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Pure red cell aplasia and protein-losing enteropathy in a patient with systemic lupus erythematosus.

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We report the case of a young woman with
systemic lupus erythematosus (SLE) complicated by
protein-losing enteropathy, pure red cell aplasia
(PRCA), transient anisocoria, laboratory evidence of
autoimmune thyroiditis, and immune thrombocytopenia. Protein-losing enteropathy and PRCA are unusual
manifestations of SLE (1,2) which, to our knowledge,
have not been previously reported to occur in the same
Case report. This 22-year-old white woman
presented at age 17 with extreme fatigue, palpitations,
and pallor, 2 weeks after a mild febrile illness characterized by upper and lower respiratory tract symptoms. She had taken acetaminophen and propoxyphene hydrochloride for dysmenorrhea 3 weeks
previously and pseudoephedrine hydrochloride and
chlorpheniramine maleate during the antecedent respiratory illness.
Laboratory studies revealed a hematocrit value
of 14.6%, red blood cell count of 1.59 X 106/pl,
hemoglobin of 4.7 gm/IOO ml, reticulocyte count of
0.3%, and haptoglobin level of 110 mg/dl. The direct
Coombs’ test showed a positive result. The white
Louis W. Heck, MD, Graciela S. Alarcbn, MD, Gene V.
Ball, M D: Division of Clinical Immunology and Rheumatology ,
University of Alabama at Birmingham; Robert L. Phillips, MD,
Lanning B. Kline, MD: Eye Foundation Hospital, Birmingham,
Alabama; Hernan Moreno, MD: Norwood Clinic, Birmingham,
Alabama; Basil I. Hirschowitz, MD: Division of Gastroenterology,
University of Alabama at Birmingham; Alan N. Baer, MD, Emmanuel N. Dessypris, MD: Division of Hematology, Vanderbilt University School of Medicine, Nashville, Tennessee.
Address reprint requests t o Louis W. Heck, MD, UAB
Division Of Clinical ~mmunology and Rheumatology, University
Station, Birmingham, AL 35294.
Submitted for publication November 2, 1984; accepted in
revised form March 7, 1985.
Arthritis and Rheumatism, Vol. 28, No. 9 (September 1985)
blood cell (WBC) count and differential cell count,
platelet count, and renal and hepatic function findings
were normal. A bone marrow biopsy demonstrated
marked erythroid hypoplasia. There were 0.5% pronormoblasts, 0.5% basophilic normoblasts, normal
iron stores, and normal myeloid and platelet precursors without infiltration of tumor cells. The myeloid: erythroid ratio was 87 : 1. Antinuclear antibody
(ANA) was positive at a titer of 1:10,240 with a
nucleolar pattern, and anti-DNA binding was 14%
(normal 6%).
A chest radiograph failed to demonstrate an anterior chest mass.
The impression was that she had PRCA without
thymoma. She received transfusions of packed red
cells and was treated with prednisone, 80 mg/day,
which was tapered over a 3-month period and then
discontinued. Her hematocrit value returned to normal
and has remained stable.
Four years later, she presented to the University of Alabama at Birmingham Medical Center complaining of progressive fatigue, dizziness without syncope, periorbital edema with facial swelling, and
intermittent pupillary asymmetry. She had also experienced skin photosensitivity manifested by the development of erythematous macules on the exposed skin
after brief periods of sun exposure, associated with
profound malaise, and in some instances, fever. The
only remarkable finding on examination was generalized facial swelling. The laboratory evaluation was
unrevealing, showing normal wBC and differential
counts, platelet count, and renal, hepatic, and thyroid
function. except there were persistently abnormal
serology results, with ANA titers of 1 : 160 (homageneOuS pattern) and 1 :640 (nucleolar pattern), antiDNA of 19%, and a positive finding on direct Coombs’
test. Rapid plasma reagin test (undiluted) gave positive
results. The Treponema pallidurn hemagglutination
test result was negative.
Six months later, she complained of pupillary
asymmetry without visual changes, loss of sweating
ability, and ptosis. In direct bright light the patient’s
right pupil measured 4 mm, and the left pupil was 3.5
mm. These measurements increased in the dark to 6
mm on the right and 4 mm on the left. After instillation
of 2 drops of 10% cocaine in each eye, both pupils
dilated briskly. After a 45-minute period, the right
pupil measured 10 mm and the left pupil was 9 mm.
The negative result on the cocaine test ruled out an
oculosympathetic paralysis (3). Examination by slit
lamp revealed moderate conjunctival edema in both
eyes. The ocular motility and funduscopic examination results were unremarkable. One week later, both
pupils were of equal size.
