Treatment of Pulmonary Vasculitis

Benjamin Terrier, MD, PhD; Loïc Guillevin, MD


Semin Respir Crit Care Med. 2018;39(4):504-510. 

In This Article

Immune Complex Small Vessel Vasculitis

Alveolar hemorrhage is a very rare manifestation of IgA vasculitis and cryoglobulinemia vasculitis (CryoVas); therefore, data on therapeutic management of such patients are lacking and based on those of other severe manifestations, mainly renal involvement.

IgA Vasculitis

Treatment of severe involvement in adults IgA vasculitis remains controversial, with no evidence that combination of glucocorticoids and immunosuppressive agents improved long-term outcome.[29,30]

By analogy with other severe autoimmune diseases, CYC has been used in adult patients with organ- or life-threatening manifestations in only one randomized controlled trial. Pillebout et al compared corticosteroids with or without CYC in patients with severe IgA vasculitis, mainly proliferative glomerulonephritis and/or gastrointestinal manifestations, but none of them had pulmonary involvement. In this trial, 54 patients with biopsy proven IgA vasculitis and severe manifestations were included. At 12 months, no difference was found between the two groups in terms of remission rate, renal outcomes, deaths, and adverse events, but the trial was underpowered, including only one quarter of patients initially planned. However, overall survival at 12 months was 96% with glucocorticoids plus CYC compared with 79% with glucocorticoids alone (p = 0.08), adding some controversies on the interest of immunosuppressive agents in this disease.[31]

RTX was also used in adult patients with organ- or life-threatening manifestations in case series, but none in randomized controlled trials. Maritati et al recently reported 22 patients with adult-onset IgAV who had received RTX either for refractory/relapsing disease or because they had contraindications to conventional glucocorticoid and immunosuppressive therapy. Twenty-two patients were included, mainly with renal involvement, but no patient had pulmonary involvement. Twenty patients (90.9%) achieved remission, and 7 of those 20 patients (35%) had subsequent relapse of disease, with a good safety profile of RTX.[32]

Cryoglobulinemia Vasculitis

The therapeutic management of CryoVas must be individualized according to the underlying disorder and the severity of disease.[33]

In patients with hepatitis C virus (HCV)–related CryoVas, optimal antiviral regimen is the current standard of care for patients with mild-to-moderate disease activity,[34,35] whereas more aggressive treatment is needed in patients presenting with severe disease. The use of conventional immunosuppressive agents is associated with a poor outcome with an increased mortality after adjustment for vasculitis severity.[36] In contrast, short-term corticosteroids and/or TPE were not associated with a poor outcome and could be used according to initial presentation to control severe and life-threatening manifestations.

In contrast, several groups have reported on the efficacy of RTX in patients with HCV-related CryoVas naive, resistant or intolerant to antiviral therapy, with a good safety profile and no worsening of the infection.[37–41] In this setting, RTX should be combined to antiviral agents, but RTX monotherapy was also an effective and well-tolerated option for severe CryoVas in HCV-positive patients nonresponders or intolerant to antiviral therapy.

In HCV-negative patients, optimal therapeutic management has yet to be defined as no study has evaluated the best strategies. In patients with severe vasculitis, treatment is based on glucocorticoids usually combined with RTX, and according to disease severity with initial TPE. We reported the efficacy and safety of treatments in the largest series published so far of patients with noninfectious mixed CryoVas. Using Cox-marginal structural models, RTX and glucocorticoids showed the greater therapeutic efficacy compared with glucocorticoids alone and glucocorticoids plus alkylating agents to achieve complete clinical, renal, and immunologic responses and a prednisone dosage less than 10 mg/d at 6 months. However, this regimen was also associated with severe infections, particularly when high doses of glucocorticoids were used, whereas death rates did not differ between the therapeutic regimens.[42]