Nodermosis

Diseases of SKIN
GENODERMATOSES
Dr Antony George
Dept. of Oral & Maxillofacial Pathology
1. White Spongy Nevus
Antony George Oral & Maxillofacial Pathology

White spongy nevus
Also known as Cannon’s Disease.
Etiopathogenesis
Mutation of 12q & 17q.
Autosomal dominant trait of high penetrance &
variable expressivity.
Defect in keratinization of oral mucosa.

Over expression of cytokeratin (CK4, CK13) in stratum
spinosum.

White spongy nevus
Clinical Features
Appears at birth or early childhood.
Bilateral asymptomatic white lesion.
Buccal mucosa appears thickened, corrugated with

spongy texture and white opalescent hue.
Other sites involved – ventral tongue, soft palate,
alveolar mucosa, nasal mucosa.
Ragged white areas may be removed by gentle

rubbing without bleeding.

White spongy nevus

White spongy nevus
Histopathology
Hyperparakeratosis with deep parakeratin plugs.
Acanthosis and intracellular edema of stratum
spinosum.
Superficial spinous cell layer show clear cells or

vacuolated cells with pyknotic nuclei having
eosinophilic condensation in perinuclear region.
Pathognomic feature of white spongy nevus.
Identified in cytologic preparation of buccal smear with PAP
stain (exfoliative cytology).
EM study show tangled mass of cytokeratin filaments.

White spongy nevus

White spongy nevus
Treatment
No treatment required.
Benign lesion.
To be differentiated from other white potentially malignant
lesions.
Prognosis is good.

2. Epidermolysis Bullosa

Epidermolysis Bullosa (EB)
Inherited vesiculobullous mucocutaneous
disease.
Defect in cell junctions

Cell-cell adhesive cell junction – desmosomes.
Cell-matrix adhesive cell junction – hemidesmosomes.
Depending on defective mechanism 21 different

epidermolysis bullosa variants identified.

Epidermolysis Bullosa (EB)
Epidermolysis bullosa can be classified as
1. Hereditary
Histopathologically (depending on level of clefting)
classified as
a) Simplex epidermolysis bullosa (SEB)
b) Junctional epidermolysis bullosa (JEB)
c) Dystrophic epidermolysis bullosa (DEB)
2. Acquired
Epidermolysis bullosa acquisita (EBA)

a. Simplex epidermolysis bullosa
Simplex epidermolysis bullosa
Mildest form.
Autosomal dominant (AD).
Mutation of 12q & 17q leading to defective CK5 &
CK14.
Vesiculobullous lesions on hand & feet due to defect
in desmosomal cell junctions.
Blisters heal in 2-10 days without scaring.
Mucous membrane & oral cavity usually not
affected.
Muscle dystrophy maybe seen due to defective
plectin formation.
Simplex epidermolysis bullosa
Histopathology
Intraepithelial clefting.
Desmosomal cell junctions affected.
Defective CK5 & CK14 gene produce defective anchoring
filaments.

b. Junctional epidermolysis bullosa
Junctional epidermolysis bullosa
Most severe fatal form – epidermolysis bullosa letalis.
Autosomal recessive (AR).
Mutation of 1q, 10q, 17q & 18q.
Defect in hemidesmosomes.
Laminin 5, type 17 collagen, α6β4 integrin, BP Ag II.
Most result in death at birth due to sloughing of skin

during passage through birth canal or die within 3 months
of birth.
If baby survives
Hemorrhagic blisters of palate.
Erosions of perioral and perinasal areas.
Anodontia or hypodontia.
Enamel hypoplasia with enamel pitting of deciduous teeth.
Junctional epidermolysis bullosa
Histopathology
Sub epithelial clefting at level of lamina lucida.
Hemidesmosomal cell junctions affected.
Defect in Laminin 5, type 17 collagen, α6β4 integrin, BP Ag II

c. Dystrophic epidermolysis bullosa
Dystrophic epidermolysis bullosa
Broadly two variants
1. Dominant Dystrophic Epidermolysis Bullosa – AD.
Pasini type.
Cockayne-Touraine type.
2. Recessive Dystrophic Epidermolysis Bullosa – AR.
Generalized gravis type.
Inverse type.
Mutation of COL7A1 gene causing defect in type 7

collagen.
More than 200 different distinct mutations identified.

