Case Nº4 - FJM

A 68-year-old woman was admitted to our hospital with
general fatigue, palpitation, shortness of breath and leg
edema. She was diagnosed as having rheumatoid arthritis
(RA) at age 59 years at another hospital. She had since been
treated with nonsteroidal anti-inflammatory drugs, gold sodium
thiomalate and steroids. When she consulted our hospital,
clinical classification was stage IV and class II, due to
the bilateral erosive arthritis in her hands, wrists, knees and
feet.

In 1996 (at age 62 years), pancytopenia, which might
have been induced by gold sodium thiomalate, gradually developed.
This medication was discontinued, but the pancytopenia
persisted. Over the subsequent year, findings on gastrointestinal
endoscopy and abdominal computed tomography
revealed contracted liver, splenomegaly and esophageal
varices. Laboratory data showed no antigens or
antibodies for hepatitis virus, or antibodies for mitochondria
or smooth muscle, with the exception of antinuclear antibody
(ANA). Esophageal variceal banding ligature was thus performed.
Physical examination demonstrated deformities of the bilateral
joint of the hands, wrists, and feet. Swan-neck, boutonniere
deformity and radial deviation at the wrists with
ulnar deviation of the digits were noted in both hands.
Respiratory and heart sounds were normal. The spleen was
palpable about 5 cm below the left costal margin. Slight pitting
edema was observed in the bilateral lower extremities.

Laboratory findings are shown in Table 1. Urinalysis was
within the normal range. Neutropenia and hypoproteinemia
worsened, and hypoalbuminemia at 2.0 g/dl was detected.
Elevated levels of total bilirubin and aspartate aminotransferase
were observed, and the Child-Pugh classification was C (10 points).
ANA was positive at a titer of 640 (homogenous
and speckled), but other antibodies were negative.
Abdominal computed tomography revealed contracted liver,
splenomegaly, ascites and enlarged serpiginous
splenic vein.






























During admission, oral prednisolone was discontinued
due to various infections, including bacterial pneumonia and
methicillin resistant Staphylococcus aureus (MRSA) colitis.
Subcutaneous administration of granulocyte colony stimulating
factor (three times a week) was thus performed, while
ascites was simultaneously treated with diuretics. Laparoscopic
liver biopsy was not performed due to marked ascites
and neutropenia. Liver dysfunction worsened gradually and
ascites became prominent. She developed
hepatic encephalopathy and died from hepatic failure
and emaciation on March 31, 2003. Autopsy was not permitted.

¿What is the diagnosis?

Needle autopsy of the liver confirmed chronic hepatitis, the lobular architectures were maintained, while part of the portal field exhibited fibrosis including piecemeal necrosis, and was invaded by inflammatory cells and numerous lymphocytes with plasma cells (Fig. 3A, 3B). Pathological findings were consistent with a diagnosis of chronic hepatitis, which appeared to be AIH, although inflammatory cell invasion was not severe. According to the criteria of the International Autoimmune Hepatitis Group (Table 3A, 3B), the patient scored 19 points based on laboratory findings, pathophysiological consequences and clinical course, and her condition was diagnosed as AIH.

Discussion
In 1924, Felty first called attention to five cases with a
triad of RA, splenomegaly and neutropenia (5). This combination
of disorders was designated Felty’s syndrome in a
subsequent report by Hanrahan and Miller (6). This syndrome
frequently induces extra-articular features including
liver involvement, while common hepatic abnormalities are
nodular regenerative hyperplasia, abnormal lobular architecture,
portal fibrosis and cirrhosis (7–11). Thorne et al reported
a tendency for patients with abnormal liver findings to
have a higher incidence of vasculopathy and Felty’s syndrome
patients should be screened for portal hypertension as
they have an increased likelihood of bleeding from esophageal
varices (9). Indeed, in this patient, esophageal varices
were observed. The most common liver involvement in patients
with Felty’s syndrome is nodular regenerative
hyperplasia (12, 13). Goritsas et al recommended that signs
of portal hypertension and/or intrahepatic cholestasis in RA
patients should alert the physician to the possibility of nodular
regenerative hyperplasia, even in the absence of Felty’s
syndrome (14). However, the cause of hepatic nodular regenerative
hyperplasia in patients with Felty’s syndrome remains
unresolved.
In the present case, contracted liver was thought to be
clinically liver cirrhosis based on blood test, abdominal computed
tomography and ultrasonography findings. However,
liver autopsy findings revealed chronic hepatitis. Histological
findings showed a basically normal architecture and
338 Internal
a partly piecemeal necrosis in the portal triad field, in addition
to infiltration of lymphocytes with plasma cells, which
suggested AIH.
AIH was first reported by Mackay et al in 1965. The characteristic
pathologic features were chronic active hepatitis
with piecemeal necrosis, lobular involvement, and bridging
necrosis with lymphocytes and plasma cells (15). The clinical
features were similar to chronic viral hepatitis. For diagnosis
of AIH, it was recently recommended to use the
scoring system of the International Autoimmune Hepatitis
Group (16). According this scoring system, the present patient
was diagnosed as having autoimmune hepatitis with a
score 19 points. Kaise et al reported that one in 49 patients
with Felty’s syndrome exhibits concomitant AIH (11). Based
on that report, it is certain that AIH in Felty’s syndrome is
extremely rare.

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Splenomegaly in patients with Felty’s syndrome might be
due to expansion of the sinusoidal pulp, as indicated by
wider separation of the periarterial lymphoid sheaths and
hyperplastic germinal center (17). In the present case, we are
convinced that increasing blood flow to the spleen due to
splenomegaly caused portal hypertension, congestion of
blood within the liver, and chronic hepatitis gradually worsened
to liver failure.
The present patient had contracted liver disease of unknown etiology. Chronic hepatitis compatible with AIH was
diagnosed based on an international scoring system and the
pathological findings of needle autopsy respectively. In patients
with Felty’s syndrome, severe hepatitis is rarely observed
and correlations with the liver are difficult to confirm.
When treating Felty’s syndrome patients with severe liver
dysfunction, AIH should be considered. Inaba et al reported
a case in which the patient had been treated by prednisolone
for AIH and was diagnosed as having Felty’s syndrome (18).
This report raises the possibility that our patient had AIH when she was diagnosed with RA and prednisolone therapy suppressed the clinical features of AIH. Retracing the clinical course, liver dysfunction may have developed after steroid therapy was discontinued. If this was the case scenario, the response to therapy in this patient should, in fact, be considered as a relapse with a score of 21 points. In the present
patient, the most difficult point was that steroid therapy had
to be discontinued due to life threatening infections (MRSA
colitis, recurrent pneumonia) which might have been due to
neutropenia and steroid therapy. Interruption of steroid therapy
in this patient may have been a crucial event in the ultimate
clinical course.

Reference

- Felty’s Syndrome with Chronic Hepatitis and
Compatible Autoimmune Hepatitis: A Case Presentation