'Rhupus' Syndrome
Richard S. Panush, MD; N. Lawrence Edwards, MD; Selden Longley, MD; Ella Webster, MD
\s=b\ Occasionally patients with overlapping features of rheu-
matoid arthritis (RA) and systemic lupus erythematosus (SLE),
termed "rhupus," have been encountered. We wanted to
ascertain the frequency of such patients and determine
whether they represent a unique overlap syndrome. Of ap-
proximately 7000 new patients evaluated over 11 years, we
identified six patients who had, on the average, 6.7 American
Rheumatism Association criteria for RA and 4.2 criteria for
SLE. Criteria for RA included chronic symmetric arthritis with
morning stiffness (six patients); subcutaneous nodules (two
patients); positive rheumatoid factors test (four patients); and
radiologic erosions (four patients). The criteria for SLE in-
cluded malar rash (three patients); discoid lupus erythema-
tosus (two patients); biopsy-proved nephritis (one patient);
photosensitivity (one patient); leukopenia/thrombocytopenia
(four patients); positive antinuclear antibodies or lupus ery-
thematosus cell test (six patients); hypocomplementemia (two
patients); and abnormal results from skin biopsy (two pa-
tients). During observations of up to ten years, the conditions
of three patients were stable or improved, one died, and two
were unavailable for follow-up. Patients usually did not have
conditions that evolved to classic rheumatic disease patterns.
Rhupus was not common and did not occur more frequently
(0.09% prevalence among our patients) than expected from
chance concurrence of SLE and RA (calculated at 1.2%). These
observations confirm that rhupus indeed exists as a syndrome
manifested by patients sharing features of probable coinci-
dental concurrence of RA and SLE, but not as a unique clinical
pathologic or immunologic syndrome. Appreciation of these
patients with rhupus is important since their therapy and
outcome differ from those having RA or SLE alone.
(Arch Intern Med 1988;148:1633-1636)
"Dheumatoid arthritis (RA) and
-* * matosus
systemic lupus erythe-
(SLE) are common rheumatologic diseases.
We and others have occasionally encountered patients who
exhibited features of both.1-7 Schur1 first used the term
"rhupus syndrome" to describe patients with a "mixture of
signs and symptoms of systemic lupus erythematosus and
the related diseases such as rheumatoid arthritis." It is
unclear whether patients with rhupus represent a distinct
Accepted for publication March 24, 1988.
From the Division of Clinical Immunology, Rheumatology, and Allergy,
Department of Medicine, College of Medicine, University of Florida (Drs
Panush, Edwards, Longley, and Webster), and the Clinical Immunology
Section, Medical and Research Services, Veterans Administration Medical
Center (Drs Panush, Edwards, and Longley), Gainesville.
Reprints not available.
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clinical and immunologie entity or the coincidental occur¬
rence of RA and SLE. We sought to resolve these questions
by identifying patients with rhupus and comparing them
with patients having either SLE or RA, and by comparing
prevalence of rhupus with the expected coincidence of SLE
and RA among our patients.
PATIENTS AND METHODS
We undertook a retrospective study covering 11 years (1972 to
1983) of experience at the University of Florida and affiliated
Veterans Administration Medical Center in Gainesville. Approxi¬
mately 7000 new patient consultations were evaluated during this
period.
Patients considered to have rhupus were selected on the basis
of meeting American Rheumatism Association (ARA) criteria for
either RA8 or SLE,9 all or most criteria for the alternate diagnosis,
and who could not clearly be placed in one or the other diagnostic
category. Forty-two consecutive patients given a diagnosis of SLE
and 31 consecutive patients diagnosed as having RA during the
same period also were selected for review.
The three groups (rhupus, RA, and SLE) were compared with
respect to diagnostic criteria as well as other clinical features.
These included clinical characteristics (malar rash, discoid lupus
erythematosus [DLE], photosensitivity, polyarthritis, subcuta¬
neous nodules, and renal involvement); epidemiology (age, sex,
and race); laboratory studies (anemia [hematocrit, s0.37]; leuko-
penia [white blood cell count, s4 109/L]; thrombocytopenia
[platelet count, <150xl09/L]; elevated Westergren erythrocyte
sedimentation rate [ESR] [&20mm/h]); immunologie data (anti-
nuclear antibody [ANA] titers and pattern, rheumatoid factor
[RF], C3 and C4 levels, and VDRL); roentgenographic features;
therapy; and outcome.
RESULTS
Patient Identification
Six patients were identified with overlapping criteria for
both RA and SLE who could not be clearly designated as
having either RA or SLE. They constituted our study
group. The diagnostic criteria for RA and SLE fulfilled
individually by these patients are summarized in Table 1.
Epidemiologie Features
Patients with rhupus were significantly (P<.05) younger
and more often female than patients with RA, but this was
not the case when compared with patients with SLE (Table
2). The observed prevalence for RA in our patient popula¬
tion was 15% and for SLE was 8.9%. Therefore, the
expected coincidence of RA and SLE in our patient
population would be 1.2%. However, the observed preva¬
lence for rhupus was 0.09%, more than tenfold less than
expected.
 Table 1.—Diagnostic Criteria for Rheumatoid Arthritis and Table 2.—Clinical Features of Patients With
Systemic Lupus Erythematosus Fulfilled by Patients With 'Rhupus Syndrome'*
'Rhupus Syndrome'
RA Rhupus SLE
Patient* Feature (n 31)
=
(n 6)
=
(n 42)
=

