The Emergency Medicine Approach to Vasculitides
Author: Brit Long, MD, CAPT (EM Resident Physician at SAUSHEC; USAF) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) & Justin Bright, MD (@JBright2021)
A 25 year-old female is suddenly rolled back in a wheelchair into your resuscitation area. As you walk into the room, you see a pale, ashen lady with a diffuse red rash holding an emesis basin between her legs filled with a mixture of sputum and blood. You glance up to the monitor as your nurse places a second peripheral IV, and you see an oxygen saturation of 88%, RR of 28, BP of 105/92, HR of 122, and temperature of 99.1. She continues to cough and is barely able to speak due to increased work of breathing. You immediately call for intubation equipment and medications. The intubation goes well with ketamine and rocuronium, despite blood pooling in the oropharynx. The post intubation chest xray demonstrates diffuse infiltrates.
The patient’s husband is brought back, and you start to gather a history as the vitals and patient improve. The husband states the patient began spitting and coughing blood yesterday. She has a history of lupus, for which she sees a rheumatologist. You call her rheumatologist and the medical ICU. Both recommend high-dose corticosteroids.
This patient with SLE developed diffuse alveolar hemorrhage (DAH), one of the many life-threatening complications of this vasculitis. This post will provide a quick overview of vasculitides and the essential emergent complications.
Systemic vasculitides are chronic, inflammatory, autoimmune disorders with multi-organ complications. If not discovered and managed, these diseases cause significant morbidity and mortality. Vasculitides are characterized by inflammatory damage of blood vessels. Diagnosis is difficult due to the multitude of symptoms and often vague patient complaints. Almost all patients have diffuse pain, arthralgia/arthritis, elevated temperature, fatigue, and weight loss. Around 1 in 2000 adults are affected in the U.S., with a predominance of adults over 65 years, though a second peak exists in the 15-30 year age group.1-4
Most cases result from activation of the immune and complement systems, which causes vessel wall damage. This damage leads to stenosis or vessel weakening, resulting in end organ ischemia and/or vessel rupture respectively.3,4
Classification can be broken into two different mechanisms: blood vessel size versus organ system involvement.2,3
If utilizing vasculature size for classification, three classes exist: 1. Large vessel including Giant cell arteritis (GCA) and Takayasu’s arteritis, 2. Medium vessel including polyarteritis nodosa, Buerger’s disease, Kawasaki disease; and 3. Small vessel including Goodpasture’s disease, Wegener’s granulomatosis, microscopic polyangiitis, Churg-Strauss disease, Behçet’s disease, and Henoch-Schonlein purpura.2,4
A second classification system includes the pattern of organ system involvement such as pulmonary-renal, cutaneous, and environmental/foreign antigen exposure.
Systemic Lupus Erythematosus (SLE)
SLE is an autoimmune disease affecting multiple organs and is present in 20-70 per 100,000 people. Women are the predominant patient population (90% of cases), with African Americans also disproportionately affected. Multiple factors including genetics, environment, race, hormones, immunology, and medications are implicated. Ultimately, cellular contents are released as cell death occurs, with resultant formation of autoantibodies that mediate organ specific inflammation. Criteria for diagnosis include four of the following: malar rash, discoid rash, photosensitivity, oral ulcers, non-erosive arthritis, serositis, renal disorder, neurologic disorder, hematologic disorder, immunologic disorder (positive serology for anti-DNA antibody, anti-Sm antibody, or antiphospholipid antibody), or positive antinuclear antibody.2,5
