Abstract
Bullous pemphigoid (BP) is an autoimmune blistering disease that is treated with high dose immunosuppression due to lack of specific targets. Staphylococcus aureus is a commensal bacterium implicated inflammatory and autoimmune disorders because of its secretion of toxins with superantigen effects. We prospectively evaluated S. aureus colonization and its production of toxic shock syndrome toxin-1 (TSST-1) in 28 new onset BP patients. Inclusion criteria were active blistering and linear basement membrane IgG/C3 or a serum ELISA >14 for BP180 IgG. Bacterial swabs were obtained from the lesion interior, nares and unaffected skin of BP patients and nares and anatomically matched skin of 28 age- and sex-matched controls. Staphylococcal growth was assessed on blood agar, and TSST-1 production by cultured S. aureus isolates and in blister fluid was evaluated by immunoblot. S. aureus colonization of BP lesions was 3-6-fold higher than the nares or unaffected skin from the same patients (p≤0.300) and 6-fold higher than control nares or skin (p≤0.0015). Evaluation of superantigen gene profiles using PCR indicated that 96% of BP patients are colonized with a clonal strain of TSST-1+ S. aureus. Colonization and circulating levels of TSST-1 neutralizing antibodies, measured by ELISA, did not correlate. Interestingly, S. aureus colonization was not observed in patients who had received prior antibiotics. In colonized patients with severe disease, addition of anti-staphylococcal antibiotics resulted in clinical improvement and eliminated lesional colonization. This study shows that BP lesions harbor a clonal strain of TSST-1 producing S. aureus that is not evident in the general elderly population. Thus, immunosuppressive therapies should be balanced with the knowledge that S. aureus is likely present in BP lesions and the knowledge that antibiotics may play an important therapeutic role through bacterial clearance.
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