Tuesday, October 23, 2012

The Vasculitides: Polyarteritis Nodosa

Polyarteritis nodosa (PAN) is a necrotizing vasculitis that affects medium and small arteries throughout the body.  The inflammation causes fibrinoid necrosis of the arterial media and a cellular infiltrate predominantly of neutrophils and leukocytes.  Aneurysms form as a result of this weakening of the arterial media.

Almost any organ or organ system can be affected, kidneys, liver, spleen, the heart, the lower extremities, the skin, the nervous system (e.g. mononeuritis multiplex)...but the classic presentation is numerous small aneurysms in the kidney (below) or liver. Constitutional symptoms (fever, weight loss) are also common, but obviously not very specific findings.

"Right renal arteriogram shows one small aneurysm of an upper lobar branch (arrow) and irregular ectasia of the main renal artery (arrowhead)." (ref 1)

On angiography PAN presents with ectasia and narrowing of the medium-sized arteries, as well as with the previously mentioned microaneurysms. The visceral artery microaneurysms have been reported to occur more frequently at vascular bifurcations and have a tendency to bleed.  Clearly, due to their small size, an angiographic technique with high spatial resolution is necessary for evaluation (selective DSA, well-timed CTA)

46 year-old male with known polyarteritis nodosa and new hemorrhage.  (Courtesy Dr. D. Eschelman)

46 year-old male with known polyarteritis nodosa and new hemorrhage.  (Courtesy Dr. D. Eschelman)

46 year-old male with known polyarteritis nodosa and new hemorrhage.  (Courtesy Dr. D. Eschelman)

Stenosis and occlusion of the arteries is also common, and in one study, 98% of angiograms demonstrated occlusive lesions, which is even more sensitive than renal microaneurysms, which have been reported as occuring in 70% of patients.

PAN should be on the differential for digital vasculitis along with Buerger's disease (thromboangiitis obliterans) and connective tissue diseases. PAN can mimic atheroembolic disease in the hands. Testicular pain/orchitis due to testicular artery ischemia is also considered another characteristic, although uncommon, symptom.

One critical differentiating point is that PAN does not affect the lungs.  If pulmonary vessels are affected, another vasculitis should be considered.

The American College of Rheumatology has specified a set of criteria for the clinical diagnosis of PAN with about 82-86% sensitivity/specificity. The criteria are partly to differentiate PAN from microscopic polyangiitis, which were previously lumped together, but are now considered separate entities (from an angiography point of view, MPA does not cause renal microaneurysms or stenoses, which is useful for diagnosis). Since, historically, PAN has often been conflated with other small and medium vessel vasculitides (such as SLE or RA vasculitis, Wegener's, and even giant cell arteritis), its incidence and prevalence is not entirely certain. It seems to be a rare entity, with an incidence in Europe reported at 5-10/per million. PAN is classically said to occur at 40-60 years of age, but can occur in children and in the elderly. Some claim it has a male predominance, others do not.

1990 American College of Rheumatology clinical criteria for PAN. (ref 2)  Note #9 -- arteriography (of whatever modality) is considered an important criterion for diagnosis.

Dermatologic-only PAN is considered a different entity than systemic PAN with dermatologic findings. Incidentally, since MPA tends to affect smaller vessels than PAN, it is thought that many cutaneous lesions (vascular purpura, etc.) are actually more common with MPA.  In fact the "nodosa" term in PAN may have originated from an early conflation with MPA.

An association between hepatitis B (and perhaps HIV) with PAN has been noted. Hepatitis C does not seem to be a contributing factor. IV drug use has also been associated with it.  50% have no known cause.

The etiology of PAN is not entirely known yet, but considered to result from deposition of immune complexes. Histologically, the vasculitis appears in different stages in the same tissue, suggesting cyclical immune damage rather than a single event. Current treatment is targeted against the inflammatory nature of the disease with steroids and cyclophosphamide as primary therapies. Aneurysms may resolve with treatment.

Nonselective embolization in the setting a PAN microaneurysm bleed has been reported as an imperfect, but perhaps necessary measure.

1. Stanson AW, Friese JL, Johnson CM, et al. "Polyarteritis Nodosa: Spectrum of Angiographic Findings" January 2001 RadioGraphics, 21, 151-159.
2. Lightfoot RW Jr, Michel BA, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa. Arthritis Rheum 1990;33:1088-93.
3. "Rutherford's Vascular Surgery" Cronenwett and Johnston. 7th ed (2010)
4. "Abram's Angiography" Baum S, ed. 4th ed. (1997)
5. "Vasculitis" Ball GV and Bridge SL. (2002)
Case courtesy of Dr. Dave Eschelman, Thomas Jefferson University Hospital