LINEAR IMMUNOGLOBULIN A BULLOUS DERMATOSIS
Linear immunoglobulin A (IgA) bullous dermatosis is an infrequently encountered autoimmune blistering disease that was originally described in 1979. This disease has a characteristic immunofluorescence staining pattern that is used to differentiate it from other blistering diseases such as dermatitis herpetiformis. As the name implies, linear IgA is deposited along the length of the dermal-epidermal junction. Chronic bullous disease of childhood is considered by most to be the same disease, although there are a few clinical differences in age at onset and associations that can be used to justify separating them into two distinct, albeit very similar, entities. Most cases of chronic bullous dermatosis of childhood are idiopathic, whereas most cases of linear IgA bullous dermatosis are drug induced and occur in an older population.
Clinical
Findings: Linear IgA bullous dermatosis is rare and is estimated to occur in 1 of
every 2,000,000 people. There is no race or sex predilection. It occurs most
frequently in the adult population. The blistering disease has an insidious
onset with small vesicles that may mimic dermatitis herpetiformis. The blisters
are pruritic and do not have the same burning sensation as occurs in dermatitis
herpetiformis, nor is there any relationship to dietary intake. The bullae in
linear IgA bullous dermatosis are characteristically arranged in a “string of
sausages” configuration. Each bulla is elongated and tapers to an end, with a
small area of intervening normal-appearing skin before the tapering beginning
of a new bulla. This string can be linear or annular in orientation. The
blisters are tense and eventually rupture and heal with minimal scarring.
Mucous membrane involvement is frequently seen and can resemble that of mucous
membrane pemphigoid.
Chronic
bullous disease of childhood manifests in early childhood (4-5 years of age). The blistering is similar to that of
linear Ig bullous dermatitis, and the histological findings are identical.
Blistering in chronic bullous disease of childhood is more often localized to
the abdomen and lower extremities but may occur anywhere on the skin; it also
commonly affects mucous membranes. Chronic bullous disease of childhood is most
often idiopathic, whereas linear IgA bullous dermatosis can also be seen in
association with underlying medications, malignancies, or other autoimmune
conditions. Many medications have been implicated in causing linear IgA bullous
dermatosis, with vancomycin being the most common by far.
Histology:
The
immunofluorescence staining pattern is characteristic and shows linear IgA all
along the basement membrane zone. This is highly specific and sensitive for the
diagnosis of linear IgA bullous dermatosis and chronic bullous disease of
childhood. Routine hematoxylin and eosin staining shows a subepidermal blister
with an underlying neutrophilic infiltrate. This can be impossible to
distinguish from dermatitis herpetiformis or bullous lupus, so immunostaining
is required.
Pathogenesis:
The
exact target antigen in linear IgA bullous dermatosis is unknown. It is
speculated that the IgA antibodies are directed against a small region of
bullous pemphigoid antigen 180 (BP180). Other possible antigens exist and have
been localized to the lamina lucida and lamina densa regions of the basement
membrane. The reason for formation of these anti- bodies and how certain
medications induce them are unknown. Once present, the antibodies target the
basement membrane zone and cause inflammation by various mechanisms, ultimately leading to disruption
of the dermal-epidermal junction and blistering.
Treatment:
The
first line of therapy is dapsone. Patients respond quickly to this medication.
Low doses of dapsone are usually all that is needed. Alternative substitutes
for dapsone include sulfapyridine and colchicine. Oral prednisone can be
helpful initially, but because of the long-term side effects, patients should
be transitioned to one of the other medications mentioned. Drug-induced variants
of this blistering disease are best treated by recognizing the common culprits and removing them
immediately. Over a period of a few weeks, most patients who have discontinued
the offending medication return to a normal state. If the disease is found to be
associated with an underlying malignancy or other autoimmune condition, therapy
with dapsone is warranted. Treatment of the underlying condition should also be
undertaken. If the malignancy or the associated disease is put into remission,
there is a good possibility that the blistering disease will remit as well.