Dominant dystrophic epidermolysis bullosa
Extremities primarily affected more than mucosa.
Vesicles on areas exposed to low grade trauma
Knuckles, elbows, knees.
Ulcerations heal with scaring and keloid formation.
Fingernails maybe lost.
Oral manifestations
Gingival erythema, tenderness and recession.
Mucosal ulceration that heal with scaring.
Reduced labial vestibule depth due to scaring.
Teeth are usually not affected.

Recessive dystrophic epidermolysis bullosa
More debilitating form – usually die before 20th
birthday.
Vesicle and bullae form with minor trauma during
normal activity.
Hands, feet, buttocks, scapulae.
Wide spread secondary skin
infections.
Repeated ulceration & healing
with scaring leads to fusion of
fingers – mitten-like deformity.
Recessive dystrophic epidermolysis bullosa….
Dystrophic nails which may fall off.
Hypotrichosis.
Painful blisters and ulcers - even soft diet induce bullae,
vesicle and ulceration.
Microstomia due to repeated scaring.
Ankyloglossia.
Esophageal strictures with hoarseness of voice and
dysphagia.
Hypoplastic teeth.
High carious index due to soft diet and poor oral hygiene.
Histopathology
Sub epithelial clefting below lamina lucida.
Hemidesmosomal cell junctions affected.
Defect in type VII collagen.

Epidermolysis bullosa
Special Investigations
Immuno-fluorescence (IF) and immuno-
histochemical (IHC) techniques to identify
1. Anti-keratin antibody.
2. Anti-Bullous Pemphigod Ag-2 Ab.
3. Anti-collagen VII Ab.
Simplex: Anti-keratin stains roof, while Anti-BP-2
and Anti-collagen VII stains floor of bulla.
Junctional: Anti-keratin and Anti-BP-2 stains roof of
bulla, while Anti-collagen VII stains floor of bulla.
Dystrophic: All three antibody stain roof of bulla.

Epidermolysis bullosa
Treatment
No cure.
Genetic counseling.
Local wound care with sterile topical antibiotics
dressings.
Oral antibiotics if cellulitis present.
Soft diet but maintain adequate nutrition.
Maintain oral hygiene.
Topical sodium fluoride application to prevent caries
Plastic surgery maybe advocated (poor results)
Recessive dystrophic EB predisposed to cutaneous
squamous cell carcinoma.
Epidermolysis Bullosa Acquisita
Epidermolysis Bullosa Acquisita
Autoimmune vesiculobullous lesion. (Not Hereditary)
Auto-antibodies IgG produced against type VII
collagen anchoring fibrils located below the lamina
densa.
Clinically resemble Junctional EB.
Sub epithelial clefting at level of lamina lucida.

Hemidesmosomal cell junctions affected.
Anti collagen VII Ab and IgG auto-antibodies stains
floor of bulla.

3. Peutz-Jeghers Syndrome

Peutz-Jeghers syndrome
Hereditary intestinal polyposis syndrome.
Rare disease. 1 in 1,20,000.

Autosomal Dominant.
Mutation of STK 11 gene located at 19p13.3 cause
defect in serine and threonine kinase enzymes.
Young adults.
No gender predilection.

Clinical Features
Intestinal hamartomatous polyps.
Intestinal hemorrhage.
Abdominal pain due to intestinal obstruction.
Mucocutaneous melanocytic macules 1-5 mm in
size with bluish black discoloration.
Hands, fingers, toes.
Perioral & perinasal skin.
Vermilion zone.
Oral mucosa (66-90%).
Anal and perianal skin.
Genitalia.
Clinical Features….
Precocious puberty.
Rectal mass and prolapse.
Prognosis
Prone to cancer – 15-18 times greater risk.
GIT tract – gastrointestinal adenocarcinoma.
Pancreas.
Reproductive tracts , ovary, breast.
Lungs.

4. Hereditary Hemorrhagic
Telangiectasia (HHT)

Hereditary hemorrhagic telangiectasia
Osler-Weber-Rendu syndrome.
Osler’s disease.
Autosomal Dominant defect.

1. Mutation of endoglin gene located at 9q34.
2. Mutation of activin receptor like kinase 1 (ALK 1) –
12q.
Telangiectasia appear shortly after birth and

becomes conspicuous by puberty.

Pathophysiology
Defect in blood vessel wall integrity.
Defect in endothelial cell junctions and degeneration of
endothelial cells along with weakness of peri-vascular
connective tissue leads to dilation and rupturing of
capillaries leading to aneurysms, arteriovenous
malformations and telangiectasia.

Site
Face, neck, chest, hands & feet.
Lips, gingiva, buccal mucosa, palate, tongue, floor of
mouth.
Nasal and oro-pharyngeal mucosa.
Conjunctiva.
Gastrointestinal mucosa.
Genitourinary mucosa.

