What are the other Names for this Condition? (Also known as/Synonyms)

• Kussmaul-Maier Disease
• Panarteritis Nodosa
• Periarteritis Nodosa

What is Polyarteritis Nodosa? (Definition/Background Information)

• Polyarteritis Nodosa (PAN) is a rare and mostly systemic form of vasculitis, which are a group of disorders that result in the inflammation of the blood vessels. The condition is mostly described in middle-aged and older adults, affecting the medium-sized blood vessels in the body. PAN may affect the skin, gastrointestinal tract, joints, heart, and/or the nervous system
• In vasculitis, when inflammation of the blood vessels occurs, it causes thickening of the blood vessel walls, thus narrowing the arteries supplying blood and oxygen to the various parts of the body/organ. This can result in organ dysfunction. Chronic inflammation of the walls can also weaken it, leading to the formation of aneurysms that can rupture and cause severe internal bleeding
• Even though Polyarteritis Nodosa is a chronic condition with periods of remission (absence of symptoms) and recurrence, its manifestation may be varied in individuals - such that it may only affect the skin, or a single organ of the body, or affect several body systems and organs. Thus, the signs and symptoms, diagnosis, and treatment of the condition can vary significantly from one individual to another
• The cause of Polyarteritis Nodosa is generally unknown, but it may be an autoimmune condition that is triggered by certain infections. The condition is not seen in the background of a family history. Previously, prior to the advent of suitable vaccinations, PAN was associated with hepatitis B virus infection
• In order to establish a diagnosis of Polyarteritis Nodosa, a wide variety of tests and exams may be performed that include blood and urine tests, radiological studies such as an angiogram, and a tissue biopsy, when needed
• An early diagnosis and appropriate treatment of Polyarteritis Nodosa, via corticosteroid therapy and immunosuppressive medications, can lead to a good prognosis. However, a late recognition and delayed management of the condition can severely worsen the outcomes

Who gets Polyarteritis Nodosa? (Age and Sex Distribution)

• Polyarteritis Nodosa is a rare disorder that may be seen across a wide age group, from children to older adults. A majority of the cases are seen in the 45 to 65 year age group
• Even though both males and females are affected, a greater number of cases are reported in men than in women
• It is observed worldwide and can affect people of all racial and ethnic backgrounds
• The prevalence rate in the US is around 30-45 cases per million population

What are the Risk Factors for Polyarteritis Nodosa? (Predisposing Factors)

In a vast majority of cases, the risk factors for Polyarteritis Nodosa are not clearly established. It is believed that the condition may be associated with the following factors:

• Viral and bacterial infections
• Vaccinations
• Use of medications

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Polyarteritis Nodosa? (Etiology)

Polyarteritis Nodosa (PAN) is the inflammation of medium-sized blood vessels of the body. The condition is categorized as is a form of medium-sized blood vessel vasculitis and it can cause injury to several body systems.

• The exact cause of development of the condition is not well-established. Researchers believe that PAN may develop from immune system abnormalities triggered by certain infections, medication use, or vaccinations
• When the blood vessels are affected, it leads to their constriction causing reduced blood flow to the involved region. This often results in weakened and scarred blood vessel walls, and dysfunction of the organs and body region due to lowered blood supply, causing a set of associated signs and symptoms
• Earlier, Polyarteritis Nodosa was associated with hepatitis B viral infection in a majority of cases. However, after the development of a suitable vaccine for the infection, the number of cases of PAN has considerably decreased

What are the Signs and Symptoms of Polyarteritis Nodosa?

The severity of signs and symptoms of Polyarteritis Nodosa may vary from one individual to another. In some, it may be mild, resulting in a delayed diagnosis of the condition. In other individuals, it may be severe. The signs and symptoms depend on the organs and body systems affected. In some individuals, only the skin is involved (called cutaneous Polyarteritis Nodosa); while in others, a single body organ or several body organs, including the digestive tract, heart, muscles and joints, nerves, and the kidneys may be affected.

The common signs and symptoms of Polyarteritis Nodosa that develop over weeks and months may include:

• Fever
• Skin rashes
• Headaches
• Fatigue
• Weakness and malaise
• Pain that may affect the chest, back, or abdomen
• Shortness of breath
• Pain in the testicles

Based on the involvement of the various organs/systems, any or all of the following signs and symptoms may be noted. It is important to note that the combination of signs and symptoms varies from individual to individual.

