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Polyarteritis Nodosa

Article  in  Techniques in vascular and interventional radiology · December 2014

DOI: 10.1053/j.tvir.2014.11.005 · Source: PubMed

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Polyarteritis Nodosa
Travis Howard, MD, Kinza Ahmad, BS, Jerome (Allen) A. Swanson, MD, and
Sanjay Misra, MD

The first description of polyarteritis nodosa (PAN) was in 1852 by Karl Rokitansky, a
pathologist at the University of Vienna. The initial report describes a 23-year-old man
who had a 5-day history of fever and diarrhea. Since then, the definition of PAN has
evolved. The currently accepted definition of PAN comes from the 2012 Chapel Hill
Conference, which classified PAN as a necrotizing arteritis not associated with
antineutrophil cytoplasmic antibodies of medium or small arteries without glomerulo-
nephritis or vasculitis in arterioles, capillaries, or venules.
Tech Vasc Interventional Rad 17:247-251 C 2014 The Authors. Published by Elsevier Inc.
All rights reserved.

KEYWORDS Polyaarteritis, nodosa, imaging technique, treatment

T he requirement for negative results for antineutro-

phil cytoplasmic antibody (ANCA) serology test in
polyarteritis nodosa (PAN) is a useful new change that
allows for discrimination between PAN and ANCA-
associated vasculitides, which otherwise have similar
presentations pathologically and clinically. PAN can
solely involve a single organ or present systemically.1 It
may affect any organ, but for unknown reasons it spares
the pulmonary and glomerular arteries. PAN can be
idiopathic, or it can be associated with an infectious
etiology such as hepatitis B virus (HBV). PAN has been
associated with various infectious viruses including HBV
and human immunodeficiency virus, and the prevalence
of infection-associated PAN is related to the prevalence of
the infections themselves.2 For example, with the devel-
opment of a vaccine for HBV vaccine, the percentage of
patients with PAN who have HBV have decreased from
36% to less than 5%.3,4
In European countries, the incidence of PAN ranges
from 0-1.6 cases per million and the prevalence is about 31
cases per million.5 The mean age of patients at diagnosis is
51 years, and men are more frequently involved although
people of any age, sex, and ethnicity can be affected.5
Angiography remains the gold standard for imaging
diagnosis.
Department of Radiology, Mayo Clinic, Rochester, MN.
Address reprint requests to Sanjay Misra, MD, FSIR, FAHA, Mayo Clinic,
Department of Radiology, Rochester, MN 55905. Tel.: þ507 293
3793; fax: þ503 494 4324. E-mail: misra.sanjay@mayo.edu
1089-2516/14/$ - see front matter & 2014 The Authors. Published by Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1053/j.tvir.2014.11.005
Clinical Evaluation of the
Patient—Physical Examination,
History, Laboratory Tests, and
Treatment
The typical presentation of PAN involves the skin or
peripheral nerves.5 The skin can be involved and exhibit
a range of lesions including purpura, livedoid, subcuta-
neous nodules, and necrotic ulcers. The main neurologic
manifestation is mononeuritis multiplex, which can
present with wrist or foot drop etc. Subacute presentation
consists of vague symptoms including fever, weight loss,
malaise, headache, and myalgia. The spectrum of disease
ranges from involving a single organ to polyvisceral failure.
Patients with involvement of the kidneys typically
present with hypertension, renal insufficiency, or renal
failure. Renal hemorrhage may also present with sponta-
neous subcapsular and perirenal hemorrhage. With acute
renal hemorrhage, patients may represent with Wunder-
lich syndrome: acute flank pain, flank mass, and hypo-
volemic shock.6 Gastrointestinal (GI) symptoms consist of
ischemia, infarction, abdominal pain, weight loss, bowel
perforation, hemorrhage, pancreatitis, appendicitis, and
cholecystitis. The brain, eyes, pancreas, lungs, testicles,
ureters, breasts, and ovaries are rarely involved. Five-year
survival rate for untreated PAN is 13%.7,8 The outcome of
PAN has improved in patients receiving treatment; 5-year
