139: Systemic Necrotizing Arteritis Flashcards
What is the broad definition of vasculitis?
Vasculitis is defined broadly as inflammation of blood vessels, which can affect a single organ, particularly the skin, and is characterized by inflammation being a major, but not the only, pathologic process.
How are systemic vasculitides classified?
Systemic vasculitides are classified primarily by the size of the predominant vessel involved (small, medium, or large) and then further subdivided or grouped as appropriate.
What are the most widely used criteria for classifying vasculitis?
The most widely used criteria for classifying vasculitis include the classification criteria of the American College of Rheumatology and the disease definitions of the Chapel Hill Consensus Conference.
What is leukocytoclastic vasculitis?
Leukocytoclastic vasculitis does not refer to a specific disease but is a pathologic description that often, but not always, applies to vasculitis in the skin or other organs.
What demographic factors influence the occurrence of different forms of vasculitis?
Different forms of vasculitis show demographic variations, such as Takayasu arteritis being more common in females, Kawasaki disease primarily affecting young children, and Giant cell arteritis being limited to older adults.
What is the significance of demographic differences in vasculitides?
Demographic differences among vasculitides are of scientific interest as they provide clues to etiology and can assist in developing a differential diagnosis.
What role do genetic risk factors play in the epidemiology of vasculitides?
Vasculitides with strong regional variation have genetic risk factors in the HLA region, although these epidemiologic tendencies do not fully exclude the diagnosis of a specific form of vasculitis in any individual.
What is a common manifestation of vasculitis?
Skin disease.
What is the demographic characteristic of idiopathic vasculitis?
Considered rare and classified as ‘orphan’ diseases in the US.
Which demographic group is more affected by Takayasu arteritis?
Females more than males.
What age group is primarily affected by Kawasaki disease?
Young children.
What is a notable characteristic of giant cell arteritis?
It is limited to older adults.
In which regions is Behçet disease more common?
Countries in the Eastern Mediterranean, Japan, and Korea.
What factors influence the appearance of cutaneous vasculitis?
The appearance of cutaneous vasculitis reflects:
- Size and depth of the involved vessels
- Severity of inflammation and red blood cell extravasation
- Density of damaged vessels and resulting tissue destruction
How does vasculitis caused by immune complexes typically present on the skin?
Vasculitis caused by immune complexes in the dermal microvasculature often first appears as a tiny, bright red circle due to red blood cell extravasation. It becomes palpable once it reaches about 2 mm in diameter, and a high density of such lesions may produce areas of confluent purpura and/or central necrosis or ulceration.
What are the common presentations of small-vessel vasculitis in the skin?
Common presentations of small-vessel vasculitis in the skin include:
- Palpable purpura (classic presentation)
- Nonpalpable purpura (round or angular borders)
- Papules
- Urticarial lesions
- Nodules of different sizes and depths
- Bullous lesions
- Ulcers
- Edema in and near visibly affected areas
What symptoms may accompany purpura or livedo in vasculitis?
Purpura or livedo may be asymptomatic or produce pain that is often described as stinging or burning, but sometimes as itching. Nodules and ulcers are usually painful. Severe pain in a region not affected by nodules, ulcers, or confluent purpura should raise suspicion for neuropathy or inflammatory arthritis.
What are the two pathways involved in small-vessel vasculitides?
The two pathways involved in small-vessel vasculitides are:
1. Immune complex deposition: Immune complexes can form in response to microbes, autoantigens, or drugs, leading to activation of neutrophils and necrotizing vasculitis.
2. Non-immune complex mediated pathology: This likely involves ANCA, which activates neutrophils and contributes to necrotizing vasculitis.
What role do T cells play in large-vessel vasculitides?
In large-vessel vasculitides, T cells activate macrophages in the walls of large arteries. In conditions like Giant Cell Arteritis (GCA), IL-17-secreting (Th17) and interferon-γ-secreting (Th1) cells are prominent, and T cells enter the artery wall via the vasa vasorum, keeping the endothelium intact.
What is the significance of genetic factors in vasculitis?
Genetics appear to contribute modestly to ANCA-associated vasculitis, with identified genes associated with the specificity of the antibody to PR3 or MPO. In large-vessel vasculitides like GCA and Takayasu arteritis, genetics also contributes modestly via the HLA locus, indicating a potential genetic predisposition to these diseases.
What initial questions should be addressed when diagnosing vasculitis with skin lesions?
When a patient presents with skin lesions concerning for possible vasculitis, the following questions should be sought quickly:
1. Is the lesion due to vasculitis? This is often determined by skin biopsy, which is indicated in many cases of palpable purpura or other lesions when a diagnosis of vasculitis is not otherwise easily established.
What is the initial appearance of vasculitis caused by immune complexes in the dermal microvasculature?
It often appears as a tiny, bright red circle due to red blood cell extravasation.
What happens to lesions caused by immune complexes as they grow?
They become palpable once they reach about 2 mm in diameter.
What is a classic presentation of small-vessel vasculitis in the skin?
Palpable purpura.
What are some other presentations of small-vessel vasculitis?
Nonpalpable purpura, papules, urticarial lesions, nodules, bullous lesions, ulcers, and edema.
What symptoms may purpura or livedo produce?
They may be asymptomatic or produce pain described as stinging, burning, or itching.
What should severe pain in a region not affected by nodules or ulcers raise suspicion for?
Neuropathy or inflammatory arthritis.
What are the known causes of vasculitis?
