Overview of and approach to the Vasculitides in adults: Definition, Clinical manifestation, Diagnosis, Classification of Vasculitis, Differential Diagnosis and Therapy

Source: www.scielo.br

Definition

Vasculitis is an inflammation of vessels, characterized by infiltration of the vessel wall with leukocytes due to an unknown mechanism. This infiltration of the wall leads to the destruction of the wall, with complications such as bleeding and stenosis with an ischemic disease as a result.

Vessels that are affected differently in size and location according to the underlying vasculitis type.

Vasculitis can be primary or secondary to another condition.

Clinical manifestation

There are no specific or sensitive diagnostic symptoms.

However, the presence of systemic symptoms with single/multiple organ dysfunction, should lead to thinking about vasculitis.

:Some symptoms

• Fatigue
• Abdominal pain
• Arthralgia
• Fever
• Arterial hypertension
• Renal insufficiency
• Neurological symptoms
• Purpura

: suggestive symptoms of some vasculitis

Mononeuritis multiplex is suggestive for polyarteritis nodosa

Palpable purpura is suggestive for cutaneous vasculitis of hypersensitivity typ. Purpura with another organ dysfunction is suggestive for IgA vasculitis or microscopic polyangiitis

Pulmonary with renal involvement is suggestive for wegner’s vasculitis or anti-GBM antibodies.

Diagnosis

: History

Important aspects of history:

Medicine: some medication cause hypersensitivity vasculitis

Disease history: hepatitis c: may cause mixed cryoglobulinemia and some cases of polyarteritis

Systemic lupus erythematosus SLE: secondary vasculitis

Age of patients: age-specific distribution of different vasculitides

 Physical examination

Palpable purpura?

Mononeuritis multiplex?

Laboratory tests

• ANA: may suggest connective tissue disorder such SLE
• Complement level: may be low in mixed cryoglobulinemia und SEL BUT not in most other vasculitides
• ANCA:
• cANCA (against protease 3): strongly suggests a diagnosis of granulomatosis with polyangiitis (Wegener’s)
• pANCA (against myeloperoxidase): suggests a diagnosis of microscopic polyangiitis

Nonspecific tests: to asset the function/ association of other organs:

creatinine

Liver enzyme tests

Hepatitis serology

CK

ESR

Urine analysis

Blood/Tissue culture

Electromyography: 

by neuromuscular symptoms and suspected systemic vasculitis

Tissue biopsy: 

essential for establishing the diagnosis.

Angiography:

helps by vasculitis of large/medium vessels, less sensitive are Angio-CT/ Angio-MRT/ Ultrasound

Classification of vasculitis

• Large vessel vasculitis
• Medium vessel vasculitis
• Small vessel vasculitis
• Secondary vasculitis:
• Viral infection
• Connective tissue disorders

Source: www.sciencedirect.com

ACR Criteria (American college of rheumatology): These criteria try to differ diagnosed vasculitis from each other: the diagnosis is always established histologic: 

