2. • Vesicles and bullae are accumulations of fluid within or
under the epidermis.
• Subepidermal blisters occur between the dermis and
the epidermis. Their roofs are relatively thick and so
they tend to be tense and intact.
• Intra-epidermal blisters appear within the prickle cell
layer of the epidermis, and so have thin roofs and
rupture easily to leave an oozing denuded surface.
• Subcorneal blisters, which form just beneath the
stratum corneum at the outermost edge of the viable
epidermis, and therefore have even thinner roofs.
6. The pemphigus family
• Pemphigus is severe and potentially life-threatening.
Types
1. Pemphigus vulgaris
• is the most common, which accounts for at least three-
quarters of all cases, and for most of the deaths.
2. Pemphigus vegetans
3. Superficial pemphigus
• also has two variants: the generalized foliaceus type and
localized erythematosus type.
4. Paraneoplastic pemphigus
• arrises in association with a neoplasm such as thymoma,
Castleman’s tumour or lymphoma.
7. Cause
• Autoimmune diseases, (IgG) antibodies bind to
antigens within the epidermis, mainly desmoglein
3 (in pemphigus vulgaris) and desmoglein 1 (in
superficial pemphigus), causing the keratinocytes
to fall apart (acantholysis).
• Pemphigus vulgaris is particularly common in
Ashkenazi Jews and people of Mediterranean or
Indian origin.
8. Presentation
Pemphigus vulgaris
• is characterized by flaccid blisters of the skin and
mouth which rupture easily to leave widespread
painful erosions.
• Most patients develop the mouth lesions first.
• Shearing stresses on normal skin can cause new
erosions to form (a positive Nikolsky sign).
Other types
• In the vegetans variant, heaped-up cauliflower-like weeping areas are present in
the groin and body folds.
• In pemphigus foliaceus blisters are so superficial, and rupture so easily, that the
clinical picture is dominated more by weeping and crusting erosions than by
blisters.
9.
10.
11.
12. Course
• Prolonged, even with treatment
• the mortality rate of pemphigus vulgaris is still at
least 15%.
• About one-third of patients with pemphigus
vulgaris will go into complete remission within 3
years.
• Superficial pemphigus is less severe.
• With modern treatments, most patients with
pemphigus can live relatively normal lives, with
occasional exacerbations.
13. Complications
• Side effects of high doses of steroids and
immunosuppressive drugs and are now the leading
cause of death.
• Infections of all types are common.
• Severe oral ulcers make eating painful.
Differential diagnosis
• Widespread erosions may suggest a pyoderma,
impetigo, epidermolysis bullosa or ecthyma.
• Mouth ulcers can be mistaken for aphthae, Behçet’s
disease or a herpes simplex infection.
• Scalp erosions suggest bacterial or fungal infections.
14. Investigations
• Biopsy shows that the vesicles are intra-
epidermal, with rounded keratinocytes floating
freely within the blister cavity (acantholysis).
• Direct immunofluorescence of adjacent normal
skin shows intercellular epidermal deposits of IgG
and C3
• Indirect immunofluorescence or assays (ELISA)
can also be used to confirm the diagnosis.
16. Treatment
Systemic steroids
• Resistant and severe cases need very high doses of systemic
steroids, such as 80–180 mg/day prednisolone because
prednisolone up-regulates the expression of desmoglein molecules
on the surfaces of keratinocytes, in addition to their anti-
inflammatory effect
• The dose is reduced only when new blisters stop appearing.
Immunosuppressive agents
• such as azathioprine, gold salts or cyclophosphamide and, recently,
mycophenylate mofetil, are often used as steroid-sparing agents.
• Plasmapheresis and administration of intravenous immunoglobulin.
Other
• Rituximab
• Dapsone
17. The pemphigoid family
• Pemphigoid is an autoimmune disease.
