Polyarteritis nodosa causes

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Ali Poyan Mehr, M.D. [2] Associate Editor(s)-in-Chief: Olufunmilola Olubukola M.D.[3] Cafer Zorkun, M.D., Ph.D. [4]; Haritha Machavarapu, M.B.B.S.

Overview

Hepatitis B and PAN

The pathogenesis of polyarteritis nodosa (PAN) is unknown, and no animal model is available for study. Hepatitis B virus (HBV) infection is strongly linked with PAN. Evidence for immune complex–induced disease is confined to HBV-related PAN; the role of immune complexes in non-HBV-related PAN remains unclear. ^{null 6}

Impaired function of endothelial cells may be part of idiopathic PAN or a consequence of it; in HBV-PAN, virus replication may directly injure the vessel wall.^{null 10} Endothelial dysfunction can perpetuate the inflammation through cytokine and adhesion molecule production. ^{null 9}

HBV-associated vasculitis almost always takes the form of PAN. HBV-PAN may occur at any time during the course of acute or chronic hepatitis B infection, although it typically occurs within 6 months of infection. ^{null 10}

The activity of HBV-PAN does not parallel that of the hepatitis, and symptoms are the same as those of idiopathic PAN. Small studies have found that gastrointestinal manifestations, malignant hypertension, renal infarction, and orchiepididymitis were more common in HBV-PAN. ^{null 10}

HBV was once the cause of up to 30% of PAN cases. ^{null 11} Widespread use of the hepatitis B vaccine has significantly decreased the incidence of HBV-PAN, which is now estimated to account for less than 8% of all PAN cases. ^{null 12}

Genetic associations

Loss-of-function mutations in CECR1 (alsoknown as ADA2), the gene that encodes adenosine deaminase 2 (ADA2), have been associated with a spectrum of vascular and inflammatory phenotypes that includes polyarteritis nodosa. ^{null 13}  Navon Elkan and colleagues identified six families with multiple cases of systemic and cutaneous polyarteritis nodosa, most of which had onset during childhood. In all the families, disease was traced to recessive mutations in CECR1 that resulted in reduced activity of ADA2. ^{null 14}

Possible roles of ADA2 include regulation of the proliferation of activated T cells and macrophages and the differentiation of monocytes to macrophages. Reduction in ADA2 activity  may affect the adenosine inflammatory-response pathway. ^{null 14}

Similarly, Gonzalez Santiago et al report two siblings with novel compound heterozygous mutations in CECR1 who were diagnosed with cutaneous PAN in early childhood. ^{null 15}

In a study of patients with early-onset livedo reticularis and/or hemorrhagic/ischemic strokes in the context of inflammation or PAN, Caorsi et al detected biallelic homozygous or compound heterozygous CECR1 mutations in 15 of 48 patients from 43 families. In patients with CECR1 mutations, the mean age of onset of disease was 24 months (6 months to 7 years). ^{null 16}

Other disease associations

Controversy has surrounded the potential association of hepatitis C virus (HCV) with PAN. HCV may be linked to cutaneous PAN, a benign, limited form of PAN. In a study of 16 patients with cutaneous PAN, 5 tested positive for hepatitis C. ^{null 17} HCV-associated PAN has also been described in 31 patients included in a larger 161 patient cohort with HCV-related vasculitis in France. ^{null 18} Despite the presence of serum cryoglobulins, these patients were diagnosed with HCV-PAN on the basis of typical histopathologic features of PAN and/or the presence of microaneurysms and/or multiple stenoses on abdominal and/or renal angiography.

A number of other infectious organisms have been reported in association with PAN or PAN-like diseases, but causal evidence is inconsistent. These organisms include varicella-zoster virus, parvovirus B-19, cytomegalovirus, human T-cell leukemia virus, streptococcal species, Klebsiella species, Pseudomonas species, Yersinia species, Toxoplasma gondii, Rickettsiae, trichinosis, and sarcosporidiosis.^{[[null 19], [null 20]]} Recently, reports of associations with PAN and human immunodeficiency virus ^{null 21} and cutaneous PAN and tuberculosis ^{null 22} have been published as well.

Some syndromes, including rheumatic diseases, malignancies, and infections have been associated with clinical syndromes indistinguishable from idiopathic PAN. Rheumatoid arthritis (RA) and Sjögren syndrome have been associated with PAN. Notably, the incidence of RA-associated vasculitis has decreased greatly since the 1980s, likely attributable to improvements in the management of RA. ^{null 23} Cutaneous PAN occurring with HLA-B39 spondyloarthritis, ^{null 24} common variable immunodeficiency, ^{null 25} and psoriatic arthritis in an 11-year-old boy ^{null 26} have also been reported.

Hematologic malignancies, such as hairy cell leukemia and, in one case, angioimmunoblastic T cell lymphoma, have been associated with PAN-like vasculitides. ^{[[null 27], [null 28]]}

Causes

Common Causes

The primary cause of PAN is idiopathic, but secondary causes include hepatitis B virus infection , hepatitis C virus infection, and hairy cell leukemia . Polyarteritis nodosa is a disease of unknown cause that affects arteries, the blood vessels that carry oxygenated blood to organs and tissues. It occurs when certain immune cells attack the affected arteries. More adults than children get this disease. It damages the tissues supplied by the affected arteries because the tissues are not receiving the oxygen and nourishment they need. People with active Hepatitis B and Hepatitis C may develop this disease.

Drug Side Effect

• Sulfasalazine