survival rate is approximately 80%.9 The survival rates for
patients with HBV-associated PAN is lower than for
patients with non–HBV-associated disease. With fulminant
or polyvisceral disease 5-year survival rate is less than 15%.
247
248 T. Howard et al.
serum creatinine, muscle enzyme concentrations, liver
function studies, HBV and hepatitis C virus serologies,
and urinalysis. Acute-phase proteins are typically elevated,
as evidenced by increased erythrocyte sedimentation rate
and C-reactive protein concentrations, but are neither
sensitive nor specific enough for the diagnosis of PAN to
substantially affect diagnostic decision making.
Blood cultures should be obtained in all patients
suspected of having a systemic vasculitis to exclude
endovascular infection. Additional laboratory testing is
valuable in narrowing the differential diagnosis. These
include the following assays, depending upon the alter-
native diagnoses being considered based upon the patients'
signs and symptoms: ANCA, antinuclear antibody, C3 and
C4, cryoglobulins, serum and urine immunofixation
electrophoresis to test for monoclonal gammopathy, and
testing for human immunodeficiency virus.
The American College of Rheumatology has established
10 criteria for the classification of PAN in a patient with a
vasculitis.12 The sensitivity and the specificity for the
diagnosis of polyarteritis is 82% and 87%, respectively,
in the patient with a documented vasculitis in whom at
least 3 of the following criteria are present: otherwise
Figure 1 A 27-year-old man who presented with headache,
unexplained weight loss greater than 4 kg, livedo retic-
hypertension, and renal insufficiency. A left renal artery
angiogram demonstrates multiple small aneurysms (red
ularis, testicular pain or tenderness, myalgias (excluding
arrows) with segmental or subsegmental irregular narrowing that of the shoulder and hip girdle), weakness of muscles,
(yellow arrows). tenderness of leg muscles, mononeuropathy or polyneur-
opathy, new-onset diastolic blood pressure greater than
90 mm Hg, elevated levels of serum blood urea nitrogen
(440 mg/dL or 14.3 mM/L) or creatinine (41.5 mg/dL or
Relapse occurs in 40% of patients with a median survival 132 μM/L), evidence of HBV infection via serum antibody
rate of 33 months. Overall, 50% of patients with abdomi- or antigen serology, characteristic arteriographic abnor-
nal involvement develop acute surgical abdomen with a malities not resulting from noninflammatory disease
mortality rate of 12.5%.
The French Vasculitis Study Group has established a
large, well-characterized longitudinal cohort of patients
with PAN and reported a comprehensive series of studies
on the natural history and treatment of this disorder. In
1996, using regression analytical techniques, this group
derived the “five-factor score” (FFS) as a simple prognostic
tool for clinicians to use when evaluating patients with
various forms of vasculitis, including PAN.10,11 The FFS
was revised in 2011 based upon additional data and for
PAN now only includes 4 factors associated with increased
mortality: (1) older than 65 years, (2) cardiac symptoms,
(3) GI involvement, and (4) renal insufficiency (plasma
creatinine 41.7 mg/dL [150 μM/L]). The original FFS had
included central nervous system disease (dropped from
the score in 2011) but did not include age (included in
2011). The FFS has been used to stratify patients in
treatment studies; this tool is helpful in both interpreting
the data and formulating an approach to treatment of PAN.
However, the FFS is based upon mortality and is not
designed to predict either relapse or long-term morbidity,
both of which are also important outcomes that influence
treatment decisions in PAN.
There is no diagnostic laboratory test for PAN. Labo- Figure 2 A 54 year-old woman with nonhealing ulcerations on her
ratory tests can help determine the extent of organs legs and distal gangrene. A left renal artery angiogram demon-
affected and their degree of involvement. These include strates small aneurysms (red arrows).
Polyarteritis nodosa 249

