The role of IgM gammopathy in the pathogenesis of urticaria and the other manifestations of the Schnitzler syndrome is poorly understood. It likely does not depend on whether the underlying lymphoid disorder is an overt WM or a monoclonal gammopathy of undetermined significance.1 In our patients, as in the literature, immunofluorescence studies did not document a pathogenic role for monoclonal IgM because the studies showed cutaneous IgM deposits in only some cases with, in addition, different localizations from one case to another.1 Similarly, antiskin autoantibody activity of the IgM could be documented by Western blotting in only few patients.11 Conflicting data were also reported on potential anti–IL-1α autoantibody activity of the monoclonal immunoglobulin.12,13 An alternative hypothesis would not implicate the monoclonal IgM by itself but rather the production of 1 or several cytokines or chemokines by clonal B-cell proliferation or by its cellular environment.13 This hypothesis might be more in accordance with the effect of pefloxacin we noted, which occurred without modifying the level of the monoclonal IgM in any case. As with all fluorinated 4-quinolones, pefloxacin, a nalidixic acid analogue, exerts its bactericidal effect by inhibiting DNA gyrase (a type II topoisomerase), most probably by binding to DNA.14 In addition to their antibacterial properties, fluoroquinolones have been shown to modify immune and inflammatory responses implicating T cells and macrophages, by mechanisms that may involve regulation of messenger RNA for cytokines such as IL-1, IL-2 and its receptors, interferon-γ, granulocyte-macrophage colony-stimulating factor, and IL-3.15 Modulation of the production of other cytokines, including IL-8 and IL-6, were also observed in experimental models.15 Although other antibiotic classes such as macrolides may have immunomodulatory effects,16 only quinolone appears to be effective in the treatment of Schnitzler syndrome. Within the quinolone class, pefloxacin appears to be the most efficient (B.A. and J.-P.F., unpublished data, March 2006). It is ineffective in classical chronic urticaria (data not shown), whereas we did not have the opportunity to assess its efficacy in urticarial vasculitis without monoclonal IgM gammopathy.