Updated: 7/12/2019

Granulomatosis with Polyangiitis

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Questions
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Snapshot
  • A 55-year-old man presents to the emergency department due to coughing up blood in the morning. His symptoms are accompanied by fever, arthralgias affecting the wrists and knees, and unintentional weight loss over the course of 3 months prior to presentation. The patient also noticed mild shortness of breath. On physical exam, there is mild nasal crusting and bloody nasal discharge. There are no lesions in the mouth. There is tenderness to palpation of the wrist and knees. Laboratory testing is significant for an elevated erythrocyte sedimentation rate, C-reactive protein, and a creatinine of 2.5 mg/dL (his creatinine is normally 0.9 mg/dL). A radiograph of the chest demonstrates pulmonary nodules. 
Introduction
  • Clinical definition
    • small- to medium-sized vessel vasculitis and granulomatosis that affects
      • upper and lower respiratory tract and kidneys 
    • previously known as Wegener granulomatosis
  • Epidemiology
    • incidence
      • can occur at any age but typically between 65-75 years of age
  • Etiology
    • unclear but may involve both genetic and environmental components
  • Pathogenesis
    • antiproteinase-3 (PR3 ANCA/c-ANCA) antibodies present in ~95% of cases 
    • T-cell mediated hypersensitivity reaction that leads to granuloma formation
  • Associated conditions
    • rapidly progressive glomerulonephritis
  • Prognosis
    • glucocorticoids can lead to remission at 6 months in > 90% of patients
Presentation
  • Symptom/physical exam 
    • upper respiratory symptoms
      • sinusitis (most common)
      • recurrent otitis media
      • otalgia
    • lower respiratory symptoms
      • hemoptysis
    • renal symptoms
      • hematuria
    • skin
      • leukocytoclastic angiitis
Imaging
  • Radiography
    • indication
      • should be performed in all patients with pulmonary involvement likely secondary to ANCA-associated vasculitis
        • computerized tomography scan is also performed
    • views
      • chest
    • findings
      • single or multiple nodules/masses in ~66% of cases
      • nodules may be cavitated
Studies
  • Labs
    • ↑ C-reactive protein and erythrocyte sedimentation rate
    • positive PR3 ANCA/c-ANCA testing  
  • Biopsy the site of active disease
    • confirms the diagnosis
    • demonstrates granulomas, giant cells, necrosis, and vasculitis
Differential
  • Microscopic polyangiitis
    • differentiating factor
      • does not present with nasopharyngeal involvement, which is seen in granulomatosis with polyangiitis
      • no granuloma formation
      • MPO-ANCA/p-ANCA positive
  • Polyarteritis nodosa
    • differentiating factor
      • renal infarcts, artery stenosis, and visceral microaneurysms are classic for polyarteritis nodosa
      • not associated with ANCA antibodies
Treatment
  • Medical
    • high-dose glucocorticoids 
      • indication
        • initial treatment option in patients with non-life or organ-threatening disease
          • typically given with methotrexate
    • high-dose glucocorticoids with cyclophosphamide or rituximab
      • indication
        • initial treatment option in patients with life- or organ-threatening disease
Complications
  • Pulmonary hemorrhage
  • Respiratory failure
  • Uremia
  • Renal failure
  • Palpable purpura and other vascular lesions
 
 

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Questions (3)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M2.RH.4769) A 45-year-old male presents to the emergency room complaining that he has been coughing up blood-tinged sputum. Since this morning, the patient reports he has coughed up around 1/4 cup of "phlegm" mixed with blood. A review of systems is also notable for fatigue and night sweats that began two nights ago, but he denies any recent changes in weight. His past medical history is significant for hypertension, chronic sinusitis, and childhood asthma. His current medications include metoprolol and amlodipine. He is a smoker with a 20 pack-year history. The patient’s temperature is 99°F (37.2°C), blood pressure is 126/76 mmHg, pulse is 72/min, and respirations are 14/min with an oxygen saturation of 98% O2 on room air. A physical exam is notable for oral ulcers. A chest radiograph is performed and is shown in Figure A. Labs are drawn and are listed below:

Serum:
Na+: 144 mEq/L
Cl-: 109 mEq/L
K+: 4.3 mEq/L
HCO3-: 23 mEq/L
Urea nitrogen: 46 mg/dL
Glucose: 100 mg/dL
Creatinine: 3.0 mg/dL

Leukocyte count and differential:
Leukocyte count: 12,000/mm^3
Segmented neutrophils: 60%
Bands: 3%
Eosinophils: 3%
Basophils: < 1%
Lymphocytes: 28%
Monocytes: 5%
Hemoglobin: 13.0 g/dL
Hematocrit: 50%
Platelets: 200,000/mm^3

Urine:
Epithelial cells: 5/hpf
Glucose: negative
Proteins: 25 mg/dL
RBC: 15/hpf
Red cell casts: 7/hpf
WBC: 1/hpf
Leukocyte esterases: negative
Nitrites: negative
Bacteria: none

Based on the information above, which of the following is most likely to be abnormal?
Review Topic

QID: 109138
FIGURES:
1

Sputum acid-fast stain

6%

(2/31)

2

Test for anti-myeloperoxidase

16%

(5/31)

3

Test for anti-proteinase 3

55%

(17/31)

4

Renal arteriogram

13%

(4/31)

5

Sputum cytology

6%

(2/31)

M2

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SUBMIT RESPONSE 3

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(M2.RH.4672) A 42-year-old female reports progressively worsening dyspnea and cough for the past year. She also complains of concurrent joint pains in her bilateral knees, elbows, and wrists. Upon further history, the patient notes that she has “really bad allergies”, with symptoms of nasal congestion, sinus pressure, and nosebleeds a few times each month. Urinalysis is positive for 1+ blood and 2+ protein. Her creatinine is elevated at 1.3 mg/dL. Physical exam reveals the following in her lower extremities (Figure A). Biopsy of these lesions yields the following findings (Figure B). What is the most likely positive serologic finding in this patient? Review Topic

QID: 107185
FIGURES:
1

Antineutrophil cytoplasmic antibodies recognizing myeloperoxidase

35%

(9/26)

2

Antineutrophil cytoplasmic antibodies recognizing proteinase 3

58%

(15/26)

3

Autoantibodies recognizing cyclic citrullinated peptide

0%

(0/26)

4

Autoantibodies recognizing nuclear RNA-binding proteins

4%

(1/26)

5

Antibodies that precipitate and aggregate upon exposure to cold temperature

0%

(0/26)

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SUBMIT RESPONSE 2
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