Epidermolysis bullosa acquisita induced by GM-CSF: a role for eosinophils in treatment-related toxicity.
A patient treated with granulocyte-macrophage colony-stimulating factor (GM-CSF) developed eosinophilia and epidermolysis bullosa acquisita. The bullae were subepidermal, and filled with an inflammatory infiltrate composed predominantly of eosinophils. Immunofluorescence studies disclosed linear deposition of IgG, IgA and C3 at the basement membrane zone and immunoelectron microscopy demonstrated antibody deposition in the lamina densa and sublamina densa region; however, the patient's serum did not contain circulating antibody to basement membrane zone antigens. Staining with monoclonal antibodies revealed dense deposits of both eosinophil peroxidase and eosinophil major basic protein at the dermal-epidermal junction. The eosinophilia and skin lesions resolved upon discontinuation of GM-CSF. This case provides evidence for two hypotheses: (1) GM-CSF induced proliferation and activation of eosinophils may contribute to some of the toxicities of GM-CSF treatment, and (2) activated granulocytes, including eosinophils, may mediate blister formation in epidermolysis bullosa acquisita.
Ward
J C
JC
Department of Medicine, University of Minnesota Medical School, Minneapolis.
Gitlin
J B
JB
Garry
D J
DJ
Jatoi
A
A
Luikart
S D
SD
Zelickson
B D
BD
Dahl
M V
MV
Skubitz
K M
KM
D000368:Aged; D000911:Antibodies, Monoclonal; D003176:Complement C3 / Q000032:analysis; D004804:Eosinophils / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D016107:Epidermolysis Bullosa Acquisita / Q000097:blood / Q000139:chemically induced* / Q000276:immunology; D005455:Fluorescent Antibody Technique; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000009:adverse effects*; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D008297:Male; D016253:Microscopy, Immunoelectron
D000911:Antibodies, Monoclonal; D003176:Complement C3; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D016178:Granulocyte-Macrophage Colony-Stimulating Factor