Polyarteritis Nodosa

 

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Original Editors - Josh Bixler from Bellarmine University's Pathophysiology of Complex Patient Problems project.

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Definition/Description

Polyarteritis nodosa (PAN), also known as periarteritis nodosa or Kussmaul-Maier disease, is a serious ideopathic vascular disease that commonly affects both small and medium-sized arteries throughout the body. It falls under the category of primary systemic vasculitis, and more specifically as a necrotizing inflammation without vasculitis of the arterioles, capillaries, or venules. Due to the inflammatory nature of the disease, arteries become swollen and blood flow is diminished. The inflammation, which affects the entire arterial wall, typically manifests where the arteries branch and ultimately the affected vessel tissues become necrotic. As the outer and inner layers of the artery swell, blood clots can form and potentially damage various organs and tissues in the body such as the liver, kidneys, heart, GI tract, testes, and muscles.

Prevalence

• Development and diagnosis of the disease seems to occur between the ages of 40 and 60.
• While it affects adults more so than children, it can present at any age.
• Twice as likely to occur in men than women.
• Can affect every ethnicity and race.
• Rare disease, but estimates of frequency in the US are around 77/1,000,000.
• Internationally, reports have listed frequency in south Sweden at 1.6/1,000,000; 4.6/1,000,000 in England; 30.7/1,000,000 in Paris, France.

Characteristics/Clinical Presentation

Polyarteritis nodosa is clinically similiar to many diseases such as hepatitis B and C infections, Churg-Strauss syndrome, Kawaski's disease, hypersensitivity angitis, as well as Cogan's syndrome. The speed at which the disease affects an individual often varies. Within months, it may initially present with mild symptoms that rapidly progress to fatal symptoms, or it can develop into a chronic state that incapacitates the individual. With the exception of the lungs, polyarteritis nodosa has the ability to affect many organs and organ systems at the same time by damaging the arteries that supply blood flow. The heart, intestines, liver, and kidney arteries are prevalently damaged. Listed below are some of the most common symptoms associated with this disease, affecting the skin, joints, brain, nerves, heart, digestive tract, liver, and kidneys:

Ankle affected by PAN

• Rashes with raised patches along arteries, discoloration of fingers or toes, blotches that appear purple
• Joint pain and inflammation, muscle aches and pain
• Fever, headaches, strokes, seizures
• Weakness, numbness, tingling, or hand or foot paralysis
• Angina and myocardial infarctions
• Peritonitis (infection of the abdomen), nausea, vomiting, bloody diarrhea, intestinal tears, and rapid weight loss
• Liver damage and failure
• Hypertension, edema, decreased output of urine, urine with high levels of protein 
  

Associated Co-morbidities

• Cholecystitis
  File:PAN Peripheral neuropathy.jpg
• Pericarditis
• Myocarditis
• Arrhythmias
• GI hemorrhage
• CHF
• Infections
• Hypertension
• Peripheral neuropathies

Medications

Typically corticosteroids and drugs that suppress the immune system are prescribed. One such steroid is prednisone, which allows the affected individual some pain relief and can help stop the disease from causing more damage. Also, to further address the inflammation, cyclophosphamide is often prescribed in combination with the prednisone. If the cause of polyarteritis nodosa is related to a hepatitis infection, and the inflammation has been limited, 

anti-viral medication along with plasmapheresis is used to combat the infection.

Diagnostic Tests/Lab Tests/Lab Values

Diagnosis:

Currently there is not a single gold standard test for diagnosing an individual with PAN, rather a cluster of tests and criteria are used to do so. Patient history, blood testing, biopsies from affected sites, and angiograms are all common procedures used to direct the physician with their diagnosis. To further assist with this process, in 

1990 the American College of Rheumatology established criteria to help differentiate PAN from other similiar diseases:

1. Weight loss > 4 kg

Loss of 4 kg or more of body weight since illness began, not due to dieting or other factors

2. Livedo reticularis

Mottled reticular pattern over the skin or portions of the extremities or torso

3. Testicular pain or tenderness

Pain or tenderness of the testicles, not due to infection, trauma, or other causes

4. Myalgias, weakness or leg tenderness

Diffuse myalgias (excluding shoulder and hip girdle) or weakness of muscles or tenderness of leg muscles

5. Mononeuropathy or polyneuropathy

Development of mononeuropathy, multiple mononeuropathys, or polyneuropathy

6. Diastolic BP >90 mm Hg

Development of hypertension with diastolic BP higher than 90 mm Hg

7. Elevated BUN or creatinine

Elevation of BUN >40 mg/dl or creatinine >1.5 mg/dl, not due to dehydration or obstruction

