Diagnostic Approach
There are lots of challenges with diagnosing vasculitis. First, the signs and symptoms of vasculitis could be minimal or wide spread depending on the number of organ systems involved (1). Second, there are many other illnesses that resemble the clinical manifestation of vasculitis (1). Third, clinicians need to differentiate between primary and secondary vasculitis (1). Lastly, there are nearly 20 types of primary vasculitis (1). Clinicians must follow a rational approach to evaluate patients who are suspected of having vasculitis. The general diagnostic approach can be summarized with these 5 questions:
1) “Is this a condition that could mimic the presentation of vasculitis?” (1)
2) “Is there a secondary underlying cause?” (1)
3) “What is the extend of vasculitis?” (1)
4) “How do I confirm the diagnosis of vasculitis?” (1)
5) “What specific type of vasculitis is this?” (1)
Step 1: Rule out other conditions that resemble vasculitis
Several medical conditions mimic the clinical presentations of vasculitis and must be considered for differential diagnosis. Infection and vasculitis share many similar signs and symptoms: fever, muscle pain, joint pain, malaise, weight loss, normochromic normocytic anemia, and elevated white blood cell count, platelets, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) (1). It is essential to perform infection screen in all patients with suspected vasculitis, especially those experiencing systemic inflammation. Other than infections, there are several other conditions that also present in similar fashion as vasculitis (Table 1.)
Table 1. Medical conditions that resemble vasculitis. Referenced from (1-2).
Infections
Bacterial endocarditis
Disseminated gonococcal infection
Pulmonary histoplasmosis
Coccidiodomycosis
Syphilis
Lyme disease
Rocky mountain spotted fever
Whipple’s disease
Coagulopathies / thombotic microangiopathies
Antiphospholipid antibody syndrome
Thrombotic thrombocytopenic purpura
Sickle cell disease
Atheroembolic disease
Embolisation from atrial myxoma
Cholesterol emboli from atheroma
Non-inflammatory vessel wall disorders
Amyloidosis
Survy
Antiglomerular basement membrane disease (Goodpasture’s syndrome)
Step 2: Rule out secondary underlying causes
Although some infections resemble vasculitis, certain infections can lead to the development of vasculitis (1). These infections include hepatitis B, hepatitis C, human immunodeficiency virus (HIV), mycobacteria, and syphilis (1). If an underlying infection is present and not recognized, the use of immunosuppressant therapy could lead to fatal consequences (1).
Inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, Sjogren’s syndrome, irritable bowel disease, and sarcoidosis are also secondary causes of vasculitis (1). In addition, certain types of malignancies including hematological, solid tumor, and lung cancer may also cause vasculitis (1). Majority of secondary vasculitis are extremely rare except for those associated with rheumatoid arthritis (1). In the case of vasculitis secondary to rheumatoid arthritis, vasculitis is seldom the initial presentation of this inflammatory disease (1).
Vasculitis may also be a complication of certain medication therapy. The most frequently implicated drug is propylthiouracil, an anti-thyroid medication (3). Other agents reported to cause drug-induced vasculitis include anti-tumor necrosis factor-alpha agents, sulfasalazine, minocycline, hydralazine, and D-penicillamine (3). To diagnose drug-induced vasculitis, there needs to be a clear temporal-relationship between the onset of symptoms and administration of the implicated medication (3).
Step 3: Evaluate the extend of vasculitis
Evaluation of organ involvement is crucial for the assessment of vasculitis. Many signs and symptoms of vasculitis are not as obvious, therefore a thorough history, physical exam, diagnostic imaging, blood tests are often required to assess the extent of involvement (1). If vital organs such as the kidney, lung, or heart are threatened, aggressive treatment therapy may be required to prevent organ failure (1).
Step 4: Confirm the diagnosis of vasculitis
Tissue biopsy is the gold standard for diagnosis of vasculitis. Common sites of biopsy include the skin, lung, kidney, artery, muscle, and nasal mucosa (1). In certain large or medium vessel vasculitis, angiograms may be performed instead of biopsy because it may be impossible to obtain tissue sample (1).