Infection-related vasculitis and drug-induced vasculitis are known causes; most other types have unknown etiology.
What types of vasculitis are often diagnosed based on clinical grounds alone?
IgA Vasculitis (Henoch-Schönlein) in children and Behçet disease.
What findings are typically sought in a biopsy for small-vessel vasculitis?
Fibrinoid necrosis, extravasation of erythrocytes, and neutrophils with nuclear debris.
What is the role of acute phase reactants in diagnosing vasculitis?
Acute phase reactants such as ESR.
What is the importance of a thorough review of systems (ROS) in diagnosing vasculitis?
It helps identify organ system involvement and assess the overall severity of illness.
What should be assessed during a physical examination for suspected vasculitis?
Vital signs, eye inspection, nasal cavity visualization, lymphadenopathy, and joint examination.
What role does medical history play in diagnosing vasculitis?
It helps identify other diseases that may have vasculitis as a component or cause skin lesions that mimic vasculitis.
What are some concerning symptoms that may indicate urgent referral in suspected vasculitis cases?
New visual impairment, painful or red eyes, hoarseness or stridor, and hearing loss.
What is the significance of biopsy in diagnosing vasculitis?
It helps confirm the type of vasculitis and establish a diagnosis other than vasculitis.
What additional findings can help establish a specific diagnosis of vasculitis?
Additional findings that can help establish a specific diagnosis include results from specialized laboratory tests, medical interviews, physical examinations, and radiographic imaging.
What is the recommended diagnostic approach for a patient suspected of having vasculitis with skin lesions?
A skin biopsy is often indicated, especially in cases of palpable purpura or other lesions when a diagnosis of vasculitis is not otherwise easily established.
What is the role of specialized laboratory tests in diagnosing vasculitis?
They can provide additional findings that help establish a specific diagnosis, though results may take several days.
How can the severity of symptoms guide the treatment approach in vasculitis?
Some causes of cutaneous vasculitis require no treatment, while others may need immediate hospitalization for therapy.
What critical questions should be asked if a diagnosis of vasculitis is obtained?
If a diagnosis of vasculitis is obtained, it is imperative to ask: 1. Is it possible to make a diagnosis of a specific type of vasculitis for the patient? 2. Does the patient need immediate treatment and/or hospitalization?
How can a clinician limit the types of vasculitis under consideration during diagnosis?
A clinician can limit the types of vasculitis under consideration by obtaining a thorough medical history and conducting a detailed physical examination. This approach helps prioritize the ordering of diagnostic tests and avoids unnecessary testing.
What are the typical features of acute neutrophilic vasculitis that can be identified through biopsy?
The typical features of acute neutrophilic vasculitis that can be identified through biopsy include:
1. Fibrinoid necrosis
2. Extravasation of erythrocytes
3. Extravasation of neutrophils with release of nuclear debris (leukocytoclasia)
4. Presence of immune deposits
What symptoms may indicate that a patient’s vasculitis is not limited to the skin?
Relatively mild symptoms, such as mild arthralgias, can be a clue that the disease is not limited to the skin. More concerning symptoms, like hemoptysis or painful red eyes, may indicate more severe systemic involvement.
What factors should be considered in a patient’s medical history when suspecting vasculitis?
When suspecting vasculitis, it is critical to consider factors such as:
1. Full medical history
2. Medication use (prescription, nonprescription, and herbal)
3. Exposure to toxins or infectious diseases
4. Recent travel and sick contacts
5. Risks for sexually transmitted diseases
What additional features, when seen with leukocytoclastic vasculitis, are suggestive of specific diseases?
Certain features that are strongly suggestive of particular diseases when seen in addition to LCV include:
| Disease | Suggestive Features |
|———|———————|
| Granulomatosis with polyangiitis | Extravascular granulomas with geographic necrosis |
| Eosinophilic granulomatosis with polyangiitis | Eosinophil-rich extravascular granulomas |
| IgA vasculitis (Henoch-Schönlein) | Predominance of IgA over IgG/IgM by IF |
| Drug hypersensitivity | N/A |
| Postinfectious vasculitis | N/A |
| Cryoglobulinemia | N/A |
| Vasculitis secondary to SLE, Sjögren syndrome, or RA | Presence of deposits of IgG, IgM, and/or complement |
What are avascular granulomas?
Avascular granulomas are a type of granuloma that lacks a vascular component.
What is the hallmark of IgA vasculitis (Henoch-Schönlein)?
Predominance of IgA over IgG/IgM by immunofluorescence (IF).
What is drug hypersensitivity?
A hypersensitivity reaction to a drug.
What is postinfectious vasculitis?
Vasculitis that occurs after an infection.
What is cryoglobulinemia?
A condition characterized by the presence of cryoglobulins, which are immune complexes that precipitate in the cold.
What indicates vasculitis secondary to SLE, Sjögren syndrome, or RA?
Presence of deposits of IgG, IgM, and/or complement.
What is the role of acute phase reactants in diagnosing vasculitis?
Acute phase reactants such as ESR and CRP may be elevated in vasculitis, but their sensitivity and specificity are not particularly high.
What is the importance of autoimmune serologies in the diagnosis of vasculitis?
Testing for autoantibodies is critical in establishing the type of vasculitis present, but serologic testing alone is never diagnostic.
What is the predictive value of positive ANCA testing in diagnosing vasculitis?
The predictive value depends on the clinical setting; higher specificity is seen for biopsy-proven vasculitis.
How does the processing of tissue differ for conventional histopathology and immunofluorescence testing?
It requires either 2 biopsies or a single biopsy to be divided before processing, which may damage the tissue.
What is the histologic finding of leukocytoclastic vasculitis (LCV) helpful for?
It is helpful in confirming the diagnosis of vasculitis but does not establish an etiology.
What microscopy features may suggest but not diagnose vasculitis?
Leukocytoclasia without fibrinoid necrosis.
What is a nonspecific finding in vasculitis diagnosis?
A perivascular infiltrate, particularly if it consists predominantly of mononuclear cells or even if it is neutrophilic.
What features are strongly suggestive of specific diseases when seen in addition to LCV?
Extravascular granulomas with geographic necrosis for Granulomatosis with polyangiitis and eosinophil-rich extravascular granulomas for Eosinophilic granulomatosis with polyangiitis.
What is the significance of IgA predominance in IgA vasculitis?
It is suggestive but not diagnostic.
How is vasculitis often diagnosed?
By biopsy of other organs such as kidney, lung, muscle, or peripheral nerve.
Why are kidney or lung biopsies more likely to show pathology diagnostic of a particular disease compared to skin biopsies?
Because they are more likely to reveal specific pathological changes associated with vasculitis.
What is the importance of renal function tests in vasculitis?
They are crucial because renal disease is common in many vasculitides and often asymptomatic until end-stage renal failure occurs.
What should be performed on all patients suspected of having vasculitis?
Urinalysis (both dipstick and microscopic examinations).
What does the presence of blood on routine dipstick tests indicate?
It needs to be followed by an examination for RBC casts.
What is critical to estimate the glomerular filtration rate (GFR) in vasculitis?
Serum creatinine.
What are the common findings in small-vessel vasculitis affecting the glomeruli?
Hematuria, accompanied by RBC casts and proteinuria.
What is the role of liver function tests (LFTs) in diagnosing vasculitis?
They provide a baseline if potentially hepatotoxic drugs are to be used for treatment but are of limited value in diagnosing vasculitis.
What should be ordered on all patients suspected of having vasculitis?
A complete blood count (CBC).
What does severe anemia indicate in the context of vasculitis?
It is a clue to serious gastrointestinal involvement from various forms of vasculitis.
What do elevated ESR and CRP indicate in vasculitis?
They indicate inflammation but are not particularly helpful in establishing or excluding a diagnosis of vasculitis.
What is the significance of testing for autoantibodies in vasculitis?
It is critical for establishing the type of vasculitis present, but serologic testing alone is never diagnostic.
What percentage of patients with microscopic polyangiitis test positive for ANCA?
90%.
What does modern ANCA testing include?
IF staining of neutrophils for c-ANCA or p-ANCA patterns and ELISAs for specific autoantigens (PR3 and MPO).
What is the significance of a biopsy showing fibrinoid necrosis and leukocytoclasia in a patient with suspected vasculitis?
These findings are typical features of acute neutrophilic vasculitis and help confirm the diagnosis of vasculitis.
A patient with vasculitis presents with hematuria and RBC casts. What type of vasculitis is most likely?
Small-vessel vasculitis affecting the glomeruli is most likely, as it is associated with hematuria and RBC casts.
What is the significance of a biopsy showing extravascular granulomas with geographic necrosis?
This finding is strongly suggestive of granulomatosis with polyangiitis.
What is the significance of Antinuclear Antibodies (ANA) in diagnosing SLE and Sjögren syndrome?
ANA is extremely sensitive (>95%) for SLE but not specific.
How does rheumatoid factor (RF) relate to the diagnosis of vasculitis?
Rheumatoid factor is rarely useful in establishing the diagnosis or specific type of vasculitis.
What is the role of cryoglobulins in vasculitis?
Cryoglobulins are immune complexes that precipitate in the cold and are associated with clinical syndromes where vasculitis is prominent.
What laboratory tests are useful for assessing complement levels in vasculitis?
C3 and C4 levels are usually sufficient for assessing patients with cutaneous vasculitis.
What infectious diseases should patients with suspected vasculitis be screened for?
Patients should be screened for hepatitis B and C infections.
What is the classification of vasculitides according to the size of the vessel involved?
Vasculitis can be classified into small, medium, and large vessel types.
What is the etiology of most types of vasculitis?
The etiology of most types of vasculitis is unknown, except in cases of infections such as hepatitis.
How long should a skin lesion be clinically apparent before considering a biopsy?
It is generally recommended to biopsy a skin lesion that has been clinically apparent for 48 hours.
What is the absolute eosinophil count used for in relation to eosinophilic granulomatosis with polyangiitis?
It is used to differentiate untreated patients with eosinophilic granulomatosis with polyangiitis from those with asthma and atopy.
What percentage of microscopic polyangiitis presents with ANCA?
ANCA presents in approximately 70% of cases of microscopic polyangiitis.
What is the most common cause of cryoglobulinemia?
Cryoglobulinemia most commonly results from chronic infection with the hepatitis C virus.
What is the significance of antinuclear antibodies (ANA) in diagnosing SLE or Sjögren syndrome?
ANA is extremely sensitive (>95%) for SLE but not specific.
What percentage of Sjögren syndrome patients test positive for rheumatoid factor, anti-Ro (SSA), or anti-La (SSB) antibodies?
80%.
How useful is rheumatoid factor in establishing the diagnosis of vasculitis?
Rheumatoid factor is rarely useful in establishing the diagnosis or specific type of vasculitis.
What is cryoglobulinemia commonly associated with?
Chronic infection with hepatitis C virus, RA, SLE, Sjögren syndrome, and hematologic malignancies.
What does the complement test CH50 measure?
Total hemolytic complement, but it is cumbersome and suffers from variability between laboratories.
What is the clinical significance of C3 and C4 complement levels in vasculitis?
C3 and C4 are usually sufficient for assessing patients with cutaneous vasculitis.
What infections should patients with suspected vasculitis affecting small or medium-sized arteries be screened for?
Hepatitis B and C infections.
What is the relationship between endocarditis and vasculitis?
Endocarditis can cause true vasculitis through deposition of immune complexes.
What is the recommended time frame to biopsy a clinically apparent skin lesion?
Generally recommended to biopsy after 24 hours.
What is the etiology of most types of vasculitis?
Most types of vasculitis have an unknown etiology, except for certain conditions like infections.
A patient with suspected vasculitis has a positive ANCA test. What additional findings would increase the specificity for ANCA-associated vasculitis?
Positive tests for anti-PR3 or anti-MPO ANCA increase specificity for ANCA-associated vasculitis.
A patient with suspected vasculitis has low C4 levels but normal C3 levels. What type of vasculitis is this finding most consistent with?
This finding is most consistent with cryoglobulinemic vasculitis.
What is the significance of a positive rheumatoid factor (RF) in a patient with suspected vasculitis?
A positive RF is seen in 70% of rheumatoid arthritis cases and >95% of rheumatoid vasculitis cases.
What is the role of ANCA testing in diagnosing vasculitis, and what are its limitations?
ANCA testing is critical for diagnosing ANCA-associated vasculitis but is not diagnostic on its own.
A patient with suspected vasculitis has a history of chronic hepatitis C infection. What type of vasculitis should be considered?
Cryoglobulinemic vasculitis should be considered.
What is the recommended approach for a patient with suspected vasculitis and normal ESR and CRP values?
Active vasculitis can have normal ESR and CRP values, so clinical judgment and additional diagnostic tests are necessary.
What are the associations of cocaine and methamphetamine with cutaneous vasculitis?
Cocaine and methamphetamine are associated with cutaneous vasculitis and/or arterial vasospasm.
What is the role of levamisole in relation to cocaine use?
Levamisole is an antihelminthic and immunomodulatory agent that is often an adulterant in illegal cocaine.
What imaging is recommended for patients suspected of having vasculitis?
A chest radiograph is recommended for screening any patient suspected of having vasculitis.
How is sinus involvement assessed in granulomatosis with polyangiitis?
CT of the sinuses is useful for diagnosis, staging, and restaging.
What is the central role of angiography in vasculitis?
Angiography plays a central role in the diagnosis and management of large- and medium-vessel vasculitis.
What is the utility of nerve conduction studies and EMG in vasculitis?
Nerve conduction studies and EMG should not replace a full neurologic examination.
What is the significance of audiology testing in patients with ANCA-associated vasculitis?
Audiology testing is used to diagnose and distinguish between conductive and sensorineural hearing loss.
What drugs are associated with cutaneous vasculitis and arterial vasospasm?
Cocaine and methamphetamine.
What nasal condition can result from cocaine use?
Destructive nasal disease as severe as that seen in ANCA-associated vasculitis.
What is levamisole and its relevance to cocaine?
An antihelminthic and immunomodulatory agent, it is an adulterant of illegal cocaine.
What are the characteristics of vasculopathy associated with levamisole?
Destructive vasculopathy/vasculitis with gangrenous lesions.
What imaging is recommended for patients suspected of having vasculitis?
Chest radiograph.
When is a chest CT indicated in suspected vasculitis cases?
For patients with pulmonary symptoms.
What is the role of CT of the neck/trachea in vasculitis diagnosis?
It is an adjunct to direct laryngoscopy if subglottic stenosis is suspected.
Why is sinus imaging important in granulomatosis with polyangiitis?
Sinus involvement is extremely common in this condition.
What is the utility of CT of the sinuses in vasculitis?
CT of the sinuses is useful for diagnosis, staging, and restaging.
What is a chest radiograph?
A chest radiograph is an imaging technique used to visualize the structures within the chest.
When is a chest CT indicated in suspected vasculitis cases?
For patients with pulmonary symptoms, as plain radiographs may not detect small nodules or infiltrates.
What is the utility of CT of the sinuses in vasculitis?
Useful for diagnosis, staging, and restaging.
What is the central role of angiography in vasculitis?
In the diagnosis and management of large- and medium-vessel vasculitis.
What is the limitation of conventional catheter-based dye angiography?
It does not allow visualization of most small vessels despite having the highest resolution.
What is the purpose of nerve conduction studies and EMG in vasculitis?
To provide objective evidence of neuropathy and distinguish between compressive and non-compressive neuropathy.
When is audiology testing indicated in patients with ANCA-associated vasculitis?
Baseline audiogram is advised for all patients with an established diagnosis of ANCA-associated vasculitis.
What type of hearing loss is commonly missed in small-vessel vasculitis?
Sensorineural hearing loss.
What imaging modality is recommended for a patient with granulomatosis with polyangiitis presenting with subglottic stenosis?
CT of the neck/trachea is recommended as an adjunct to direct laryngoscopy if subglottic stenosis is suspected.
What should be considered in the differential diagnosis for a patient with vasculitis and a history of drug use, including methamphetamines?
Drug-induced vasculitis should be considered, as methamphetamines are associated with cutaneous vasculitis and/or arterial vasospasm.
What is the role of CT angiography in the diagnosis of vasculitis?
CT angiography is used to establish the type of vasculitis (e.g., multiple aneurysms in polyarteritis nodosa) and evaluate arterial supply in cases of gangrene.
What should be considered for a patient with vasculitis presenting with destructive nasal disease and a history of cocaine use?
Levamisole-adulterated cocaine use should be considered, as it is associated with destructive vasculopathy and positive tests for both anti-MPO and anti-PR3 ANCA.
What are the common clinical features of Microscopic Polyangiitis (MPA)?
- Small, sometimes medium-sized vessels
- Pauci-immune glomerulonephritis (majority)
- Pulmonary hemorrhage
- Peripheral and cranial neuropathy
- Musculoskeletal symptoms
- Constitutional symptoms common
- Skin lesions: Palpable purpura is the most common lesion
- Rare features: vasculitis of medium-sized vessels leading to digital ischemia, subcutaneous nodules, livedo reticularis, deep ulcers
- Cardiac and GI involvement are less common
- Positive ANCA, usually with specificity for antibodies to myeloperoxidase (MPO)
What distinguishes Granulomatosis with Polyangiitis (GPA) from Microscopic Polyangiitis (MPA)?
- All features of MPA plus symptoms due to necrotizing granulomatous inflammation
- Chronic inflammation of the upper airway (90% of cases)
- Common manifestations include cavitary pulmonary nodules, orbital pseudotumor, and subglottic stenosis
- More frequent eye involvement (scleritis and episcleritis)
- ANCA positivity in multiple organ involvement, primarily C-ANCA/anti-PR3
What are the unique features of Eosinophilic Granulomatosis with Polyangiitis (EGPA)?
- History of asthma (often severe or poorly controlled)
- Blood eosinophilia
- Common nasal polyps
- Constitutional symptoms
- Pulmonary infiltrates on chest imaging (eosinophilic pneumonia)
- Most common presentation of severe vasculitis is acute peripheral neuropathy
- Cutaneous disease is more common than in systemic granulomatous vasculitis or MPA, with 50% of lesions being palpable and nonpalpable purpura
How is vasculitis associated with other autoimmune diseases characterized?
- Mostly small, some medium-sized vessels
- Common in systemic lupus (10% to 36%) and Sjögren syndrome (10%)
- Rare in rheumatoid arthritis
- Clinical manifestations include peripheral neuropathy, GI ischemia, CNS disease, and other rare visceral involvement
- Inflammatory bowel disease and relapsing polychondritis can involve small, medium, or large vessels
What is the relationship between malignancy and vasculitis?
- Vasculitis can be temporally associated with a solid malignancy
- Small-vessel vasculitis of the skin is the most common type
- Remission of vasculitis after surgical resection of the tumor (without other therapy) suggests a causal relationship
What are the main characteristics of microscopic polyangiitis?
It involves small to medium-sized vessels, pauci-immune glomerulonephritis, pulmonary hemorrhage, peripheral and cranial neuropathy, musculoskeletal symptoms, constitutional symptoms, and common skin lesions like palpable purpura.
What is a common skin lesion associated with microscopic polyangiitis?
Palpable purpura is the most common lesion.
What distinguishes granulomatosis with polyangiitis from microscopic polyangiitis?
Granulomatosis with polyangiitis includes symptoms due to necrotizing granulomatous inflammation and chronic inflammation of the upper airway.
What are common pulmonary manifestations of granulomatosis with polyangiitis?
Cavitary pulmonary nodules are common and significant.
What unique features are associated with eosinophilic granulomatosis with polyangiitis?
History of asthma, blood eosinophilia, and nasal polyps are unique features.
What is the most common presentation of severe eosinophilic granulomatosis with polyangiitis?
Acute peripheral neuropathy is the most common presentation.
In which autoimmune diseases is vasculitis relatively common?
Vasculitis is relatively common in systemic lupus and Sjögren syndrome.
What type of vasculitis is most commonly associated with malignancy?
Small-vessel vasculitis of the skin is the most common type associated with malignancy.
What suggests a causal relationship between vasculitis and malignancy?
Remission of vasculitis after surgical resection of the tumor without other therapy suggests a causal relationship.
What vasculitis should be considered for a patient with a history of asthma presenting with nasal polyps and eosinophilic dermatitis?
Eosinophilic granulomatosis with polyangiitis should be considered, as it is associated with asthma, nasal polyps, and eosinophilic dermatitis.
What is the significance of cavitary pulmonary nodules in a patient with granulomatosis with polyangiitis?
Cavitary pulmonary nodules are a common and important feature of granulomatosis with polyangiitis, indicating necrotizing granulomatous inflammation.
What is the clinical significance of nasal polyps in a patient with suspected vasculitis?
Nasal polyps are a common feature of eosinophilic granulomatosis with polyangiitis and can help differentiate it from other types of vasculitis.
What type of vasculitis is most likely for a patient presenting with subcutaneous nodules and livedo reticularis?
Microscopic polyangiitis is most likely, as it can involve medium-sized vessels and present with subcutaneous nodules and livedo reticularis.
What type of vasculitis is most likely for a patient presenting with hemoptysis and diffuse alveolar hemorrhage?
Microscopic polyangiitis is most likely, as it is associated with pulmonary hemorrhage and diffuse alveolar hemorrhage.
What type of vasculitis should be considered for a patient with a history of Sjögren syndrome?
Vasculitis associated with other autoimmune diseases, such as Sjögren syndrome, should be considered.
What is the significance of eosinophil-rich skin biopsies in a patient with suspected vasculitis?
Eosinophil-rich skin biopsies are common in eosinophilic granulomatosis with polyangiitis but are not unique to this disease.
What is cutaneous leukocytoclastic angiitis and when should it be diagnosed?
Cutaneous leukocytoclastic angiitis is a histologic term defined by the absence of evidence of systemic disease. The diagnosis should be tentatively made if a patient has biopsy-proven vasculitis, no evidence of involvement of other organ systems, and no clinical or laboratory evidence supporting a specific form of vasculitis or a coexisting autoimmune inflammatory disease.
What are the common associations and follow-up considerations for cutaneous leukocytoclastic angiitis?
Approximately 20% of cases follow a wide range of infections, and another 20% are associated with drug exposure. Patients should be followed carefully for the possible evolution to a more systemic form of vasculitis.
What is drug-induced vasculitis and how is it diagnosed?
Drug-induced vasculitis accounts for 20% of cases of cutaneous small-vessel vasculitis. It is often indistinguishable from other causes of small-vessel vasculitis. Establishing a diagnosis may lead to avoiding glucocorticoids and immunosuppressive drugs, but careful follow-up is required as drug discontinuation alone may not resolve the disease and severe disease may necessitate treatment.
What are the clinical features of polyarteritis nodosa?
Polyarteritis nodosa is an idiopathic vasculitis of medium-sized vessels affecting one or multiple organ systems. Classic features include:
1. Skin disease
2. Myalgia
3. Hypertension (from renal artery involvement)
4. Abdominal pain
5. Neuropathy
6. Testicular pain
What are the common cutaneous features of polyarteritis nodosa?
The most common cutaneous features of polyarteritis nodosa include:
- Livedo reticularis/racemosa: a lacy pattern of cutaneous blood vessels on the legs.
- Painful cutaneous nodules or ulcers.
- Digital ischemia.
What are the key characteristics of giant cell arteritis?
Giant cell arteritis (temporal arteritis) is characterized by:
- Occurrence in adults older than 50 years.
- Common cranial arteritis leading to:
- Headache (70%-80%)
- Jaw claudication (50%)
- Monocular blindness (15%)
- Polymyalgia rheumatica symptoms in 30%-40% of cases.
- Constitutional symptoms like fever, malaise, and weight loss are common.
- Diagnosis is confirmed by temporal artery biopsy.
What is Takayasu arteritis and its typical presentation?
Takayasu arteritis is a rare condition (prevalence <1:100,000) primarily affecting young adults, predominantly females (90%). Typical presentations include:
- Limb claudication
- Dizziness
- Constitutional symptoms
- Severe hypertension (from renal artery stenosis)
- Cerebral infarction and coronary occlusions are less common but life-threatening complications.
- Diagnosis is made by angiography.
What can hematologic malignancies with or without associated paraproteinemias result in?
Vasculitis.
What is cutaneous leukocytoclastic angiitis defined by?
The absence of evidence of systemic disease.
Under what conditions should the diagnosis of cutaneous leukocytoclastic angiitis be tentatively made?
If a patient has biopsy-proven vasculitis with no evidence of involvement of other organ systems and no clinical or laboratory evidence supporting a specific form of vasculitis or a coexisting autoimmune inflammatory disease.
What percentage of cutaneous leukocytoclastic angiitis cases follow infections?
20%.
What is a common cause of drug-induced vasculitis?
Drug exposure, accounting for 20% of cases of cutaneous small-vessel vasculitis.
What is polyarteritis nodosa?
Idiopathic vasculitis of medium-sized vessels affecting one or multiple organ systems.
What are common symptoms of classic polyarteritis nodosa?
Combination of skin disease, myalgia, hypertension, abdominal pain, neuropathy, and/or testicular pain.
What is the typical presentation of Takayasu arteritis?
Limb claudication, dizziness, constitutional symptoms, and severe hypertension.
What is the most common cutaneous feature of polyarteritis nodosa?
Livedo reticularis/racemosa, painful cutaneous nodules or ulcers, and digital ischemia.
What is the primary method for diagnosing giant cell arteritis?
Temporal artery biopsy.
What type of vasculitis is most likely for a patient presenting with painful cutaneous nodules and ulcers?
Polyarteritis nodosa is most likely, as it is associated with painful cutaneous nodules and ulcers.
What type of vasculitis is most likely for a patient presenting with jaw claudication and monocular blindness?
Giant cell arteritis is most likely, as it is associated with jaw claudication and monocular blindness.
What is the clinical significance of polymyalgia rheumatica in a patient with suspected vasculitis?
Polymyalgia rheumatica is associated with giant cell arteritis and presents with pain and stiffness of the shoulder and hip girdles.
What type of vasculitis is most likely for a patient presenting with constitutional symptoms and limb claudication?
Takayasu arteritis is most likely, as it is associated with constitutional symptoms and limb claudication.
What type of vasculitis is most likely for a patient presenting with scalp necrosis and palpable nodularity of the temporal artery?
Giant cell arteritis is most likely, as it is associated with scalp necrosis and palpable nodularity of the temporal artery.
What type of vasculitis is most likely for a patient presenting with encephalopathy and multiple small strokes?
Primary vasculitis of the CNS is most likely, as it is limited to the CNS and presents with encephalopathy and multiple small strokes.
What is the clinical significance of a patient with vasculitis and a history of hematologic malignancy?
Hematologic malignancies can result in vasculitis, and remission of vasculitis after tumor resection suggests a causal relationship.
What is the clinical course and prognosis of vasculitis?
The severity of vasculitis varies widely and has the potential to cause permanent damage. All forms of vasculitis are treatable. Recurrence rates differ among types:
- Granulomatosis with polyangiitis (anti-PR3 antibodies) recurs in >50% without long-term treatment.
- Microscopic polyangiitis (anti-MPO antibodies) recurs in <50%.
- Polyarteritis nodosa and eosinophilic granulomatosis with polyangiitis also recur in <50%.
- Eosinophilic granulomatosis with polyangiitis often requires long-term treatment due to high recurrence rates.
- IgA vasculitis is usually monophasic in children but can be chronic in adults.
- Cryoglobulinemic vasculitis secondary to hepatitis C is often cured by virus eradication but recurs without it.
Mortality is about 10% in the first 3-6 months for severe cases affecting vital organs, with predictors of higher risk including advanced age and prior organ damage.
What are the management strategies for vasculitis?
Management of vasculitis typically involves two phases:
-
Remission Induction:
- High-dose glucocorticoids with a steady dose taper.
- Short course (3-6 months) of a rapid-acting immunosuppressive agent (e.g., cyclophosphamide, rituximab, methotrexate).
-
Remission Maintenance:
- Prolonged use of a non-cyclophosph.
What are the management strategies for vasculitis?
Management of vasculitis typically involves two phases:
- Remission Induction: High-dose glucocorticoids with a steady dose taper and a short course (3-6 months) of a rapid-acting immunosuppressive agent (e.g., cyclophosphamide, rituximab, methotrexate).
- Remission Maintenance: Prolonged use of a non-cyclophosphamide-based regimen to allow glucocorticoids to be reduced or discontinued.
What are the risks associated with glucocorticoid therapy in vasculitis?
Glucocorticoids are the mainstay of therapy for vasculitis due to their rapid and reliable response. However, they come with numerous risks, especially at high doses or with long-term use, including acute and chronic toxicities, potential substantial damage from chronic or recurrent use, and increased risk of infections.
What are the roles of other immunosuppressives in the treatment of vasculitis?
Other immunosuppressives play significant roles in the treatment of vasculitis:
- Cyclophosphamide: Proven effectiveness for ANCA-associated vasculitides and standard care for severe forms, but has serious toxicities related to cumulative dose (e.g., infertility, bladder cancer).
- Cyclophosphamide-sparing regimens: Transition to less toxic agents like methotrexate or azathioprine after initial treatment.
- Maintenance therapy: Mycophenolate, cyclosporine A, and other agents are used for ongoing management.
- Apremilast: Specifically for mucocutaneous manifestations of Behçet disease.
What are the biologic therapies used in vasculitis treatment?
Biologic therapies aim to be either cyclophosphamide-sparing or glucocorticoid-sparing:
- Rituximab: A B cell-depleting therapy as effective as cyclophosphamide for induction of remission in ANCA-associated vasculitis.
- Mepolizumab: A monoclonal antibody targeting interleukin 5, effective in treating eosinophilic granulomatosis with polyangiitis.
- Tocilizumab: A monoclonal antibody targeting interleukin 6, used for treating giant cell arteritis.
What is the common clinical course of vasculitis regarding severity and treatment potential?
The severity of vasculitis varies widely, but all forms are treatable.
What is the recurrence rate of granulomatosis with polyangiitis in the absence of long-term treatment?
Recurs in more than 50%.
What is the typical treatment approach for severe forms of vasculitis?
Two phases: remission induction with high-dose glucocorticoids and a rapid-acting immunosuppressive agent, followed by remission maintenance with a non-cyclophosphamide regimen.
What are the predictors of higher risk of mortality in vasculitis patients?
Advanced age and prior organ damage, such as kidney or cardiac damage.
What is the role of glucocorticoids in the treatment of vasculitis?
They are the mainstay of therapy for vasculitis, providing a rapid and reliable response.
What is the significance of cyclophosphamide in the treatment of ANCA-associated vasculitis?
It is proven effective and is the standard of care for initial treatment of severe forms of vasculitis.
What is the treatment approach for IgA vasculitis in children compared to adults?
IgA vasculitis is usually monophasic or resolves after a few episodes in children but is more likely to be chronic in adults.
What is the purpose of biologics in the treatment of vasculitis?
To be either cyclophosphamide-sparing or glucocorticoid-sparing.
What is the expected outcome of cryoglobulinemic vasculitis secondary to hepatitis C virus after virus eradication?
It is usually cured by eradication of the virus, but may recur in the absence of eradication.
What are the potential side effects of glucocorticoids in vasculitis treatment?
Numerous risks at high doses or with long-term use, including increased risk of infection.
What are the two phases of treatment for severe vasculitis, and what medications are typically used?
The two phases are remission induction (using high-dose glucocorticoids combined with cyclophosphamide, rituximab, or methotrexate) and remission maintenance (using non-cyclophosphamide-based regimens to taper glucocorticoids).
What is the role of glucocorticoids in the treatment of vasculitis, and what are the risks associated with their use?
Glucocorticoids are the mainstay of therapy for vasculitis due to their rapid and reliable response. However, they carry risks of acute and chronic toxicities, including substantial damage from chronic or recurrent use.
What are the predictors of higher mortality risk in patients with vasculitis?
Predictors include advanced age, prior organ damage (e.g., kidney damage in granulomatosis with polyangiitis), and cardiac damage in eosinophilic granulomatosis with polyangiitis.
What is the role of methotrexate in the treatment of vasculitis?
Methotrexate is used as a cyclophosphamide-sparing agent for remission maintenance in ANCA-associated vasculitis.
What is the role of batacept in the treatment of giant cell arteritis?
Batacept is a CTLA-4 immunoglobulin that is being investigated for its potential use in treating giant cell arteritis.
What has been the outcome of using anti-TNF agents for granulomatosis with polyangiitis or giant cell arteritis?
Anti-TNF agents have shown highly disappointing results for both granulomatosis with polyangiitis and giant cell arteritis.
What is the evidence regarding the efficacy of colchicine and antibiotics in treating vasculitis?
Good evidence is generally lacking for the efficacy of colchicine, antibiotics (such as dapsone), and other alternative therapies in treating vasculitis.
What is the controversy surrounding plasma exchange in patients with AAV and severe renal disease?
Plasma exchange is controversial, but there is some evidence for its efficacy in patients with ANCA-associated vasculitis (AAV) and severe renal disease, as well as possibly in forms of cryoglobulinemic vasculitis.
What is a common error in diagnosing vasculitis based on physical examination and laboratory findings?
A common error is establishing a firm diagnosis of vasculitis based solely on physical examination and laboratory findings, as not all purpura is due to vasculitis and not all skin disease in vasculitis is purpuric.
Why is it important to perform a biopsy when diagnosing skin lesions in suspected vasculitis?
A biopsy is crucial for diagnosing skin lesions in suspected vasculitis because many types of skin lesions improve with glucocorticoid treatment, making response to empiric treatment not diagnostically useful.
What are some common issues related to the initiation of immunosuppressive therapy in systemic vasculitis?
Common issues include undertreatment or delayed initiation of immunosuppressive therapy, failure to recognize multiorgan system disease, and reluctance to initiate immunosuppressive medications other than glucocorticoids.
What is a common error regarding the duration of glucocorticoid treatment in vasculitis?
A common error is extending the course of treatment with medium-high doses of glucocorticoids beyond what is necessary to control an acute flare of vasculitis or its more serious manifestations.
What are the potential consequences of vasculitis if not managed properly?
Vasculitis can be organ- and life-threatening, with rapid progression to emergency situations, even after a long period of slowly changing or indolent disease.
What is the role of abatacept in the treatment of giant cell arteritis?
Abatacept is a CTLA-4 immunoglobulin used in the treatment of giant cell arteritis.
What has been the outcome of using anti-TNF agents for granulomatosis with polyangiitis or giant cell arteritis?
The use of anti-TNF agents has been highly disappointing for these conditions.
What is the evidence for the efficacy of colchicine and antibiotics in treating vasculitis?
Good evidence is generally lacking for the efficacy of colchicine, antibiotics (like dapsone), and alternative therapies.
What is the controversy surrounding plasma exchange in vasculitis treatment?
Plasma exchange is controversial, but there is some evidence for its efficacy in patients with AAV and severe renal disease, and possibly in forms of cryoglobulinemic vasculitis.
What is a common error in diagnosing vasculitis based on physical examination?
Establishing a firm diagnosis based solely on physical examination and laboratory findings is a common problem; not all purpura is due to vasculitis.
What is the importance of biopsy in diagnosing skin lesions related to vasculitis?
A diagnosis of vasculitis in the skin should not be made without a biopsy, unless there is a clearly established diagnosis based on other evidence.
What is a common issue regarding the initiation of immunosuppressive therapy in systemic vasculitis?
Undertreatment or delayed initiation of immunosuppressive therapy is a common problem for patients with systemic vasculitis.
What is a common error related to glucocorticoid treatment in vasculitis?
Extending the course of treatment with medium-high doses of glucocorticoids beyond what is necessary to control an acute flare is a common error.
What are the potential consequences of vasculitis diseases?
These diseases can be organ- and life-threatening, with rapid progression to emergency situations.
What is a characteristic of vasculitis progression?
Vasculitis can accelerate rapidly even after a long period of slowly changing or indolent disease.
What are the common errors in diagnosing vasculitis based on physical examination and laboratory findings?
Common errors include diagnosing vasculitis without a biopsy, assuming all purpura is due to vasculitis, and relying on glucocorticoid response as a diagnostic tool.
What is the significance of a positive anti-IL5 biologic in the treatment of vasculitis?
Anti-IL5 biologics, such as mepolizumab, are effective in treating eosinophilic granulomatosis with polyangiitis.
What is the significance of a positive anti-IL6 biologic in the treatment of vasculitis?
Anti-IL6 biologics, such as tocilizumab, are used for the treatment of giant cell arteritis.
Where is the Dead Sea located?
On the border between Israel and Jordan.
What is the lowest point on the Earth’s surface?
The Dead Sea shoreline.
What is the average level on which the Dead Sea is located?
396 meters (below sea level).
How long is the Dead Sea?
74 km.
How much saltier is the Dead Sea as compared with the oceans?
7 times.
What is the volume content of salt in the Dead Sea?
30%.
Why can the Dead Sea keep swimmers afloat?
Due to high salt content.
Why is the Dead Sea called Dead?
Because only simple organisms can live in it.
Why only simple organisms can live in the Dead Sea?
Because of high salt content.
