Autoimmune Skin Disorders
Overview
The skin is a very easy organ in which to investigate autoimmune disease, due to its accessibility for biopsy (see Box 10.1).
Autoantibodies can be detected by either direct immunofluorescence (DIF) of snap-frozen biopsies or indirect immunofluorescence (IIF) using the patient’s serum.
Use of hypertonic saline prior to staining of biopsies splits the epidermis away from the dermis, between the lamina lucida and the lamina densa, and allows the site of autoantibody binding to be more clearly identified. This is important in distinguishing epidermolysis bullosa acquisita from bullous pemphigoid.
Significant disease may be present with little or no circulating antibody and therefore DIF plays a major role in diagnosis.
Reliable results require an experienced laboratory!
Bullous pemphigoid
Presentation
Disease of the elderly characterized by the presence of tense itchy blisters over limbs and trunk.
Blistering stage may be preceded by papules or urticaria.
Mucous membranes may be involved in up to one-third of patients.
Immunopathology and diagnosis
Blister is subepidermal on histology.
DIF and IIF show mainly linear IgG and C3 at the dermo-epidermal junction, binding to the epithelial side of the basement membrane (on a saline-split preparation).
On immunoelectron microscopy the IgG is located on the lamina lucida.
Other immunoglobulin classes may be detected.
Drug reactions may cause similar bullous lesions but with negative immunofluorescence.
IgE and eosinophil counts may be raised, although these are not diagnostically useful.
Autoantibodies
Two autoantigens have been identified:
BPAg1, 230kDa (chromosome 6)
BPAg2, 180kDa (chromosome 10).
BPAg1 is similar to desmoplakin I and is likely to form part of the hemi-desmosome, which provides the major site of attachment between the internal cytoskeletal proteins and the external matrix.
Antibodies to BPAg1 are only found in bullous pemphigoid.
BPAg2 is also a hemi-desmosomal protein, but antibodies are also found in herpes gestationis.
Treatment
Mild disease can be treated with topical steroids.
Severe disease requires high-dose oral steroids, which can be tapered once remission is obtained.
Remission may be sustained once steroids are withdrawn.
Additional immunosuppressive therapy is rarely required, but azathioprine, cyclophosphamide, ciclosporin, mycophenolate mofetil, and dapsone have all been used.
Plasmapheresis has been found not to be of benefit.
HdIVIg may be of benefit.
Tetracycline and niacinamide have also been proposed as treatment, although this is controversial. The mechanism of action is obscure.
Herpes gestationis and cicatricial pemphigoid
Herpes gestationis
Presentation
Rare itchy and blistering rash associated with pregnancy.
Onset is in the second or third trimester or occasionally in the immediate post-partum period.
Infant may also be affected due to transplacental passage of the IgG antibody. This usually resolves spontaneously as maternal antibody decays.
The umbilicus is involved, in contrast with another rare disease: pruritic urticaria and plaques of pregnancy (PUPP).
May recur in subsequent pregnancies and in response to hormonal changes during the menstrual cycle or the oral contraceptive pill.
Immunogenetics
Associated with HLA-DR3 and DR4.
C4 null alleles are increased
Immunopathology
Autoantibodies
Autoantigen is the 180kDa BPAg2 antigen (see ‘Bullous pemphigoid’, p.242), and DIF shows linear deposits of C3 at the dermo-epidermal junction in almost all cases, with IgG in up to 50%.
Treatment
Treatment is with steroids (20-60mg/day) together with antihistamines to control itch.
This may pose problems for the pregnancy (increased incidence of ‘small for dates’) and careful monitoring is required.
Pemphigus vulgaris
Presentation
Serious blistering disease which is invariably fatal if unrecognized and untreated.Stay updated, free articles. Join our Telegram channel
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