Polyarteritis nodosa overview
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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: Sargun Singh Walia M.B.B.S.[3] Olufunmilola Olubukola M.D.[4] Cafer Zorkun, M.D., Ph.D. [5]; Haritha Machavarapu, M.B.B.S.
Overview
Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis that typically affects the medium (and occasionally, small-sized) muscular arteries. The Chapel Hill International Consensus Conference (CHCC) has differentiated PAN from microscopic polyangiitis which primarily affects small vessels [1]. The diagnosis of PAN is challenging due to of lack of a serological marker, and lack of specific histological characteristics. Polyarteritis nodosa unlike most other vasculidities is not Antineutrophil Cytoplasmic Antibodies (ANCA) positive [2]. PAN is a rare disease and often affects multiple organs but strikingly, PAN does not affect the lungs. The organs commonly affected by PAN include the kidneys, skin, joints, muscles, nerves, and gastrointestinal tract.
While it often has a multisystem presentation at diagnosis, variants like single-organ disease and cutaneous-only PAN do occur as well. PAN has been associated with hepatitis B and C virus infection.
Historical Perspective
Polyarteritis nodosa was first described macroscopically by the pathologist K. Rokitansky in 1842.He described the presence of aneurysms macroscopically and therefore missed the inflammatory nature of this disease.Polyarteritis nodosa was better described in 1866 by A. Kussmaul and R. Maier who provided a clinical description of a patient.Kussmaul and Maier introduced the term “periarteritis nodosa” to describe the nodules observed in intermediate-sized vascular arteries but this term was later changed to “Polyarteritis nodosa” when these nodules showed the involvement of all layers of the artery.
Classification
There is no established system for the classification of polyarteritis nodosa.
Pathophysiology
The exact pathogenesis of PAN is not fully understood.It is a disease of unknown cause that affects arteries, the blood vessels that carry oxygenated blood to organs and tissues.PAN affects the medium sized arterial vessels.PAN does not affect large arterial vessels, capillaries, small arterioles and venous system. It occurs when certain immune cells attack the affected arteries.Inflammation starts in the vessel intima and results in fibrinoid necrosis by destroying the internal and external elastic lamina.Aneurysms and thrombi may develop at the site of lesions.One hypothesis is that this condition is caused by antibodies against HBV, via atype IIII hypersensitivity reaction.Due to inflammation of the medium to small sized vessels in PAN and the presence of impaired endothelial function, there could be direct endothelial cell activation and damage resulting from proinflammatory cytokines or antibodies (anti-endothelial cells antibodies).Mutation in CECR1 can lead to vascular and inflammatory disorders which also include PAN.
Causes
The common causes of PAN are idiopathic, Hepatitis B infection, Hepatitis C infection, hairy cell leukemia and drug induced. Less common causes include varicella-zoster virus, parvovirus B-19, cytomegalovirus, human T-cell leukemia virus etc.
Differentiating Polyarteritis Nodosa from other Diseases
Polyarteritis nodosa must be differentiated from other diseases that cause may lead to medium vessel vasculitis. The diseases that can lead to medium vessel vasculitis are polyarteritis nodosa, kawasaki disease, infections, cardiovascular diseases and systemic diseases.
Epidemiology and Demographics
The incidence of polyarteritis nodosa is approximately 3 to 4 per 100,000 individuals worldwide.The prevalence among alaskan population suffering with hepatitis Binfection is approximately 7.7 per 100,000 individuals.Patients of all age groups may develop polyarteritis nodosa.There is no racial predilection to polyarteritis nodosa.Males are more commonly affected by polyarteritis nodosa than females.Population prevalence estimates for polyarteritis nodosa (PAN) range from 2 to 33 per million across the European Countries.
Risk Factors
Common risk factors in the development of PAN include hepatitis B virus infection and age 40 to 60. Less common risk factors in the development of PAN include hairy cell leukemia, hepatitis C virus and male sex.
Screening
There is insufficient evidence to recommend routine screening for polyarteritis nodosa.
Natural History, Complications and Prognosis
PAN if left untreated, the disease is fatal in most cases. The most serious associated conditions generally involve the kidneys and gastrointestinal tract. Common complications of PAN include Stroke,Kidney failure, heart attack,Intestinal necrosis and perforation. Prognosis is generally good if the treatment is started.Therapy results in remissions or cures in 90% of cases. Guillevin and coworkers have described five prognostic factors that predict high probability of mortality and are considered indications for another immunosuppressive drug in addition to prednisone.