• The IgG antibodies bind to two main antigens:
most commonly to BP230, and less often to
BP180 at the basement membrane activating
complement starting an inflammatory cascade
causing the epidermis to separate from the
dermis
• Antibodies titre does not correlate with
clinical disease activity.
18. Presentation
• Chronic, usually itchy, blistering disease, mainly affecting
the elderly.
• Usually no precipitating factors can be found, but rarely
ultraviolet light or radiation therapy
• The skin often erupts with smooth, itching red plaques in
which tense vesicles and bullae form
• Occasionally they arise from normal skin.
• The flexures are often affected
• mucous membranes usually are not.
• The Nikolsky test is negative.
• It is not fatal
• factors carrying a high risk include old age, the need for
high steroid dosage and low serum albumin levels.
19.
20. Course
• Pemphigoid is usually self-limiting and treatment can
often be stopped after 1–2 years.
Complications
• Discomfort and loss of fluid from ruptured bullae.
• Systemic steroids and immunosuppressive agents carry
their usual complications if used long term
Differential diagnosis
• other bullous diseases
• Immunofluorescence helps to separate it from these
21. Investigations
• Direct immunofluorescence shows a linear band
of IgG and C3 along the basement membrane
zone.
• Indirect immunofluorescence identifies IgG
antibodies that react with the basement
membrane zone in some 70% of patients
• A subepidermal blister is often filled with
eosinophils.
• Most patients have peripheral blood eosinophilia.
22.
23. Treatment
• in the acute phase, prednisolone or prednisone at
a dosage of 40–60 mg/day is usually needed to
control the eruption
• The dosage is reduced as soon as possible, and
patients end up on a low maintenance regimen of
systemic steroids, taken on alternate days until
treatment is stopped.
• Immunosuppressive agents such as azathioprine
may also be required.
• For unknown reasons, tetracyclines and
niacinamide help some patients.
24. Pemphigoid gestationis (herpes
gestationis)
• This is pemphigoid occurring in pregnancy, or in the
presence of a hydatidiform mole or a choriocarcinoma.
• As in pemphigoid, most patients have linear deposits of
C3 along the basement membrane zone
• The condition usually remits after the birth but may
return in future pregnancies.
• It is not caused by a herpes virus: the name herpes
gestationis should be discarded now
• Treatment is with systemic steroids.
• Oral contraceptives should be avoided, because their
hormones may precipitate the disease.
25. Cicatricial pemphigoid
Like pemphigoid itself, but
• other antigens at the dermal–epidermal junction are sometimes
targeted such as laminin 5
• its blisters and ulcers occur mainly on mucous membranes such as
the conjunctivae, the mouth and genital tract, but bullae on the
skin itself are uncommon.
• Lesions heal with scarring; around the eyes this may cause
blindness, especially when the palpebral conjunctivae are affected
• The condition tends to persist and treatment is relatively ineffective
• Very potent local steroids, dapsone, systemic steroids and
immunosuppressive agents are usually tried.
• Good eye hygiene and the removal of ingrowing eyelashes are
important.
26.
27. Linear IgA bullous disease
• clinically similar to pemphigoid, but affects children as well
as adults.
• Blisters arise on urticarial plaques, and often grouped, and
on extensor surfaces, than is the case with pemphigoid.
• The so-called ‘string of pearls sign’, seen in some affected
children, is the presence of blistering around the rim of
polycyclic urticarial plaques.
• The conjunctivae may be involved.
• linear deposits of IgA and C3 at the basement membrane
zone
• IgG is sometimes also found.
• The disorder responds well to oral dapsone.
28. Dermatitis herpetiformis
• A very itchy chronic subepidermal vesicular disease, in
which the vesicles erupt in groups as in herpes simplex –
hence the name ‘herpetiformis’.
Cause
• Gluten-sensitive enteropathy (sprue, adult celiac disease is
always present, but most patients do not suffer
enteropathy as it mild, patchy and involves only the
proximal small intestine.
• A range of antibodies can be detected in serum, notably
directed against tissue transglutaminase, reticulin, gliadin
and endomysium
• The IgA deposits in skin clear slowly after the introduction
of a gluten-free diet.
