POLYARTERITIS NODOSA | home
DEFINITION AND GENERALITY
PERIARTERITIS NODOSA (POLYARTERITIS NODOSA)PAN
Periarteritis
Polyarteritis
For nearly 100 years after its description, almost all types of vasculitis were called PAN
. Classic polyarteritis nodosa (PAN) was initially described by Kussmaul and Maier in 1866. In 1948, the term "microscopic polyarteritis" was introduced in the literature by Davson. Subsequently, the Chapel Hill Consensus Conference on the nomenclature of systemic vasculitis held in 1992 officially adopted the term polyarteritis nodosa.
Tends to involve medium-sized blood vessels that have muscular walls, particularly those supplying blood to the gastrointestinal tract and nerves.
Picture credit: KU Medical Center
a very good definition to remember for the PAN:
A disease characterized by segmental inflammation and necrosis of medium-sized muscular arteries, with secondary ischemia of tissue supplied by affected vessels.
serious disease and has a VERY high mortality unless treated with immunosuppression...usually in the form of prednisone and Cyclophosphamide
It essentially consists of an inflammatory reaction in the wall of blood vessels - resulting in occlusion of the vessels and starvation of the tissues of bloodflow and oxygen.
The result is severe tissue damage.
The blood vessel wall is infiltrated with neutrophil
inflammation of a medium-sized deep dermal artery.fibrinoid necrosis. This finding is typical of polyarteritis nodosa and other forms of vasculitis involving medium-sized arteries
necrotizing vasculitis of medium-sized arteries
usually in male adults associated with hepatitis B antigen ,, hepatitis C, or both [of immunoglobulin and viral antigens circulating in the blood and deposited in inflamed vessels. Moreover, antiviral therapy can remit the vasculitis in some of these patients.]HB surface antigen (HBsAg)- anti-HBsAg complexes are present in the circulation and deposited along with C' in the vascular lesions of such patients.
common in injection drug users
Polyarteritis nodosa is probably mediated by deposition of immune complexes
kidney: most frquently involved organ (85%)
multiple small intrarenal aneurysms aneurysms may disappear (thrombosis) or appear in new locations
arterial narrowing and thrombosis (chronic/healing stage)
multiple small cortical infarcts
associated with hypertension and renal failure
chest involvement (70%)
cardiomegaly/pericardial effusion (14%)
wedge shaped/round peripheral infiltrates simulating PE (14%)
interstitial lower lung field pneumonitis
also may involve :
liver (66%),
mesenteric vessels (50%),
skeletal muscle (39%),
skin (20%)
Pathophysiology:
Lesions are segmental and tend to involve bifurcations and branches of arteries.
Involvement of venules is not seen with classic PAN.
Acute stage - Polymorphonuclear neutrophils infiltrate all layers of the vessel wall
Subacute stage - Infiltration of mononuclear cells becomes more prominent
Chronic stage - Fibrinoid necrosis of the vessels causes thrombosis and infarction of the tissues. Aneurysmal dilatations, up to 1 cm in size, of the involved arteries are characteristic findings of PAN.
Kidney lesions show predominant arteritis without glomerulonephritis. However, in patients with severe hypertension, glomerulosclerosis may be superimposed with glomerulonephritis.
In classic PAN pulmonary arteries are not involved;
bronchial artery involvement is uncommon.
PAN is one of the few types of vasculitis characterized by the predisposition to the formation of aneurysms (outpouchings of blood vessel walls, induced by weakening caused by inflammation).
Occasionally, such aneurysms rupture, leading to a surgical emergency.
In this angiogram [SEE ABOVE] of a patient with PAN, large aneurysms of the artery supplying blood to the spleen are demonstrated.
The striking abnormalities of this angiogram (left) are contrasted with the appearance of a normal mesenteric angiogram (right). This is a normal mesenteric angiogram from a patient who underwent the procedure on suspicion of vasculitis involving the gastrointestinal tract. Note the smooth, normal caliber
Mortality/Morbidity: When it is untreated, the 5-year survival rate is 13%. Nearly one-half of patients die within the first 3 months of onset. Corticosteroid treatment improves the 5-year survival rate to 50-60%. When it is combined with other immunosuppressants, the 5-year survival rate may increase to more than 80%.
Cause of death - Renal failure is the most common cause followed by CNS disease. Other causes include gastrointestinal complications (bowel infarcts and perforations) and cardiovascular diseases.
Intractable hypertension adds to the late morbidity and mortality.
Fever, weight loss, and malaise are present in over one-half of cases; renal failure and hypertension in 60%; arthritis, arthralgia, and myalgia in 64%; peripheral neuropathy and mononeuritis multiplex in 51% of patients.
Breed: n/a
Race: No known racial predisposition.
Sex: Men are affected more frequently than women (male-to-female ratio is 1.6:1).
Age: Commonly, onset is between 40-60 years.
The earliest clues that the patient has vasculitis come usually from the skin (where vasculitis may appear as palpable purpura, livedo reticularis, digital gangrnen, or tender nodules), or the peripheral nervous system (where infarction of one mixed motor and sensory nerve after another results in mononeuritis multiplex, one of the most specific clues that a patient has vasculitis).
The disease can occur by itself or in conjunction with other autoimmune disorders, such as:
rheumatoid arthritis,
Wegener's,
or giant cells arteritis [temporal arteritis]
Autoimmune diseases related to polyarteritis are :
Wegener's granulomatosis,
Churg-Strauss syndrome,
Takayasu's arteritis,
temporal or giant cell arteritis
Renal involvement eventually develops in most and is accompanied by hypertension in half of patients, whereas Wegener's granulomatosis rarely elevates the blood pressure.
Polyarteritis nodosa also commonly involves:
the gut (abdominal angina, hemorrhage, perforation),
heart (myocarditis, myocardial infarction),
eye (scleritis).
