Discussion
GPA, previously known as Wegener’s granulomatosis, is the most common pulmonary vasculitis and is associated with anti-neutrophil cytoplasmic antibodies (ANCA) to proteinase 4 (PR3). Microscopic polyangiitis (MPA) and eosinophilic granulomatosis, and polyangiitis (Churg Strauss syndrome) are also associated with ANCAs, often against myeloperoxidase (MPO), and are grouped within ANCA-associated vasculitis4. GPA is a rare disease with an estimated incidence of 0.4-11.9 cases per 1 million person-years predominantly affecting populations of European descent, while MPA predominates in Asian populations5. The typical age of onset is 45-65 years with no sex predilection. Our patient was a 26-year-old Asian woman, demonstrating that any age group and ethnicity might be affected.
GPA is heterogeneous in its spectrum and severity of presentation. Up to 80% of patients present with prodromal clinical features of systemic inflammation, such as fever, weight loss, fatigue, myalgia, and arthralgia4. Rarely, patients may present more acutely over days. It commonly affects the upper respiratory tract (e.g., sinuses, nose, ears, pharynx, trachea), lower respiratory tract, and kidneys. A varying degree of disseminated vasculitis can occur that can affect any organ. Pulmonary involvement is seen in 50-90% of cases6. It can manifest as cough, dyspnea, and a wide variety of imaging abnormalities such as single or multiple nodules, cavitation, ground-glass opacities, consolidation (reflecting inflammation or alveolar hemorrhage), effusions, stenosis of trachea and bronchi, and rarely fibrosis6,7. Glomerulonephritis occurs in 70-85% of patients, with the characteristic lesion being a segmental focal glomerulonephritis, with rapidly progressive glomerulonephritis (RPGN) seen in fulminant cases4. The onset and course are variable, and ESRD develops in 11-32% of the patients8.
Our patient developed sudden onset of respiratory symptoms without any prodrome, which is uncommon. Imaging revealed dense consolidation of the entire right lung and peripheral infiltrates in the left lung, and she tested positive for SARS-CoV-2. This clinical picture resembled COVID-19 pneumonia very closely. No upper-respiratory tract involvement was seen, and microscopic hematuria was seen, which is non-specific. As a result, she was initially managed with therapy directed towards COVID-19 pneumonia. The lack of improvement with COVID-19-directed treatment, the nodular non-blanching violaceous skin lesions on bilateral legs, and left foot numbness (that eventually progressed to distal sciatic neuropathy) raised suspicion for GPA in this case. Skin involvement can present as palpable purpura, nodules, ulcers, and maculopapular rashes and can correlate with active disease. A biopsy can demonstrate leukocytoclastic vasculitis or granulomatous vasculitis, which are not specific to GPA9. Nervous system involvement is less common but presents most commonly as mononeuritis multiplex, as seen in our case. Other reported manifestations to include cerebral infarction or bleeding, seizures, cranial nerve palsies, altered mental status, meningismus, quadriparesis, or paraparesis10,11.
A biopsy was pursued to confirm the diagnosis in our case. A VATS-guided biopsy of the lung was performed rather than a kidney biopsy, as the yield was likely to be low in the presence of only microscopic hematuria. Histopathological features of GPA described in the literature include necrotizing vasculitis involving venules, arterioles, and capillaries, granulomatous inflammation with/without parenchymal necrosis, micro-abscesses, and fibrosis4. Histopathological examination of the lung specimen of our patient revealed alveolar hemorrhage, micro-abscesses, and necrotizing vasculitis consistent with GPA, even in the absence of granulomas.
Treatment of GPA is divided into the induction phase, to achieve remission in 3 months, and the maintenance phase, to maintain remission. Glucocorticoids, along with either cyclophosphamide or rituximab, are the standard of care for inducing remission in severe diseases, such as in our case12. Rituximab is becoming preferred with growing evidence supporting its efficacy and benefits, such as fertility preservation, superiority in PR3- ANCA positive patients, and relapsing disease5. Thus, rituximab was preferred over cyclophosphamide in our patient with subsequent stabilization of her condition over several days.