8. Hepatitis B virus

Presenece of hepatitis B surface antigen or antibody in serum

9. Arteriographic abnormality

Arteriogram showing aneurysms or occlusions of the visceral arteries, not due to arteriosclerosis, fibromuscular dysplasia, or other noninflammatory causes

10. Biopsy of small or medium-sized artery containing PMN

Histologic changes showing the presence of granulocytes or granulocytes and mononuclear leukocytes in the artery wall

* For classification purposes, a patient shall be said to have polyarteritis nodosa if at least 3 of these 10 criteria are present. The presence of any 3 or more criteria yields a sensitivity of 82.2% and a specificicy of 86.6%. BP = blood pressure; BUN = blood urea nitrogen; PMN = polymorphonuclear neutrophils.

Lab tests peformed may include:

• Complete Blood Count (CBC): An elevated WBC count may be present.
• Arteriogram and X-ray: View possible damage to the small and medium sized arteries which includes stenoses and aneurysms.
• Erythrocyte Sedimentation Rate (ESR): Often elevated
• C-reactive protein: Often elevated
• Immunoglobulin levels: Possibly elevated
• Biopsy of affected tissues: Affected tissue samples are taken to be viewed under a microscope.
• Electromyography (EMG): Identifies nerve involvement and provides site for potential nerve biopsy.

Etiology/Causes

The cause of PAN remains unknown, but there does appear to be a link to drug reactions, viral infections, and the body's immune system. Adverse drug reactions to iodide or pencillin, or indiviudals with active hepatitis B or C appear to be at a higher risk for developing this disease. In fact, for approximately every five individuals affected by PAN, one of those people has active hepatitis B.

Systemic Involvement

Due to its involvement with the arterial system, PAN has the ability to affect many systems in the body, notably the nervous, integumentary, renal, and GI system. Listed below are the systems most commonly affected and what is typically seen:

Nervous System:

• Peripheral neuropathy (50-70% of the time) with the individual experiencing numbness, tingling, or burning sensations in the extremities
• CNS lesions
  File:PAN LE.jpg

  Lower extremity with livedo reticularis

Integumentary System: (most commonly seen affecting the legs)

• Purpura
• Livedo reticularis
• Ulcers
• Nodules
• Gangrene

Renal System:

• Flank pain
• Hypertension
• Decreased kidney function (dialysis may be needed in some cases)
• Protein in urine

Gastrointestinal System:

• GI bleeding
• Abdominal pain
• Nausea/vomiting
• Constipation
  

  Kidney affected by PAN
• Melena
• Hematochezia
• Possible hemmorrhage or perforation (rare)

Musculoskeletal System:

• Arthralgia
• Myalgia
• Arthritis (less common)

Cardiac System:

• Chest pain
• Tachycardia
• Pericarditis
• Myocarditis
• Arrhythmias
• Dyspnea
• Possible myocardial infarctions or congestive heart failure

Ophthalmologic:

Aneurysms in the liver, spleen, both kidneys, and lumbar arteries.

• Blurred vision
• Scleritis

Genitourinary System:

• Testicular pain (unilateral)
• Testicular infarction

Neuropsychiatric:

• Headache
• Depression
• Psychosis

Pulmonary System:

• Involvement of the lungs is very rare

Medical Management (current best evidence)

Medicinal Treatment and Prognosis:

Treatment is neccesary, and corticosteroids (prednisone) and immunosuppressants (cyclophosphamide) are prescribed to help manage the symptoms and allow for healing of the vascular lesions. Cessation of the medication often leads to relapses and those who do not recieve treatment will likely die within 2 to 5 years. With the medication, affected individuals are now seeing survival rates at 90% for 5 years and up to 70% for 10 years. However, if the individual is also affected with hepatitis B, treatment becomes much more complex as these medications can make the hepatitis B infection worse. If hepatitis B is present as well, the current thought is to treat the vasculitis for two weeks using prednisone, and then undergo plasmopharesis while addressing the infection using anti-viral therapy with lamivudine.

