A 45-year-old man with asthma comes to the physician because of a 1-month history of progressively worsening shortness of breath and cough. He also has a history of chronic sinusitis and foot drop. Current medications include an albuterol inhaler and inhaled corticosteroid. Physical examination shows diffuse wheezing over both lung fields and tender subcutaneous nodules on both elbows. Laboratory studies show a leukocyte count of 23,000/mm3 with 26% eosinophils and a serum creatinine of 1.7 mg/dL. Urine microscopy shows red blood cell casts. Which of the following is the most likely diagnosis in this patient?

Eosinophilic granulomatosis with polyangiitis

Granulomatosis with polyangiitis

A 50-year-old man comes to the physician for the evaluation of recurrent episodes of chest pain, difficulty breathing, and rapid heart beating over the past two months. During this period, he has had a 4-kg (8.8-lb) weight loss, malaise, pain in both knees, and diffuse muscle pain. Five years ago, he was diagnosed with chronic hepatitis B infection and was started on tenofovir. His temperature is 38°C (100.4°F), pulse is 110/min, and blood pressure is 150/90 mm Hg. Cardiopulmonary examination shows no abnormalities except for tachycardia. There are several ulcerations around the ankle and calves bilaterally. Laboratory studies show: Hemoglobin 11 g/dL Leukocyte count 14,000/mm3 Erythrocyte sedimentation rate 80 mm/h Serum Perinuclear anti-neutrophil cytoplasmic antibodies negative Hepatitis B surface antigen positive Urine Protein +2 RBC 6-7/hpf Which of the following is the most likely diagnosis?

Granulomatosis with polyangiitis

A 27-year-old male presents to clinic complaining of coughing up small amounts of blood daily for the past week. He denies smoking, sick contacts, or recent travel. Chest radiographs demonstrates interstitial pneumonia with patchy alveolar infiltrates suggestive of multiple bleeding sites. Urinalysis is positive for blood and protein. A positive result is returned for anti-glomerular basement membrane antibody (anti-GBM Ab). What is the most likely diagnosis?

Granulomatosis with polyangiitis (Wegener's)

Systemic lupus erythematosus (SLE)

A 45-year-old man comes to the physician because of fatigue and joint pain for 8 months. He has pain in both knees, both elbows, and diffuse muscle pain. He does not have dyspnea. He also had several episodes of a nonpruritic rash on his lower extremities. Eight years ago, the patient was diagnosed with hepatitis C. His temperature is 37.9°C (100.2°F), pulse is 90/min, and blood pressure is 140/90 mm Hg. Examination of the lower extremities shows raised purple papules that do not blanch when pressure is applied. Cardiopulmonary examination shows no abnormalities. Laboratory studies show: Hemoglobin 13.9 g/dL Leukocyte count 8,500/mm3 Platelets 160,000/mm3 Serum Creatinine 1.1 mg/dL ALT 123 U/L AST 113 U/L Further evaluation of this patient is most likely to show which of the following findings?

Granulomatous inflammation of vessels

Elevated perinuclear anti-neutrophil cytoplasmic antibodies

A 30-year-old woman presents to the clinic because of fever, joint pain, and a rash on her lower extremities. She admits to intravenous drug use. Physical examination reveals palpable petechiae and purpura on her lower extremities. Laboratory results reveal a negative antinuclear antibody, positive rheumatoid factor, and positive serum cryoglobulins. Which of the following underlying conditions in this patient is responsible for these findings?

Systemic lupus erythematosus (SLE)

A 40-year-old woman comes to the emergency department because of difficulty walking for the past 4 hours. She first noticed her symptoms after getting up this morning and her foot dragging while walking. She feels tired. She has a history of chronic sinusitis. Six months ago, she was diagnosed with asthma. Current medications include an albuterol inhaler and inhaled corticosteroids. Her temperature is 38.9°C (102°F), pulse is 80/min, and her blood pressure is 140/90 mm Hg. Auscultation of her lungs shows diffuse wheezing over bilateral lung fields. Physical examination shows tender subcutaneous nodules on the extensor surfaces of the elbows. There are palpable, non-blanching erythematous lesions on both shins. Dorsiflexion of the right foot is impaired. Sensation to pinprick, light touch, and vibration is decreased over the ulnar aspect of the left forearm. Laboratory studies show: Hemoglobin 11.3 g/dL Leukocyte count 24,500 Segmented neutrophils 48% Eosinophils 29% Lymphocytes 19% Monocytes 4% Platelet count 290,000/mm3 Serum Urea nitrogen 32 mg/dL Creatinine 1.85 mg/dL Urine Blood 2+ Protein 3+ Which of the following is the most likely diagnosis in this patient?

Eosinophilic granulomatosis with polyangiitis

Granulomatosis with polyangiitis

A 57-year-old woman presents to her family physician because of sinusitis and nasal drainage for 3 months. The nasal drainage is purulent and occasionally hemorrhagic. She has only temporary improvement after trying multiple over the counter medications. Over the last 2 weeks, she also has fatigue and joint pain, mainly affecting the ankles, knees, and wrists. Vital signs include: temperature 36.9°C (98.4°F), blood pressure 142/91 mm Hg, and pulse 82/min. On examination, there is inflammation and bleeding of the nasal mucosa, along with tenderness to percussion over the maxillary sinuses. Urine dipstick reveals 4+ microscopic hematuria and 2+ proteinuria. Which of the following is the most likely diagnosis?

