5. PV is an autoimmune, intraepithelial,
blistering disease affecting the skin and
mucous membranes.
mediated by circulating autoantibodies
directed against keratinocyte cell junction
proteins termed desmogleins.
Definition
6. binding of IgG autoantibodies to
keratinocyte desmosomes results in a
loss of cell-cell adhesion, a process
termed acantholysis.
Spaces formed between cells are filled
by transudate fluid causing a blister.
7. occurs worldwide.
incidence varies from 0.5-3.2 cases per
100,000.
PV incidence is increased in patients of
Ashkenazi Jewish descent and those of
Mediterranean origin.
Frequency
8. Sex
Male-to-female ratio is approximately equal.
Age
Mean age of onset is approximately 50-60
years; however, the range is broad.
9. Mortality/Morbidity
PV is a potentially life-threatening
autoimmune mucocutaneous disease.
mortality rate is approximately 5-15%.
Prognosis is worse in patients with
extensive disease and in older patients.
10. The cause of Pemphigus remains unknown;
however, several potentially relevant factors
have been identified.
Genetic factors: Predisposition to pemphigus is
linked to Certain major histocompatibility
complex (MHC) class II molecules,
Etiology
11. PEMPHIGUS should
encourage the physician to
consider
pesticides (PE),
malignancy (M),
pharmaceuticals (P),
hormones (H),
infectious agents (I),
gastronomy (G),
ultraviolet light (U),
and stress (S).
14. Antibodies develop to deep intraepidermal
suprabasal desmosomal proteins common
to both skin and mucosa, so the blister is
deeper in location.
Mucosal lesions may precede cutaneous
lesions by months.
Patients with mucosal lesions may present
to dentists, oral surgeons, or
gynecologists.
Physical
15. patients have ill-defined, irregularly
shaped, gingival, buccal or palatine
erosions, which are painful and slow to
heal.
The erosions extend peripherally with
shedding of the epithelium.
16. Erosions may spread to involve the larynx
with subsequent hoarseness.
The patient often is unable to eat or drink
adequately because the erosions are so
uncomfortable.
Other mucosal surfaces may be involved,
including the conjunctiva, esophagus, labia,
vagina, cervix, penis, urethra, and anus.
24. The primary lesion of PV is a flaccid blister filled
with clear fluid that arises on normal skin or on an
erythematous base.
The blisters are fragile; therefore, intact blisters
may be sparse.
The contents soon become turbid, or the blisters
rupture producing painful erosions, which is the
most common skin presentation.
Erosions often are large because of their tendency
to extend peripherally with the shedding of the
epithelium.
Skin:
25.
26.
27.
28.
29. Nails: Acute paronychia, subungual
hematomas, and nail dystrophies have
been reported with PV.
30. Nikolsky sign: In patients with active blistering,
firm sliding pressure with a finger separates
normal-appearing epidermis, producing an
erosion. This sign is not specific for PV and is
found in other active blistering diseases.
Asboe-Hansen sign: Lateral pressure on the
edge of a blister may spread the blister into
clinically unaffected skin.
33. In some patients, erosions tend to develop
excessive granulation tissue and crusting, and
these patients display more vegetating lesions.
This type of lesion tends to occur more
frequently in intertriginous areas and on the
scalp or face.
The vegetating type of response can be more
resistant to therapy and can remain in one place
for long periods of time.
36. IgG develops against a superficial epidermal
desmosomal Ag named DsG1.
Acantholysis and separation occurs
subcorneally.
The patient presents with exfoliative skin
lesions and very superficial erosions with mild
crusting.
Usually no mucosal lesions.
40. (also known as "Senear–Usher syndrome") is
simply a localized form of pemphigus
foliaceus together with LE or seborrheic
dermatitis like manifestations on photo-
exposed areas.
42. Histopathology
Pemphigus vulgaris shows detachment of
keratinocytes from each other due to loss of
desmosome integrity, causing acantholysis
and intraepidermal bulla formation.
