Nikolsky Sign

Immunobullous diseases
Dermatologic Diseases
• Production of autoantibodies
• Against epithelial cell constituents
(desmoglein, desmoplakin, plakoglobin) or
basement membrane molecules (BPA)
• Direct and indirect immunofluorescence
• Pemphigus
• Pemphigoid
Immunobullous Diseases
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Nikolsky Sign
Induced bulla on normal-appearing
mucosa or skin
Pemphigus
• Vulgaris (common); oral involvement
– Oral lesions first to show and last to go
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Vegetans; subtype of vulgaris
Erythematosus
Foliaceous
Paraneoplastic; lymphoma, leukemia; rarely
benign l
• Hailey-Hailey disease; familial
Pemphigus Vulgaris
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~ 50 years-old
No sex predilection
Oral ulcerations and erosions
Any mucosal site
Vesicles and bullae are thin and friable
50% of patients have oral lesions prior to skin
All patients have oral lesions
Ocular lesions that heal without scarring
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Histopathologic Features
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Intraepithelial separation
Intact basal cell layer
Acantholysis
Tzanck cells
Chronic inflammation
Immunofluorescent studies: IgG, IgM, C3
Antibodies raised against desmoglein 3
Indirect: 80-90% circulating antibodies
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Treatment
• Systemic and topical steroids
• Immunosuppressive drugs (azathioprine)
• Without treatment 60-80% of patients die
Pemphigoid
• Benign mucous membrane pemphigoid
• Antibodies against components of the
basement membrane
• Twice as common as pemphigus
• Clinical behavior different than pemphigus
• Cicatricial pemphigoid
Clinical Features
• ~ 50-60 year-old patients
• Females twice as males
• Oral lesions; conjunctiva; nasal, laryngeal (can lead
to obstruction), esophageal, vaginal mucosa and
skin
• Vesicles and bullae clinically present
• Areas of superficial ulcerations
• DESQUAMATIVE GINGIVITIS
• OCULAR INVOLVEMENT: dry eyes and blindness
• Nikolsky sign
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APRIL 2001
WORDS TO REMEMBER
• Symblepharon: scar developing between
the bulbar and palpebral conjuctiva
• Entropion: Inward turn of the eyelids
• Trichiasis: Rubbing of the eyelashes
against the globe of the eye
• Dyspareunia: Pain during attempts at
intercourse
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Histopathology
• Subepithelial separation
• Mild chronic inflammation
• Continuous linear band at the basement
membrane; IgG, IgM, C3, IgA
• IgG and IgA: more severe disease
• Indirect immunofluorescence: 5%
Treatment
• Topical steroids
• Systemic steroids
• Refer patient for ocular, cutaneous or
genital disease
Customized Trays
MAY 2001
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Types of Pemphigoid
• Antiepiligrin (against laminin-5): more
widespread involvement
• Bullous pemphigoid: most common;
limited; oral mucosal involvement
uncommon; presence of eosinophils in the
bullae; bullous pemphigoid antigen;
circulating autoantibodies in 40-70% of
patients; some patients experience
spontaneous remission
Lesions Mimicking Pemphigoid
• Linear IgA disease
– Skin lesions: annular, targetoid, bullous
– Oral lesions: Ulcerated preceded by bullae
• Angina bullosa hemorrhagica
– Painful blood-filled vesicles affecting the soft
palate; no scar, trauma or corticosteroid inhaler
use
• Epidermolysis bullosa aquisita
– Autoantibodies against collagen type VII
(anchoring fibrils); IgG in the bottom of the bulla
Paraneoplastic Pemphigus
• Lymphoreticular malignancy
• Cross-reactivity between antibodies
produced in response to malignancy and
constituents of the epithelium and the
basement membrane
• Skin and oral mucosa
– Lips: similar to erythema multiforme
• Bullae on the palms and soles
• Occasionally, skin lesions are similar to
lichen planus
Histopathology
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Pemphigoid and pemphigus features
Lichenoid mucositis
IgG and complement
Antibodies raised against desmoplakin I
and II, major bullous pemphigoid antigen,
evoplakin, periplakin, desmoglein
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Erythema multiforme
Treatment
• High morbidity and mortality rate
• Steroids and other immunosuppressive
medications
Erythema multiforme
• Mild to severe and life-threatening
• Mild disease: oral ulcers
• Severe forms
– Erythema multiforme major: Stevens-Johnson
syndrome
– Epidermal necrolysis (Lyell’s disease)
• Young adults, 20s or 30s
• Men>Women
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Ulcers and blisters
Mucosa and skin
Immunologically mediated disorder
Preceding infection: HSV or Mycoplasma
Pneumoniae
• Drugs: antibiotics and analgesics
• Immunofluorescence is non-confirmatory
Erythema multiforme
• Fever, malaise, headache, cough, sore
throat
• Recurring episodes
• Oral lesions
– Large, shallow ulcerations with irregular borders
– Hemorrhagic crusting of vermilion
– Patients may get dehydrated
– Lips, buccal mucosa, tongue, floor of mouth
– Palate and gingiva relatively spared
• Skin lesions:~ 50% of patients
• Target lesions
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Stevens-Johnson syndrome
• Most frequently medication-related
• Ocular or genital lesions should be present
together with oral and skin lesions
• Symblepharon
Toxic epidermal necrolysis
