Polyarteritis Nodosa in a Patient with Type 1
Olga Giouleme, Alexander Mpoumponaris, Spiridon Aslanidis, Panagiotis Anagnostis,
Panagiotis Giamalis, Nikolaos Nikolaidis, Themistoklis Vasiliadis,
and Nikolaos Evgenidis
Abstract: Polyarteritis nodosa is a systemic necrotizing vasculitis
that affects small- and medium-sized arteries. Liver involvement in
patients with polyarteritis nodosa has been described, and ranges
from asymptomatic elevation of aminotransferases to hepatic aneu-
rysm rupture. We describe the case of a patient with type 1 auto-
immune hepatitis and compensated liver cirrhosis who developed
classic polyarteritis nodosa, complicated with cytomegalovirus and
repeated urinary tract infections. After a long bedridden hospitaliza-
tion, the patient’s condition was stabilized. She is currently in good
health, with well-controlled blood pressure, and stable kidney and
liver function. To our knowledge, this is the first case report in the
literature with concurrent appearance of both diseases.
Key Words: autoimmune hepatitis, liver involvement in collagen
diseases, polyarteritis nodosa
tients with PAN typically present with fatigue, fever, hyper-
tension, rash, renal insufficiency, mononeuritis multiplex, and
gastrointestinal disorders. Involvement of gastrointestinal (GI)
patients can have either general symptoms, such as abdominal
pain, or severe and life-threatening complications such as intra-
abdominal aneurysmal rupture.2Liver involvement in PAN can
range from asymptomatic elevation of serum aminotransferases
to rupture of hepatic arterial aneurysms.3,4Acute and chronic
hepatitis B (HBV) and, more recently, hepatitis C virus (HCV)
have been associated with PAN.5,6
olyarteritis nodosa (PAN) is a systemic necrotizing vas-
culitis affecting small- and medium-sized arteries.1Pa-
Autoimmune hepatitis (AIH) is a chronic hepatitis asso-
ciated with hypergammaglobulinemia and circulating anti-
bodies that shows a female preponderance and usually re-
sponds well to immunosuppressive treatment.7Type 1 AIH is
associated with positive antinuclear (ANA) and smooth mus-
cle autoantibodies (ASMA).7
We present the case of a female patient with type 1 AIH,
who developed hypertension and renal insufficiency and was
diagnosed with classic PAN. To our knowledge, this is the first
case involving coexistence of both diseases in the same patient.
A 58-year-old female patient was admitted to our de-
partment with evidence of hepatic failure (ascites, stage 1
encephalopathy, jaundice, prolonged prothrombin time, and
aspartate aminotransferase (AST) were 103 IU/L (range
5–35), and levels of alanine aminotransferase (ALT) were
157 IU/L (range 5–35), while alkaline phosphatase was 95
IU/L (range 40–120). She had no history of drug or alcohol
abuse. From her family history, her brother and daughter
were suffering from sarcoidosis. Virological tests were neg-
ative for hepatitis A and HCV, and revealed physical im-
munity to HBV. Serum ceruloplasmin, alpha 1 antitrypsin
levels, and ferritin were normal. ANA and ASMA were
both positive in high titers (ANA 0.5/500 and ASMA
(continued next page)
From the Division of Gastroenterology and Hepatology and Rheumatology,
2nd Propedeutic Department of Internal Medicine, Hippokration Hospi-
tal, Aristotle University of Thessaloniki; and Department of Nephrology,
Hippokration Hospital, Aristotle University of Thessaloniki, Thessal-
Reprint requests to Panagiotis Anagnostis, Sarantoporou 10 Str, Thessaloniki
54640, Greece. Email: firstname.lastname@example.org
Accepted March 31, 2010.
Copyright © 2011 by The Southern Medical Association
• To our knowledge, this is the first case report describ-
ing coexistence of autoimmune hepatitis type 1 with
classic polyarteritis nodosa.
• Opportunistic infections may decompensate liver
nisolone), had a favorable outcome in this case.
Southern Medical Journal • Volume 104, Number 1, January 2011
(Case Report continued from previous page)
1/1,280), along with over three-fold rise in immunoglobu-
lin G (IgG; 5,500 mg/dL, range 751–1,560). Doppler ul-
veins and no evidence of thrombosis of hepatic veins, while a
computed tomography (CT) scan revealed cirrhotic appear-
ance of the liver without lymphadenopathy and enlarged
spleen. Although a liver biopsy was not possible due to pro-
1 AIH and prednisone 60 mg/day was initiated, with weekly
tapering and subsequent improvement of both clinical and
50 mg/day, along with prednisone 10 mg/day.
