Download Otoimmun Büllü Hastalıklar

Autoimmune Blistering Diseases
Idiopathic, chronic blistering diseases
are included here.
Pemphigus
Pemphigus patients have IgG
autoantibodies against
intercellular material (cell
membrane?)
Antigen is a 130 kd polypeptide
linked to plakoglobulin on
binding sites
Patients have both of circulating
antibodies (in serum) and
deposited antibodies (in
epidermis)
Antibody titration
Circulating antibody
titration is correlated
with disease activity.
When disease
improves titration
decreases and when
disease worsens
titration increases.
IgG immunoglobulins
are deposited in
Stratum spinosum,
above stratum basale
(suprabasal) or in
stratum granulosum
(subcorneal).
Acantholysis
Intercellular material
dissolves after
antigen-antibody
reaction.
Desmosomes try to
bind keratinocytes
weakly in this
phase. But first
trauma leads to
disrupt of
desmosomes and
keratinocytes
becomes free. This
entity is called
acantholysis.
Space, between keratinocytes is filled by fluid and blister formation occurs. Blister is situated in
epidermis (intraepidermal blister). The roof of the blister consists of some superficial epidermal
strata, so, roof of the blister is easily disrupted and blister opens. Secondary elementary lesion of
the pemphigus blister is erosion. Erosion heals without scarring.
Clinical Types of Pemphigus
Pemphigus vulgaris
(Suprabasal)
Pemphigus vegetans
(Suprabasal)
Pemphigus foliaceus
(Subcorneal)
Pemphigus erythematosus
(seborrheicus) (Subcorneal)
Pemphigus vulgaris
Disease generally begins in adolescent ages.
Male/female ratio is equal. Initial lesions are almost
always in the mouth. Mouth blisters easily open and
remain painful erosions.
Pemphigus
vulgaris
The erosion can be differentiated from other diseases by
the lack of spontaneous healing.
The localized phase lasts 2-3 months. During this period the
patient is seen by specialists interested in oral area and is
frequently misdiagnosed.
Pemphigus
vulgaris
Later, blisters form
on the skin due to
trauma. These
open and become
erosions.
Generally erosions
dominate the
whole body.
Pemphigus
vulgaris
There are no
subjective symptoms
on the skin. Intact
blisters can be seen on
non-traumatized skin.
Blisters typically appear on
normal skin without
erythema and are fragile,
slack and shrivel up.
Pemphigus vulgaris
Wide areas of erosions are seen in a severe case.
Pemphigus vulgaris
The skin around the
blister has normal
appearance
macroscopically, but
intercellular material
has dissolved there
and desmosomes are
only binding
structure.
Pemphigus vulgaris
• When one press at the top of the blister, desmosomes disrupt by blister fluid
pressure. So, blister widens through the normal skin (1).
• After hours of a frictional trauma on perilesional skin, a blister occurs on the
trauma site (2).
• One can easily pull the blister roof along the normal skin, like a peach
Pemphigus vulgaris
These three entities are
called as "Nikolsky
phenomenon" and shows
acantholysis.
Pemphigus vulgaris
Smear material taken from the blister floor is mounted on a slide and
stained by Giemsa (Tzanck smear). One can see a typical keratinocytes
with large and dark stained nucleus and narrowed cytoplasm. These
cells are also called as "Tzanck cells" or "acantholytic cells". This
phenomenon shows acantholysis.
Pemphigus vulgaris
Definitive diagnosis should be made by intraepidermal
blister formation and acantholysis.
Pemphigus vulgaris
%25-40
Pemphigus vulgaris
have the worst
prognosis in
pemphigus group.
Patients die in one
year if they do not
treat. Recent mortality
rate is 25-40% and
mortality causes are
the side effects of high
dose of corticosteroids
mainly.
Pemphigus
vegetans
Initial features are the
same with pemphigus
vulgaris as blisters and
erosions in the mouth
and skin. But
pemphigus vegetans
patients develop
vegetating masses on
inguinal and axillary
folds. Prognosis is
severe, but milder than
pemphigus vulgaris.
Pemphigus
foliaceus
There are generalized subcorneal
blisters. The blister roof
consists only stratum corneum,
so blister roof is very thin.
Blister fluid is easily reabsorbed
and blister roof is desquamated.
Blisters appear on an
erythematous base. In the scaly
phase pemphigus mimics an
erythemato-squamous disease
or an erythroderma. Practically
mouth is not involved.
Pemphigus
erythematosus
(seborrheicus)
Subcorneal blisters are
localized on
seborrheic areas as
face, midline of the
chest and back. The
lesions mimic
seborrheic dermatitis,
but scales are not as
greasy as seborrheic
dermatitis.
Paraneoplastic
pemphigus
Develops due to an
underlying malignancy.
It is most frequently
seen with hematologic
malignancies such as
non-Hodgkin
lymphoma, chronic
lymphocytic leukemia.
Paraneoplastic
pemphigus
The most
important clinical
sign is
hemorrhagic
painful oral
erosions. Skin
lesions are
polymorphic and
diagnosis may be
difficult.
Paraneoplastic pemphigus
• It is similar to erythema multiforme due to
the polymorphic symptoms. The other
similar diagnosis is bullous pemphigoid.