Signs and symptoms related to the skin and underlying tissue (integumentary system):

• Formation of ulcer sores or nodules
• Elevated swellings
• Pain and discomfort
• Itchiness of skin causing irritability
• Dryness of skin
• Discoloration of skin (pigmentation changes)
• Bleeding on scratching of skin
• Any skin of the body surface may be involved

Signs and symptoms related to the gastrointestinal (GI) system:

• Nausea and vomiting
• Difficulty in swallowing
• Hiccups
• Hoarse voice
• Indigestion; feeling of fullness after eating a small amount of food
• Heartburn or acid reflux (gastroesophageal reflux disease or GERD)
• Loss of appetite
• Abdominal pain and discomfort
• Abdominal bloating and distension
• Irregular bowel movements
• Passing gas; belching or flatus
• Constipation or diarrhea
• Blood in stool
• Unintended loss of weight

Signs and symptoms related to the heart and blood vessels (cardiovascular system):

• Sweating and discomfort
• Heart palpitations
• Blood in sputum
• Confusion
• Abnormal heartbeats (arrhythmias)
• Dizziness or lightheadedness
• Fainting (syncope)

Signs and symptoms related to the muscles and joints (musculoskeletal system):

• Inflammation of the muscles and joints
• Muscle and joint pain, involving one or more joints
• Tenderness of the muscles
• Muscle stiffness and spasms
• Swollen joints
• Joint stiffness
• Muscle weakness, especially involving the upper or lower limbs, often with sudden onset
• Loss of muscle mass
• Muscle contracture
• Difficulty climbing stairs and walking
• Difficulty with other motor skills, including jumping, hopping, and running
• Difficulty in bending or stretching one’s back
• Limited range of motion; decreased joint function
• The condition may involve any joint in the body such as the knee, elbow, shoulder, hip, etc.

Signs and symptoms related to the brain and spinal cord (central nervous system) and peripheral nervous system (cerebrovascular system):

• Headaches that may be of sudden onset; persistent headaches
• Damage to peripheral nerves
• Numbness and tingling sensation
• Muscle weakness; loss of strength
• Neck pain
• Back pain
• Visual impairment such as blurred vision, double vision or poor eyesight
• Hearing loss
• Insomnia or loss of sleep, or excessive sleepiness (usually during daytime)
• Tremors
• Seizures or convulsions
• Lack of coordination; unsteadiness
• Dizziness; vertigo
• Confusion
• Fainting
• Change in behavior
• Mental impairment
• Memory loss

Signs and symptoms related to the kidney and urinary bladder (genitourinary system):

• Unexplained fever
• Night sweats
• Difficulty in urinating; presence of burning sensation
• Pain while urination, frequent urge to urinate
• Presence of blood in the urine
• Feeling of obstruction while urinating
• Inflammation of the bladder (cystitis)
• Sharp pain in the back or lower abdomen that radiates to the groin
• Chronic pain in the pelvis
• Fluid accumulation in the lower legs (pedal edema)

The specific signs and symptoms of the underlying condition, if any, may be additionally noted.

How is Polyarteritis Nodosa Diagnosed?

A diagnosis of Polyarteritis Nodosa depends on the body system or organ that is affected. In many cases, a diagnosis is made on the basis of an angiogram, to visualize the affected region, and/or a tissue biopsy of the involved organ, such as the skin, muscle, nerve, or kidney.

The diagnosis may involve the following tests and examinations:

• Complete physical examination and a thorough medical history
• Assessment of the presenting signs and symptoms

Tests and procedures based on the different body part/organ or system that is affected may include any of the following.

• Blood and urine tests related to overall inflammatory and autoimmune activity:
  • Complete blood count (CBC) with differential: This measures the red blood cell count and hemoglobin levels in blood
  • Erythrocyte sedimentation rate (ESR): ESR is a blood test that can help the healthcare provider identify any inflammatory activity within the body
  • C-reactive protein (CRP) test: This blood test measures the amount of a protein, called C-reactive protein, in blood. It also provides information on the inflammation condition of the body
  • Anti-nuclear antibody (ANA) test: ANA test identifies the antinuclear antibodies within the blood
  • Basic metabolic panel tests
  • Anti-streptolysin O (ASO) titer test, if a streptococcal infection is the suspected trigger
  • Specific antibodies test
  • Protein electrophoresis and immunofixation electrophoresis tests
  • Complement blood test
  • Cryoglobulin blood test
  • HIV antibody blood test
  • Urine tests for protein and presence of blood
  • Urinalysis

Tests and procedures related to the skin and underlying tissue (integumentary system):

