Thanks to Jen for presenting the case of a middle-aged lady with h/o HTN on hydralazine and PE noted to have progressively worsening glomerulonephritis and a discoid skin rash, with anti-MPO and anti-histone antibody positive serologies concerning for drug-induced ANCA associated vasculitis!
- Many cases of drug-induced lupus are actually drug-induced ANCA vasculitis!
- Medications associated with drug induced ANCA-vasculitis include hydralazine (most common and most severe presentation), followed by methimazole/PTU, and minocycline.
- Drug-induced vasculitis tends to present with anti-histone antibody positivity (sensitive but less specific). Drug-induced ANCA vasculitis can be anti-MPO positive especially in the case of hydralazine.
- Treatment involves witholding the offending agent. In the case of hydralazine induced ANCA-vasculitis, steroids and additional immunosuppressive therapy (cytoxan or rituxan) are also indicated to reduce progression to ESRD.
- >500 eos ⇒ eosinophilia
- > 1500 eos ⇒ severe eosinophilia
- > 5000 eos ⇒ severe eosinophilia at risk of end organ damage
- Etiology (NAACP-P)
- Monoclonal leukemias (eosinophil proliferation)
- Polyclonal: T cell lymphomas, Hodgkin lymphoma, some solid organ tumors (cervical, ovarian, gastric, colon, urotherlial, and squamous cell carcinomas)
- Adrenal insufficiency (super rare)
- EGPA, RA
- Parasites: remember that only multicellular parasites can cause eosiniphilia
- Other bugs: ABPA, cocci, HIV
- Primary eosinophilic syndromes
- M:F is 1:1 but hydralazine induced lupus is more common in women
- Mechanism is poorly understood and genetic predisposition may play a role. More likely to happen in patients who are slow acetylators
- Anti-histone antibodies: 95% sensitive
- Other antibodies are uncommon
- Drugs: long list!
- Procainamide, hydralazine, chlorpromazine, quinidine, minocycline, PTU, statins, anti-TNF agents, IFN, methyldopa
- Weaker associations: AEDs, antimicrobials, beta blockers, lithium, HCTZ, amiodarone, cipro etc.
- Stop offending agent
- Joint symptoms: NSAIDs
- Skin symptoms: topical steroids
- Hydral-induced vasculitis: need cytotoxic or other immunosuppressive therapy. Treatment similar to ANCA positive vasculitis
- Resolution of symptoms weeks to months
Drug induced ANCA positive vasculitis:
- Patients typically present with constitutional symptoms, arthralgias/arthritis, and cutaneous vasculitis
- Strongest association with hyperthyroidism meds, hydralazine, and minocycline (hydral is the most common)
- Rare, but should be aware of this association because it impacts management and because it is often not diagnosed until too late in the disease course. In fact, many cases of drug induced lupus are actually drug induced ANCA-associated vasculitis
- In a small case series of hydral-induced ANCA-associated vasculitis of 10 patients, 90% had renal involvement of whom 7 recovered at 6 month follow up (though one required HD).
- Hydralazine-induced ANCA vasculitis is generally p-ANCA pattern with anti-MPO positivity (might also have anti-lactoferrin or anti-elastase)
- Treatment involves immunosuppression with steroids and cytoxan or rituxan.
- Non-hydralazine drug-induced ANCA vasculitis is typically treated with stopping the offending agent and has a better prognosis than its hydralazine-induced counterpart. In fact, ANCA positivity without clinical vasculitis is common especially in cases involving PTU.