Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is classically characterized by pauci-immune necrotizing crescentic glomerulonephritis; however, immune complex deposition is increasingly recognized in a subset of patients, and its clinical significance remains incompletely defined. Coexistence with membranous nephropathy (MN)-like features is uncommon and may complicate diagnosis and treatment. We report a 37-year-old woman with persistent urinary abnormalities detected during routine health screening. Laboratory evaluation showed proteinuria (1.83 g/gCr), microscopic hematuria (> 50 red blood cells/high-power field), mildly impaired kidney function [estimated glomerular filtration rate (eGFR) 51.4 mL/min/1.73 m[2]], elevated myeloperoxidase (MPO)-ANCA levels, and no hypocomplementemia. Kidney biopsy revealed crescentic glomerulonephritis with granular IgG, C3, and C1q deposition in mesangial and capillary wall regions, together with subepithelial electron-dense deposits suggestive of MN-like features. IgG subclass staining was positive for IgG1-3 but negative for IgG4. Glomerular staining for PLA2R, THSD7A, and NELL1 was negative, whereas glomerular EXT1 staining was positive and EXT2 staining was negative. Overall, the clinicopathological profile was not typical of primary MN. Further evaluation demonstrated anti-SSA antibody positivity and objective ocular findings consistent with Sjögren's syndrome (SjS). Following treatment with high-dose corticosteroids, rituximab, and avacopan, kidney function and urinary abnormalities gradually improved, although proteinuria declined relatively slowly. This case was characterized by MPO-ANCA-associated crescentic glomerulonephritis with immune complex deposition and membranous features in the setting of SjS. The findings highlight the diagnostic difficulty of attributing the membranous component to a single disease process and suggest the involvement of complex and overlapping autoimmune mechanisms.

Raynaud phenomenon (RP), a vascular disorder affecting the small arteries and arterioles of the extremities, is characterized by episodic vasospastic attacks. In primary RP (PRP), these episodes cause changes in skin color, ranging from white (pallor) to blue (cyanosis) due to reduced tissue perfusion, followed by red (hyperemia) upon reperfusion, often triggered by environmental factors or emotional stress. RP is classified into 2 major types: PRP and secondary RP (SRP). PRP and SRP share similar symptoms, but differ in pathogenesis, severity, duration, and potential complications. PRP usually affects women in the second decade of life and typically follows a benign course. SRP usually occurs later in life, secondary to an underlying systemic condition. Unlike PRP, SRP may result in digit ischemia or tissue loss in severe cases. There is a scarcity of clinical trials evaluating treatment options for patients with RP. Management involves both lifestyle modifications and pharmacologic therapies. Although much remains unknown about the pathophysiology, management, and quality of life in RP, emerging evidence suggests that advanced imaging modalities may facilitate earlier detection of SRP. Treating the underlying disease is essential to improving vascular symptoms and preventing complications in SRP. This scientific statement reviews current evidence on quality of life measures for individuals with RP and on medical management, botulinum toxin therapy, and surgical intervention for severe cases.

Polyarteritis nodosa (PAN) is an uncommon systemic vasculitis involving predominantly medium-sized arteries. Its heterogeneous presentation and relapsing-remitting course often lead to diagnostic delay. We report a 68-year-old male with a 15-month history of progressive peripheral neuropathy, recurrent vasculitic rash, renal impairment, and testicular pain. Laboratory investigations revealed elevated inflammatory markers, positive rheumatoid factor, type II cryoglobulins, and negative antineutrophil cytoplasmic antibody (ANCA). Complement levels were normal on repeated testing, and urinalysis showed isolated proteinuria without red blood cells or casts, arguing against other differentials like cryoglobulinemic vasculitis and glomerulonephritis. Skin biopsy demonstrated leukocytoclastic vasculitis. After excluding secondary causes, including hepatitis B, ANCA-associated vasculitis (granulomatosis with polyangiitis and microscopic polyangiitis), IgA vasculitis, and cryoglobulinemic vasculitis, a diagnosis of systemic idiopathic PAN was established. Cyclophosphamide was considered but avoided due to pre-existing renal impairment. The patient was treated with high-dose prednisolone for induction, followed by low-dose azathioprine as a steroid-sparing agent, with subsequent clinical improvement. This case illustrates the diagnostic difficulty of distinguishing PAN from cryoglobulinemic vasculitis when overlapping serological features are present, and the consequences of delayed recognition on organ function.

Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is a relatively uncommon autoimmune disease, predominantly causing kidney or lung injury. Pituitary dysfunction is exceedingly rare in microscopic polyangiitis (MPA). Rupture or hemorrhage of renal artery aneurysms is also scarcely reported in AAV, especially in MPA. In this study, we describe a 68-year-old woman who presented with shortness of breath at rest, polydipsia, and polyuria. In addition to an increased p-ANCA titer (1:10) and the presence of anti-myeloperoxidase antibodies, T1-weighted magnetic resonance imaging of the head revealed pituitary injury. A diagnosis of MPA accompanied by pulmonary intestinal disease, central diabetes insipidus, and hypophysitis was confirmed. The patient responded to intravenous methylprednisolone and immunoglobulin. However, 1 week after admission, she complained of a sudden onset of sharp pain in her right waist area, accompanied by weakness, nausea, syncope, and hypotension. The hemoglobin level decreased from 95 to 47 g/L and abdominal computed tomography revealed a large perirenal hematoma surrounding the right kidney. The patient was immediately administered methylprednisolone pulse therapy (500 mg/day for 3 days) and cyclophosphamide (CTX; 0.6 g), followed by fluid resuscitation, blood transfusion, hemostatic therapy, and infusion of fresh frozen plasma. Arterial angiography demonstrated active bleeding of the interlobular artery of the right kidney, and selective arterial embolization was performed. Fortunately, she responded well to glucocorticoid and CTX therapy and did not relapse during the 5-year follow-up. Pituitary involvement accompanied by spontaneous rupture of a renal aneurysm is an extremely rare complication of MPA and has not been reported before.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a small-vessel vasculitis associated with anti-neutrophil cytoplasmic antibodies and characterized by blood and tissue eosinophilia, severe respiratory manifestations, and multiorgan involvement. The management of newly diagnosed EGPA still relies on therapeutic strategies that were initially validated for other forms of anti-neutrophil cytoplasmic antibody-associated vasculitis, including microscopic polyangiitis and granulomatosis with polyangiitis. Whereas the long-term prognosis of microscopic polyangiitis and granulomatosis with polyangiitis depends primarily on controlling initial organ involvement and preventing relapses, EGPA is distinguished by chronic involvement of both upper and lower respiratory airways, which often necessitates prolonged glucocorticoid therapy. Data from clinical trials suggest that targeting the IL-5 pathway with mepolizumab or benralizumab can effectively control persistent respiratory symptoms and reduce the need for glucocorticoids, yet the role of these agents in the management of EGPA at the time of diagnosis and in the long term remains to be defined. Emerging retrospective data on therapies targeting other type 2 cytokines (such as IL-4, IL-13 and thymic stromal lymphopoietin) suggest potential benefits for relapsing respiratory symptoms; however, prospective evidence remains limited and safety has yet to be established. This Review discusses the role of these new targeted therapies in the management of EGPA, alongside historical treatments.

Anti-neutrophil cytoplasmic antibody (ANCA) is an important serological marker for autoimmune diseases, particularly ANCA-associated vasculitis (AAV). AAV frequently presents with refractory rhinosinusitis as an initial manifestation, yet ANCA testing in patients with rhinosinusitis continues to face challenges, including inconsistent subtype classification, variable detection performance, and difficulties in early identification, leading to misdiagnosis and delayed treatment. This narrative review focuses on the diagnostic value of ANCA in AAV-related rhinosinusitis, encompassing granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). We summarize the research progress on ANCA detection and its association with clinical, imaging, and pathological features, aiming to provide a theoretical reference for early clinical diagnosis, individualized intervention, and improved patient prognosis.

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the central nervous system caused by reactivation of John Cunningham (JC) virus in a subset of immunocompromised individuals. This case report describes a rare case of progressive cavitary lesion in PML with only one other documented case in the world. The patient is a 63-year old male with medical history of microscopic polyangiitis who had previously undergone cyclophosphamide treatment and was on chronic immunosuppression with mycophenolate and high dose prednisone who presented to the emergency department with stroke-like symptoms. A series of magnetic resonance imaging (MRI) demonstrated a non-enhancing multifocal lesion in his frontal lobe that progressed into a cavitary lesion. PML was diagnosed using imaging presence of periventricular white matter lesions and positive JC virus in the cerebrospinal fluid. Stereotactic biopsy followed by histological staining of the samples and immunohistochemistry confirmed the diagnosis. We emphasize cavitary lesions as an extremely rare, but potential development of PML that appears to correlate with aggressive neurocognitive decline and has no identified associations.