Diagnosis
History and Symptoms
Patients with polyarteritis nodosa may have an acute presentation.The prodrome of polyarteritis nodosa can range from anywhere between weeks to months. Polyarteritis nodosa is a multiorgan disorder but can also be seen in a single organ. Common symptoms include fatigue, weakness, fever,abdominal pain, decreased appetite etc
Physical Examination
Physical examination plays an important role in diagnosing polyarteritis nodosa. Arteritis can be suspected with the presence of multiple mononeuropathies.Signs of ischemia such as extremity ischemia, hypertension and renovascular disease can help in diagnosing polyarteritis nodosa. Skin examination of patients with polyarteritis nodosa can show Livedo reticularis, ulceration, digital ischemia, and nodules. Polyarteritis nodosa may present with ophthalmologic symptoms like retinal vasculitis, retinal detachment and cotton-wool spots. Cardiovascular examination of patients with polyarteritis nodosa shows hypertension, tachycardia, pericardial friction rub, arrhythmias and congestive heart failure. Abdominal examination of patients with polyarteritis nodosa shows abdominal tenderness and gastro-intestinal bleeding. Neuromuscular examination of patients with polyarteritis nodosa shows sensory and/or motor neuropathies and mononeuritis multiplex.
Laboratory Findings
There are no specific lab tests for diagnosing polyarteritis nodosa. Diagnosis is generally based upon the physical examination and a few laboratory studies that help to confirm the diagnosis. Laboratory findings helpful in the diagnosis of polyarteritis nodosa include CBC, ESR, C-reactive protein, p-ANCA, Hepatitis B surface antigen and hepatitic C serologies, elevated levels of liver enzymes, elevated creatinine level and hypergammaglobulinemia.
Electrocardiogram
There are no ECG findings specific to polyarteritis nodosa but patients may present with arrhythmia.
Chest X Ray
There are no x-ray findings associated with polyarteritis nodosa.
CT
CT scan may be helpful in the diagnosis of polyarteritis nodosa. Findings on CT scan of GI tract suggestive of polyarteritis nodosa include bowel wall thickening, mesenteric vascular engorgement, ascites, bowel obstruction and diffuse mucosal fold thickening.
MRI
MRI is useful to identify hemorrhage and ischemia in the central nervous system. New MRI techniques utilize perfusion weighted images and blood diffusion to distinguish intracranial hemorrhage and reversible ischemia. MRI can also be used to image the abdomen when there is GI involvement.
Echocardiography or Ultrasound
There are no echocardiography/ultrasound findings associated with PAN.
Other Imaging Findings
Arteriography is the best imaging study to diagnosis of PAN. Findings on an arteriography diagnostic of PAN include microaneurysm, saccular aneurysm and tortuous vessels showing irregular lumina, segmental luminal narrowing or dilatation, infarctions, vascular irregularity and segmental occlusions.
Other Diagnostic Studies
EMG and nerve conduction studies can be done in cases of nerve involvement and help in nerve biopsy. Tissue biopsy (reveals inflammation in small arteries, called arteritis).
Treatment
Surgery
Surgical intervention is not recommended for the management of polyarteritis nodosa.
Medical Therapy
Treatment involves medications to suppress the immune system such as prednisone and cyclophosphamide. Addition of immunosuppressants like cyclophosphamide, methotrexate, azathioprine to corticosteroid therapy has better prognosis. Patients with hepatitis B associated polyarteritis nodosa are treated with corticosteroid therapy, antiviral agents and plasma exchanges. Unlike hepatitis B associated PAN, Hepatitis C associated PAN is treated with Rituximab and corticosteoid therapy without antiviral agents, emphasizing the B cell targeted therapy. Mild cases of cutaneous polyarteritis nodosa are treated with nonsteroidal anti-inflammatory drugs. Severe cases are treated with corticosteroid and adjunctive therapy. Antibiotics are added to the treatment of patients with antecedent streptococcal infections or high ASO titer.Intravenous immunoglobulin is suggested for treatment of corticosteroid therapy resistant cases, but the effect is transient. It is also used in the treatment of Parvovirus B19 associated polyarteritis nodosa
Primary Prevention
There are no established measures for the primary prevention of polyarteritis nodosa.
Secondary Prevention
There are no established measures for the secondary prevention of polyarteritis nodosa.
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
References
- ↑ Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL; et al. (1994). "Nomenclature of systemic vasculitides. Proposal of an international consensus conference". Arthritis Rheum. 37 (2): 187–92. PMID 8129773.
- ↑ Kallenberg CG, Brouwer E, Weening JJ, Tervaert JW (1994). "Anti-neutrophil cytoplasmic antibodies: current diagnostic and pathophysiological potential". Kidney Int. 46 (1): 1–15. PMID 7933826.