Granulomatosis with polyangiitis

A 62-year-old man presents to the emergency department with hematuria and hemoptysis that started in the morning. He notes that he has had frequent lung infections throughout his adult life, the most recent being 2 weeks ago. He also mentions that he has had hematuria twice before but never as severe as he is having currently. His medical history is otherwise non-significant, and his only medication is acetaminophen as needed. His blood pressure is 136/92 mm Hg, heart rate is 86/min, respiratory rate is 16/min, and temperature is 37.0°C (98.6°F). Chest radiography shows a resolving right middle lobe airspace opacity. His initial laboratory tests are notable for elevated erythrocyte sedimentation rate and C-reactive protein level. While in the examination room, the patient develops a spontaneous nosebleed. What is the most likely diagnosis?

Granulomatosis with polyangiitis

Post-streptococcal glomerulonephritis

Small vessel vasculitis — USMLE Lesson

Classification - The Vessel Vandals

ANCA-Associated Vasculitis (AAV) / Pauci-Immune: Characterized by few or no immune deposits.
- GPA (Granulomatosis with Polyangiitis): c-ANCA (anti-PR3). Affects sinuses, lungs, kidneys. 📌 GPA = "C-shaped" granulomas → c-ANCA.
- MPA (Microscopic Polyangiitis): p-ANCA (anti-MPO). No granulomas.
- EGPA (Eosinophilic GPA): p-ANCA (anti-MPO). Asthma, eosinophilia.
Immune Complex-Mediated:
- IgA Vasculitis (HSP)
- Cryoglobulinemic Vasculitis (often Hep C-assoc.)
- Anti-GBM Disease

Histology of ANCA-associated and immune complex vasculitis

⭐ GPA, MPA, and Anti-GBM disease can all present as a pulmonary-renal syndrome; ANCA testing and biopsy are key to differentiation.

ANCA-Associated - The Antibody Attack

Pathogenesis: Autoantibodies targeting neutrophil enzymes (Anti-Neutrophil Cytoplasmic Antibodies) trigger neutrophil activation, degranulation, and endothelial damage, leading to necrotizing vasculitis.
Key Antibodies & Associations:
- c-ANCA (Cytoplasmic): Targets Proteinase 3 ($PR3$). Strongly linked to Granulomatosis with Polyangiitis (GPA).
- p-ANCA (Perinuclear): Targets Myeloperoxidase ($MPO$). Associated with Microscopic Polyangiitis (MPA) and Eosinophilic Granulomatosis with Polyangiitis (EGPA).

P-ANCA vs C-ANCA Immunofluorescence Patterns

Pathophysiology Flow:

⭐ Exam Favorite: ANCA-associated vasculitides cause a "pauci-immune" glomerulonephritis. This means kidney biopsies show necrotizing glomerulonephritis with little to no immunoglobulin or complement deposition on immunofluorescence, a key diagnostic feature.

Clinical Syndromes Quick View:
- GPA (Wegener's): c-ANCA/PR3. Triad: Upper/Lower respiratory tract granulomas + Renal failure.
- MPA: p-ANCA/MPO. No granulomas. Affects lungs & kidneys.
- EGPA (Churg-Strauss): p-ANCA/MPO. Asthma + Eosinophilia + Vasculitis.

Immune Complex - Clumpy Capillary Cloggers

Immune complexes (Ag-Ab) deposit in small vessel walls, triggering complement activation & neutrophilic inflammation. This leads to vessel wall damage and necrosis (leukocytoclastic vasculitis).

Hallmark: Palpable purpura (non-blanching), especially on lower extremities.
Key Types:
- IgA Vasculitis (Henoch-Schönlein Purpura): Most common in children post-URI. Tetrad: palpable purpura, arthralgias, abdominal pain, renal disease (IgA nephropathy).
- Cryoglobulinemic Vasculitis: Strongly associated with Hepatitis C. Presents with purpura, weakness, arthralgia (Meltzer's triad).

⭐ IgA Vasculitis (HSP) is the most common systemic vasculitis in children, often triggered by an upper respiratory infection.

Palpable Purpura in Small Vessel Vasculitis

Diagnosis & Treatment - The Counter-Offensive

Labs: Start with ANCA testing.
- c-ANCA (anti-PR3) → Granulomatosis with Polyangiitis (GPA)
- p-ANCA (anti-MPO) → Microscopic Polyangiitis (MPA) or Eosinophilic Granulomatosis with Polyangiitis (EGPA)
Biopsy: Gold standard for confirmation. Skin, kidney, or lung are common sites showing leukocytoclastic vasculitis.
Urinalysis: Look for hematuria, proteinuria, and red blood cell casts (glomerulonephritis).

Histopathology of Leukocytoclastic Vasculitis

⭐ GPA, MPA, and EGPA are often called "ANCA-associated vasculitides" (AAV), linking the diagnostic marker directly to the diseases.

High‑Yield Points - ⚡ Biggest Takeaways

ANCA-associated vasculitides (AAV) are pauci-immune and cause rapidly progressive glomerulonephritis (RPGN).

GPA (c-ANCA/PR3) features a classic triad: upper/lower respiratory tract disease and glomerulonephritis.

MPA (p-ANCA/MPO) resembles GPA but critically lacks granulomas and significant upper airway signs.

EGPA (p-ANCA/MPO) is uniquely marked by asthma, peripheral eosinophilia, and neuropathy.

IgA Vasculitis (HSP) is an immune-complex disease with a tetrad of palpable purpura, arthralgias, abdominal pain, and renal disease.

Unlock the full lesson and continue reading

Signup to continue reading this lesson and unlimited access questions, flashcards, AI notes, and more

Scan to download app

UNLOCK FREE ACCESS