EPIDERMOLYSIS BULLOSA ACQUISITA
Epidermolysis bullosa acquisita (EBA) is a rare chronic autoimmune blistering disease that is caused by auto-antibodies against type VII collagen. EBA has many features in common with the dominantly inherited form of the blistering disease, dystrophic epidermolysis bullosa (DEB). DEB is caused by a genetic defect in collagen VII that leads to a reduced amount or total lack of this type of collagen. Collagen VII serves as the anchoring fibrils that attach the epidermis via a series of protein connections to the dermis. Any defect in the production of collagen VII or abnormal destruction of this protein leads to blistering of the skin. EBA has been shown to be associated with a number of underlying systemic diseases, including inflammatory bowel disease, leukemia, and other autoimmune diseases.
Clinical
Findings: EBA is an extremely rare disease that affects 1 in 2,000,000 to
3,000,000 people. It is almost always seen in the adult population, with the
peak incidence in the fifth decade of life. A small number of cases of children
affected by EBA have been reported. There is no race or sex predilection. EBA
manifests with blister formation or with fragile skin and erosions from slight
trauma. This can have a similar clinical appearance to porphyria cutanea tarda
(PCT). The blistering is most frequently located in regions that experience
mechanical friction or trauma. The dorsal surfaces of the hands are almost
always involved, and patients complain of skin fragility and blister formation
after slight trauma. The blisters heal slowly with scar- ring, and on close
inspection, milia are found in the region of the healed blister. The mucous
membranes are frequently involved, and oral disease can lead to weight loss.
Other clinical variants of EBA have been described, and they typically mimic
the clinical appearance of other autoimmune blistering diseases. For this
reason, the only method to correctly diagnosis any blistering disease is by
correlation of clinical and pathological findings.
Pathogenesis:
EBA
is caused by the production of autoantibodies directed against type VII
collagen. The noncollagenous portions
of type VII collagen are the most antigenic sections. Type VII collagen is the
main component of the anchoring fibrils found within the dermis. The antibodies
that have been found are in the immunoglobulin G subclass. They activate
complement, which results in inflammation and destruction of the anchoring
fibrils, eventually leading to fractures within the dermal-epidermal junction
and, ultimately, to blistering. The etiology of antibody formation is not fully
understood.
Histology:
Biopsy
specimens of EBA show a cell-poor subepidermal blister. The amount of
inflammation is often minimal, but in some subtypes of the disease a lymphocytic
infiltrate can be appreciated. The histological differential diagnosis includes
bullous pemphigoid, and only with immunostaining can one decisively make the
correct diagnosis. With immunohistochemical staining for collagen IV, the main
component of the lamina densa, the blistering can be localized to the plane
above the lamina densa in bullous pemphigoid or below the lamina densa in EBA.
The salt-split skin method has also been used to split skin through the lamina
lucida by incubating the skin specimen in 1M NaCl. Immunofluorescence staining
of the split skin shows staining below the split in EBA and above the split in bullous
pemphigoid.
Treatment:
Therapy
is difficult. Treatment of any underlying autoimmune disease or malignancy may
help keep the blistering disease under control. Even with therapy, EBA tends to
run a chronic waxing and waning course with frequent flares. Immunosuppressive
agents have been used in EBA with varying success. Azathioprine, methotrexate,
prednisone, intravenous immunoglobulin (IVIG), rituximab, mycophenolate
mofetil, and cyclophosphamide have all been used. Dapsone and colchicine have had anecdotal reports of
success as well.
Supportive
care is critical. Protection of the skin from trauma can help decrease blister
formation. Early detection of infection and intervention to treat super-
infection are critical. Even with all the current treatment strategies that
have been attempted for EBA, the disease tends not to go into remission and
remains chronic in nature.