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Most severe form
Almost always medication-related
Sloughing of skin and mucosal surfaces
Older people, females
Can lead to death
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Treatment
Lupus erythematosus
• Systemic steroids for minor and major
erythema multiforme
• Oral lesions may be managed with elixirs or
syrups
• Chronic erythema multiforme related to
HSV: continuous use of acyclovir
• Toxic epidermal necrolysis: No steroids,
burn units of hospitals
• Immunologically mediated disease
• Connective tissue or collagen-vascular
disease
• Systemic lupus erythematosus
• Chronic cutaneous lupus erythematosus
• Subacute cutaneous lupus erythematosus
Systemic lupus erythematosus
Systemic lupus erythematosus
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Difficult diagnosis initially
Women (~x10); early 30s
Fever, weight loss, arthritis, fatigue
Half the patients develop characteristic rash
Sunlight worsens lesions
Kidneys: 50%, can lead to kidney failure
Libman-Sacks endocarditis: vegetations in
the valves
• Labs
– Anemia
– Leukopenia
– Lymphopenia
– Thrombocytopenia
– Proteinuria
– Nephrotic syndrome
• Proteinuria 3.5 g/day
• Na and water retention
Systemic lupus erythematosus
• Oral lesions
– 5-40%
– Lichenoid
– Irregular ulcerations
– Lupus cheilitis on the vermilion
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Chronic cutaneous lupus
erythematosus
Limited disease
Discoid lupus erythematosus
Lesions exacerbated by sun exposure
Scarring
Oral lesions look like erosive LP
Rarely seen in absence of skin lesions
Erythematous lesions with radiating striations
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Subacute cutaneous lupus
erythematosus
• Between SLE and CCLE
• Skin lesions
• Photosensitivity
Treatment
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Antimalarial medications
Systemic steroids
Combination
Variable prognosis
– Men worse than women
– 5-year survival ~ 95%
Oral manifestations of
Scleroderma
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Microstomia
Limited mouth opening
Xerostomia
Sjögren syndrome
Widening of the PDL
Resorption of posterior ramus, coronoid
process, chin and condyle; also tooth
resorption
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Vitiligo
Common Skin Lesions
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Autoimmune condition
Loss of melanocytes and pigment
Spontaneous repigmentation rarely
Macular and patchy areas of depigmentation
Perioral and periocular tissues
Nape of neck, areas of trauma (knees, elbows,
hands)
• TX: Tanning creams, cosmetic cover ups,
sunscreen for affected areas, PUVA (psoralens
and UV light)
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Rosacea
• Papular and pustular inflammation
• Hair follicles
• Middle third of the face
– Erythema, telangiectasia, small papules,
rhinophyma
– Absence of comedones of acne
– Small cysts may form
• Unknown cause
• TX: tetracycline, metronidazole
Xanthelasma
• Yellow papules plaques or macules
• Hyperlipidemia
• Upper eyelids
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Seborrheic Dermatitis
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Papulosquamous eruption
? Zinc deficiency, immunosuppression
Gradual onset
Pruritus increased with perspiration
Worsening in winter
Scalp, eyelid margins, nasolabial folds, cheeks,
forehead
• Yellowish, red, gray to white, nummular and
psoriasiform
• More men
• TX: mild steroids, ketoconazole (pityrosporum
ovale)
Seborrheic Keratosis
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Benign epidermal proliferation
Increasing frequency with age
Solitary or multiple lesions
Greasy-feeling keratotic crust that is loosely
attached
• Can be pigmented and large
• Those cosmetically objectionable should be
removed
Leser-Trélat sign
• Multiple seborrheic keratoses
• Sudden appearance
• Internal malignancy
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Psoriasis
• Common skin disease; 2%
• Strongly linked to heredity
• Triggering factors: systemic infections, stress,
drugs
• Increased turnover of keratinocytes
• Periods of exacerbation and remission
• Koebner’s phenomenon (presence of lesions along
the area of injury)
Psoriasis
• Erythematous macule or plaque covered by
silvery scales
• When scales are removed, red pinpoint
bleeding spots develop (Auspitz sign)
• Seronegative polyarthritis
• Geographic tongue
• TX: Topical and systemic preparations, PUVA
Basal cell carcinoma
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Most prevalent skin cancer
Midface
Men > Women
Sun exposed skin
Long sun exposure, Gorlin syndrome
Indurated pearly papule Æ central
ulceration and crust, slow relentless
growth, can be hyperpigmented
• TX: excision
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Keratoacanthoma
• Epidermal tumor
• Probably the most benign form of
cutaneous SCCa
• Muir-Torre syndrome
• Firm, smooth dome-shaped nodule,
central crater
• 1-2.5 cm in 6-8 weeks
• May involute within 6 months
Squamous cell carcinoma of
the skin
• Compared to BCCa increased risk for regional
lymph node metastasis
• Fair skinned individuals
• Slightly raised ulcer with raised indurated
borders
• Wart-like, plaques, papules
• Those associated with sun exposure and actinic
keratosis behave better
• SCCa arising in actinic cheilitis tends to invade
and metastasize earlier than other sun exposed
skin
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