Systemic lupus erythematosus and amyloidosis.

Abstract

Amyloidosis in association with Systemic Lupus Erythematosus (SLE) has rarely been reported. We report a patient with "SLE" and Amyloidosis presenting with recurrent bloody diarrhea and review the relevant literature.

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Clinical rheumatotogy, 1997, 16, N ° 3
Case Report
Systemic Lupus Erythematosus and Amyloidosis
I. AL-HOQAIL*' H. NADDAF*" A. AL-RIKABI**" H. AL-ARFAJ*'
A. AL-ARFAJ*
Summary
has rarely been reported. We report a patient with "SLE" and Amyloidosis pre-
senting with recurrent bloody diarrhea and review the relevant literature.
Amyloidosis in association with Systemic Lupus Erythematosus (SLE)
Key words
SLE, Amyloidosis, SAA, Bloody Diarrhea
INTRODUCTION
Amyloidosis is an abnormal proteinaceous substance
deposited between cells in many body tissues and or-
gans in a variety of clinical disorders (1). Secondary amy-
loidosis associated with chronic inflammatory disorders
is well recognized but its association with Systemic Ira-
pus Erythematosus is very unusual (2).
The usual manifestation in these patients is proteinurea.
From our survey of the literature, only one case present-
ed with diarrhea, gastrointestinal bleeding and pro-
teinurea (3).
Our case reported here presented with recurrent bloody
diarrhea but without proteinurea.
CASE REPORT
A 40-year old unmarried woman presented with a five-
year history of symmetrical, intermittent polyarthritis af-
fecting both small and large joints. This was associated
with intermittent fever. The joint pain had increased over
the last two years. She was managed elsewhere with dif-
ferent non-steroidal anti-inflammatory drugs (NSAIDs)
with little benefit. She also reported recurrent attacks of
mucous, fresh bloody diarrhea five times per day over
one year. The patient was investigated elsewhere for par-
asites and other infectious causes but the results were
negative. Despite that, she was treated with courses of
metronidazole with no response. She denied any history
of abdominal or chest pain, weight loss, loss of appetite,
or night sweat. She also denied any history" of skin rash-
es, Raynaud's, photosensitivity, hair fall, ulcers (neither
From the *Department of Medicine, "'Department of Pathology King
Khalid University Hospital
oral nor genital), convulsions or psychological distur-
bances. There was no history of chronic infections, oth-
er inflammatory conditions and no family history of amy-
toidosis or malignancies.
Examination showed normal vital signs, cardiovascu-
lar and respiratory systems. Abdominal examination re-
vealed palpable liver at 3 cm below the costal margin with
a liver span of 12 cm in mid-clavicular line. There was no
splenomegaly, other organomegaly or ascites. Joint exami-
nation showed synovitis of Proximal Interphalangeal joints,
Metacarpo-phalangeat joints, and wrist joints.
Laboratory evaluation showed Hb 73 g/L, MCV 63.7
fl, MCH 17.4 pg, MCHC 273 g/L, WBC 7.34 x 109/L with
a normal differential count, platetets count of 79000,
erythrocytes sedimentation rate of 85 mm. Coagulation
profile showed high partial thromboplastin time of 4%7
sec (normal 26-39), Positive Lupus Erythematosus cells
test and Prothrombintime was normal (26-39). Lupus an-
ti-coagulant test was positive. Urea, creatinine and elec-
trolytes were normal. Liver function test revealed an al-
kaline phosphatase of 163 UfL (39-117), GT 73 U/L (7-
32), otherwise normal. Stool was positive for occult blood
and pus cells but negative for microscopy and culture.
Bence Jones proteins were not detected. Serum protein
electrophoresis was normal. Twenty-four hours urine col-
lection for total protein, creatinine and creatinine clear-
ance were normal. C-reactive protein 12 mg/L (N 1 - 6).
Immunological investigation revealed>Rheumatoid
factor negative, anti-nuclear antibody titre of 1:5120 by
indirect immunofluorescence, done twice, Anti-double
strand antibody (Anti-DNA) by ELISA was 144 (N 0-100),
Complement components C3 0.92 g/L (normal 0.7 - 1.3),
and C4 0.53 g/L (normal 0.2- 0.5). Serum analysis showed
high level of serum amyloid associated protein (SAA).
Chest x-ray, Electrocardiogram and echocardiogram were
normal.

