Hematology, Oncology & Immunology · Topic 26 of 26

Autoimmune & Vasculitic Emergencies

Rheumatology · autoimmune emergencies

Autoimmune & Vasculitic Emergencies

Lung bleeding plus nephritis is a pulmonary-renal syndrome: send anti-GBM and ANCA, give pulse steroids, and plasma-exchange anti-GBM disease.

Key numbers

Pulse methylprednisolone, then rituximab or cyclophosphamideIV pulse × 3–5 days

01 · Defined byAlveolar hemorrhage plus nephritis: pulmonary-renal syndrome

Diffuse alveolar hemorrhage plus glomerulonephritis (hematuria, red cell casts, rising creatinine) is a pulmonary-renal syndrome — usually anti-GBM disease or ANCA vasculitis, less often lupus; lung and kidney findings may appear weeks apart.

02 · GivePulse methylprednisolone, then rituximab or cyclophosphamide

Induce remission with pulse IV methylprednisolone (often 1 g) daily for 3–5 days, then prednisone about 1 mg/kg/day; for ANCA vasculitis add rituximab or cyclophosphamide, with avacopan as a steroid-sparing option.

03 · DoScleroderma renal crisis: ACE inhibitor now

Scleroderma renal crisis — sudden severe hypertension, AKI and microangiopathic hemolysis, mostly in early diffuse cutaneous disease with anti-RNA polymerase III — needs a prompt ACE inhibitor, which greatly prolongs survival; glucocorticoids raise the risk.

Causes & risk factors

Why it happens

Screen for hepatitis B before rituximabRituximab carries boxed warnings for hepatitis B reactivation (fulminant hepatitis), progressive multifocal leukoencephalopathy, fatal infusion reactions and severe mucocutaneous reactions: screen every patient for HBV before the first dose.

Screen for Strongyloides before high-dose steroidsBefore high-dose glucocorticoids in a patient from or traveled to an endemic area, screen for Strongyloides — steroids can trigger fatal hyperinfection with gram-negative bacteremia.

Presentation

What you'll see

Alveolar hemorrhage: hemoptysis absent in one-thirdDiffuse alveolar hemorrhage causes dyspnea, cough, new alveolar infiltrates and a falling hematocrit, often with respiratory failure; hemoptysis is absent in up to one-third, so serial BAL returning progressively bloodier, with hemosiderin-laden macrophages, confirms it.

GPA: sinuses, lung nodules, kidneys, c-ANCAGranulomatosis with polyangiitis involves the upper airway (sinusitis, epistaxis, crusting, septal perforation), lungs (nodules, cavities, hemorrhage), kidneys (glomerulonephritis) and nerves (mononeuritis multiplex); most active cases are c-ANCA/PR3-positive.

Diagnosis & monitoring

Work-up

Catastrophic APS: clots in 3 or more organsSuspect catastrophic antiphospholipid syndrome with multiorgan failure (≥ 3 organs) from small-vessel thrombosis and positive antiphospholipid antibodies; treat with anticoagulation, high-dose glucocorticoids and plasma exchange and/or IVIG, sometimes rituximab or eculizumab.

Do right now

In this order

First moves

Send anti-GBM, ANCA, anti-dsDNA and complement

→

Pulse methylprednisolone, then rituximab or cyclophosphamideIV pulse × 3–5 days

→

Anti-GBM disease: immediate plasma exchange

Why each step

Send anti-GBM, ANCA, anti-dsDNA and complementWork up a pulmonary-renal syndrome with urinalysis, creatinine, CBC, chest CT and serologies: anti-GBM antibodies, ANCA (PR3/c-ANCA for GPA, MPO/p-ANCA for MPA), anti-dsDNA with low complement (lupus); kidney or lung biopsy confirms.

Pulse methylprednisolone, then rituximab or cyclophosphamideInduce remission with pulse IV methylprednisolone (often 1 g) daily for 3–5 days, then prednisone about 1 mg/kg/day; for ANCA vasculitis add rituximab or cyclophosphamide, with avacopan as a steroid-sparing option.

Anti-GBM disease: immediate plasma exchangeAnti-GBM (Goodpasture) disease — linear IgG along glomerular or alveolar capillaries — needs immediate plasma exchange plus high-dose glucocorticoids and cyclophosphamide; prognosis is good when treatment starts before respiratory or kidney failure.

Management

Orders

Severe lupus flare: pulse steroids plus immunosuppressantOrgan-threatening lupus (nephritis with impaired function, myocarditis, CNS disease, alveolar hemorrhage) gets methylprednisolone 1 g IV daily for 3 days, then prednisone 0.5–1 mg/kg/day, plus an immunosuppressant.

Lupus nephritis: steroids plus mycophenolate or cyclophosphamideInduce proliferative (class III or IV) lupus nephritis with glucocorticoids plus mycophenolate or IV cyclophosphamide, sometimes adding belimumab or a calcineurin inhibitor (voclosporin, tacrolimus); give an ACE inhibitor or ARB for proteinuria or hypertension.

Hydroxychloroquine for every lupus patientContinue hydroxychloroquine in every patient with SLE regardless of severity — it reduces flares and mortality and may lower thrombosis with antiphospholipid antibodies.

PJP prophylaxis with prolonged high-dose steroidsPatients on prolonged glucocorticoids (prednisone > 20 mg/day for 4 weeks or more) are generally offered Pneumocystis prophylaxis with TMP-SMX (see Infections in the Immunocompromised Host).

Red flags & don'ts

Avoid harm

No DOACs in high-risk antiphospholipid syndrome avoidAvoid direct oral anticoagulants in high-risk antiphospholipid syndrome — arterial thrombosis or triple-positive antibodies — because of excess recurrent thrombosis; indefinite warfarin (INR 2–3) is standard.

The rules

Know these

Plasma exchange: not routine in ANCA vasculitisPlasma exchange did not reduce death or end-stage kidney disease in severe ANCA vasculitis; it remains standard for anti-GBM disease and is reserved for selected refractory vasculitis.

Anti-GBM disease or ANCA vasculitis?

Commonly confused

Serology	Anti-GBM antibodies
Organs	Lungs and kidneys
Plasma exchange	Immediate — the mainstay
Immunosuppression	High-dose glucocorticoids plus cyclophosphamide

Commonly confused

Tell apart

High CRP in lupus: think infectionLow C3/C4 and rising anti-dsDNA track active lupus, especially nephritis; CRP may stay normal in a flare, so a high CRP in a febrile lupus patient points to infection or serositis.

More detail

Reference

Show 6 reference facts

Rituximab alone, or methotrexate, azathioprine or mycophenolate, maintains remission in ANCA vasculitis; rituximab lowers relapse risk.

Cyclophosphamide causes hemorrhagic cystitis, bladder cancer and infertility; mesna is sometimes given with IV dosing to prevent cystitis.

ANCA can be positive in endocarditis, cocaine use, tuberculosis and lupus; propylthiouracil and levamisole-adulterated cocaine can cause drug-induced pulmonary-renal syndrome.

In alveolar hemorrhage, DLCO may be increased because intra-alveolar hemoglobin takes up carbon monoxide.

Scleroderma renal crisis usually occurs in the first 4–5 years of diffuse disease and can occur without acute hypertension, so clinical suspicion is needed even with normal blood pressure.

After lupus nephritis induction, immunosuppression continues for at least 2 years; patients who reach kidney failure can receive a kidney transplant.

Pearl

Scleroderma renal crisis is the exception that proves the rule: ACE inhibitor, not steroids.