The conventional treatment for the autoimmune
bullous skin diseases is broad-spectrum immunosuppressive regimen typically combining systemic
corticosteroids with adjuvant immunosuppressive therapeutic agents.
Orphan diseases in the
pemphigus,
pemphigoid, and
epidermolysis bullosa acquisita groups of clinical disorders are often clinically severe, requiring long-term treatment with such drugs or
drug combinations.
Rituximab, a chimeric recombinant
monoclonal antibody targeting CD20(+) B cells, has recently been suggested to be effective in the treatment of
pemphigus with relatively few adverse effects. The clinical value of
rituximab in other immune-mediated blistering diseases has been less thoroughly examined. We report a case of a woman who presented initially with the Brunsting-Perry phenotype of
cicatricial pemphigoid who subsequently developed severe generalized subepidermal
blisters healing with
scarring and milia formation thought to be clinically compatible with
epidermolysis bullosa acquisita, although
type VII collagen autoantibodies were never identified. Treatment with a number of conventional systemic agents was unsuccessful and complicated by methicillin-resistant Staphylococcus aureus-induced cutaneous
ulcers and near-fatal gram-negative
sepsis. This woman has enjoyed an 18-month complete clinical remission after a single inductive 4-week cycle of intravenous
rituximab. This outcome supports the idea that systemic memory B-cell depletion with drugs such as
rituximab should be considered for therapeutically refractory subepidermal autoimmune blistering diseases in addition to intraepidermal autoimmune blistering diseases. A potential role for the immunologic phenomenon of
epitope spreading in the generation of overlapping features of autoimmune blistering diseases, and its contribution to therapeutic refractoriness ("hardening"), is discussed.