• Dermoscopy: It is a diagnostic tool where a dermatologist examines the skin using a special magnified lens
• Wood’s lamp examination: In this procedure, the healthcare provider examines the skin using ultraviolet light. It is performed to examine the change in skin pigmentation
• Punch biopsy of skin for immunofluorescence studies, especially direct immunofluorescence studies. The immunofluorescence deposits can be performed with fluorescein-labeled antibodies against IgG, IgM, IgA, and C3
• Skin biopsy: A skin biopsy is performed and sent to a laboratory for a pathological examination. The pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis

Tests and procedures related to the gastrointestinal (GI) system:

• Liver function tests
• Viral hepatitis panel
• Imaging studies that may include:
  • X-ray of chest or abdomen
  • Ultrasound studies of the chest or abdomen
  • CT scan of chest or abdomen
  • MRI studies of abdominal organs
  • Gastrointestinal angiographic studies
  • Magnetic resonance cholangiopancreatography (MRCP): It is a special MRI exam of the hepatobiliary and pancreatic systems
• Upper GI endoscopy: An endoscopic procedure is performed using an instrument called an endoscope, which consists of a thin tube and a camera. Using this technique, the radiologist can have a thorough examination of the insides of the upper GI tract
• Colonoscopy: A colonoscopy is a test that allows the physician to look at the inner lining of the colon and rectum. A typical colonoscopy involves using a thin, flexible tube (called a colonoscope), with an attached video camera, to view the colon and rectum
• Exploratory laparoscopy (diagnostic laparoscopy) may be required, if gastrointestinal symptoms are present. In this procedure, the abdomen is examined using a minimally-invasive technique, and a tissue biopsy and tissue for culture obtained
• Tissue biopsy: A biopsy of the affected region is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy sample under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy sample under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis

Tests and procedures related to the heart and blood vessels (cardiovascular system):

• Electrocardiogram (EKG or ECG): It is used to measure the electrical activity of the heart to detect arrhythmias
• Electrophysiological studies of the heart, to determine where arrhythmia is getting generated in the heart, is often helpful
• Checking oxygen levels in blood through the skin using a pulse oximeter
• Checking oxygen levels in blood using an arterial blood gas test
• Radiological imaging studies that include:
  • CT scan of the thorax
  • MRI scan of the heart
  • Echocardiography: This procedure uses sound waves to create a motion picture of the heart movement. It can help show the size and shape of the heart and how well the chambers and valves are working
  • Doppler ultrasound: Sound waves are used to measure the speed and direction of blood flow
• Cardiac catheterization: The passage of a thin catheter into the right or left side of the heart to diagnose (and may be treat) cardiovascular conditions
• Tissue biopsy:
  • A tissue biopsy is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
  • Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
  • Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, and very rarely, electron microscopic studies to assist in the diagnosis

Tests and procedures related to the muscles and joints (musculoskeletal system):

• Laboratory tests, which may include:
  • Creatine kinase test: It is used to measure the amount of creatine kinase in blood. The enzyme creatine kinase is released by the muscle and into the bloodstream, when any deterioration has occurred
  • Rheumatoid factor blood test
  • Cyclic citrullinated peptide antibody blood test (anti-CCP)
• Electromyogram (EMG): Electromyographic studies to determine the region of muscle that is affected
• Radiological imaging studies of the affected region such as:
  • X-ray studies
  • CT scans
  • MRI scans
  • Ultrasound imaging: An ultrasound imaging equipment uses high-frequency sound waves to generate a more detailed image of affected region
  • Musculoskeletal angiographic studies
• Fine needle aspiration (FNA) of joint fluid: Occasionally, fluid may accumulate around a joint, which results in pain and disability. Analysis of this joint will provide clues regarding the cause of joint fluid accumulation
• Muscle biopsy: A biopsy of the affected muscle tissue is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy sample under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy sample under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis

Tests and procedures related to the brain and spinal cord (central nervous system) and peripheral nervous system (cerebrovascular system):

• Neurological, motor skills, and cognitive assessment: Checking intellectual ability, memory, mental health and function, language skills, judgment and reasoning, coordination and balance, reflexes, sensory perceptions (space, sight, hearing, touch)
• Electroencephalography (EEG)
• Electromyography with nerve conductivity tests
• Imaging studies that may be performed include:
  • X-ray of head and neck and/or vertebral column
  • CT scan of the head and neck region and/or vertebral column
  • MRI scan of the central nervous system (brain and spine)
  • Cerebral angiographic studies
• Cerebrospinal fluid analysis, where a spinal tap test may be performed

