Hypersensitivity Vasculitis

Updated: Sep 04, 2018
  • Author: Mital Patel, MD; Chief Editor: William D James, MD  more...
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Overview

Background

Hypersensitivity vasculitis, which is usually represented histopathologically as leukocytoclastic vasculitis (LCV), is a term commonly used to denote a small-vessel vasculitis. There are many potential causes of hypersensitivity vasculitis; however, up to 50% of cases are idiopathic.

Hypersensitivity vasculitis may present clinically as cutaneous disease only or it may be a cutaneous manifestation of systemic disease. The internal organs most commonly affected in hypersensitivity vasculitis are the joints, gastrointestinal tract, and kidneys. Hypersensitivity vasculitis may be acute and self-limited, recurrent, or chronic. Overall, hypersensitivity vasculitis has a favorable prognosis, particularly when no internal involvement is present. Note the image below.

Hypersensitivity vasculitis. Hypersensitivity vasculitis.
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Pathophysiology

Hypersensitivity vasculitis is thought to be mediated by immune complex deposition. [1] In this form of vasculitis, circulating antigens in the body (produced by factors such as medications, infections, and neoplasms) induce antibody formation. These antibodies bind to the circulating antigen and create immune complexes, which then deposit within vessels, activating complement and inducing inflammatory mediators. Inflammatory mediators, adhesion molecules, and local factors may affect the endothelial cells and play a role in the manifestations of this disease. [2]

Additionally, autoantibodies, such as antineutrophil cytoplasmic antibody (ANCA), may be associated with disease manifestations. In ANCA-mediated vasculitis, intracellular proteins from neutrophils become expressed on the cell surface, leading to formation of antibodies (ANCA). These autoantibodies then bind neutrophils, subsequently leading to neutrophil adhesion to vessel walls and cellular activation.

Overall, however, the exact mechanisms causing hypersensitivity vasculitis remain to be elucidated.

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Etiology

One third to one half of cutaneous vasculitis cases are idiopathic; the remainder have a variety of causes.

Antibiotics are the most common drugs to cause hypersensitivity vasculitis, particularly beta-lactams. Nonsteroidal anti-inflammatory drugs and diuretics also frequently cause vasculitis. However, almost all drugs and drug additives are potential causes. [3, 4] Hydralazine, minocycline, propylthiouracil, and levamisole-adulterated cocaine use should be considered in patients with ANCA-associated vasculitis. [5]

Various infections may be associated with vasculitis. Upper respiratory tract infections (particularly beta-hemolytic streptococcal infection) and viral hepatitis (particularly hepatitis C) are most often implicated. Hepatitis C is a commonly recognized cause of vasculitis, likely secondary to the presence of cryoglobulins. However, when 1614 patients with hepatitis C were studied, vasculitis occurred in only 12 patients (9 with cryoglobulinemia, 3 without). Interestingly, cryoglobulins were present in roughly 40% of those tested; many patients with cryoglobulins (98%) did not have vasculitis despite an abnormal circulating paraprotein. Hepatitis B has been implicated in some cases of vasculitis in the past. HIV infection may also be associated with some cases of cutaneous vasculitis.

Occasionally, ascertaining whether a drug (eg, antibiotic) or an infection (eg, upper respiratory tract infection) is responsible for the disease is impossible because the occurrence of vasculitis postdates both the infection and the drug therapy used to treat the infection.

Foods or food additives may also cause vasculitis.

Collagen-vascular diseases account for 10-15% of cases of cutaneous vasculitis. In particular, rheumatoid arthritis, Sjögren syndrome, and lupus erythematosus may have an associated hypersensitivity vasculitis. The presence of vasculitis often denotes active disease and possibly a poorer prognosis.

Inflammatory bowel disease, ulcerative colitis, or Crohn colitis may be associated with cutaneous vasculitis.

Malignancy accounts for 1-5% of cases of cutaneous hypersensitivity vasculitis. Lymphoproliferative diseases are more common (particularly hairy cell leukemia); however, any type of tumor at any site may be related to cutaneous vasculitis. Effective management of malignancy can lead to resolution of the hypersensitivity vasculitis. [6]

Small-vessel hypersensitivity vasculitis may be seen uncommonly in patients with a larger-vessel vasculitis, such as granulomatosis with polyangiitis (formerly Wegener granulomatosis ), polyarteritis nodosa, or eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome ). [7]

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Epidemiology

Frequency

United States

The incidence of hypersensitivity vasculitis is unknown, but the condition is presumed to be relatively rare. A 2014 population-based study in Minnesota found the incidence of cutaneous leukocytoclastic vasculitis in adults (including IgA vasculitis as well as other types of small-vessel vasculitis) to be at 45 cases per million. [8]

International

Several studies from Spain have been conducted on hypersensitivity vasculitis. [9, 10, 11, 12, 13] Hypersensitivity vasculitis reportedly has an incidence of 10-30 cases per million people per year. Henoch-Schönlein purpura (HSP), a small-vessel vasculitis characterized by deposition of immunoglobulin A (IgA) immune complexes, reportedly has an incidence of 14 cases per million people per year.

Race

Hypersensitivity vasculitis is reported most often in the white population, but epidemiologic studies are not available to assess whether hypersensitivity vasculitis is associated with any specific ethnic group or skin type.

Sex

Although hypersensitivity vasculitis appears to affect men and women in approximately equal numbers, some of the studies from Spain suggest that hypersensitivity vasculitis is slightly more common in men than in women. [13]

Age

Hypersensitivity vasculitis may occur at any age. In both adults and children, Henoch-Schönlein purpura (HSP) may present in a clinically identical fashion to hypersensitivity vasculitis, and biopsy with direct immunofluorescence is typically needed to distinguish the two. HSP is a specific small-vessel vasculitis associated with the presence of vascular IgA deposition. However, by definition, HSP is a clinically defined entity and some authorities may make this diagnosis even if IgA deposition is absent. The classic tetrad of HSP consists of palpable purpura, arthritis, abdominal pain, and hematuria. HSP typically follows a respiratory infection and is more common in the pediatric population.

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Prognosis

The prognosis of patients with cutaneous vasculitis depends on the underlying syndrome and the presence of end-organ dysfunction. Patients with disease that primarily affects the skin and/or the joints have a good prognosis. Some patients develop a relapsing disease course, admixed with symptom-free periods. A subset of patients (< 10%) can develop chronic, unremitting disease with recurrent episodes of painful purpura and even ulceration, which can have a considerable impact on quality of life. [14, 15] There is increased morbidity and the potential for mortality if the kidneys, gastrointestinal tract, lungs, heart, or central nervous system are involved.

Patients with granulomatosis with polyangiitis (Wegener granulomatosis), polyarteritis nodosa, eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome), or severe necrotizing vasculitis have increased morbidity and mortality. Treatment with corticosteroids and/or immunosuppressive/cytotoxic agents is potentially a life-saving intervention.

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