"5 Factor Score" - The likelihood of mortality is increased should any of the 5 factors listed below be present:

• Involvement of CNS
• Involvement of  the GI system (infarction, pancreatitis, bleeding, perforation)
• Cardiomyopathy
• Renal insufficiency (serum creatine >1.58 mg/dL)
• Proteinuria (>1 g/d)

Non-Hepatitis B Virus (non-HBV) related PAN treament with a 5 factor score of 1 or greater:

• oral prednisone with a disease modifying antirheumatic drug (DMARD)
  
• intravenous methylprednisone
  
• cyclophosphamide

Non-Hepatitis B Virus (non-HBV) related PAN treatment with a 5 factor score of 0 or greater:

• oral prednisone
  
• DMARD
  
• cyclophosphamide
  

Hepatitis B Virus (HBV) PAN treatment:

• oral prednisolone with or without intravenous methylprednisolone
• plasmopharesis with lamivudine

Surgery:

Medication is the typical treatment for individuals with PAN, however surgery is necessary should the affected individual present with appendicitis, cholecystitis, pancreatitis, infarction of the digestive tract, hemorrhage, or bowel perforation. Poor outcomes are typically seen with these surgeries with the exception of the procedures for appendicitis or cholecystitis, which have outcomes similiar to those not affected by the disease.

Emerging treatments for PAN:

• Use of intravenous immunoglobulin (IVIG) for those individuals who don't have hepatitis B infection, yet don't respond to conventional treatment.
• Use of anti-tumor necrosis factor (TNF)-alpha therapy for more resistant forms of this disease.
• Use of B-cell therapy for those individuals who don't repsond to the conventional treatment.
• Use of iterferon alfa for those individuals with PAN and the hepatitis B virus in mild/moderate cases.

Additional Information:
EULAR Recommendations for the Management of Primary Small and Medium Vessel Vasculitis: http://www.vasculitis.org/images/documents/smallmediumvessel.pdf

Physical Therapy Management (current best evidence)

The current best treatment for PAN primarily consists of medical management with the use of the corticosteroids and immunosuppressant drugs. With the nature of the disease, many systems are affected and currently there is no practice pattern for which PAN falls under in the Guide to Physical Therapy Practice (2nd ed.). However, once the patient is medically stable, a physical therapist can help address limitations the individual may be experiencing due to the multiple system involvement. As PAN affects each individual differently, a physical therapist can work with this patient based on their unique needs, and ultimately towards acheiving their personal goals and activities of daily living.

Alternative/Holistic Management (current best evidence)

At the present time, there is no known alternative or hollistic approaches to treating this disease, but a healthy lifestyle and diet is recommended. It's important to note that any alternative or hollisitic approaches added to one's life could potentially affect their current treatment and should be discussed with a physician.

Differential Diagnosis

• Hepatitis B and C infections
• Antiphospholipid syndrome
• Atrial myxoma
• Takayasu's arteritis
  
• Horton's disease
  
• Churg-Strauss syndrome
  
• Cholesterol embolism
• Wegener's granulomatosis
  
• Cryoglobulinemia
• Microscopic polyangiitis
• Ehlers-Danlos syndrome
• Cogan's syndrome
• Goodpasture syndrome
• Infective endocarditis
• Kawasaki disease
• Henoch-Schoenlein purpura
• Hypersensitivity angitis
• Systemic lupus erythematosus

Case Reports/ Case Studies

Polyarteritis Nodosa in a Patient With Type 1 Autoimmune Hepatitis: case report: http://www.medscape.com/viewarticle/735069

Isolated Polyarteritis Nodosa Presenting as Acute Epididymo-Orchitis: a case report: http://www.journalmc.org/index.php/JMC/article/view/97/90

A Case Of Juvenile Polyarteritis Nodosa With Intestinal Hemorrhage And Multiple Cranial Nerve Palsy: http://www.ispub.com/journal/the_internet_journal_of_rheumatology/volume_2_number_1_57/article/a_case_of_juvenile_polyarteritis_nodosa_with_intestinal_hemorrhage_and_multiple_cranial_nerve_palsy.html

An Unusual Complication of Polyarteritis Nodosa with Massive Retroperitoneal Hemorrhage: a case report: http://www.intarchmed.com/content/3/1/31

Polyarteritis nodosa: a case study: http://www.immunologyclinic.com/case.asp?chap=10&case=12

Resources

The Vasculitis Foundation: http://www.vasculitisfoundation.org/polyarteritisnodosa

The Johns Hopkins Vasculitis Center: http://www.hopkinsvasculitis.org/types-vasculitis/polyarteritis-nodosa/

Merck Manual: http://www.merckmanuals.com/home/sec05/ch069/ch069b.html

Polyarteritis Nodosa Support Network: http://www.pansupportnetwork.org/

Recent Related Research (from Pubmed)

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References

see adding references tutorial.