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Hairy cell leukemia presenting as a lupus-like illness.

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We describe a young Hispanic man who presented with features suggestive of a diagnosis of systemic
lupus erythematosus. Eventually, a bone marrow biopsy
was performed, and it revealed the presence of hairy cell
leukemia. This case of a lupus-like syndrome should be
added to the list of reported rheumatic syndromes that
are associated with hairy cell leukemia.
Various rheumatic syndromes have been described in association with the presence of malignancy. The presenting symptoms are often those of the
rheumatic disease rather than of the malignancy. We
present here our findings in a Hispanic man whose
initial signs and symptoms were consistent with a
diagnosis of systemic lupus erythematosus (SLE).
With worsening of his condition and failure to respond
to standard therapy for SLE, he was referred to our
hospital for further evaluation. During the course of
the hospitalization, the patient experienced various
From the Departments of Medicine and Pathology, Walter
Reed Army Medical Center, Washington, DC, and the Department
of Medicine, Malcolm Grow United States Air Force Medical
Center, Andrews Air Force Base, Maryland.
The views expressed herein are those of the authors and do
not purport to reflect the position of the Departments of the Army,
Air Force, or Defense.
Maj. Roger W. Strickland, MD, MC, USA: Assistant Chief,
Rheumatology Service, Department of Medicine, Walter Reed
Army Medical Center; Maj. Alex Limmani, MD, MC, USAF:
Fellow, Rheumatology Service, Department of Medicine, Malcolm
Grow USAF Medical Center, Andrews Air Force Base; Capt. James
G. Wall, MD, MC, USA: Fellow, Hematology-Oncology Service,
Department of Medicine, Walter Reed Army Medical Center; Maj.
Jayashree Krishnan, MD, MC, USA: Staff, Department of Pathology, Walter Reed Army Medical Center.
Address reprint requests to Maj. Roger W. Strickland, MD,
Rheumatology Service, Waiter Reed Army Medical Center, Washington, DC 20307-5001.
Submitted for publication July 16, 1987; accepted in revised
form September 22, 1987.
Arthritis and Rheumatism, Val. 31, No. 4 (April 1988)
manifestations of a typical acute flare of SLE. The
presence of a striking leukopenia, however, caused us
to broaden the scope of the evaluation, and eventually,
we performed a bone marrow biopsy. Examination of
the biopsy specimen yielded the primary diagnosis of
hairy cell leukemia (HCL). Complete resolution of the
rheumatic symptoms was accomplished only after a
splenectomy was performed as treatment for the HCL.
This case underscores the association of HCL
with autoimmune disease, and documents lupus-like
syndromes as autoimmune manifestations associated
with this malignancy.
Case report. The patient, a 3 l-year-old Hispanic
man, was in excellent health until August 1985 when,
over a period of 3 weeks, he developed a symmetric
polyarthritis that involved his feet, ankles, knees,
elbows, hands, and shoulders. He also had a low-grade
fever, night sweats, and morning stiffness that lasted
for 4 hours. Evaluation at the referring hospital revealed the following values: rheumatoid factor (RF)
titer 1:20, antinuclear antibody (ANA) titer 1 :400,
positive LE cell preparation, Westergren erythrocyte
sedimentation rate (ESR) 42 mm/hour, positive Creactive protein, peripheral white blood cell (WBC)
count 4,500 cells/mm3, hematocrit 40%, and hemoglobin 12.6 gm/dl. Arthrocentesis had been performed on
his left knee; examination of the fluid revealed 405 red
blood cells/mm3 and 486 WBC/mm3, with 80% polymorphonuclear and 20% mononuclear cells. Cultures
of the fluid were negative. He was diagnosed as having
SLE, and treatment with aspirin and indomethacin
was begun. The patient experienced no significant
relief of his symptoms with this regimen, and he was
given ibuprofen, which provided partial relief.
In September 1985, leukopenia (2,400 WBC/
mm3) was noted. A review of his medical records
revealed WBC counts of 2,400/mm3 in 1984 and
8,800/mm3in 1978. By late September 1985, the arthritis and fever were resolving, and by October 1985,
these symptoms had almost completely resolved. The
leukopenia, however, worsened, a mild anemia developed, and the patient was transferred to our hospital.
Review of the patient’s medical history, social history,
family history, and other review of systems yielded no
significant findings.
