DERMATOLOGY LECTURE NOTES
The vasculitides are a heterogeneous group of clinicopathological entities that share the common feature of vascular inflammation and injury. There is no universally acceptable classification of these group of disorders. While a number of underlying causes can be identified in some disorders, the aetiology is unknown in many. The pathogenetic mechanisms involved are mainly immunological, immune complex mediated tissue injury being the most commonly incriminated factor.
ETIOLOGY & PATHOGENESIS
While some forms of vasculitides may be ascribed to underlying factors like infections, malignancy, drug reactions or connective tissue disorders, the cause may remain undetermined in many vasculitic syndromes. Immunologic damage by immune-complex deposition or cell-mediated hypersensitivity is responsible in the majority of cases.
The possible immunopathologic mechanism in the causation of vasculitis are:
1. Deposition of circulating antigen-antibody complex or in -situ formation of immune complex within the vessel wall. This leads to complement activation and chemotactic attraction of neutrophils by complement components. Subsequent phagocytosis of such complexes with liberation of neutrophil granular products leads to vascular damage.
2. Cell-mediated hypersensitivity: Antigenic exposure may attract lymphocytes which liberate cytokines causing tissue damage and further activation of macrophages and lymphocytes.
3. Failure to clear the antigen may lead to persistent inflammation and eventual formation of epithelioid cells and giant cells, giving rise to a granulomatous tissue reaction.
Whatever the underlying mechanism, vascular inflammation and necrosis ensues which is often accompanied by thrombosis. These pathologic changes result in tissue ischaemia, necrosis and infarction, leading to a variety of clinical manifestations depending on the anatomic structures involved.
Perivascular cellular infiltration is a common histological finding in many disease entities, but for a definitive diagnosis of vasculitis, the presence of vascular damage, particularly in the form of fibrinoid degeneration, is necessary. Vasculitis may involve blood vessels of varying calibers and this feature forms the basis of a useful pathological classification of vasculitis. An infiltrate, composed of a variety of cell types, like neutrophils, lymphocytes, and histiocytes may invade the vessel wall and the surrounding tissue. Extravasation of red cells is a prominent feature in many vasculitides. Granulomatous inflammation with giant cell formation is a characteristic finding in some types.
Vasculitis is a taxonomistís nightmare. Diseases with diverse causes and pathology may share the same symptomatology. On the other hand, a disease may show different histopathologic features at different periods in its evolution. Many diseases have overlapping features and it is impossible to formulate a classification scheme that unifies clinicopathological, etiological and immunological features of different diseases.
I. Immune- complex mediated vasculitis:
Vasculitis due to cellular
Classification based on caliber of blood vessel involved:
I. Large vessel vasculitis:
II. Medium vessel
Classification based on cellular
composition of the infiltrate:
Leukocytoclastic vasculitis (LCV): Neutrophils are
predominant. Cellular fragments and nuclear debris (leukocytoclasia) are
found in the infiltrate.
II. Lymphocytic vasculitis:
V. Giant cell arteritis:
I. Systemic necrotizing vasculitis :
∑ Microscopic polyangiitis
II. Giant cell vasculitis
III. Predominantly Cutaneous small vessel vasculitis :
Cryoglobulinemia, complement deficiency, alpha1 antitrypsin deficiency Inflammatory bowel disease, Chronic active hepatitis, intestinal bypass surgery, primary biliary cirrhosis ,Relapsing polychondritis
syndromes with leukocytoclastic
Features in an individual patient will depend on the specific vasculitic syndrome and the degree and extent of organ systems involved.
Constitutional: Fever, malaise, headache, weight loss etc
Palpable purpura Persistent urticaria
Subcutaneous nodules Ulcers
Necrotic papule Infarcts
Renal Proteinuria Hematuria
Acute and chronic renal failure
Respiratory: Nasal obstruction, discharge, bleeding
Cough, Hemoptysis Dyspnea
GI : Dysphagia Pain Vomiting Bleeding
CVS: Hypertension Thrombosis Ischemia
Eyes: Uveitis Retinal vasculitis
Nervous system: Peripheral neuropathy
For salient features of major vasculitic syndromes : CLICK HERE
1. Screening Tests:
CBC ESR CRP ASO titre
2. Focused Tests:
ANA C3, C4, CH50
3. Biopsy of appropriate tissue:
Skin Temproral artery
Kidney Testes etc
Unexplained multisystem disease, PUO
Hemorrhagic pustules Livedo reticularis Infarcts
II. History, Clinical exam and Lab investigations to detect general features of inflammation and tissue ischemia and to delineate organ systems involved.
III. Syndrome recognition: recognize vasculitic syndromes based on clinical findings and lab features and the patterns of organ system involved.
III. Confirmation of diagnosis: By biopsy and angiography
IV. Exclusion of underlying cause like infections, connective tissue disorder or malignancy
Treatment will depend on the specific syndromes, the degree and severity of organ system involvement and the underlying cause if any.
1. Remove underlying cause: Withdraw drug, treat infection.
2. In mild cases no treatment or symptomatic measures like simple analgesics and rest will suffice.
3. Predominantly cutaneous vasculitis may respond to Dapsone, colchicine, hydroxycloroquine.
4. Systemic vasculitides or severe cutaneous vasculitis will require systemic steroids with or without immunosuppressive agents like cyclophosphamide, azathioprine or methotrexate. Cyclosporine may also be used in certain cases.
5. Symptomatic / specific
measures for organ system failure.