Polyarteritis Nodosa

Article Author:
Monica Stanton
Article Editor:
Vivekanand Tiwari
Updated:
1/31/2019 12:33:28 PM
PubMed Link:
Polyarteritis Nodosa

Introduction

Polyarteritis Nodosa (PAN) is a systemic necrotizing vasculitis first described in 1866 by Adolph Kussmaul and Rudolph Maier. [1]It typically affects medium-sized arterial vessels but may affect small-sized arterial vessels. Unlike other small-sized arterial vessel vasculitides, polyarteritis nodosa is not typically associated with anti-neutrophil cytoplasmic antibodies (ANCA). It is a systemic disease process though there is a limited form of the disease called cutaneous polyarteritis nodosa (CPAN). Even with the limited form of the disease, there is a significant morbidity secondary to digital ulcerations, ischemia, and painful skin nodules. Though rare, patients with CPAN can progress to systemic polyarteritis nodosa (PAN).

Etiology

Primary cases of PAN are idiopathic. Secondary PAN is less frequent and often seen in hepatitis B, hepatitis C, and malignancies such as hairy cell leukemia. [2][3]

Epidemiology

PAN is usually diagnosed in middle-aged and older adults. Men tend to be more affected than women. According to a French study, the prevalence of PAN per 1000000 adult was 30.7. [4]

Pathophysiology

Hepatitis B-associated PAN is believed to arise secondary to immune complexes. [5] However, the mechanism in which immune complexes leads to medium vessel inflammation is unknown, and immune complexes play less of a role in other subsets of the disease. Affected vessels become thickened and inflamed through intimal proliferation. This leads to vessel narrowing and decreased blood flow, predisposing affected vessels to thrombosis.  Inflammation not only leads to vessel narrowing but the weakening of the vessels which leads to aneurysm development. These changes result in ischemia and infarction, leading to the clinical manifestations seen. PAN affects multiple systems including renal, skin, neurologic, cardiac, gastrointestinal, and muscular. The kidney is the most commonly affected organ. Inflammation of renal arteries can lead to aneurysms and rupture, while intimal proliferation and luminal narrowing can lead to glomerular ischemia.

History and Physical

Patients with PAN and renal involvement most often present with hypertension. [6]Long-standing hypertension and vasculitis involving the coronary arteries can lead to heart failure, and patients may report associated symptoms including dyspnea and edema.[7] As in other vasculitides, patients may present with systemic signs. They may report generalized fatigue, weight loss, fevers, arthralgias, and skin lesions. The skin lesions may appear as tender, erythematous nodules similar to erythema nodosum. [8]They also may present with palpable purpura as seen in other forms of vasculitis. Other skin changes include livedo reticularis and ulcerations. The skin manifestations may be limited or diffuse but are often visible in the lower extremities.

A thorough review of symptoms also should include gastrointestinal (GI) and muscular complaints. Patients may report abdominal pain early in the disease process. [9]The pain may be continuous or intermittent but often occurs after meals. This constellation of symptoms has been described as "intestinal angina." Patients also may report nausea, vomiting, melena, or diarrhea. A stool occult should be performed on patients even without an overt history of GI bleeding.  GI symptoms are a result of mesenteric arteritis, predominantly affecting the small intestines. Severe disease can lead to ischemia and perforation. If muscle involvement occurs, patients may report myalgias and generalized weakness .

Patients may report symptoms of neurologic disease. The most common neurologic deficit in patients with PAN is mononeuritis multiplex, occurring in nearly 70% of patients with the disease.[10] Radial, ulnar, and peroneal nerves are the most common nerves involved, and patients can experience sensory and motor deficits.

Evaluation

There is no definitive laboratory test for PAN. Diagnosis is mainly clinical. Laboratory studies are most often obtained to assess organ involvement and rule out other disease processes. Laboratory tests should include serum creatinine and urinalysis to assess renal function as well as a liver panel and creatinine kinase.Hepatitis B and hepatitis C serologies are essential to rule out secondary causes of PAN. Erythrocyte sedimentation rate and C-reactive protein may be elevated but are not specific to PAN and often are elevated in other vasculitides. The following lab tests are particularly helpful to assess for other disease processes and vasculitides: antineutrophil cytoplasmic antibodies, antinuclear antibodies, complement levels (C3 and C4), cryoglobulins, serum and urine immunofixation electrophoresis (SPEP and UPEP), rheumatoid factor, and human immunodeficiency virus serology. A biopsy of an affected organ should be performed to confirm the diagnosis.[9] An alternative to biopsy is mesenteric or renal arteriography. These studies will often show aneurysms and constrictions in larger vessels as well as possible occlusion of smaller arteries. CT and MRI have been used when a less invasive technique is desired.

