From the Guidelines
A negative ANA and ANCA result does not rule out vasculitis in the lungs, and a comprehensive evaluation is necessary to identify the specific type of vasculitis. The diagnostic approach should include:
- High-resolution CT scans of the chest
- Pulmonary function tests
- Bronchoscopy with bronchoalveolar lavage
- A lung biopsy is often necessary to confirm the diagnosis when serological markers are negative
- Additional testing should include complete blood count, comprehensive metabolic panel, erythrocyte sedimentation rate, C-reactive protein, and testing for other potential causes such as infections or malignancies 1.
According to the most recent guidelines, treatment typically begins with corticosteroids, usually prednisone at 0.5-1 mg/kg/day for 4-6 weeks followed by a gradual taper 1. For more severe cases or steroid-resistant disease, immunosuppressive agents like cyclophosphamide, azathioprine, mycophenolate mofetil, or rituximab may be added 1. Treatment duration typically ranges from 6-24 months depending on disease severity and response. Regular monitoring of disease activity, medication side effects, and organ function is essential. The approach is individualized because ANCA-negative vasculitis represents a heterogeneous group of disorders including isolated pulmonary capillaritis, drug-induced vasculitis, IgA vasculitis, and others that may have distinct treatment requirements and prognoses.
It's also important to note that a positive biopsy is strongly supportive of a diagnosis of vasculitis and biopsies should be performed to assist in establishing a new diagnosis of AAV and for further evaluation of patients suspected of having relapsing vasculitis 1. Additionally, ANCA testing should be performed in all patients with suspected EGPA, and ANCA are detectable in 30–40% of patients with EGPA 1.
In terms of treatment, for remission induction in patients with new-onset, active EGPA, glucocorticoids should be administered as initial therapy, and in patients with severe disease, cyclophosphamide or rituximab should be added 1. For remission maintenance, in patients with severe EGPA, rituximab, mepolizumab or traditional DMARDs in combination with glucocorticoids should be used 1.
Overall, the diagnostic and treatment approach for lung vasculitis with negative ANA and ANCA results requires a comprehensive evaluation and individualized treatment approach, taking into account the specific type of vasculitis and disease severity.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Diagnostic Approach
- A negative Antinuclear Antibody (ANA) and Antineutrophil Cytoplasmic Antibody (ANCA) result does not entirely rule out vasculitis in the lungs, as some forms of vasculitis can be ANCA-negative 2.
- Eosinophilic granulomatosis with polyangiitis (EGPA) is an example of an ANCA-associated vasculitis that can be ANCA-negative in up to 60% of cases 2.
Treatment Approach
- Treatment of ANCA-associated vasculitis (AAV) has improved over the last decade, with currently available strategies able to induce remission in the majority of cases 3.
- Rituximab has been shown to be effective in inducing remission in AAV, and may be superior to cyclophosphamide in relapsing disease 4.
- Combination treatment with rituximab, low-dose cyclophosphamide, and plasma exchange has been shown to be effective in severe ANCA-associated vasculitis, with high rates of disease remission and low rates of relapse 5.
- Combination therapy with rituximab and cyclophosphamide has also been shown to be effective in inducing remission in ANCA vasculitis, with rapid tapering of high-dose glucocorticoids and low rates of serious infections 6.
Considerations
- The presence of negative ANA and ANCA results should not delay the initiation of treatment, as some forms of vasculitis can be life-threatening and require prompt intervention 2.
- A comprehensive diagnostic workup, including clinical evaluation, imaging studies, and laboratory tests, is necessary to establish a diagnosis of vasculitis and guide treatment decisions 2, 4, 3, 5, 6.