Eight months later, she complained of increased fatigue and facial swelling and was noted to
have a platelet count of 82,000/mm3,albumin level of
2.3 gm/dl, elevated thyroid-stimulating hormone level
(9.3 pU/ml; normal <8), and positive antithyroglobulin antibody (1 :25,600) and antimicrosomal antibody
(1 :2,048) with borderline low thyroxine level (3.5 pg/
dl). The direct Coombs’ test result continued to be
positive. The antibody eluted from the erythrocyte
was an IgG panagglutinin. A bone marrow biopsy
demonstrated a slightly increased number of megakaryocytes. Urinalysis results were normal, and she
excreted <150 mg of protein in 24 hours. Results of a
computed tomography scan of the chest were negative
for thymoma. Treatment with L-thyroxine, 100 pg/
day, was started.
Over the next 2 weeks, she experienced increasing periorbital edema and facial swelling without
pedal edema. The serum albumin level decreased to
1.65 gm/dl, and the platelet count was 49,000/mm3.
Using a monoclonal antibody technique (4), we found
4,947 molecules of IgG bound per platelet (normal
<300), consistent with immune thrombocytopenia.
Other laboratory tests revealed a WBC count of 7,200/
mm3 with a normal differential cell count and a hematocrit value of 39%. Serum aspartate aminotransferase, alanine aminotransferase, gamma glutamyltransferase, alkaline phosphatase, lactate dehydrogenase,
blood urea nitrogen, creatinine, quantitative immunoglobulin tests, and urinalysis all gave normal results.
The serum protein electrophoresis pattern was normal
except for a marked reduction in the albumin peak.
The prothrombin time was 9.9 seconds (control 12.7),
and partial thromboplastin time was 24 seconds (control 27). C3 level was 63 mg/dl (normal 81-165) and C4
was 11 mg/dl (normal 11-31).
Since renal and hepatic findings were normal,
protein-losing enteropathy was suspected as the cause
of the hypoalbuminemia. ‘Cr-labeled human albumin
(70 pCi) was administered intravenously, and there
were 4 consecutive 24-hour stool collections. The
percent of the infused chromium excreted in the feces
was 8.6% (normal 2.75). A barium radiographic series
of the upper gastrointestinal tract with small bowel
follow-through demonstrated diffuse edema of the
stomach and throughout the small bowel. A duodenal
biopsy showed an increased number of submucosal
lymphocytes with no perivascular infiltrate or dilated
lymphatic vessels. She was treated with prednisone,
20 mg daily. Two weeks later, the facial swelling and
periorbital edema had completely cleared, the serum
albumin level was 3.9 gm/dl, and the platelet count was
141,000/mm3. Prednisone has been tapered to 5 mg
daily, and she remains free of symptoms 6 months
Discussion. This patient meets 4 criteria considered indicative of a definite diagnosis of SLE (5). She
had unequivocal PRCA and protein-losing enteropathy, which are not mentioned in standard rheumatology textbooks as manifestations of SLE (1,2). In
addition, she had transient anisocoria and laboratory
evidence of autoimmune thyroiditis and immune
thrombocytopenia. We do not know if the transient
anisocoria, which has not recurred, was a central
nervous system manifestation of SLE.
PRCA has been described in 7 patients with
SLE (6-12). In 1 case report, PRCA was the presenting manifestation (7), as it was in our patient. One clue
that the PRCA was not the usual acute, self-limited
form (primary) associated with drugs or infections was
the detection of anti-DNA antibodies during the aplasia and their persistence over 4 years. Positive ANA
has been described in patients with PRCA (13). In
serial evaluations of 29 patients who had pure red cell
aplasia, ANAs were found in several, but only 2
patients with documented SLE had significant titers of
anti-DNA antibodies (Dessypris E, Krantz S: unpublished observations). No history of drug ingestion,
which has been associated with the development of
PRCA (13), was obtained.
The mechanism of red cell aplasia in our patient
is unknown, but it may have been immunologically
mediated, as has been described in the primary form
involving antibodies to marrow erythroblasts (14), to
erythroid colony-forming units (CFU-E) and burstforming units (15), or to erythropoietin (16). The IgG
fra.ction has been demonstrated to inhibit erythroid
colony growth in 1 SLE patient with PRCA (7). IgG
inhibitors of allogeneic and autologous CFU-E growth
in vitro have also been detected in the sera of patients
with SLE (Dessypris E, Krantz S: unpublished observations).
Systemic lupus erythematosus is an uncommon
cause of protein-losing enteropathy (17); only 6 patients with SLE have been reported to have this
syndrome (18-23). Two histologic studies of the involved intestinal tissue have reported findings of venulitis (22) and lymphangiectasia (23) as potential mechanisms underlying enteric protein loss. Neither
appeared in the intestinal biopsy specimen from our
patient. Except for 1 patient with intestinal lymphangiectasia (23), improvement with modest doses of
corticosteroids has been noted in most of the reported
patients (19-22), and the reversal of protein-losing
enteropathy was indeed dramatic in our patient.
Both pure red cell aplasia and protein-losing
enteropathy should be considered to be manifestations
of SLE. Furthermore, SLE should be included in the
differential diagnosis of both entities. Most importantly, both of these syndromes are treatable with small or
modest amounts of corticosteroids.
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lupus, patients, protein, systemic, red, erythematosus, losing, pure, cells, aplasia, enteropathy
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