Rupture of renal or mesenteric micoaneurysms can simulate an acute abdomen
The organs most affected in PAN are the
Skin - with ulceration. Nerves - with neuropathy and mononeuritis and potential for paralysis.
Kidneys - with nephritis and potential for renal failure
Bowel - with abdominal pain and bowel perforations.
Abdominal viscera - including gallbladder etc..
Common Signs and Symptoms
Poor function or pain in any of the organs mentioned above can be a symptom.
Fatigue,
weight loss,
fever a general feeling of ill health (malaise),
headache
muscle aches (myalgias)
and/or abdominal pain.
The illness is usually characterised initially by :-
from General Health Encyclopedia
Weight loss
Fever and sweats: In fact a pyrexia (fever) of unknown origin - may be the only sign early on.
Malaise
Fatigue.
Arthralgia
Myalgia
Anaemia
Skin ulcers
Abdominal pain
Hypertension.
Coronary arteries may also be involved as can many othe viscera.
Damage to affected arteries may result in abnormally increased blood pressure (hypertension),
"ballooning" (aneurysm) of an arterial wall,
the formation of blood clots (thrombosis),
obstruction of blood supply to certain tissues,
and/or tissue damage and loss (necrosis) in certain affected areas.
Other symptoms and findings are often present, depending upon which areas of the body are affected
Diagnosis of polyarteritis nodosa :
is confirmed by a biopsy of involved tissue or angiography.
Treatment is directed toward decreasing the inflammation of the arteries.
Tests showing inflammation:
elevation of blood sedimentation rate
and c-reactive protein.
white blood cell count
and platelet count can be elevated,
the red blood count is decreased (anemia).
The Hepatitis B virus tests (antigen and antibody) can be found in 10-20% of patients.
Urine testing can show protein and red blood cells in the urine.
In patients with nerves affected, nerve function tests are abnormal.
The diagnosis of polyarteritis nodosa is confirmed by a biopsy of involved tissue which reveals the inflamed blood vessels (vasculitis).
The vasculitis of the bowel and kidneys can often be detected with an angiogram (x-ray testing while contrast "dye" is infused into the blood vessels).
Anaemia
Elevated White cell count.
High ESR and CRP.
The urine examination may show protein and blood.
Nerve conduction abnormality on electrical testing of involved nerves.
Angiography : The blood vessels may be visualised on visceral angiography (the investigation of choice), as having weakness in their walls and outpouchings - called microaneurysm's.
Tissue biopsy is desirable - skin / kidney / Muscle / rectal / abdominal fat / sural nerve being frequently chosen as biopsy sites
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The American College of Rheumatology established criteria for the classification of polyarteritis nodosa in 1990.
For classification purposes, a patient is said to have polyarteritis nodosa if at least 3 of the following 10 criteria are present:
Weight loss greater than/equal to 4 kg. Livedo reticularis (a mottled purplish skin discoloration over the extremities or torso).
Testicular pain or tenderness. (occasionally, a site biopsied for diagnosis).
Muscle pain, weakness, or leg tenderness.
Nerve disease (either single or multiple).
Diastolic blood pressure greater than 90mmHg (high blood pressure).
Elevated kidney blood tests (BUN greater than 40 mg/dl or creatinine greater than 1.5 mg/dl).
Hepatitis B virus tests positive (for surface antigen or antibody).
Arteriogram (angiogram) showing the arteries that are dilated (aneurysms) or constricted by the blood vessel inflammation.
Biopsy of tissue showing the arteritis (typically inflamed arteries).
Complications:
stroke renal failure
heart attack
intestinal necrosis and perforation
the most common mechanism of disease in necrotizing vaseulitis is the immune-complex mediated damage to vessel wall, every effort to remove circulating immune complexes by apheresis or by an efficient reticuloendothelial system could be of benefit.
seven out of eight patients with chronic and refractory to aggressive corticosteroid therapy leukocytoclastic vasculitis, experienced considerable relief from their symptoms after intermittent courses of plasma exchange17; additionally, diets with reduced contents of macromolecular antigens i.e. those restricting from meat and allowing rice, fruits and vegetables, led to the regression of purpura and laboratory parameters in 24 controlled patients suffering from mixed cryoglobulinemia of essential origin, acting possibly by restoring a saturated mononuclear phagocytic system18.
Occasionally hepatitis C is associated with necrotizing vasculitis or even systemic forms of the disease19.
In these patients, immunosuppressants are usually of no value; instead, plasma exchange or interferon in low doses improve most cases20.
The careful evaluation of the patients with necrotizing vasculitis will reveal an autoimmune disorder in one third of cases3.
Especially when infarctive or widespread ecchymotic lesions exist, a search for lupus anticoagulant or cryoprotein will help to elucidate and manage the underlying disorder.
Cryogolobulins are found in almost 3% of all cases of vasculitis: when they are monoclonal, a purpura of the exposed surfaces of the body appears after cold exposure; in the mixed type, an investigation for Systemic Lupus Erythematosus, Szogren's syndrome or Rheumatoid arthritis must be made and appropriate therapy initiated. The safety of modern y-globulin intravenous preparations make their use a promising mode of therapy, especially for those patients with disease refractory to other treatment modalities; doses of 0.4gr/kg/day for 4 days may suffice21.
The herglobulinemic purpura of Waldenstrom is usually diagnosed when a woman with extensive, recurring purpura, appearing like "pepper" dots, manifests abnormal serum protein electrophoresis. When the disease is primary, and this is the rule, the course is chronic and benign requiring only bed rest. Although chlorambucil, and much more rarily prednisone, may temporarily reduce skin lesions, therapy as a whole is considered disappointing and unwarranted22
lupus