Three months later, a liver biopsy was performed,
and histological examination was evident of interface
hepatitis, mild inflammation (I1) and intense fibrosis (F4)
with progression to cirrhosis (Fig. 1). The score for AIH
(according to the diagnostic criteria for AIH set by the
International Autoimmune Hepatitis Group) was 17
points pre- and 19 points post-treatment, making the di-
agnosis of AIH definite.8
Eight months later, while the disease was in remission
with azathioprine 100 mg/day and prednisone 7.5 mg/day,
the patient complained of mild arthralgias of the joints of
the lower and upper extremities and was admitted to our
clinic for further evaluation. A bone scan with99mTechne-
tium-Methyl diphosphonate (99mTc-MDP) showed in-
creased uptake in the left phalange and both tarsal joints.
Electromyogram showed sensory polyneuropathy affecting
both legs. The investigation for other causes of arthritis and
neuropathy was negative, and the diagnosis of immune-
mediated polyneuropathy was made.
While she was on prednisolone 10 mg/day in the fol-
lowing months, she developed progressive renal failure,
along with hypertension (230/130 mm Hg). Upon further
investigation, she showed reduced blood flow in both kid-
neys (nephrogram), and magnetic resonance angiography
(MRA) showed a narrowed right kidney artery without he-
modynamic disturbance in the arterial flow, as was shown
on nephrogram. The diagnosis of polyarteritis nodosa was
speculated based on the clinical picture, and a biopsy of
skin and muscle from the right gastrocnemial muscle was
obtained. Histological examination showed polymorphonu-
clear leucocytes infiltration and fibrinoid necrosis of the
wall of two medium-sized arteries, evident of PAN (Fig. 2).
Based on the American College of Rheumatology criteria
for PAN, our patient had a total of seven (out of ten) pos-
itive parameters (three are warranted for the diagnosis of
PAN), and the diagnosis of classical PAN (anti-neutrophilic
cytoplasmic antibodies [ANCA]-negative) unrelated to
HBV was established.9
Our patient denied kidney biopsy and was initially
treated with high doses of corticosteroids (500 mg methyl
prednisolone per day) for three days, followed by 60 mg
prednisolone/day along with 2 mg/kg of body weight
cyclophosphamide and lacidipine. Kidney function was
stabilized, and her blood pressure was controlled. Fifteen
days later a second nephrogram showed no differences
from the first, and prednisolone was tapered gradually.
One month after the diagnosis of PAN, the patient was
discharged with stable kidney function (blood urea 140–
150 mg/dL and creatinine 1.8–1.9 mg/dL), well-con-
trolled blood pressure, and absence of ascites. She was
on cyclophosphamide 100 mg/day, prednisolone 32 mg/
day orally, and furosemide 40 mg/day.
One month later she was readmitted with stage 2 en-
cephalopathy, elevated ammonia levels (112 mg/dL, range
0–35 mg/dL), and hyponatremia (121 mmol/L). Thorough
laboratory investigation led to the diagnosis of cytomega-
lovirus infection. Although the opportunistic infection was
treated successfully, in the following five months the pa-
tient developed repeated urinary infections with subsequent
encephalopathy and refractory ascites that needed evacua-
tion every three to four days. Serum ascites albumin gradi-
ent (SAAG) was always ?1.1 g/dL. Ascites was initially
treated with furosemide, and when urinary tract infections
ing was initiated in order to increase body mass. Her con-
dition improved gradually, and she was discharged seven
months after her admission. She was able to walk with
support, her liver and kidney functions were stable and
without ascites. Chemoprevention for urinary infection was
The patient has an intense follow up as an outpatient.
She has gained 10 kg, walks without support, and her
liver and kidney function do not show any signs of pro-
gression of PAN or liver cirrhosis due to AIH. Azathio-
prine 50 mg/day has been added as immunomodulatory
agent for the treatment of both autoimmune diseases.
Seventeen months after initial diagnosis of PAN, cirrho-
sis was well-compensated, and abdominal MRA did not
show any progression of stenosis or aneurysm formation.