Clinical Features
Multi organ arteriovenous malformations (AVM)
Lungs.
Liver.
Brain.
Spider like telangiectasia
Oral cavity – scattered red papules of 1-2mm that blanch
on diascopy.
Epistaxis.
Intestinal hemorrhage.
Bleeding and clotting time are normal.
Chronic iron deficiency anemia.
Treatment
Selective cryosurgery / electrocautery.
Laser ablation.
Skin grafts to replace nasal mucosa.

5. Ectodermal Dysplasia

Ectodermal Dysplasia
Two or more ectodermal derived anatomic structure
fail to develop.
Rare disorder – 1 in 1 lakh births.
Can be AD, AR or X-linked mutations.

150 subtypes reported.
Most common subtype

Hypohidrotic ectodermal dysplasia
(Christ-Siemens-Touraine syndrome)

Hypohidrotic Ectodermal Dysplasia
X-linked inheritance – Xq12-13.1
Female are carriers (show no signs of disease).
Males are only affected.
Clinical Features
1.Alopecia or sparse hair – fine short brown hair.
2.Lack of sweat glands – heat intolerance.
3.Lack of sebaceous glands – dry scaly skin.
4.Lack of lacrimal glands – dry eyes; photophobia.
5.Lack of mucous glands in respiratory & GIT mucosa.

6.Nails are thin, brittle, dystrophic, with ridging.
7.Deficient hearing & vision.
8.Periocular skin show wrinkling & pigmentation.
9.May show deficient fingers / toes.
10.Short stature.
11.Hoarseness of voice.
12.Intelligence is normal.

Facial deformities
Frontal bossing
Saddle nose
Sunken cheeks
Low set ears
Mid face hypoplasia; may show cleft lip / palate.
Protuberant thick lips due to decreased vertical height.
Oral manifestations
Hypodontia or anodontia
Conical / pegged shaped teeth.
Delayed eruption of permanent teeth.
Xerostomia due to lack of salivary glands.
High palatal arch.

Histopathology
Atrophic, flat epidermis & mucosa.
Decreased number of adnexal structures, mucous &
salivary glands.
Treatment
Hair replacements.
Replacement of missing teeth – implants.

6. Ehler-Danlos syndrome (EDS)

Ehler-Danlos syndrome
Heterogeneous group of inherited connective
tissue disorder that affects skin, joints & blood
vessels.
Characterized by joint hyper-mobility, cutaneous
fragility & hyper-extensibility.
Rubber Man.
1 in 4,00,000 people.
AD, AR or X-linked-R.

11 types of EDS with varied etiology,
biochemical and clinical features – 6 major & 5
minor types.
Hypermobility type (type III) most common type.
Kyphoscoliosis type (type VI) is life threatening due
to large blood vessel rupture (aneurysm) and visceral
perforation.
Mutations in 6 major types could be
Fibrous proteins: COL1A1, COL1A2, COL3A1, COL5A1,
COL5A2 & TNXB.
Enzymes: ADAMTS2 & PLOD1.
Underlying collagen deformity is different for each type.
Genetic Chromosome
Types Formerly Transmission
Defect Location
Types I & II COL5A1 9q34.2

Classic type Gravis form COL5A2 2q14-q32 AD
Mitis form COL1A1 17q21.33
Hypermobility COL3A1 2q32.2

Type III AD
type TNXB 6p21.3
Type IV
Vascular type Ecchymotic COL3A1 2q32.2 AD, AR
type
Kyphoscoliosis Type VI
PLOD1 1p36.3 AR
type Ocular type
Arthrochalasis Type VII COL1A1 17q21.33

AD
type A&B COL1A2 7q21.3
Dermatosparaxis
Type VII C ADAMTS2 5q23-q24 AR
type
Types V, VIII,
Others AD, AR, XLR
IX, X and XI
Clinical Features: Skin Manifestations
White, soft, doughy feel & underlying vessels are
sometimes visible.
Easily hyper-extensible – easy to pull & stretch but once
released immediately returns to its original state.
Cutaneous fragility with frequent bruises and lacerations.
Poor wound healing with scar formation = cigarette-paper–
like scars (observed on knees) – papyraceous scarring.
Easy dehiscence and difficulty in suturing wounds.
Molluscoid pseudotumors – small spongy tumors found
over scars and pressure points made of adipocytes
surrounded by fibrous capsule.


