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Systemic lupus erythematosus occurring in a patient with multiple myeloma.

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9. Mortensen JP, Lamm LU: Quantitative differences between
complement factor-B phenotypes. Immunology 42505-51 1,
10. Hill GS, Hinglais N, Tron F, Bach JF: Systemic lupus
erythematosus: morphologic correlation with immunologic and
clinical data at the time of biopsy. Am J Med 64:61-79, 1981
11. Wolf E, Spencer KM, Cudworth AG: The genetic susceptibility
type I (insulin-dependent) diabetes: analysis of the HLA-DR
association. Diabetologia 24:224-230, 1983
Systemic lupus erythematosus occurring in a patient
with multiple myeloma
To the Editor:
In contrast to conditions seen in mouse models of
systemic lupus erythematosus (SLE) (e.g., [New Zealand
black x New Zealand white] and MRLflpr mice) (l), the
coexistence of monoclonal gammopathy and SLE in humans
is distinctly uncommon (2,3). In all of the cases reported,
dysglobulinemia complicated the course of existing SLE.
We describe here a patient in whom SLE appeared during
the course of multiple myeloma that had been diagnosed and
treated for 2 years.
The patient, a 78-year-old man with an IgGK
monoclonal gammopathy diagnosed 6 years previously, presented to us with malignant changes which were characterized by: a rise in serum IgG levels to 26.45 gmfliter, along
with a decrease in levels of IgM and IgA; K light chain
proteinuria; bone marrow studies demonstrating 1557o imma’
ture plasma cells; mild anemia (hemoglobin 6.5 mmoles/
liter); normal white blood cell and platelet counts; an erythrocyte sedimentation rate (ESR) of 88 m d h o u r ; a fibrinogen
level of 5.6 gmlliter; normal creatinine and calcium levels;
punched-out lesions on lateral radiographs of the skull,
without other osteolytic findings; and normal total hemolytic
complement (CH50) and C3 levels.
‘Treatment consisted of monthly chemotherapy with
melphalan (6 mg/day for 4 days) and prednisone (50 mg/day
for 4 days). One year after initiation of treatment, the patient
showed clinical improvement. Laboratory studies revealed
an IgG level of 12 gdliter, an ESR of 33 mm/hour, and
stabilization of the skull lesions. After 2 years, the patient’s
clinical improvement allowed us to decrease the frequency
of treatments to once every 2 months. Eight months later,
the patient presented with a rapid deterioration of his general
condition, with onset of asthenia and anorexia, loss of 5 kg of
body weight within 1 month, and pain in the joints of his
upper extremities.
Examination disclosed erythematous lesions in sunexposed areas, swelling of his hands and elbows without
limitation of motion, and nasal ulcerations without ulcerous
pharyngitis or stomatitis. There seemed to be no relapse of
the multiple myeloma: his IgG level was 22.3 gm/liter; bone
marrow studies showed immature plasma cells at a level
similar to that of 8 months earlier (10%); skeletal radiographs
revealed no new lesions; there was no proteinuria; he had
hemoglobinemia at 6.8 mmolesfliter; and he had leukopenia
of 2,800/mm3, with mild neutropenia of 1,600/mm3. However, his ESR had increased to 112 m d h o u r ; the CH5O level
had decreased to 24 unitdm1 (normal 40-60); C3 was 0.66
400 0
300 TEST
Figure 1. Chronologic graph of the disease course in a patient with monoclonal gammopathy. The onset of
systemic lupus erythematosus is indicated by the initiation of prednisone (top right). ESR = erythrocyte
sedimentation rate; CH50 = total hemolytic complement.
gm/liter (normal 1.23-1.67); C4 was 0.09 gm/liter (normal
0.241.6);C l q was 81 mg/liter (normal 92-113); and factor B
was 0.09 gm/liter (normal 0.16-0.24).
Using HEp-2 cells as substrate, antinuclear antibodies (ANA) were demonstrated at a titer of 1:320 (normal
<1:81D), with a speckled pattern, and tests using Crithidia
luciliae demonstrated anti-double-stranded (anti-native)
DNA antibodies at a titer of >1:4,096 (normal <25). This
was confirmed by Farr test (369 units/ml; normal <25).
Antibodies to soluble nuclear antigens were present, but
were of undefined specificity. Direct immunofluorescence
study of a skin biopsy sample of an uninvolved area revealed
microgranular deposition of IgA (3+), IgM (3+), and C3
( 1 +) at the dermal-epidermal junction, but not in the blood
vessel walls. No cryoglobulinemia was found, and tests for
rheumatoid factor showed negative results.
The patient was diagnosed as having SLE and was
treated with prednisone at a dosage of 1 mg/kg/day. He
experienced a dramatic improvement in his general condition: the joint pain disappeared; his ESR decreased to 17
mm/hlour; anti-native DNA antibodies were 120 unitdm1
(measured by Farr test); and there was an increase in CH50
to a level of 41 unitdm1 and in C3 to a level of I . 1 gmfliter.