Figure 3 A 60-year-old man who developed acute onset of burning paresthesias in his toes and feet followed by
blistering ischemic lesions involving his toes with skin breakdown, splinter hemorrhages involving his fingers, and
swelling involving his right third finger. The results of ANCA serology tests were negative. Angiogram of both the
hands demonstrates segmental narrowing and microaneurysms (red arrows). (Color version of figure is available
online.)

processes, biopsy of small- or medium-sized artery con-
taining polymorphonuclear cells. Glucocorticoids remain
the first-line treatment with remission occurring in 50% of
patients. With the addition of cyclophosphamides, remis-
sion or cure approaches 90% of the patients. HBV-
associated PAN requires the addition of antivirals as well.
Plasma exchange or plasmapheresis may have added
benefit in refractory cases.
commonly involved include kidneys (70%-80%), GI tract,
peripheral nerves, skin (50%), skeletal muscles and mes-
entery (30%), and central nervous system (10%). Com-
puted tomography (CT) and magnetic resonance (MR) are
less invasive and provide evidence of end-organ damage,
arterial wall thickening, and arterial occlusion.

Indications for the Procedure—

Imaging
Arteriography and cross-sectional imaging can be used as
alternatives to tissue biopsy for the diagnosis and are
typically performed analyzing the mesenteric or renal
circulation.7 These studies can often be diagnostic, dem-
onstrating multiple aneurysms and irregular constrictions
in the larger vessels with occlusion of smaller penetrating
arteries (Figs. 1 and 2). Other findings can include multi-
ple peripheral aneurysms of 1-5 mm, occlusions, irregular
stenoses, and diffuse wall thickening of medium-sized
arteries (Figs. 1-4). For unknown reasons, PAN typically
occurs at small and medium vessel bifurcations. Locations
When or When Not to Perform
the Procedure
The diagnosis of PAN is made based on the findings of the
tissue biopsy or in conjunction with angiography. Rapid
diagnosis is necessary owing to progression of life-
threatening complications such as acute renal failure, renal
or perirenal hematoma, GI hemorrhage or perforation,
liver infarct, and even cardiac failure. A patient with
decreased renal function is a relative contraindication for
contrast administration. In general, a glomerular filtration
rate greater than 60 mL/min should be considered safe. A
glomerular filtration rate of 30-60 mL/min should warrant
250
Figure 4 A 79-year-old woman with dissection (red arrow) of her superior mesenteric artery on sagittal CT (A) and
axial CT (B) with irregular narrowing (red arrow) of renal arteries (C). (Color version of figure is available online.)
caution, and a reduced contrast agent dose and postpro-
cedure intravenous fluids might help reduce the renal
toxic effects of contrast administration.
Care Continuity
Patients with cutaneous-only PAN or other single-organ
presentations of PAN must also be followed regularly for
the possible development of disease in new organ systems.
In addition to clinical examinations and appropriate
follow-up of patient-reported symptoms, periodic testing
by measuring serum creatinine and a urinalysis can help
monitor for asymptomatic renal disease. Erythrocyte
sedimentation rate and C-reactive protein may correlate
with disease activity. Follow-up angiography is not
required unless there are signs or symptoms suggestive
of new disease, concerns for ischemia that may require
intervention, or aneurysms that are at risk for expansion or
rupture and may require intervention. Depending on the
anatomical location and size of affected arteries, MR
imaging or CT angiography may be substituted for
catheter-based angiography. The choice of which imaging
modality (MR, CT, or catheter-based) to use will depend
upon the availability of equipment and expertise at a
T. Howard et al.
medical center and may be influenced by an interest in
using the same approach used for prior evaluations to
allow for direct comparisons.
References
1. Tesar V, Kazderova M, Hlavackova L: Rokitansky and his first
description of polyarteritis nodosa. J Nephrol 17:172-174, 2004
2. Jennette JC, Falk RJ, Bacon PA, et al: 2012 revised International
Chapel Hill Consensus Conference Nomenclature of Vasculitides.
Arthritis Rheum 65:1-11, 2013
3. Patel N, Patel N, Khan T, et al: HIV infection and clinical spec-
trum of associated vasculitides. Curr Rheumatol Rep 13:506-512,
2011
4. Mahr A, Guillevin L, Poissonnet M, et al: Prevalences of polyarteritis
nodosa, microscopic polyangiitis, Wegener's granulomatosis, and
Churg-Strauss syndrome in a French urban multiethnic population
in 2000: A capture-recapture estimate. Arthritis Rheum 51:92-99,
2004
5. Hernandez-Rodriguez J, Alba MA, Prieto-Gonzalez S, et al: Diagnosis
and classification of polyarteritis nodosa. J Autoimmun 48-49:84-89,
2014
6. Katabathina VS, Katre R, Prasad SR, et al: Wunderlich syndrome:
Cross-sectional imaging review. J Comput Assist Tomogr 35:
425-433, 2011
7. Balow JE: Renal vasculitis. Kidney Int 27:954-964, 1985
8. Frohnert PP, Sheps SG: Long-term follow-up study of periarteritis
nodosa. Am J Med 43:8-14, 1967
Polyarteritis nodosa
9. Pagnoux C, Seror R, Henegar C, et al: Clinical features and outcomes in
348 patients with polyarteritis nodosa: A systematic retrospective study of
patients diagnosed between 1963 and 2005 and entered into the French
Vasculitis Study Group Database. Arthritis Rheum 62:616-626, 2010
10. Guillevin L, Pagnoux C, Seror R, et al: The Five-Factor Score
revisited: Assessment of prognoses of systemic necrotizing vasculi-
tides based on the French Vasculitis Study Group (FVSG) cohort.
Medicine 90:19-27, 2011
View publication stats
251
11. Bourgarit A, Le Toumelin P, Pagnoux C, et al: Deaths occurring
during the first year after treatment onset for polyarteritis nodosa,
microscopic polyangiitis, and Churg-Strauss syndrome: A retrospec-
tive analysis of causes and factors predictive of mortality based on
595 patients. Medicine 84:323-330, 2005
12. Lightfoot RW Jr, Michel BA, Bloch DA, et al: The American College
of Rheumatology 1990 criteria for the classification of polyarteritis
nodosa. Arthritis Rheum 33:1088-1093, 1990