Joints
Hyper-extensible – digit joints most commonly affected.
Dislocations occur – patients usually able to reduce them.

Vision problems due to deformed cornea.
Eversion of upper eye-lid.
Mitral valve prolapse.
Rupture of intestines, uterus, eyeball (seen only in
vascular type)
Premature rupture of membrane during pregnancy.
Platelet aggregation failure (platelets do not clump
together properly).
Muscle weakness with easy tendency to fall down,
poor body control & may have difficulty in walking.
Mental development is normal.
Gorlin sign – patient can touch tip of nose with
tongue.
Oral mucosal fragility and friability leading to
bruising and bleeding to minor trauma.
Recurrent subluxation of TMJ.
Marked periodontal disease with loss of teeth by
age of 30 in type VIII.
Hypoplastic teeth with malformed stunted roots.
Increased tendency to form pulp stones.
Delayed eruption.

Criteria for Diagnosis
1.Dorsiflexion of little finger by more than 90° with
forearm flat on table.
2.Passive apposition of thumb to flexor forearm.
3.Hyperextension of elbow by more than 90°.

Criteria for Diagnosis….
4.Hyperextension of knee by more than 10°.
5.Forward flexion of trunk until palms rest easily on
floor.
6.Evaluation of skin extensibility.

Treatment
Extreme caution during surgical procedures –
bleeding, difficulty in suturing, scaring.
Oral vitamin C (4gm) – critical cofactor for collagen
synthesis.
Kyphoscoliosis type (type IV) have poor prognosis
Arterial aneurysms, valvular prolapse & spontaneous
pneumothorax.
Sudden death after visceral perforation or after rupture of
large vessel (abdominal or splenic vessel).

Thank You

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Nodermosis

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Diseases of SKIN

Antony George Oral & Maxillofacial Pathology

Defect in keratinization of oral mucosa.

Antony George Oral & Maxillofacial Pathology

Bilateral asymptomatic white lesion.

Buccal mucosa appears thickened, corrugated with

Ragged white areas may be removed by gentle

Antony George Oral & Maxillofacial Pathology

Antony George Oral & Maxillofacial Pathology

Superficial spinous cell layer show clear cells or

Antony George Oral & Maxillofacial Pathology

Antony George Oral & Maxillofacial Pathology

Antony George Oral & Maxillofacial Pathology

Antony George Oral & Maxillofacial Pathology

Defect in cell junctions

Depending on defective mechanism 21 different

Antony George Oral & Maxillofacial Pathology

Antony George Oral & Maxillofacial Pathology

Antony George Oral & Maxillofacial Pathology

Most result in death at birth due to sloughing of skin

Antony George Oral & Maxillofacial Pathology

Mutation of COL7A1 gene causing defect in type 7

Antony George Oral & Maxillofacial Pathology

Antony George Oral & Maxillofacial Pathology

Antony George Oral & Maxillofacial Pathology

Antony George Oral & Maxillofacial Pathology

Sub epithelial clefting at level of lamina lucida.

Antony George Oral & Maxillofacial Pathology

Antony George Oral & Maxillofacial Pathology

Rare disease. 1 in 1,20,000.

Antony George Oral & Maxillofacial Pathology

Antony George Oral & Maxillofacial Pathology

Antony George Oral & Maxillofacial Pathology

Autosomal Dominant defect.

Telangiectasia appear shortly after birth and

Antony George Oral & Maxillofacial Pathology

Antony George Oral & Maxillofacial Pathology

Antony George Oral & Maxillofacial Pathology

Antony George Oral & Maxillofacial Pathology

Antony George Oral & Maxillofacial Pathology

Can be AD, AR or X-linked mutations.

Most common subtype

Antony George Oral & Maxillofacial Pathology

Antony George Oral & Maxillofacial Pathology

Antony George Oral & Maxillofacial Pathology

Antony George Oral & Maxillofacial Pathology

Antony George Oral & Maxillofacial Pathology

Antony George Oral & Maxillofacial Pathology

Antony George Oral & Maxillofacial Pathology

Types I & II COL5A1 9q34.2

Hypermobility COL3A1 2q32.2

Arthrochalasis Type VII COL1A1 17q21.33

Antony George Oral & Maxillofacial Pathology

Antony George Oral & Maxillofacial Pathology

Antony George Oral & Maxillofacial Pathology

Antony George Oral & Maxillofacial Pathology

Antony George Oral & Maxillofacial Pathology

Antony George Oral & Maxillofacial Pathology

Antony George Oral & Maxillofacial Pathology

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