Background After the introduction of biologic therapy, the frequency of rheumatoid vasculitis (RV) has decreased, but its prognosis remains poor [1-3]. No specific biomarker in RV has been established. In laboratory findings, anti-neutrophil cytoplasmic antibody (ANCA) positivity and hypocomplementemia (HC) were reported in 39% and 14%, respectively [2]. Though depressed C4 level had been reported to predict mortality in peripheral neuropathy with necrotizing vasculitis in RA before the biologic era [4], the significance of HC remains unclear in RV in the biologic era.

Objectives To evaluate the clinical significance of HC in RV in the biologic era.

Methods We enrolled 20 Japanese RV patients (12 women; mean age 68.0 years; mean duration of RA 13.6 years, observation period of RV 4.9 years) diagnosed at 4 hospitals from 2000 to 2013. We analyzed retrospectively their clinical findings, treatment and prognosis. All patients met the Scott and Bacon criteria [5]. HC was defined as low levels of serum CH50, C3 or C4 complement; <30 U/ml, <75 mg/dl, <14 mg/dl, respectively.

Results In the present 20 patients, cutaneous (60%) and pulmonary lesions (50%) were common. Histopathological confirmation of vasculitis was available for 50%. None had ANCA positivity. HC was found in 65% at RV diagnosis. Serum CH50, C3 and C4 levels on average were 27.9 U/ml, 82.3 mg/dl and 15.7 mg/dl, respectively. Patients with depressed C3 and/or C4 levels were included in those with depressed CH50 level. Patients with HC (n=13) at diagnosis of RV were older at development of RA (54.0 years vs 47.7 years, p<0.01), and had a lower frequency of neuropathy (7.7% vs 57.1%, p=0.03), and higher rheumatoid factor (RF) level (2179 IU/ml vs 209 IU/ml, p<0.01) than those without HC. Treatment for RA before RV was corticosteroid (PSL) (75%), methotrexate (25%), biologics (20%), and others. After development of RV, PSL (95%) and biologics (65%) were most common. After the treatment, HC improved (CH50 40.8 U/ml, C3 85.1 mg/dl, C4 19.5 mg/dl) as CRP did. CH50 (p=0.02) and C4 levels (p=0.05) had significant elevation after the treatment, but C3 level did not (p=0.53). No patients developed recurrence. Severe infection developed in 35% and was fatal in 3.

Conclusions Sixty-five percent of Japanese patients with RV showed HC. Compared with RV patients who were diagnosed in almost the same period in the UK (18 patients) and USA (86 patients) reported in 2014 [1,2], a higher frequency of HC and lower positivity of ANCA were shown. Patients with HC at diagnosis of RV had different characteristics such as older age at development of RA, lower frequency of neuropathy, and higher RF level than those without HC. HC, especially CH50 and C4 levels, improved in parallel with amelioration of the activity of RV. These results suggest that HC can be a useful biomarker for the diagnosis and follow up of RV in the biologic era.

References

1. Rheumatology 2014;53:145-52.

2. Rheumatology 2014;53:890-9.

3. Curr Opin Rheumatol 2015;27:63-70.

4. Arthritis Rheum 1995;38:1618-29.

5. Am J Med 1984;76:377-84.

Disclosure of Interest None declared