Thirty days later, the patient died of a massive pulmonary
embolism. His disease course is depicted in Figure 1.
The presence of monoclonal gammopathy prior to
the onset of SLE in this man prompted us to investigate a
possible link between the appearance of S L E and
paraprotein antibody activity. Indirect immunofluorescence
study using Crithidia luciliae demonstrated positive fluorescence with rabbit anti-A antiserum (1:2,560) and with rabbit
anti-n. antiserum (1: 10,240). Furthermore, using methods
derived from those of Terasaki et a1 (4), and testing for
lymphocytotoxicity at different temperatures (4”C, 15T,
22T, and 37”C), in a panel of 30 lymphocyte suspensions,
we detected no antilymphocyte antibodies in this patient’s
serum. Last, indirect double immunofluorescence testing (5)
did not demonstrate binding of immunoglobulins from the
patient’s serum to control T lymphocytes.
In summary, we were not able to prove any direct
relationship between the patient’s monoclonal gammopathy
and the genesis of SLE. This does not, however, rule out the
existence of an indirect relationship between monoclonal
gamrnopathy and SLE, such as immune dysfunction secondary to multiple myeloma (6), or its treatment.
Eric Solary, MD
Denis Caillot, MD
Henri Guy, MD
Nils-Olivier Olsson, MD
Yves Tanter, MD
Jean-Marc Chalopin, MD
Centre Hospitalier et Universitaire
Hbpital du Bocage
Dijon, France
I . Goldstein G, Warner NL, Holmes MC: Plasma-cell tumor induction in (NZB x BALBk) FI hybrid mice. JNCI 37:135-143, 1966
2. Rubin L, Urowitz MB, Pruzanski W: Systemic lupus erythematosus with paraproteinemia. Arthritis Rheum 27:638-644, 1984
3. Jordan E, Burnstein SL, Calabro JJ, Henderson ES: Multiple
myeloma complicating the course of seronegative systemic lupus
erythematosus. Arthritis Rheum 21:266263, 1978
4. Terasaki PI, Mottironi VD, Barnett EV: Cytotoxins in disease:
autocytotoxins in lupus. N Engl J Med 283:72&728, 1970
5. Husby G , Messner RP: Detection of antilymphocyte and antibodies in patients with systemic lupus erythematosus by indirect
immunofluorescence on acetone fixed lymphocytes. J Lab Clin
Med 89246248, 1977
6. Ullrich S , Zolla-Pazner S: Immunoregulatory circuits in myeloma. Clin Haematol 11337-90, 1982
Patients’ knowledge of their antirheumatic drugs
To the Editor:
Clinical observations by one of us (JJN) suggested
that patients with rheumatoid arthritis (RA) had inadequate
knowledge of their medications. A physician’s assistant
interviewed 74 unselected, consecutive patients with classic
or definite RA ( I ) who were followed in the Outpatient
Rheumatology Clinic of the University of Pittsburgh School
of Medicine from May 1982 to May 1983. Ten patients
refused to participate in the study. For each of the drugs in
the patient’s regimen, the patient was asked to state: 1) the
name, 2) a physical description (color and shape), 3) concentration (number of milligrams, grams, grains, or milliliters), 4) dose and frequency of administration, 5) major side
effects expected, and 6) major therapeutic effect expected.
Patients were not permitted to refer to written information.
The physician’s assistant recorded responses exactly as
stated by the patient.
The responses were then compared with the physician’s notes in the chart regarding the name of the medication, the dose, and the frequency. Reference information on
drug color and shape was obtained from the Physicians’
Desk Reference (2). The important side effects and the major
therapeutic effect were determined according to a consensus
of 3 University of Pittsburgh rheumatologists and several
major reference texts.
The patients’ responses were scored as follows: If
the pronunciation of the name of the drug was perfect or only
1 syllable was incorrect, the response was scored ‘‘full
knowledge”; “partial knowledge” was designated if more
than I syllable was incorrect, but the name was recognizable
by the investigators. Any other response was scored as
“inadequate knowledge.” Generic and manufacturer’s
brand name were scored equally.
In addition, the patient was scored as having either
“full knowledge” or “inadequate knowledge” on information concerning the color and shape, concentration, dose,
and frequency of the drug.
A list of side effects and major therapeutic effects for
each medication was established, and patients were asked to
recall up to 3 side effects that they either knew about or had
experienced, as well as the major therapeutic effect. Patients
were assigned scores of “full knowledge” for 3 correct
responses, “partial knowledge” for 1 or 2 correct responses,
and “inadequate knowledge” for no correct responses.
Scoring was performed by 2 observers who had not seen the
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lupus, myeloma, patients, occurring, systemic, erythematosus, multiple
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