This disease is characterized by marked
pruritus.
• This type of pemphigus does not respond
well to treatment.
Drug Induced Pemphigus
• Develops due to drugs such as
D-penicillamine, captopril.
• Skin lesions are similar to pemphigus
foliaceus. Rarely, lesions of pemphigus
vulgaris may be seen.
• Prognosis is well in cases due to drugs
containing sulphydril group. Resolution
occurs when the drug is discontinued.
Treatment of Pemphigus
Systemic corticosteroids are given to pemphigus
patients. Initial dose must be at least 120 mg/day
prednisolone or equivalent dose of another
steroid. Dose may be increased until healing of
the erosions and ceasing of the blister crops. After
the control of the disease dose should be slowly
decreased to maintenance dose prevents the
exacerbations. Classically patient must use
corticosteroid lifelong.
Treatment of Pemphigus
• Drugs that can be combined with steroids:
–
–
–
–
Azathioprine: 50-200 mg/day (Safe)
Cyclophosphamide: 50-200 mg/day(Toxic)
Methotrexate: 15-30 mg/week
Mycophenolate mofetil (In trial phase)
These drugs are not used alone but combined with steroids. Such
combination proves smaller corticosteroid doses. In combined
therapy both of the drugs are decreased together. At the last
cytostatic is stopped and steroid in the maintenance dose is used
lifelong.
Pemphigoid
Linear IgG is deposited on the
junction between epidermis
and dermis. Epidermis
detaches from dermis and
subepidermal blister occurs.
(Subepidermal blister)
Pemphigoid
• The roof of the
blister is made
by whole
epidermis. So,
the blister is
not easily open
and tight, can
reach to very
large
diameters.
Bullous pemphigoid
Especially people
above 70 years old
are involved.
Provoking factors
are drugs such as
furocemide, 5fluorouracil and
penicilline, and
malignancies.
Bullous pemphigoid
Firstly erythema, papule with edema, vesicles or blisters appear on a scar
belongs a vaccine or burn, or on umbilicus as a localized phase. Wrong
diagnosis may be eczema, urticaria, erythema multiforme at this phase
because of the existence of pruritus.
Bullous pemphigoid
• After several
months the
disease turn into
generalized
phase. Solitary or
grouped large
blisters arranged
as a circle on
body and/or
extremities.
Bullous pemphigoid
Prognosis is better than pemphigus and 40
mg/day prednisolone is useful and sufficient
for the patients above 70 years old. Steroids
may be used higher doses for the patient
younger than 70 years old.
Cicatricial
pemphigoid
Females are involved
frequently. Mainly
orifices and around
of orifices are
involved. The
disease is mainly
localized to head.
Attacks and
remissions while
remain scars after
attacks are seen.
Cicatricial
pemphigoid
Scars become severe
after every attack
and lead to
function
disturbances. Eye
involvement may
lead to blindness.
Cicatricial pemphigoid
Local or systemic steroids, cytostatics or
dapsone may be tried, but responses are
unpredictable.
Dermatitis
herpetiformis
(Subepidermal blister)
Granular IgA
is seen at the
top of dermal
papillae. So
little
detachments
firstly appear
on these areas
and are filled
by serous fluid.
Dermatitis herpetiformis
As a result of this
phenomenon
erythematous and
edematous papules
appear. Larger
detachments lead to
vesicle or blister
formation in the later
phases. Patients have
severe itching. Two
dermatoses with the
most severe itching are
dermatitis herpetiformis
and scabies in
dermatology.
Dermatitis
herpetiformis
The disease begins in
young adolescents.
Firstly erythematous
and edematous papules
(mimicking urticaria),
secondly grouped
vesicles (mimicking
herpes simplex) appear.
And then vesicles either
transform pustules or
blisters.
Dermatitis
herpetiformis
Blisters are rarely seen in
dermatitis herpetiformis.
Bleeding, crusting,
excoriation and secondary
infection create a
polymorphism because of
severe scratching. In this
phase scabies can be
thought in differential
diagnosis. But there are not
family history and specific
features of scabies in
dermatitis herpetiformis.
Dermatitis herpetiformis
Eosinophilia and iodine sensitivity support
diagnosis but one can made diagnosis
without these features. All of the patients
have celiac disease, 75% of the patients
show clinical symptoms, and in the 25% of
the patients course of the disease is
subclinical.
Dermatitis herpetiformis
Prognosis is good. Specific therapy with
dapsone is successful. Therapy begins with
200 mg/day dapsone and gluten free diet in
adults and then dapsone is tapered
according to clinical cure. Gluten free diet
lasts lifelong.
Chronic bullous dermatosis of childhood
There are linear IgA
deposits between
dermis and
epidermis. A
subepidermal blister
is formed as a result
of dermo-epidermal
detachment.
(Subepidermal blister)
Chronic bullous dermatosis of childhood
Clinical features are the
same with bullous
pemphigoid, but the
patients are children.
Ninety percent of the
patients are under the 6
years old and the
disease lasts in 2-3
years. Pruritus is not a
unique symptom.
Chronic bullous dermatosis of childhood
Dapsone
(sulfone) and
corticosteroids
are useful in
small doses.
Web
http://www.hulusibehcet.net/dersler