)
Lentiginosis syndrome
AD
STK11 gene
CUTANEOUS CLINICAL FEATURES
Early onset lentiginosis of the lips, buccal mucosa, digits
EXTRACUTANEOUS CLINICAL FEATURES Hamartomatous polyps GIT esp jejunum —> intussusception, bleeding, malignancy (rare), Renal polyps Ureter polyps Bladder polyps Nasal polyps Bronchial polyps
ASSOCIATED MALIGNANCIES
Breast CA
Ovarian CA
Pancreas CA
COMPLICATIONS
Intussusception, bleeding from GIT polyps
Malignant degeneration of GIT polyps (rare)
Dyschromatoses
Dyschromatosis symmetrica hereditaria
Dyschromatosis universalis hereditaria
Dyschromatosis symmetrica hereditaria (punctate hyperpigmentation)
@
symmetrical dyschromatosis of the extremities
Reticulate acropogmentation of Dohi
AD
ADAR1 gene (heterozygous mutation)
Japanese, chinese ppl
CLINICAL FEATURES
Onset early childhood
Freckle-like pigmented macules on the face
Small hyperpigmented and hypopigmented macules om the dorsal hands and feet
Dyschromatosis universalis hereditaria (punctate hyperpigmentation)
Genetic heterogeneity
ABCB6 (Dyschromatosis universalis hereditaria type 3)
CLINICAL FEATURES Onset infancy/early childhood Hyper and hypopigmented macules over entire skin surface \+/- Palms and soles (unusual) \+/- hair and nails
EXTRACUTANEOUS CLINICAL FEATURES
CNS
Eyes
Haem
Hypopigmentation disorders
Piebaldism
Waardenburg syndrome
Oculocutaneous albinism
Hermansky-Pudlak syndrome
Chediak-Higashi syndrome
Hypomelanosis of Ito
Piebaldism
AD
KIT gene
SNAI2 gene
CUTANEOUS CLINICAL FEATURES
Congenital
White forelock + V shaped leukoderma mid forehead
Well demarcated irregular hypopigmented macules anterior body (upper chest, abdomen) and mid segment of limbs (bilateral, not symmetrical)
+/- face esp chin
Hyperpigmented patches (“repigmentation”) at the border or centre of hypopigmented patches
Normal pigmentation hands and feet, back
EXTRACUTANEOUS CLINICAL FEATURES
Usually nil
+/- mental retardation
+/- deafness
DDX poliosis + hypopigmentation Waardenburg syndrome (piebaldism + sensorineural deafness + increased interpupillary distance) Vitiligo (acquired) Alopecia areata (acquired) Vogt-Koyanagi-Harada syndrome Alezzandrini syndrome
DDX isolated hypopigmentation
Naevus depigmentosus
Tuberous sclerosis
GENERAL MEASURES
Sun protection of amelanotic areas
SPECIFIC RX
Epidermal cell or skin grafting
Phototherapy and TCS does not work
COURSE/PROGNOSIS
Lesions remain stable during adulthood
Waardenburg syndrome
AD (mostly)
AR ( when assoc woth Hirschsprung disease)
PAX3 gene MITF gene SLUG gene EDNRB EDN3
CUTANEOUS CLINICAL FEATURES
Congenital
Piebaldism —> white forelock, v shaped leukoderma mid forehead, hypopigmented patches
EXTRACUTANEOUS CLINICAL FEATURES
Sensorineural deafness —> non-progressive
Increased inter pupillary distance d/t increased distance between inner canthi (dystopia canthorum)
Heterochromia irides
Broad nasal root
Hyperplasia of medial eyebrows
+/- Alopecia
+/- Mild skeletal abnormalities i.e. supernumerary ribs
+/- Hirschsprung disease
MX
Sensorineural hearing loss as indicqted by severity
Oculocutaneous albinism
A