Large vessel vasculitis
Takayasu arteritis	Age of 40 years or younger at disease onset Claudication of the extremities Decreased pulsation of one or both brachial arteries Difference of at least 10 mm Hg in systolic blood pressure between arms Bruit over one or both subclavian arteries or the abdominal aorta Arteriographic narrowing or occlusion of the entire aorta, its primary branches, or large arteries in the upper or lower extremities that is not due to arteriosclerosis, fibromuscular dysplasia, or other causes	ACR Criteria (American college of rheumatology): The presence of any 3 or more criteria yield a sensitivity of 90.5% and a specificity of 97.8%
Giant cell arteritis	Age ≥50 years at time of disease onset Localized headache of new onset Tenderness or decreased pulse of the temporal artery Erythrocyte sedimentation rate (ESR) greater than 50 mm/h (Westergren) Biopsy that includes an artery and reveals a necrotizing arteritis with a predominance of mononuclear cells or a granulomatous process with multinucleated giant cells	ACR criteria The presence of 3 or more criteria yields a diagnostic sensitivity of 93.5% and specificity of 91.2%.
Medium vessel vasculitis
Polyarteritis nodosa	Otherwise unexplained weight loss >4 kg Livedo reticularis Testicular pain or tenderness Myalgias (excluding that of the shoulder and hip girdle), weakness, or polyneuropathy Mononeuropathy or polyneuropathy New onset diastolic blood pressure >90 mmHg Elevated levels of serum blood urea nitrogen (>40 mg/dL or 14.3 mmol/L) or creatinine (>1.5 mg/dL or 132 mcmol/L) Evidence of hepatitis B virus infection via serum antibody or antigen serology Characteristic arteriographic abnormalities not resulting from noninflammatory disease processes A biopsy of medium- or small-sized artery containing polymorphonuclear cells	ACR criteria The presence of 3 or more criteria yields a diagnostic sensitivity of 82% and specificity of 87%.
Kawasaki disease	Diagnosis requires the presence of fever lasting five days or more without any other explanation, combined with at least four of the five following physical findings: Bilateral conjunctival injection Oral mucous membrane changes, including injected or fissured lips, injected pharynx, or strawberry tongue Peripheral extremity changes, including erythema of palms or soles or edema of hands or feet (acute phase), as well as periungual desquamation (convalescent phase). Polymorphous rash Cervical lymphadenopathy (at least one lymph node >1.5 cm in diameter)	Criteria: Established by Tomisaku Kawasaki in 1967
Primary CNS vasculitis	Rare case, in patient with CNS symptoms and signs in combination with evidence of a cerebral vasculitis by angiography and leptomeningeal biopsy, no established criteria
Small vessel vasculitis
Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)	Asthma (a history of wheezing or the finding of diffuse high pitched wheezes on expiration) Eosinophilia of >10 percent on differential white blood cell count Mononeuropathy (including multiplex) or polyneuropathy Migratory or transient pulmonary opacities detected radiographically Paranasal sinus abnormality Biopsy containing a blood vessel showing the accumulation of eosinophils in extravascular areas	The presence of four or more of these criteria yields a sensitivity of 85 % and a specificity of 99.7 %
Granulomatosis with polyangiitis (Wegener’s)	Nasal or oral inflammation (painful or painless oral ulcers or purulent or bloody nasal discharge) Abnormal chest radiograph showing nodules, fixed infiltrates, or cavities Abnormal urinary sediment (microscopic hematuria or red cell casts) Granulomatous inflammation on biopsy of an artery or perivascular area NOTE: these criteria was made before ANCA discovery	he presence of two or more of these four criteria yielded a sensitivity of 88 percent and a specificity of 92 percent
Hypersensitivity vasculitis	Age >16 Use of a possible offending drug in temporal relation to the symptoms Palpable purpura. Maculopapular rash Biopsy of a skin lesion showing neutrophils around an arteriole or venule	The presence of three or more of these criteria had a sensitivity of 71 % and specificity of 84 %.
Henoch-Schönlein purpura (IgA vasculitis) HSP	Palpable purpura Bowel angina Gastrointestinal bleeding Hematuria Age at onset ≤20 years lesion No new medications Note: the same as above, with IgA deposition on skin and kidney	The presence of three or more of the six criteria yielded a correct classification of HSP in 87 percent
Cryoglobulinemic vasculitis	No criteria established; Diagnosis usually made by: History skin purpura low complement levels circulating cryoglobulins histology showing small vessel inflammation with immune deposits

Differential diagnosis

• most common is systemic rheumatic diseases, such as systemic lupus erythematosus.
• Fibromuscular dysplasia
• Bacteremia
• Amyloidosis
• Atherosclerosis
• Vasospasm
• Malignancies
• Ergotism 

Therapy

Therapy depends upon the nature and severity of the vasculitis. Below is the treatment concept in general, each typ of vasculitis should be treated due to its guidelines.

Hypersensitivity vasculitis:

Discontinuing the offending drug may be adequate

antihistamine for itching

short course of corticosteroids for more severe cases.

simple observation may be adequate for transitory vasculitis confined to the skin, as with mild cases of Henoch-Schönlein purpura (IgA vasculitis).

Systemic vasculitis:

glucocorticoid therapy.

patients with rapidly progressive vasculitic diseases, such as granulomatosis with polyangiitis (Wegener’s) or polyarteritis nodosa, require combination therapy consisting of a cytotoxic drug (usually cyclophosphamide) and steroids for 1-2 months.

Then the steroid dose may be reduced; therapy is usually continued for 6 to 12. 

Azathioprine and methotrexate have been used in less severe forms of vasculitis and as maintenance therapy after remission has been induced by cyclophosphamide.