T-cell involvement in drug-induced acute generalized exanthematous pustulosis.
Acute generalized exanthematous pustulosis (AGEP) is an uncommon eruption most often provoked by drugs, by acute infections with enteroviruses, or by mercury. It is characterized by acute, extensive formation of nonfollicular sterile pustules on erythematous background, fever, and peripheral blood leukocytosis. We present clinical and immunological data on four patients with this disease, which is caused by different drugs. An involvement of T cells could be implied by positive skin patch tests and lymphocyte transformation tests. Immunohistochemistry revealed a massive cell infiltrate consisting of neutrophils in pustules and T cells in the dermis and epidermis. Expression of the potent neutrophil-attracting chemokine IL-8 was elevated in keratinocytes and infiltrating mononuclear cells. Drug-specific T cells were generated from the blood and skin of three patients, and phenotypic characterization showed a heterogeneous distribution of CD4/CD8 phenotype and of T-cell receptor Vbeta-expression. Analysis of cytokine/chemokine profiles revealed that IL-8 is produced significantly more by drug-specific T cells from patients with AGEP compared with drug-specific T cells from patients that had non-AGEP exanthemas. In conclusion, our data demonstrate the involvement of drug-specific T cells in the pathomechanism of this rather rare and peculiar form of drug allergy. In addition, they indicate that even in some neutrophil-rich inflammatory responses specific T cells are engaged and might orchestrate the immune reaction.
Britschgi
M
M
Clinic of Rheumatology and Clinical Immunology/Allergology, Inselspital, Bern, Switzerland.
Steiner
U C
UC
Schmid
S
S
Depta
J P
JP
Senti
G
G
Bircher
A
A
Burkhart
C
C
Yawalkar
N
N
Pichler
W J
WJ
D000208:Acute Disease; D000328:Adult; D001706:Biopsy; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D054413:Chemokine CCL11; D018946:Chemokine CCL5 / Q000378:metabolism; D019742:Chemokines, CC; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D003875:Drug Eruptions / Q000503:physiopathology*; D005076:Exanthema / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*
C515456:CCL11 protein, human; D015704:CD4 Antigens; D016827:CD8 Antigens; D054413:Chemokine CCL11; D018946:Chemokine CCL5; D019742:Chemokines, CC; D016207:Cytokines; D015848:Interleukin-5; D016209:Interleukin-8; D015375:Receptors, Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor