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%.