The point of separation in pemphigus vulgaris
is usually in the suprabasal epidermis.
48. The aim of treatment in pemphigus vulgaris
(PV) is to
decrease blister formation,
promote healing of blisters and erosions,
and determine the minimal dose of medication
necessary to control the disease process.
Medical Care
49. Anti-inflammatory agents
Inhibit the inflammatory process by inhibiting
specific cytokine production.
Corticosteroids (Prednisone)
1-1.5 mg/kg/d PO initial every am or in divided
doses; taper as condition improves; single
morning dose is safer for long-term use, but
divided doses have more anti-inflammatory effect
SE :
- osteoprosis -DM
-hypertension hyperacidity
50. Immunosuppressive agents
adjuvants in patients with PV unresponsive to
steroids and/or other anti-inflammatory agents or
in patients unable to tolerate prednisone.
Azathioprine(Imuran)
1 mg/kg/d
Cyclophosphamides
IVIG
Rituximab (anti CD20 monoclonal antibodies)
53. is an autoimmune blistering disorder
associated with a gluten-sensitive
enteropathy (GSE)
cutaneous manifestation of celiac disease.
Gluten is a protein present in barley, rye, and
wheat.
Rice and oats belong to different species and
are generally well tolerated.
54. Pathophysiology
genetic predisposition for gluten sensitivity,
coupled with a diet high in gluten,
leads to the formation of IgA antibodies to gluten-
tissue transglutaminase (t-TG), which is found in the
gut.
cross-react with epidermal transglutaminase (e-TG)
Deposition of IgA and epidermal TG complexes in the
papillary dermis
which triggers an immunologic cascade, resulting in
neutrophil recruitment and complement activation.
55. Clinically
characterized by waxing and waning, pruritic
eruption formed of:
grouped excoriations;
erythematous, urticarial plaques; and
papules
with vesicles that are often excoriated to
erosions by the time of physical examination .
on the extensor surfaces of the elbows,
knees, buttocks, and back.
exquisitely pruritic,
59. Diagnosis
neutrophil accumulation at the
dermoepidermal junction, frequently localizing
to the papillary tips of the basement
membrane zone (dermal papillary neutrophilic
microabscesses).
direct immunofluorescence of a skin biopsy
show deposition of immunoglobulin A (IgA) in
a granular pattern in the upper papillary
dermis.
60. Treatment
Strict gluten-free diet results in normalization of
the small bowel mucosal changes and control of the
cutaneous manifestations of dermatitis herpetiformis
in most patients.
Dapsone is the mainstay of treatment.
dose : 2-4 tab/day (50 mg/tab) i.e. 100-200 mg/day
-SE: hemolysis (so monitor RBCS) & liver insult (so
monitor Serum bilirubin)
colchicine, cyclosporine, azathioprine, and
prednisone are second agents.
61. Complications :
(1) 2ry infection
(2) 2ry eczematization
(3) psychological upset up to suicidal
attempts dt severe itching
??? Increased incidence of nonHodgkin
lymphoma is reported.
62. -mainly in newborns
-infection with staph occurs through the umbilical stump
-staph produces exotoxins which digest the desmosomal
proteins causing bullous eruption of the skin
-characteristically there is very large single bulla that involve the
Trunk & may involve both lower and upper limbs, its rupture
Causes severe agonizing pain & scalding of the skin
-bullae are filled with pus
-very bad general condition, so need ICU care
Staphylococcal scalded skin
syndrome (4S syndrome)
63.
64. - treatment : in the ICU :
-(1) Fluids to replace fluid loss by oozing
-(2)antibiotics (anti-staph ) : Cloxacillin in large doses.
65. Similar to 4 S – SYNDROME , but:
-occurs at any age
- it is not dt infection , it is a hypersensitivity reaction to a
drug : antibiotics (sulpha),NSAIDS, Anticonvulsants ,
anxiolytics
- large bullae which are filled with serum not pus
- treatment :
1. stop the offending drugs
TOXIC EPIDERMAL NECROLYSIS
(TEN)