The most common presenting signs include rash, mucositis, and arthritis. Fever, fatigue, and/or weight changes are also common. Skin manifestations are present in 85% of patients. The arthritis of SLE is normally non-erosive and non-deforming; however, the patient’s pain and tenderness are often disproportionately greater than the appearance of the joint(s) would suggest. Ultimately, 75% of patients experience renal involvement, varying from microscopic hematuria and proteinuria to end-stage renal disease, the leading cause of serious morbidity and mortality. New or worsening proteinuria often precedes a renal flare. CNS disease is the second leading cause of morbidity/mortality, with headache the most common manifestation. However, cerebral venous sinus thrombosis, CNS infection, intracranial hypertension, cerebral vasculitis, and organic brain syndrome are also common. Neuropsychiatric manifestations include psychosis, depression, and mental status changes. Patients are predisposed to early onset stroke, seizures, neuropathy, and myelitis. These patients have a significantly increased risk of myocardial infarction before age 40 years due to premature atherosclerosis, vessel inflammation, and increased platelet adhesion. An ECG is essential in SLE patients presenting with chest pain, nausea/vomiting, shortness of breath, tachypnea, and weakness/fatigue. You must not miss an MI in these patients! Hematologic effects include anemia from hemolysis, thrombocytopenia, and leukopenia. Serosal membrane involvement can cause pleural effusions, peritonitis, and pericarditis, which may result in significant pericardial effusion and even tamponade. Pulmonary diseases include pneumonitis, pulmonary hemorrhage, or pulmonary hypertension. Even the gastrointestinal tract is affected, with SLE often causing pancreatitis, mesenteric vasculitis, and hepatitis. 5-7
Multiple airway complications exist, particularly with SLE and polychondritis. Patients can present with upper airway obstruction due to edema of the cricoarytenoid joints. Patients often require fiberoptic intubation with high-dose steroids. These diseases can also cause tracheomalacia, which results from destruction and necrosis of the upper airway cartilage, causing obstruction. Subglottic stenosis from Wegener’s granulomatosis (16% of patients) often requires surgical intervention. Intubation in these patients can be challenging; have multiple back-ups prepared such as bougie, video, fiberoptic, and cricothyrotomy. A “double setup” in the OR is often preferable.8
Lung involvement from infection or the disease itself is common in SLE, systemic sclerosis, Wegener’s, Churg Strauss, and polymyositis. Interstitial lung disease results from lung inflammatory cell infiltration leading to fibrosis, pulmonary hypertension, and respiratory failure. These patients often present with slowly progressing symptoms.9 Diffuse alveolar hemorrhage (DAH) is rare but can be a complication of SLE, antiphospholipid syndrome, systemic vasculitis, Wegener’s granulomatosis, polymyositis, or systemic sclerosis. Early diagnosis and treatment is vital to minimize morbidity and mortality, which is close to 50% if not diagnosed early in the disease course. These patients often present with acute dyspnea, fever, cough, and hemoptysis. The classis triad is hemoptysis, pulmonary infiltrates on imaging, and a significant drop in hemoglobin. However, the classic triad is not always present (< 50%), and patients may present with fever, clouding the picture. The most sensitive findings are anemia (up to 98%) and infiltrates on imaging (up to 85%). Unfortunately, treatments of DAH vs. pneumonia/sepsis are vastly different, with DAH requiring high-dose steroids, cyclophosphamide, local embolization, or plasma exchange. Ultimately, you must consult rheumatology, pulmonology, and critical care and discuss treatment options. Other complications include pleural effusions, intercostal muscle inflammation, arthritis of the thoracic cage joints, and pulmonary embolism.9-11
Inflammation, fibrosis, infiltration, vasculitis, thromboembolism, and coronary atherosclerosis all cause cardiac involvement, ranging from myocardial infarction, heart failure, arrhythmias, malignant hypertension, valvular heart disease, and vascular disease. Acute coronary syndromes are present in a disproportionate number of patients with vasculitis due to accelerated atherosclerosis, inflammation of vascular walls, vasospasm, and increased platelet aggregation. The risk of ACS in women with SLE is 50 times greater when compared to women of the same age!14 An initial diagnosis of pleuritis or pericarditis can be a pitfall in these patients. In a patient with chest pain or shortness of breath, you must obtain an ECG and be wary of missing ACS! Heart failure can be due to infiltration of myocardium as well as from pericardial disease, valvular disease, and conduction disturbance. Treatment for acute heart