Tests and procedures related to the kidney and urinary bladder (genitourinary system):

• Diagnostic tests may include the following:
  • Urinalysis
  • Blood tests including blood urea nitrogen (BUN) and creatinine levels
  • Kidney function tests
• Radiological studies that may include:
  • Abdominal X-ray
  • CT scan of the abdomen
  • Ultrasound scan of the kidneys
  • MRI scan of the kidney
  • Intravenous pyelogram (IVP): A dye is injected into the blood vessels and the image of kidney structure is obtained
  • Angiography of the abdominal region
• Ureteroscopy: Endoscopic study of the upper urinary tract using an endoscope inserted through the urethra
• Cystoscopy: During a cystoscopy, a narrow tube called a cystoscope is inserted to look directly into the bladder. A local anesthetic is usually administered, in order to make the examination more comfortable

Invasive diagnostic procedures such as:

• Laparoscopy: A special device is inserted through a small hole into the abdomen, to visually examine it. If necessary, a tissue sample is obtained for further analysis. Exploration of the abdomen using a laparoscope is called ‘exploratory laparoscopy’
• Laparotomy: The abdomen is opened through an incision for examination, and if required, a biopsy sample obtained. Exploration of the abdomen using laparotomy procedure is called ‘exploratory laparotomy’

Although the above modalities can be used to make the initial diagnosis, a tissue biopsy may be required to make a definitive diagnosis to begin treatment. The tissue for diagnosis can be procured in multiple different ways, and they include:

• Fine needle aspiration (FNA) biopsy: An FNA biopsy may not be helpful, because one may not be able to visualize the different morphological areas of the affected region. Hence, an FNA biopsy as a diagnostic tool has certain limitations, and an open surgical biopsy is preferred
• Core biopsy of kidney
• Open biopsy of kidney

A tissue biopsy is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis.

• Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation.
• Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, and very rarely electron microscopic studies to assist in the diagnosis

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Polyarteritis Nodosa?

The complications of Polyarteritis Nodosa are contingent on the organs affected due to reduced blood flow, the severity of the signs and symptoms, and one’s response to treatment. Severe vasculitis can cause organ failure due to severely restricted blood flow. This can occur due to formation of blood clots and/or rupture of blood vessels.

High blood pressure (hypertension) is commonly observed and it can result in severe injury to the intestine, kidney, liver, and heart. The involvement of the lungs is usually not seen.

Complications associated with the skin and underlying tissue (integumentary system):

• Emotional stress due to cosmetic concerns
• Discomfort, irritability of the affected skin
• Severe pain and itchiness of skin leading to acute discomfort and irritation, including sleep disruption
• The lesions may occasionally develop bacterial or fungal infections
• Permanent scarring

Complications associated with the gastrointestinal (GI) system:

• Inability to eat
• Weight loss and malnutrition
• GI tract bleeding
• Perforation of the GI tract
• Stricture formation of the food pipe

Complications associated with the heart and blood vessels (cardiovascular system):

• Severe arrhythmias
• Normal function of the heart is severely affected due to inflammation of the heart muscles
• It can weaken of the aorta causing aortic aneurysm, which is a potentially life-threatening complication. The risk for aneurysmal rupture from PAN is usually high
• Congestive heart failure
• Increased risk for thromboembolism (blood clot obstructing a blood vessel)
• Chronic high blood pressure in the blood vessels of the lungs

Complications associated with the muscles and joints (musculoskeletal system):

• Chronic pain and weakness of the joint affecting the quality of life
• Formation of scar tissue in the muscle and joint tissue
• Immobilization due to loss of movement
• Permanent disability

Complications associated with the brain and spinal cord (central nervous system) and peripheral nervous system (cerebrovascular system):

• Severe and persistent headaches
• Reduced performance at school or work
• Severely affected quality of life due to mental health issues

Complications associated with the kidney and urinary bladder (genitourinary system):

• Severe pain in the back or lower part of the abdomen
• Obstruction of the urinary bladder
• Blockage of the urinary tract may lead to kidney damage
• Hydronephrosis of kidneys (swollen kidneys)
• High blood pressure can result in a brain stroke or heart failure
• Erectile dysfunction
• Urinary incontinence (involuntary dripping or leakage of urine)
• Severe cases may result in kidney failure

Treatment complications: Some complications are known to take place with treatment; in some cases, due to treatment also. Immunosuppressive therapy that is used to treat Polyarteritis Nodosa may lead to certain complications that include:

• Low blood pressure
• Hyperkalemia or high levels of potassium in blood
• Tremors
• Diabetes mellitus
• Osteoporosis causing decreased bone density
• Decreased muscle function
• Long-term kidney dysfunction
• Elevated risk for malignancy
• Decrease in body immunity to fight infections

How is Polyarteritis Nodosa Treated?