Step 5: Identify the specific type of vasculitis
Once a diagnosis is made, determining the specific type of vasculitis will guide clinicians with choosing the appropriate treatment. Certain types of vasculitis will resolve spontaneously and require only symptomatic treatment, whereas other types of vasculitis require aggressive cytotoxic and glucocorticoid agents (3). To determine the specific type of vasculitis, there are many laboratory tests and procedures a clinician will utilize in clinical practice (Table 2). The histological patterns from biopsy may also guide clinicians with differentiating between different types of vasculitis.
Table 2. Common lab tests and procedures utilized during differential diagnosis of vasculitis. Referenced from (1-2).
Step 0: Basic evaluation
Complete blood count (CBC)
Coagulation studies
Renal function tests
Liver function tests
Erythrocyte sedimentation rate (ESR)
C-reactive protein (CRP)
Step 1 and 2: Rule out vasculitis “mimics” and secondary causes
Blood culture
Echocardiogram
Hepatitis B screening
Hepatitis C screening
HIV test
Antinuclear antibody (ANA)
Antiphospholipid antibodies
Antiglomerular basement membrane antibody (Anti-GMB)
Step 3: Evaluate the extend of vasculitis
Urinalysis
Chest radiography
Nerve conduction studies
Electromyography
Step 4: Confirm the diagnosis of vasculitis
Biopsy
Angiogram
Step 5: Identify the specific type of vasculitis
Antineutrophile cytoplasmic antibodies (ANCA)
Cryoglobulin
Complement levels
Eosinophil counts
IgE levels
Specific biopsy findings
References
1. Suresh E. Diagnostic approach to patients with suspected vasculitis. Postgrad Med J. 2006 Aug;82(970):483-8.
2. Langford CA, Fauci AS. Chapter 326. The Vasculitis Syndromes. In: Fauci AS, Kasper DL, Jameson JL, Longo DL, Hauser SL, eds. Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012. http://www.accesspharmacy.com.proxy.lib.uwaterloo.ca/content.aspx?aID=9138083. Accessed April 1, 2013.
3. Gao Y, Zhao MH. Review article: Drug-induced anti-neutrophil cytoplasmic antibody-associated vasculitis. Nephrology (Carlton). 2009 Feb;14(1):33-41.
1) “Is this a condition that could mimic the presentation of vasculitis?” (1)
2) “Is there a secondary underlying cause?” (1)
3) “What is the extend of vasculitis?” (1)
4) “How do I confirm the diagnosis of vasculitis?” (1)
5) “What specific type of vasculitis is this?” (1)
Step 1: Rule out other conditions that resemble vasculitis
Several medical conditions mimic the clinical presentations of vasculitis and must be considered for differential diagnosis. Infection and vasculitis share many similar signs and symptoms: fever, muscle pain, joint pain, malaise, weight loss, normochromic normocytic anemia, and elevated white blood cell count, platelets, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) (1). It is essential to perform infection screen in all patients with suspected vasculitis, especially those experiencing systemic inflammation. Other than infections, there are several other conditions that also present in similar fashion as vasculitis (Table 1.)
Table 1. Medical conditions that resemble vasculitis. Referenced from (1-2).
Infections
Bacterial endocarditis
Disseminated gonococcal infection
Pulmonary histoplasmosis
Coccidiodomycosis
Syphilis
Lyme disease
Rocky mountain spotted fever
Whipple’s disease
Coagulopathies / thombotic microangiopathies
Antiphospholipid antibody syndrome
Thrombotic thrombocytopenic purpura
Sickle cell disease
Atheroembolic disease
Embolisation from atrial myxoma
Cholesterol emboli from atheroma
Non-inflammatory vessel wall disorders
Amyloidosis
Survy
Antiglomerular basement membrane disease (Goodpasture’s syndrome)
Step 2: Rule out secondary underlying causes
Although some infections resemble vasculitis, certain infections can lead to the development of vasculitis (1). These infections include hepatitis B, hepatitis C, human immunodeficiency virus (HIV), mycobacteria, and syphilis (1). If an underlying infection is present and not recognized, the use of immunosuppressant therapy could lead to fatal consequences (1).
Inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, Sjogren’s syndrome, irritable bowel disease, and sarcoidosis are also secondary causes of vasculitis (1). In addition, certain types of malignancies including hematological, solid tumor, and lung cancer may also cause vasculitis (1). Majority of secondary vasculitis are extremely rare except for those associated with rheumatoid arthritis (1). In the case of vasculitis secondary to rheumatoid arthritis, vasculitis is seldom the initial presentation of this inflammatory disease (1).
Vasculitis may also be a complication of certain medication therapy. The most frequently implicated drug is propylthiouracil, an anti-thyroid medication (3). Other agents reported to cause drug-induced vasculitis include anti-tumor necrosis factor-alpha agents, sulfasalazine, minocycline, hydralazine, and D-penicillamine (3). To diagnose drug-induced vasculitis, there needs to be a clear temporal-relationship between the onset of symptoms and administration of the implicated medication (3).
Step 3: Evaluate the extend of vasculitis
Evaluation of organ involvement is crucial for the assessment of vasculitis. Many signs and symptoms of vasculitis are not as obvious, therefore a thorough history, physical exam, diagnostic imaging, blood tests are often required to assess the extent of involvement (1). If vital organs such as the kidney, lung, or heart are threatened, aggressive treatment therapy may be required to prevent organ failure (1).
Step 4: Confirm the diagnosis of vasculitis
Tissue biopsy is the gold standard for diagnosis of vasculitis. Common sites of biopsy include the skin, lung, kidney, artery, muscle, and nasal mucosa (1). In certain large or medium vessel vasculitis, angiograms may be performed instead of biopsy because it may be impossible to obtain tissue sample (1).
Step 5: Identify the specific type of vasculitis
Once a diagnosis is made, determining the specific type of vasculitis will guide clinicians with choosing the appropriate treatment. Certain types of vasculitis will resolve spontaneously and require only symptomatic treatment, whereas other types of vasculitis require aggressive cytotoxic and glucocorticoid agents (3). To determine the specific type of vasculitis, there are many laboratory tests and procedures a clinician will utilize in clinical practice (Table 2). The histological patterns from biopsy may also guide clinicians with differentiating between different types of vasculitis.
Table 2. Common lab tests and procedures utilized during differential diagnosis of vasculitis. Referenced from (1-2).
Step 0: Basic evaluation
Complete blood count (CBC)
Coagulation studies
Renal function tests
Liver function tests
Erythrocyte sedimentation rate (ESR)
C-reactive protein (CRP)
Step 1 and 2: Rule out vasculitis “mimics” and secondary causes
Blood culture
Echocardiogram
Hepatitis B screening
Hepatitis C screening
HIV test
Antinuclear antibody (ANA)
Antiphospholipid antibodies
Antiglomerular basement membrane antibody (Anti-GMB)
Step 3: Evaluate the extend of vasculitis
Urinalysis
Chest radiography
Nerve conduction studies
Electromyography
Step 4: Confirm the diagnosis of vasculitis
Biopsy
Angiogram
Step 5: Identify the specific type of vasculitis
Antineutrophile cytoplasmic antibodies (ANCA)
Cryoglobulin
Complement levels
Eosinophil counts
IgE levels
Specific biopsy findings
References
1. Suresh E. Diagnostic approach to patients with suspected vasculitis. Postgrad Med J. 2006 Aug;82(970):483-8.
2. Langford CA, Fauci AS. Chapter 326. The Vasculitis Syndromes. In: Fauci AS, Kasper DL, Jameson JL, Longo DL, Hauser SL, eds. Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012. http://www.accesspharmacy.com.proxy.lib.uwaterloo.ca/content.aspx?aID=9138083. Accessed April 1, 2013.
3. Gao Y, Zhao MH. Review article: Drug-induced anti-neutrophil cytoplasmic antibody-associated vasculitis. Nephrology (Carlton). 2009 Feb;14(1):33-41.