Results of the physical examination at the time
of the hospital transfer were remarkable only for mild
synovitis and a slightly decreased range of motion in
the patient’s fingers and knees. There was no adenopathy, and the spleen was not palpable. Laboratory
findings at that time included the following values:
peripheral WBC count 800/mm3 (with 16% polymorphonuclear cells, 16% band forms, 68% lymphocytes,
and normal leukocyte morphology), hemoglobin 10.5
gm/dl, hematocrit 3 1%, platelet count 155,000/mm3,
reticulocyte count 0.9%, ESR 58 mm/hour, ANA titer
1:640 (homogeneous pattern), and RF titer 1:40. Other
significant studies that showed normal or negative
results included a blood chemistry profile, urinalysis,
anti-double-stranded DNA, anti-Sm, anti-RNP, antiSS-A, anti-SS-B, monospot test, VDRL, Coombs’
test, complement levels (C3, C4, and CH50), serum
protein electrophoresis, iron, total iron binding capacity, ferritin, and chest radiograph.
Ten days after transfer, the patient developed a
pruritic, erythematous, edematous, papular rash over
his face, neck, trunk, and arms. This rash lasted 1 day
and resolved spontaneously. A punch skin biopsy
from the patient’s anterior chest showed a mild perivascular lymphocytic infiltrate, with incontinence of
pigment and no acute hydropic changes. No other
rashes were noted during his illness.
A liver-spleen scan revealed mild splenomegaly. On 3 occasions, a bone marrow aspiration was
attempted; all were unsuccessful (dry aspirations). A
biopsy of the bone marrow was performed, revealing
75% cellularity, with a mye1oid:erythroid ratio of
2-3: 1. Megakaryopoiesis and erythropoiesis were
within normal limits, and myeloid maturation arrest
was observed. There were multiple areas of atypical
lymphoid infiltrates, which were characterized by
well-defined cytoplasmic borders, abundant pale cytoplasm, and widely spaced, cleaved, round-to-oval nuclei. Red blood cell “lakes,” increased reticulin content, and pseudosinusoids were observed. Tartrateresistant acid phosphatase was positive.
The patient was diagnosed as having hairy cell
leukemia, and in November 1985, a splenectomy was
performed. Pathologic examination of the spleen revealed changes typical of HCL, with lymphoid infiltration of the white pulp, red blood cell lakes, and pseudosinusoidal formation involving the red pulp. After the
splenectomy , there was a rapid and complete normalization of the patient’s blood cell count, and he had no
further rheumatic symptoms. Serial blood cell counts
remained normal after the splenectomy, and followup
laboratory studies 6 months later showed an ESR of 4
mmhour, negative RF, and an ANA titer of 1:640.
Discussion. The man described here presented
with a lupus-like illness, but he actually had a rheumatic syndrome in association with HCL. The positive
ANA, leukopenia, arthritis, and positive LE cell preparation fulfilled the American Rheumatism Association revised classification criteria for a diagnosis of
SLE (1). The other features consistent with SLE were
rash, fever, and anemia, although the anemia was
nonhemolytic. The striking leukopenia in this patient
precipitated our evaluation that led to the diagnosis of
HCL. Although leukopenia occurs in more than 50%
of patients with SLE, the peripheral WBC count is
usually more than 2,000/mm3; fewer than 4% of SLE
patients have a more severe degree of leukopenia (2).
Lupus-like illnesses have been reported in association with various malignancies, such as Hodgkin’s
disease, myeloma, and lung, colon, and breast carcinoma (3,4). As in the patient described here, such patients tend to have positive ANA but lack specific autoantibodies against DNA, Sm, RNP, SS-A, and SS-B (4).
HCL represents 2% of all cases of leukemia. It
is a chronic lymphoproliferative disorder, with splenomegaly, cytopenias, and “hairy cells” in the blood and
bone marrow. The hairy cells are usually of B lymphocyte origin and have numerous short cytoplasmic villi.
The diagnosis is confirmed by the finding of tartrateresistant acid phosphatase in the abnormal cells (5,6).
Splenectomy has been recognized as a beneficial therapy, conventional chemotherapy has been a controversial treatment, and recently, a-interferon has been
approved as therapy for this condition (5,7).
Nonspecific complications of HCL include those
related to cytopenias and splenomegaly, such as infection, anemia, bleeding, and splenic rupture; infection is
the major cause of death. In addition, various paraneoplastic syndromes have been observed as complications
of HCL, including autoimmune syndromes, paraproteinemia, bone involvement, and amyloidosis (6). The first
reports of rheumatic syndromes associated with HCL
were of patients who had polyarteritis nodosa (8).
Subsequent reports included associations with rheumatoid arthritis (9, lo), nonerosive, intermittent, asymmet-
ric oligoarthritis ( 1 I), 1 g A ~monoclonal gammopathy
with amyloidosis (12), cutaneous leukocytoclastic vasculitis with polyarthritis and positive ANA (titer 1:80)
(12), and cutaneous leukocytoclastic vasculitis with
oligoarthritis (12). In one report (13), a young woman
with traumatic splenosis was described; she developed
a maculopapular rash on her thumbs and index fingers,
and she had a weakly positive ANA (titer l:lO), a
positive LE cell preparation, an elevated ESR, and
leukopenia. A tentative diagnosis of discoid lupus erythematosus was made, but as her clinical course became further complicated, polyarteritis nodosa and
HCL were documented (13).