The treatment of Polyarteritis Nodosa depends upon a variety of factors including:

• Severity of the signs and symptoms
• Regions of the body affected and the level of functioning of the affected organs
• Overall health status of the individual and his/her age
• Underlying cause, if any noted

If a clearly identifiable cause is not known, then the primary role of treatment of Polyarteritis Nodosa is to reduce inflammation. Often, a multidisciplinary team of specialists that include general practitioners, rheumatologists, neurologists, cardiovascular experts, nephrologists, dermatologists, among others, may be involved in the treatment. The treatment is often known to last for months and years.

The treatment methods for Polyarteritis Nodosa may include:

• Corticosteroid therapy: If only mild symptoms are observed with no severe systemic involvement (very rare), then corticosteroid therapy can bring about a remission, in many individuals
• Immunosuppressive medications using low dose cyclophosphamide, a chemotherapy agent, is usually known to be beneficial
• Administration of medications to suitably regulate the immune system
• Biologic agents using specific monoclonal antibodies to reduce inflammation
• In cases with severe symptoms, or when the affected individuals do not respond to the above-mentioned treatments, plasma exchange (plasmapheresis) or intravenous immunoglobulin (IVIG) therapy may be considered
• Rarely, vascular surgery, such as vascular bypass procedures, vascular stent placements, and removal of blood clots (thrombectomy), are found to be beneficial
• If the heart is severely affected, then the following invasive procedures may be considered:
  • Bypass surgery for large arterial blockage
  • Repair or replacement of heart valve
  • Percutaneous angioplasty for severe blocks
• If hepatitis B virus infection is noted, then the use of suitable antiviral agents may be considered
• Follow-up care with regular screening and check-ups are important and encouraged

The treatment also depends on whether there are recurring episodes of the condition. The goal of the treatment is to control the inflammation in order to achieve remission (a state where no signs and symptoms are noted) and maintenance therapy to prevent episodes of relapses.

How can Polyarteritis Nodosa be Prevented?

• Currently, there are no methods available to prevent Polyarteritis Nodosa. An early diagnosis and prompt treatment can help decrease the burden of the condition
• Maintaining a healthy lifestyle with good eating habits, adequate physical activities, and avoidance of smoking or drinking is beneficial
• Ensuring that individuals, especially children, are up-to-date on their vaccinations is important
• Patients are required to be vigilant during the remission period and report any new symptoms promptly to the healthcare provider

Regular medical screening at periodic intervals with blood tests, scans, and physical examinations, are mandatory, due to the possibility of recurrence/relapse. Often several years of active vigilance is necessary.

What is the Prognosis of Polyarteritis Nodosa? (Outcomes/Resolutions)

• The prognosis of Polyarteritis Nodosa (PAN) depends upon a variety of factors including the:
  • Severity of the condition; degree of damage to the vital organs and body systems
  • Age and overall health of the individual
  • One’s response to treatment
  • The underlying trigger, if any identified
  • Whether it is an initial episode or a recurring episode
• In general, PAN is a chronic condition that has periods of remission and relapses; a proper management of the condition with an overall treatment strategy is important. Relapses or recurrences are seen in 10% to 40% of the treated individuals. Hence, a close follow-up with adequate and timely testing is strongly recommended
• The prognosis of PAN is typically good with consistent and appropriate treatment. However, the course of the condition is difficult to predict. Moreover, the tolerance to the strong medications used in treatment, may vary considerably from one to another. This factor can also influence the overall prognosis
• About 80% of the affected individuals do well after 5 years; whereas, without treatment, less than 15% are known to survive after 5 years. Individuals with extensive condition affecting several regions of the body have poorer prognosis, than individuals in whom the condition is confined to certain part(s) of the body

Even with treatment, Polyarteritis Nodosa can relapse. If blood in cough or blood in urine is observed, then it is extremely important to contact the healthcare provider right away.

Additional and Relevant Useful Information for Polyarteritis Nodosa:

The following article link will help you understand other Vein & Vascular Health:

https://www.dovemed.com/health-topics/vein-and-vascular-center/