WG is the most common of the ANCA-associated vasculitis diseases. It is clinically characterized by a triad of upper airway involvement, lower respiratory tract involvement, and glomerulonephritis . Our patient showed negative c-ANCA but was diagnosed with WG based on clinical symptoms, imaging studies, and the microscopic findings that were not in contradiction with WG.
C-ANCA is highly sensitive (90-95%) in active, systemic WG, with a specificity of approximately 90% and is usually but not always correlated with the disease state [3, 4]. However, c-ANCA was negative in our case. CRP, ESR, and WBC are not, of course, specific markers for WG and their variation can be caused by various stressors such as infection, drugs, trauma, among others.
In WG patients with a negative c-ANCA or in whom c-ANCA is not correlated with the disease state, the evaluation of disease status and therapeutic effect are difficult because the evaluation of WG are based on symptoms, imaging studies, and non-specific inflammatory markers.
Antibodies to altered γ-globulin, so-called RF, occur in approximately 70% of patients with rheumatoid arthritis (RA) [5, 6]. A high RF level helps confirm the diagnosis of RA. In addition, RF serum level can be influenced by treatment and often falls as inflammatory activity decreases. RF is not specific for RA and is found in many diseases (e.g.; chronic infections, hepatitis, sarcoidosis, granulomatous diseases, subacute bacterial endocarditis). Noritake et al.  reported that an elevated RF was observed in about half of WG cases.
In this case, we predicted that a high RF level was useful for evaluating the disease state and measured it regularly. As expected, RF serum level correlated with the WG state. In particular, when the patient condition was complicated by a severe infection, the decreasing RF level was extremely helpful when we decided to taper the PSL.
Even if c-ANCA is positive, there are certain limitations in evaluating the WG state by c-ANCA. In a series of 106 patients, Kerr et al.  reported that c-ANCA titer temporally correlated with the WG state in only 64% of patients. In conclusion, there is no definitive marker for WG and careful and comprehensive observation of symptoms, laboratory tests, and imaging studies are most important in all cases. Nevertheless, in cases of WG with a high RF level, follow-up of this marker is thought to be of value for evaluating the disease status. Therefore, further study of WG cases with a high RF level may aid in determining the usefulness of this classical marker.