Ten definite and 2 probable cases of autoimmune disease were identified in a series of 38 patients
with HCL (6,14). Six of the patients had arthritis or
arthralgias, which were usually oligoarticular and were
usually accompanied by erythema nodosum. The
other patients with autoimmune disease had a more
severe disorder, with persistent fevers, malaise,
weight loss, rash (usually leukocytoclastic vasculitis),
and visceral involvement (lung, liver, and bowel).
Polyarteritis nodosa was not specifically sought in
these patients, but granulomatous vasculitis was found
in one patient in whom a lung biopsy was peformed.
In the reported patients with autoimmune features and HCL (8-14), the ESR has been consistently
elevated, circulating immune complexes have been
found in most (when measured), and hepatitis B antigen, ANA, and R F have been present infrequently.
When measured, cryoglobulins have not been detected. Skin biopsies, when performed, have revealed
a leukocytoclastic vasculitis or a perivascular dermatitis, without destruction of blood vessels. Hairy cells
have not been mentioned as part of the pathologic
findings in skin or synovium, but they have been found
in synovial fluid (1 1).
Clinically, the activity of the autoimmune syndrome does not parallel that of the leukemia. Fevers in
the absence of infection may sometimes represent a
manifestation of the rheumatic syndrome, although a
febrile episode in HCL must always be considered to be
caused by an infection until proven otherwise. Fever is
usually not a constitutional symptom of the HCL itself
(6). Short courses of corticosteroids or nonsteroidal
antiinflammatory drugs may be very effective in relieving the rheumatic symptoms, despite a lack of effect on
the leukemia (6). More aggressive therapy may be
indicated for polyarteritis nodosa. Investigators at one
center have advocated splenectomy for all HCL patients with an autoimmune phenomenon (6).
Thus, it is now recognized that the association
of HCL and autoimmune disease is more than fortuitous, the incidence varying from 13-26% in different
series (12,14). To the various autoimmune manifestations that have previously been reported can now be
added this case of a lupus-like syndrome. Rheumatologists as well as hematologists should be aware of the
various clinical manifestations of HCL. These manifestations are not only of importance in making a
correct diagnosis at the patient’s initial presentation,
but are also of importance in evaluating clinical events
during the course of the disease.
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Rothfield NF, Schaller JG, Tala1 N, Winchester RJ: The
1982 revised criteria for the classificationof systemic lupus
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2. Harvey AM, Shulman LE, Tumulty PA, Conley CL,
Schoenrich EH: Systemic lupus erythematosus: review
of the literature and clinical analysis of 138 cases.
Medicine (Baltimore) 33:291-337, 1954
3. Caldwell DS, McCallum RM: Rheumatologic manifestations of cancer. Med Clin North Am 70:385-417, 1986
4. McCarty GA: Autoimmunity and malignancy. Med Clin
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5. Westbrook CA, Groopman JE, Golde DW: Hairy cell
leukemia: disease pattern and prognosis. Cancer 54:500506, 1984
6. Westbrook CA, Golde DW: Clinical problems in hairy
cell leukemia: diagnosis and management. Semin Oncol
(SUPPI) 11514-522, 1984
7. Ratain MJ, Vardiman JW, Golomb HM: The role of
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Oncol (suppl) 13:21-28, 1986
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Dumont J, Seligmann M, Tannenbaum H, Esdaile J:
Hairy cell leukaemia with polyarteritis nodosa. Lancet
11:280-282, 1979
9. Crofts MAJ, Sharp JC, Joyner MV: Rheumatoid arthritis and hairy cell leukemia. Lancet II:203-204, 1979
10. Facchini A, Mariani E, Ferrolli A, Mariani AR, Gobbi
M, Zizzi F, Frizzier0 L: Hairy cell leukemia and rheumatoid arthritis: cause or effect? (letter). Arthritis
Rheum 24:1587, 1981
11. Sattar MA, Cawley MID: Arthritis associated with
hairy cell leukemia. Ann Rheum Dis 41:289-291, 1982
12. Dorsey JK, Penick GD: The association of hairy cell
leukemia with unusual immunologic disorders. Arch
Intern Med 142:902-903, 1982
13. Goedert JJ, Neefe JR, Smith FS, Stahl NI, Jaffe ES,
Fauci AS: Polyarteritis nodosa, hairy cell leukemia and
splenosis. Am J Med 71:323-326, 1981
14. Westbrook CA, Golde DW: Autoimmune disease in
hairy cell leukemia: clinical syndromes and treatment.
Br J Haematol61:349-356, 1985
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like, illness, lupus, leukemia, presenting, hair, cells
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