failure should not vary from other causes. Systemic sclerosis and several other vasculitides can cause hypertensive emergency, often in the setting of a renal crisis concurrently. Treatment requires the use of ACE inhibitors. Conduction disturbances result from altered automaticity, conduction injury, reentry pathways, and fibrosis. Sudden cardiac death can result from these arrhythmias, often due to complete heart block or QT prolongation. Arterial lesions can result from Takayasu’s arteritis, Behçet’s disease, or Giant cell arteritis. These diseases cause inflammation of the vessel wall or aortitis. The abdominal aorta is most commonly involved. Vascular inflammation weakens vessel walls causing rupture or thickening of the vessel and stenosis, resulting in stroke, claudication, TIA, and aortic insufficiency! The particular complication is dependent on the disease and vessel involved, such as Takayasu’s arteritis causing narrowing and obstruction. This may result in ischemic or claudication symptoms. Thromboembolism results from involvement of the lower extremity vasculature. Superficial thrombophlebitis and deep venous thrombosis (DVT) are common, particularly in Behçet’s disease. Have low threshold for DVT US of the lower extremities. Unfortunately vessel thrombosis can also be arterial, resulting in stroke, ACS, and peripheral gangrene.12-15
Just as with cardiovascular disease, neurologic disease is common and due to accelerated atherosclerosis, vasculitis, aneurysm, rupture, infection, and inflammation. Vasculitis of cerebral and/or spinal cord vessels can lead to stroke and neurologic deficit. GCA can cause blindness and TIA, most often in the vertebrobasilar circulation, resulting in gait disturbance, dizziness/vertigo, and vomiting.1,18,19 Takayasu’s arteritis can cause claudication (35%), stroke, and visual disturbances via stenosis of proximal large vessels, and this disease most commonly affects women younger than 40 years. Myelitis can affect focal areas of the spinal cord, resulting in progressive neurologic deficits. Neuropathy is often observed in SLE and polyarteritis nodosa, which may cause peripheral deficits and pain along a nerve distribution. These deficits may begin silently.14-16 Unfortunately SLE has a high predilection for the CNS, often resulting in seizures (11% of patients with SLE) and psychiatric disorders.6,7 Be wary of diagnosing a new psychiatric disorder in a patient with SLE without consulting rheumatology.
SLE, GCA, systemic sclerosis and other vasculitides often cause inflammation of the cornea, sclera, and optic nerve. Patients may present with eye pain, vision changes, red eye, tearing, photophobia, or diplopia.16,17 Particularly in GCA, sudden blindness can be the presenting symptom! Irreversible vision loss can occur in 1/3 of patients, and it may be painless. The only means of preventing further vision loss is high-dose IV steroids. Thus, if a patient presents with a tender temporal artery, nodularity, vision changes, high ESR (> 50), headache, and/or is above age 50 years, start steroids and consult rheumatology. Addition of CRP can improve diagnosis, as sensitivity is 97.5%! Biopsy of the temporal artery is gold standard, and steroids do not affect results as long as biopsy is completed within two to three weeks.17-20
The kidney is one of the most commonly affected organs in patients with vasculitis. With the significant morbidity and mortality in renal disease, checking renal function in patients with vasculitis is vital. Renal deterioration is usually slow and insidious, but acute failure can develop. Nephritic syndrome, renal vascular thrombosis, and rhabdomyolysis can cause acute failure.2,21 Polyarteritis nodosa in particular can cause arterial aneurysms in the renal vasculature, which may rupture.21,26 Systemic sclerosis can cause acute renal crisis, which is often early in the course of the disease (75% present in the first four years of onset).22 These patients often present with headache, vision changes, and elevated blood pressure. Hypertension management requires the use of ACE inhibitors even with renal failure.22 Wegener’s granulomatosis, Churg Strauss, microscopic polyangiitis, and Goodpasture’s syndrome commonly affect the renal system, resulting in significant proteinuria and predisposition to nephritic syndrome and the need for dialysis. If left untreated, renal disease in Wegener’s granulomatosis is correlated with a survival of five months. SLE can result in lupus nephritis with proteinuria (>2g/day), hematuria, and increased creatinine. High dose steroids and cyclophosphamide are the commonly used medications for renal disease/flare in these vasculitides, with dialysis as a last resort if needed.2,20-24
