Can infection cause vasculitis and how is it treated?

Can Infection Cause Vasculitis and How Is It Treated?

Yes, infections definitively cause vasculitis through both direct vascular wall invasion and indirect immune-mediated mechanisms, and treatment prioritizes eradicating the underlying infection with pathogen-specific antimicrobials before considering immunosuppression. 1, 2, 3

Mechanisms of Infection-Induced Vasculitis

Infections trigger vasculitis through two primary pathways 3:

• Direct vascular damage: Pathogens with endothelial tropism (Staphylococcus, Streptococcus, Salmonella, Treponema, Rickettsia, Cytomegalovirus, Herpes Simplex Virus) directly destroy the vascular wall, leading to inflammatory responses 3

• Indirect immune-mediated injury: Organisms like Mycobacterium tuberculosis, Mycobacterium leprae, Hepatitis B and C viruses, and HIV share epitopes with host tissues or modify self-antigens, triggering cross-reactive immune responses classified as Gell-Coombs type I-IV reactions 3, 4

• Molecular mimicry and impaired clearance: Infection may contribute through molecular mimicry, and defective neutrophil apoptosis or impaired clearance of apoptotic cell fragments may prolong antigen exposure 1, 2

Specific Infection-Vasculitis Associations

Viral Infections

Varicella Zoster Virus (VZV) causes cerebral vasculitis presenting with large and small artery strokes, arterial luminal irregularities, beading, or stenosis 1:

• Lumbar puncture should assess anti-VZV IgG (highest sensitivity), IgM, and PCR 1
• Acyclovir is the definitive treatment 1
• Negative VZV PCR does not exclude VZV vasculitis; empiric treatment is reasonable with high clinical suspicion 1

Hepatitis B Virus causes polyarteritis nodosa in 36-50% of cases, with acute onset typically within months of infection 4

Hepatitis C Virus causes cryoglobulinemia-associated vasculitis with predominant skin involvement (purpura on lower extremities), peripheral neuropathy, and glomerulonephritis occurring late in infection 4

HIV causes vasculopathy through multiple mechanisms including accelerated atherosclerosis, opportunistic infections, and direct vascular inflammation 1:

• Treatment combines daily aspirin with combined antiretroviral therapy (cART) to restore CD4 counts 1
• Some evidence suggests immune reconstitution syndrome may paradoxically increase stroke risk after initiating cART 1

Cytomegalovirus predominantly affects immunosuppressed patients, causing diffuse vasculitis involving the gastrointestinal tract (especially colon), central nervous system, and skin 4

Parvovirus B19 occasionally causes vasculitis during the viremic phase, typically presenting as vascular purpura on lower extremities 4

Bacterial Infections

Neurosyphilis (Treponema pallidum) causes basilar meningitis with contiguous spread to brain arteries at the skull base 1:

• Intensive treatment with penicillin G is mandated 1
• HIV testing is indicated due to 5-16% coexistence of both sexually transmitted diseases 1

Mycobacterium tuberculosis causes basilar meningitis leading to vasculitis through cerebrospinal fluid inflammation spreading to cerebral vessels 1

Bacterial meningitis can cause vasculitis requiring treatment of the underlying infection 1

Treatment Algorithm

Step 1: Identify and Treat the Infection

For suspected infectious vasculitis, treating the underlying pathogen is the primary intervention 1, 3:

• VZV vasculitis: Acyclovir 1
• Neurosyphilis: Penicillin G 1
• HIV vasculopathy: Combined antiretroviral therapy + daily aspirin 1
• Bacterial meningitis: Pathogen-specific antibiotics 1
• Hepatitis B/C-associated vasculitis: Antiviral therapy (corticosteroids and immunosuppression only after antiviral failure) 4

Step 2: Determine Need for Immunosuppression

Corticosteroids and immunosuppressive agents are second-line interventions, indicated only after antiviral/antimicrobial failure or in life-threatening presentations 4:

• For severe organ-threatening manifestations (pulmonary hemorrhage with hypoxemia, rapidly progressive glomerulonephritis), consider adding glucocorticoids with rituximab or cyclophosphamide while treating the infection 1
• Plasma exchange can be considered for diffuse alveolar hemorrhage with hypoxemia in addition to antimicrobials and immunosuppression 1

Step 3: Obtain Cultures Before Antibiotics

When infection is suspected as the vasculitis trigger, obtain appropriate cultures before initiating empiric antibiotics 1:

• Blood cultures from both central and peripheral sources 1
• Site-specific cultures (exit site drainage, tunnel drainage, cerebrospinal fluid) 1
• Modify antibiotics according to culture sensitivities 1

Critical Pitfalls to Avoid

• Do not delay pathogen-specific treatment while awaiting confirmatory testing in rapidly deteriorating patients with high clinical suspicion for infectious vasculitis 1

• Do not use immunosuppression as first-line therapy for infection-associated vasculitis; this worsens outcomes by allowing pathogen proliferation 4

• Do not assume negative VZV PCR excludes VZV vasculitis; anti-VZV IgG has higher sensitivity 1

• Do not overlook coexisting HIV in patients with neurosyphilis; test all patients given 5-16% coexistence 1

• Do not withhold Pneumocystis jirovecii prophylaxis if immunosuppression becomes necessary (trimethoprim-sulfamethoxazole for patients receiving rituximab or cyclophosphamide) 1, 5

Distinguishing Infection-Induced from Primary Vasculitis

Secondary vasculitis from infection differs from primary ANCA-associated vasculitis 2, 5:

• Withdrawal of the offending infectious agent may resolve clinical manifestations without immunosuppression 2
• Temporal relationship between infection and vasculitis onset (acute onset within months for HBV-associated polyarteritis nodosa) 4
• Specific serologic markers (anti-VZV antibodies, VDRL/RPR for syphilis, HIV antibodies, hepatitis serology) 1, 4
• Biopsy may show organisms or characteristic patterns (granulomatous inflammation in tuberculosis, viral inclusions in CMV) 3