Gastrointestinal tract involvement is frequent in patients
with PAN (33–52% of cases).2,10Clinical features include
general symptoms such as abdominal pain, nausea, vomiting,
and diarrhea, but life-threatening conditions such as GI bleed-
ing due to vasculitis of upper or lower gastrointestinal sys-
tem, ischemic colitis, perforation, aneurysmal rupture, and
Giouleme et al • Polyarteriitis Nodosa and Autoimmune Hepatitis
© 2011 Southern Medical Association
hemoperitoneum have been described.4,10,11Ascites is an un-
common clinical manifestation related with PAN, probably
due to polyseriitis.12
AIH has been associated with other autoimmune dis-
eases, such as rheumatoid arthritis, Sjo ¨gren syndrome, and
Hashimoto thyroiditis.13We have retrieved another case re-
port in the literature with PAN and AIH.14A similar case
with coexistence of PAN and AIH has also been published in
the past, but it referred to microscopic polyangiitis and not
classic PAN, as in our patient.15Liver involvement in pa-
tients with PAN ranges from asymptomatic serum amino-
transferase elevation, hepatic infarction, and intrahepatic or
extrahepatic aneurysm rupture to cirrhosis.3,16Biliary compli-
cations such as gallbladder necrosis and perforation, hemobilia,
ischemic damages to bile ducts, and acute cholecystitis have
been reported.17,18Nodular regenerative hyperplasia (NRH) can
small arteries and their adjacent veins. Liver biopsy usually re-
veals hepatic arteritis.19In a study by Matsumoto et al20, 160
livers from patients with collagen diseases were examined his-
topathologically (11 were found with PAN); all patients (100%)
with PAN had evidence of hepatic arteritis and 81.8% showed
evidence of fatty liver and hepatic congestion, but none of them
had lesions consistent with AIH.
Our patient with a family history of autoimmune disease
presented to our department with evidence of type 1 AIH with
cirrhosis, which was confirmed further by the excellent re-
sponse to therapy and the liver biopsy, which showed no
evidence of hepatic arteritis at that time suggestive of PAN.
While she was on corticosteroid and azathioprine therapy and
cirrhosis was well-compensated, she developed polyneurop-
athy and fever that required increment of corticosteroids and
raised the suspicion of an autoimmune disorder other than
AIH. Subsequently, she developed hypertension and renal
failure in a short time, and muscle biopsy confirmed the
diagnosis of PAN. Based on the proposed treatment algo-
rithm, she was treated with both prednisolone and cyclophos-
phamide and responded well.
Ascites formation in the presence of compensated cir-
rhosis (as shown from the laboratory findings) raised some
questions regarding its etiology. Although the examination of
the ascitic fluid did not reveal any evidence of malignancy
and SAAG was ?1.1 g/dL (which is suggestive of portal
hypertensive etiology), a thorough investigation for other
causes or other signs of portal hypertension was negative.
Two potential explanations for ascites formation could be
either a further deterioration of the liver function due to PAN-
related vascular abnormalities, or an increase in the perme-
ever, the development of hepatic encephalopathy, refractory
ascites, and liver impairment during the opportunistic and
repeated urinary infections led us to the conclusion that the
proposed mechanism for ascites formation was liver-related.
It is possible that in a cirrhotic liver with a fine balance of
portal pressure, the vascular changes that resulted from PAN
and the infectious factor with endotoxinemia caused the de-
velopment of ascites as the first sign of decompensation,
which returned to the previous stage when infection was re-
solved and PAN was inactive. The absence of hepatic arteritis
in biopsy specimen could be attributed to sampling error, or
to the relative short duration of the disease.
To our knowledge, this is the first case report in the
literature describing a patient with type 1 AIH coexistent with
classic PAN. Although the clinical course of the patient was
complicated, she remains until now (eight months after her
discharge) in good condition. This case report indicates the
extreme heterogenicity of autoimmune diseases, their fre-
quently complicated course, and their unique presentation in
Fig. 1 Liver biopsy (first) showing intense fibrosis and mild
Fig. 2 Muscle biopsy showing evidence of fibrinoid necrosis of
two medium-sized arteries, and polymorphonuclear inflamma-
tion evident of polyarteritis nodosa.
Southern Medical Journal • Volume 104, Number 1, January 2011
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© 2011 Southern Medical Association