Mean age, y 55t 35 38

Criteria
Sex, F:M 1:1f 5:1 3:1
Rheumatoid arthritis
Morning stiffness Malar rash, % 3t 50 33
Pain or tenderness in 1 joint DLE, % Of 33 10
Swelling in 1 joint Photosensitivity, % 3 16 19
Swelling in other joint(s) Polyarthritis, % 100t 100 52
Symmetric swelling SQ nodules, % 39 33 2t
Subcutaneous nodules Nephritis, % Of 17 31
Roentgenographic changes Anemia, % 45 50 52
Positive rheumatoid factors test Leukopenia, % 6t 50 25
Poor mucin clot Thrombocytopenia, % 9 33 31

Synovial histologie state Elevated ESR, % 75 50 79

Nodule histologie state Stage 0-I, % 25 0 100 (4 patients)
Systemic lupus erythematosus Stage ll-IV, % 75 100 (4 patients) 0
Malar rash Mean RA criteria 5.0 6.7 1.4f
Discoid rash Mean SLE criteria 1.3f 4.2 3.6
Photosensitlvlty *RA indicates rheumatoid arthritis; SLE, systemic lupus erythematosus;
Oral ulcer(s) DLE, discoid lupus erythematosus; SQ, subcutaneous; and ESR, erythro¬
Arthritis cyte sedimentation rate.
tP<.05 compared with rhupus.
Serositis
Renal disorder
Neurologic disorder
Hématologie disorder + + + ARA Classification Criteria
Immunologie disorder
-