• There is a strong association with certain human leucocyte
antigen (HLA) types, particularly HLA-DR3 and HLA-DQw2.
29. Presentation
• The extremely itchy, grouped vesicles and urticated
papules develop particularly over the elbows and
knees, buttocks and shoulders.
• They are often broken by scratching before they reach
any size. A typical patient therefore shows only
grouped excoriations.
• Sometimes a secondary eczematous dermatitis
develops from fierce scratching. Thus, the name
‘dermatitis’ comes from scratching, and ‘herpetiformis’
comes from grouping of vesicles and crusts.
30.
31.
32. Course
• Typically lasts for decades unless patients avoid gluten entirely.
Complications
• The complications of gluten-sensitive enteropathy include
diarrhoea, abdominal pain, anaemia and, rarely, malabsorption.
• Small bowel lymphomas have been reported
• proven association with other autoimmune diseases, most
commonly of the thyroid.
Differential diagnosis
• Scabies
• an excoriated eczema
• insect bites
• neurodermatitis.
33. Investigations
• Histology will be that of a subepidermal blister, with
neutrophils packing the adjacent dermal papillae.
• Direct immunofluorescence of uninvolved skin shows
granular deposits of IgA, and usually C3, in the dermal
papillae and superficial dermis
• Serum antibody tests for anti-endomysial antibodies or
tissue transglutaminase can help diagnose the
enteropathy.
• Small bowel biopsy is no longer recommended as
routine because the changes are often patchy and
serum tests are more sensitive.
34. Treatment
• A gluten-free diet, Adherence can be monitored
using the titre of antibodies to anti-endomysial
antigens or to tissue transglutaminase, which fall
if gluten is strictly avoided.
• Dapsone or sulfapyridine, although both can
cause severe rashes, haemolytic anaemia
(especially in those with glucose- 6-phosphate
dehydrogenase deficiency), leucopenia,
thrombocytopenia, methaemoglobinaemia and
peripheral neuropathy. Regular blood checks are
therefore necessary.
35. Toxic epidermal necrolysis (Lyell’s
disease)
Cause
• usually a drug reaction, most commonly to sulphonamides,
lamotrigine, barbiturates, carbamazepine or allopurinol
• graft-vs.-host disease
• AIDs
Presentation
• The skin becomes red and intensely painful, and then
begins to come off in sheets like a scald leaving an eroded
painful glistening surface
• Nikolsky’s sign is positive.
• The mucous membranes may be affected, including the
mouth, eyes, and even the bronchial tree.
36.
37. Course
• The condition usually clears if the offending drug is
stopped.
• New epidermis grows out from hair follicles so that skin
grafts are not usually needed.
• The disorder may come back if the drug is taken again.
Complications
• It is a skin emergency and can be fatal.
• Infection, and the loss of fluids and electrolytes, are life-
threatening
• Corneal scarring may remain when the acute episode has
settled.
38. Differential diagnosis
• Staphylococcal scalded skin syndrome but only the
stratum corneum is lost and is seen in infancy or early
childhood.
• Some believe that toxic epidermal necrolysis can
evolve from Stevens–Johnson syndrome because some
patients have the clinical features of both.
Investigations
• Biopsy helps to confirm the diagnosis. The split is
subepidermal in toxic epidermal necrolysis, in scalded
skin syndrome where the split is subcorneal.
39. Treatment
• The drug must be stopped
• treatment relies mainly on symptomatic management with
intensive nursing care and medical support including the
use of central venous lines, intravenous fluids and
electrolytes.
• Many patients are treated in units designed to deal with
extensive thermal burns
• The weight of opinion has turned against the use of
systemic corticosteroids.
• Intravenous IgG seems more promising and ciclosporin
treatment has been associated with a decreased mortality
rates.
• Plasmapheresis may remove triggering drugs, or
inflammatory mediators.