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Systemic lupus etythematosus and amyloidosis
423
N j_,*}' " :{ ~; ~7 ~ :; <7:~ "~ > :,,~ %,N,: ....
Fig. h Rectal biopsy: Globules of amyloid (arrow heads) are seen in
the lamina propria of the rectal mucosa. Haematoxylin and eosin stain
x 25.
Fig< 2." Rectal biopsy: Amyloid deposits in the wall of submucosal blood
vessels (arrow bead). A group of ganglion cells is seen beneath the mus-
cularis mucosa on the right side. Haematoxylin and eosin stain x 25.
Endoscopy for upper GI revealed red spots in stom-
ach and duodenum but no ulcers. Colonoscopy up to the
caecum showed normal mucosa but it exhibited bleed-
ing on touch. No polyps or masses were seen.
Rectal biopsy was taken and histopathological exami-
nation showed globules of amyloid in the lamina pro-
pria of rectal mucosa (Fig. 1). There were also amyloid
deposits in the wall of submucosal blood vessels (Fig. 2).
Special stains for amyloid (congo red) were positive. There
was no evidence of malignancy. Bone marrow biopsy
showed focal small deposits with pink homogenous ma-
terial which was also seen in the walls of some vessels.
These, too, were positive for amyloid stain (congo red).
The patient was started on prednisolone 15 mg orally
daily with good response. Her fever and arthritis disap-
peared over few days. Her diarrhoea also disappeared.
She was discharged to be followed as an out-patient but
the patient returned to her original country, Sudan.
DISCUSSION
Our patient fulfilled the ARA criteria for diagnosis of
Systemic Lupus Erythematosus (4). She had arthritis,
positive ANA, dsDNA as well as thrombocytopenia. Amy-
toidosis was confirmed in this patient by rectal and bone
marrow biopsies.
Amyloidosis has been frequently described in chronic
rheumatic diseases such as Rheumatoid Arthritis and
Ankylosing Spondylitis, but its association with "SLE" is
rather rare. We know that SLE is a disease with a female
predominance of 10:1, however, it drops to 3:2 in the re-
ported cases of SLE associated with amyloidosis (6).
In reviewing the literature, only 16 cases were report-
ed as amyloidosis associated with SLE. In four of these
cases, SLE was associated with other diseases namely
Rheumatoid Arthritis, Bronchiectasis, Ankylosing
Spondylitis, Chronic Obstructive Airway Disease and
only 11 cases had pure SLE (2). Out of these, only one
case report presented with recurrent diarrhea, gastrointes-
tinal bleeding and proteinurea (3). Our case reported
here has SLE and amyloidosis presenting with recur-
rent bloody diarrhea but without any proteinurea. Our
patient had hepatomegaly and increase in serum alka-
line phosphatase which are usually the expression of he-
patic amyloidosis (7). The reported cases which were in-
vestigated for the type of amyloidosis were found to be
"AA" type as in our case.
Two major chemical classes of amyloid have been iden-
tified: one composed of immunoglobulin light chains
called AL (Amyloid light chain), the other made up of a
non-immunoglobulin protein designated AA (Amyloid
associated). These proteins were antigenically distinct
and were deposited in different clinical disorders.
AA can be described as a unique non-immunoglobu-
lin protein with molecular weight of 8500. It is believed
to be derived from larger precursor protein in the se-
rum called "serum amyloid associated protein" (SAA)
which serves as protein component of a high-density li-
poprotein. SAA behaves as an acute phase reactant and
its serum concentration increases a thousand times with-
in 24 hours of an inflammatory stimulus. AA protein is
the major component of the amyloid deposited second-
ary to chronic inflammatory diseases(*< Usually SAA lev-
els are not elevated in patients with Systemic Lupus
Erythematosus (SLE) (5), in which the incidence of AA
amyloidosis seems to be very low.
This case highlights the rare association of G1 amyloi-
dosis and SLE in the absence of any renal involvement.

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424 I. AL-Hoqail, H. Naddaf, A. A1.-Rikabi, et al.
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3. Betsuyaku T et al. A secondary amyloidosis associated with Sys-
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the classification of Systemic Lupus Erythematosus. Arth Rheum
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6. Ellington K~ Truog L, Olivero JJ. Renal amyloidosis in Systemic
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Received: 16 September 1996
Revision-accepted: 13 January 1997
Correspondence to: Dr. Abdurhman AL-ARFAJ, E O. Box 34471, Riy-
adh 11468, SAUDI-ARABIA