- Polyarteritis Nodosa (PAN; Systemic Necrotizing Vasculitis)
- Epidemiology
- Male > Female: 1.6-2 times
- Onset age: 40 to 60 years
- Incidence: ~7/1,000,000/year
- Neuropathy
- Present in ~25% at time of diagnosis
- Occurs in ~50% to 75% during course of disease
- Hereditary form: Pediatric onset
- Neuropathy
- Mononeuritis multiplex: Motor-sensory
- Most common pattern of involvement (57%)
- Radial, median, ulnar & sciatic (peroneal) most frequent
- Occurs in with systemic features of PAN
- Course: Step-wise or progressive; Over weeks to months
- Other patterns of neuropathy
- Pain: Myalgia (Normal CK); Testicular or Ovarian
- CNS: Vasculitis may occur late in disease course
- Systemic features
- General (60%): Edema; Weight loss; Fever; Arthralgia; Fatigue
- Skin: Livido reticularis; Rash; Purpura; Ulcers
- Renal dysfunction: 80%
- Increased BUN & Creatinine
- Hypertension
- Nephrotic proteinuria
- GI: Bleeding; Infarction
- Pulmonary: Asthma in ~10%
- Cardiac: Juvenile forms
- Associated infection: Hepatitis B (30%); Hepatitis C
- Associated neoplasm: Hairy cell leukemia
- Electrodiagnostic studies
- Axonal loss
- Small CMAPs with relatively normal conduction velocities
- Often Patchy & Asymmetric
- Occasionally Distal & Symmetric
- Conduction block: With acute focal ischemic lesion; Present for ~ 1 week
- Pathology: Diagnosis by tissue biopsy
- Necrotizing vasculitis of medium
& small arterioles in epineurium
- Vessel size: 100μm to 200 μm
- Lesions are patchy: May need multiple sections to detect
- Patchy axonal loss
- Inflammation: Mononucler & Polymorphonuclear
- Other diagnostic tests
- Treatment
- Corticosteroids
- Cyclophosphamide in poorly responsive patients
- Prognosis
- Untreated disease: High mortality
- After immunosuppressive treatment
- Improvement in most over months to years
- Vasculitis Variant: ADA2 deficiency ± PAN, Young onset (DADA2; VAIHS)
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Adenosine deaminase 2 (ADA2; CECR1)
; Chromosome 22q11.1; Recessive
- Epidemiology
- > 100 patients
- Hot spots: Georgian Jews; Germans
- Genetics
- Mutations: Missense; Gly47Arg in Georgian Jews
- Allelic disorder: Sneddon syndrome
- ADA2 protein
- Major extracellular adenosine deaminase
- Catalyzes degradation of adenosine to inosine
- Secreted by myeloid cells
- Functions: Growth factor; Immunomodulation
- Levels: May be biomarker of macrophage activation syndrome in juvenile arthritis
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- Clinical
- General syndromes: Often overlap
- Inflammatory/vascular
- Immune dysregulatory
- Hematologic
- Onset age: Range 2 months to 59 years; Usual 1st & 2nd decade
- Skin
- Digital necrosis
- Livido reticularis
- Raynaud's
- Neuromuscular (45%)
- Polyneuropathy (40%)
- Vasculitis
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- Vessels involved: Epineurial small arteries
- Perivascular inflammation
- Axonal neuropathy
- Sensory + Motor
- NCV: Axon loss
- Previous history: Stroke
- Muscle
- Myositis: Inflammation
- Locations: Perivascular; Endomysial
- Cells: Lymphocytes; Eosinophils
- MRI: T2 enhancement
- Atrophy
- Cranial nerves: VII; VIII; Oculomotor; Vestibular
- Pain: Myalgia; Arthralgia
- CNS (20%)
- Ischemic strokes: Often recurrent
- Hemorrhage: Ventricular
- Myelopathy
- Systemic
- Vasculopathy (70%)
- PAN-like syndromes
- Raynaud's
- Hypertension, Renal
- Gastrointestinal: Abdominal pain; Ischemia
- Splenomegaly
- Joints: Arthritis
- Pulmonary: Frequent infections
- Fever & Infections: Recurrent
- Cardiomyopathy
- Treatments
- Anti-TNFα
- Corticosteroids
- Immunoglobulins
- ADA2-enzyme replacement therapy: Fresh-frozen plasma (FFP)
- Death: Often stroke-related
- Laboratory
- NCV: Axon loss
- Pathology (Skin)
- Arteries
- Type: Medium-sized (Similar to PAN)
- Inflammation
- Fibrinoid necrosis
- Endothelial cell damage
- Leukocytoclastic vasculitis
- Renal: Aneurysm
- Hematologic
- Hypogammaglobulinemia: Low IgA, IgG & IgM
- Cytopenia
- B-cell immunodeficiency: Adults < 200/μL
- Inflammation markers
- CRP: High; Especially with Hypogammaglobulinemia
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PAN: Diagnostic features vs other vasculitides
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- Positive predictive features
- Clinical: Mono- or Polyneuropathy
- Serum: Hepatitis B virus antigen or DNA
- Arteriographic anomalies
- Negative predictive features
- Clinical
- Asthma
- ENT signs
- Glomerulopathy
- Laboratory
- ANCA (immunofluorescence)
- Cryoglobulinemia
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Systemic vasculitides (PAN & Microscopic Polyangiitis) Common features
- Weight loss > 4 kg
- Livido reticularis
- Testicular discomfort
- Myalgia, weakness or tenderness
- Poly- or Mononeuropathy
- Diastolic blood pressure >90 mm Hg
- Renal dysfunction
- BUN > 40 mg%, or
- Creatinine > 1.5 mg%
- Hepatitis B surface Ag or Ab
- Arteriography
- Aneurysm or occlusion
- In visceral artery
- Pathology: Cell infiltrates in artery
- Polymorpho- or mononuclear
- In arterial wall
- Small or medium size
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