Inflammation and fibrosis can result in perforation, vascular rupture, infection, hemorrhage, and ischemic bowel. These patients commonly present insidiously (“abdominal angina”), often with food aversion and weight loss unlike the classic, acute thromboembolic cause of mesenteric ischemia. Hemorrhage is the most common complication, often due to polyarteritis nodosa (associated with aneurysms), medications, ischemic ulcers, or vascular rupture.26 Enteritis, common in SLE, is another entity presenting with diffuse pain, diarrhea, and nausea/vomiting. These conditions often require high dose steroids. 2,3,20-24
Vasculitis can cause infectious complications via several means: treatment resulting in immunocompromise, anatomic changes that predispose to bacterial/viral tissue entry, and direct effects of the disease. If the patient presents with symptoms/signs concerning for infection such as fever, empiric antibiotics are warranted. Lab findings such as elevated WBC or procalcitonin lack sensitivity in these settings. Opportunistic infections such as Candida, Pneumocystis jiroveci, Legionella, and Mycobacterium can result from chronic immunosuppression. Life-threatening infections include pneumonia, endocarditis, urinary septicemia, and skin infections.2,3,20-24 Particularly in SLE, valvular involvement due to fibrin deposit can result in entities called Libman-Sacks lesions, which predispose the patient to developing endocarditis.7
Cutaneous vasculitis affects superficial epidermal and dermal blood vessels, with palpable purpura as the common manifestation. Erythema nodosum causes tender subcutaneous nodules most commonly on the anterior tibial surface and is due to a hypersensitivity to medication or illness. Up to 50% of cases are idiopathic. Lesions are well-circumscribed, tender to touch, and dark red to purple in hue. NSAIDs are the usual treatment.25 Henoch-Schonlein purpura is a small vessel vasculitis that causes palpable purpura, along with arthritis, GI, and renal manifestations due to vascular IgA immune complexes. It usually affects ages less than 5 years. NSAIDs again are the usual treatment. Polyarteritis nodosa causes palpable purpura and ulceration of the extremities.20-24 At times cyanosis can be seen. Behçet’s disease has multiorgan system involvement, but the classic manifestation includes oral ulcers, genital ulcers, and uveitis. SLE most commonly causes a malar rash, which is raised erythema over the nasal bridge and malar eminences while sparing the nasal-labial folds. Discoid lesions are circular and raised lesions, often found on the face, scalp, and ears.2,3,20-24
Summary and Pearls/Pitfalls
Systemic vasculitis and SLE cause vascular inflammation and fibrosis from immune system involvement. These conditions affect multiple organ systems including the airway, pulmonary, cardiovascular, gastrointestinal, renal, cutaneous, ocular, and neurologic systems. Complications and flares affect all of these systems, along with patients subject to infectious complications. These patients often require immediate consultation with rheumatology and critical care. High-dose steroids are necessary to treat the flare, but beware of infection in these patients. Antibiotics in conjunction with steroids are normally required.
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- Hsu CL, Chen KY, Yeh PS, et al: Outcome and prognostic factors in critically ill patients with systemic lupus erythematosus: a retrospective study. Crit Care 9: R177, 2005.
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- de Prost N, Parrot A, Picard C, et al: Diffuse alveolar hemorrhage: factors associated with in-hospital and long-term mortality. Eur Respir J. Epub Oct 19, 2009.
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- Miller N: Visual manifestations of temporal arteritis. Rheum Dis Clin North Am 2001; 27: pp. 781-797.
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- Teixeira L, Mahr A, Berezné A, et al: Scleroderma renal crisis, still a life-threatening complication. Ann N Y Acad Sci 1108: 249, 2007.
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