Treatment / Management

The treatment for PAN is dependent on the severity of the disease. [11][12]Mild disease is defined as those with constitutional symptoms but with normal renal function and no significant end-organ damage or ischemia. Patients with mild symptoms and those with the isolated cutaneous disease may be treated with glucocorticoids. Initial treatment includes prednisone (1mg/kg per day) with a maximum of 60 to 80 mg per day. This dose of steroids is given over a month and then slowly tapered over six to eight months. Patients with mild disease may be resistant to or intolerant of glucocorticoids. In this population, immune modulators such as azathioprine or methotrexate may be used. In moderate to severe disease, there may be evidence of renal insufficiency, ischemic disease or symptomatic arterial stenosis, or aneurysms. Patients with moderate to severe disease are treated with glucocorticoids and another immunosuppressive agent such as cyclophosphamide.

Patients with associated hepatitis B or C infection also benefit from treatment with antivirals. For patients with mild PAN, treatment with antivirals should occur before any immunosuppressive medications are added. Patients with severe hepatitis B-associated PAN may benefit from short-term treatment with glucocorticoids and plasma exchange in addition to antiviral therapy.[13]

Hypertension should be treated with an ACE inhibitor. The hypertension in PAN is considered to be mediated through activation of renin-angiotensin system. [14]However, renal function should be monitored closely, and an alternative agent should be used if the glomerular filtration rate declines by more than 30% upon initiation of therapy. Calcium channel blockers may then be used to control hypertension.

Differential Diagnosis

The differential diagnosis of PAN and its manifestations are broad and include infectious processes as well as other vasculitides. Infectious mimics include infective endocarditis, mycotic aneurysm with emboli, and HIV. Other vasculitides on the differential include granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis (Churg-Strauss), immunoglobulin A vasculitis (Henoch-Schönlein purpura), cryoglobulinemic vasculitis, and drug-induced vasculitis.

Prognosis

Though relapse rates for PAN are lower than the ANCA-associated vasculitides, relapse rates remain high. [8]Untreated PAN has a poor prognosis; however, outcomes have significantly improved with treatment. The major causes of death include renal failure and mesenteric, cardiac, or cerebral infarction.

Enhancing Healthcare Team Outcomes

PAN is a multi-system necrotizing vasculitis which has many aspects to its treatment and management. Apart from close involvement of Rheumatologists and Primary care physicians, consultation with Nephrologist in renal failure and Infectious disease physicians in cases associated with Hepatitis B and C is required for many patients. So would be the case involving Pharmacists for effective medication management and education. A closed loop communication among the health care providers is essential for better outcomes in these patients.


References

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[2] Guillevin L,Mahr A,Callard P,Godmer P,Pagnoux C,Leray E,Cohen P, Hepatitis B virus-associated polyarteritis nodosa: clinical characteristics, outcome, and impact of treatment in 115 patients. Medicine. 2005 Sep;     [PubMed PMID: 16148731]
[3] Hasler P,Kistler H,Gerber H, Vasculitides in hairy cell leukemia. Seminars in arthritis and rheumatism. 1995 Oct;     [PubMed PMID: 8578313]
[4] Mahr A,Guillevin L,Poissonnet M,Aymé S, Prevalences of polyarteritis nodosa, microscopic polyangiitis, Wegener's granulomatosis, and Churg-Strauss syndrome in a French urban multiethnic population in 2000: a capture-recapture estimate. Arthritis and rheumatism. 2004 Feb 15;     [PubMed PMID: 14872461]
[5] Guillevin L,Lhote F,Cohen P,Sauvaget F,Jarrousse B,Lortholary O,Noël LH,Trépo C, Polyarteritis nodosa related to hepatitis B virus. A prospective study with long-term observation of 41 patients. Medicine. 1995 Sep     [PubMed PMID: 7565065]
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[8] Clinical features and outcomes in 348 patients with polyarteritis nodosa: a systematic retrospective study of patients diagnosed between 1963 and 2005 and entered into the French Vasculitis Study Group Database., Pagnoux C,Seror R,Henegar C,Mahr A,Cohen P,Le Guern V,Bienvenu B,Mouthon L,Guillevin L,, Arthritis and rheumatism, 2010 Feb     [PubMed PMID: 20112401]
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