Drug-induced linear IgA bullous dermatosis associated with ceftriaxone- and metronidazole-specific T cells.
BACKGROUND
Previous reports indicate that various drugs may induce linear IgA bullous dermatosis (LABD). The role of T cells and T-cell-derived cytokines in the pathomechanism of such skin lesions, however, has remained unclear.


OBJECTIVE
To describe a case of LABD induced by ceftriaxone and metronidazole in an 80-year-old female suffering from cholelithiasis with concomitant cholecystitis and provide evidence that drug-specific T cells and their cytokines may contribute to the development of LABD lesions.


METHODS
We performed flow cytometry analysis of peripheral blood T cells during LABD, epicutaneous testing (scratch-patch) and lymphocyte proliferation analysis (LTT) with the suspected drugs, routine histological and immunohistochemical examination of the acute skin lesions during LABD as well as of the positive epicutaneous test reactions and measurement of cytokines (IL-4, IL-5, IL-10, TNF-alpha, IFN-gamma) in the supernatant of the LTT cultures.


RESULTS
An increased number mainly of activated CD8+ cells was detected in the peripheral blood during LABD. T cell sensitization to ceftriaxone and metronidazole was confirmed by epicutaneous testing and LTT, indicating that these methods may be useful in identifying the causative drugs. Enhanced cytokine levels, particularly of IL-5, were found in the supernatant of the LTT stimulated with ceftriaxone and metronidazole. Furthermore, in situ expression of IL-5 was confirmed in the patient's skin lesions by immunohistochemistry.


CONCLUSIONS
Our findings suggest that in addition to IgA antibodies drug-specific T cells and their subsequent release of cytokines may play an important role in the pathogenesis of drug-induced LABD.
Yawalkar
N
N
Institute of Immunology and Allergology, Inselspital Bern, Switzerland.
Reimers
A
A
Hari
Y
Y
Hunziker
T
T
Gerber
H
H
Müller
U
U
Pichler
W
W
D000368:Aged; D000369:Aged, 80 and over; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002443:Ceftriaxone / Q000009:adverse effects* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D005260:Female; D005705:Gallbladder Diseases / Q000188:drug therapy; D006684:HLA-DR Antigens / Q000096:biosynthesis / Q000187:drug effects; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000187:drug effects; D015848:Interleukin-5 / Q000096:biosynthesis; D008795:Metronidazole / Q000009:adverse effects* / Q000627:therapeutic use; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012872:Skin Diseases, Vesiculobullous / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D012882:Skin Tests; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D000890:Anti-Infective Agents; D006684:HLA-DR Antigens; D007070:Immunoglobulin A; D015848:Interleukin-5; D008795:Metronidazole; D002443:Ceftriaxone; D007371:Interferon-gamma