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.