ND
Antinuclear antibody + +
*Plus sign indicates presence of criteria; minus sign,
and ND, not done.
Clinical Features
The patients with rhupus experienced malar rash, DLE,
and nephritis significantly (P<.05) more often than pa¬
tients with RA but experienced polyarthritis less often
(P<.05) (Table 2). Renal involvement occurred in one of
our patients with rhupus. A second patient with rhupus
had weakly positive IgM by immunofluorescence tech¬
nique; a diffuse granular pattern in the capillary loops was
seen on a kidney biopsy specimen, but a diagnosis of lupus
nephritis was not made; IgG, IgA, C3, and C4 stains were
negative.
Laboratory Features
Presence of anemia, thrombocytopenia, or elevated
ESRs (Table 2) did not discriminate among groups. Leu-
kopenia was significantly more common in patients with
rhupus or SLE than in patients with RA (P<.05).
Radiologie Features
All of the patients with rhupus with roentgenograms
available for examination had evidence of erosions—three
with subluxation deformities and/or swan-neck deforma¬
tion of the hands and two with ankylosis of the small joints
of the hands or wrists (Table 2). No patients with SLE
with roentgenograms available for evaluation had evidence
of erosive deforming arthritis, although some had periar-
ticular osteopenia. Twenty-five percent of the patients with
RA had early disease with either no change, positive joint
scan, or periarticular osteopenia; the remaining 75% had
stage II to IV disease.
+ +
-
Patients with RA had an average of 6.7 RA diagnostic
+ +
criteria, and patients with SLE had an average of 4.2
absence of criteria; diagnostic criteria for SLE. The patients with rhupus had
an average of 4.5 RA diagnostic criteria (P<.05 vs SLE)
and 3.5 SLE diagnostic criteria (P<.05 vs RA). The
patients with RA and SLE each had less than two criteria
for the other diagnosis (P<.05) (Table 2). All patients with
rhupus had three to six RA diagnostic criteria and all had
three to six SLE diagnostic criteria.
Serologie Features
All with
patients rhupus had either positive ANA or
lupus erythematosus cell tests (P<.05 vs RA) (Table 3)—
three had speckled patterns; one, speckled and homoge¬
neous patterns; and another, speckled, homogeneous, and
rim patterns. Two of the five had titers greater than 1:80
(1:640 and 1:1280). Patient 4 not only had multiple ANA
patterns but also had antibodies to double-stranded DNA
(anti-DS-DNA) (1:160). Four of six patients with rhupus
had positive RF tests (P<.05 vs SLE) and two were
hypocomplementemic. Patient 4 was RF negative but had
positive AN As, anti-DS-DNA, erosive deforming arthritis,
subcutaneous nodules, hypocomplementemia (not a criteria
for diagnosis of SLE), and renal involvement. Patient 5,
the second patient with high-titer ANA, was one of two
patients (patients 2 and 5) with juvenile RA (JRA) early
in the course of their disease. Patient 5 had a positive
ANA, 1:1280 speckled pattern; anti-RNP, 1:5120; and
anti-Sm, 1:20. She also had Raynaud's phenomenon, ele¬
vated creatine kinase levels, and hypocomplementemia. A
kidney biopsy specimen gave normal light microscopy
findings with immunofluorescence technique showing
weakly positive IgM in a diffuse granular pattern along
the capillary loops. Patient 2 also had JRA with subsequent
development of leukopenia and a skin rash histologically
consistent with SLE.

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 Table 3.—Serologie Features of Patients With 'Rhupus Syndrome'*
Patient
Rhupus RA SLE
Feature 6 (n 6)
=
(n 31)
=
(n 42)
=

ANA
Titer + LE prep 1:80 1:80 1:640 1:1280 1:80 100%t 32%t 100%
Pattern ND Sp,H Sp SpH.R Sp Sp Sp,H H,Sp H,Sp
DS-DNA ND ND ND 1:160 ND ND ND ND ND
RNP ND ND ND Neg 1:5120 ND ND ND 5%
RF titer 1:80 Neg 1:2560 Neg 1:160 1:2560 67%t 78% 15%t
C3 (85-181 mg/L) 126 127 112 34 64 101 94 188f 92f
C4 (14.8-42 mg/L) 19 18 30 11 ND 16 19 35 20
Comments Rash; JRA; skin Deforming Nephritis; JRA; SQ DLE; erosive
erosive biopsy for arthritis; erosive, nodules arthritis; SQ
arthritis SLE; leukopenia deforming nodules;
leukopenia arthritis weight loss
*RA indicates rheumatoid arthritis; SLE, systemic lupus erythematosus; ANA, antinuclear antibody; +LE prep, positive lupus erythematosus preparation; ND,
no data; Sp, speckled; H, homogeneous; R, rim; DS-DNA, double-stranded DNA; RF, rheumatoid factor; Neg, negative; JRA, juvenile rheumatoid arthritis; SQ,
subcutaneous; DLE, discoid lupus erythematosus; and RNP, ribonucleoprotein.
tP<.05.

Therapy high-titer RF, positive ANA and anti-DS-DNA, and path¬

Patients with rhupus were treated with nonsteroidal
anti-inflammatory drugs (NSAIDs) (three patients), anti-
malarials (three patients), and/or oral steroids (three pa¬
tients). None received gold or penicillamine; one received
immunosuppressives. In comparison, patients with SLE
were managed more often with oral steroids (78%) and
immunosuppressives (15 patients) but not with NSAIDs
(four patients), gold (0%), or penicillamine (0%). The
majority of patients with RA received NSAIDs (30 pa¬
tients), antimalarials (18 patients), and/or gold (20 pa¬
tients); occasional patients were also given steroids (12
patients) or immunosuppressives (five patients).
Outcome
Follow-up was complete for four patients
information
with rhupus, 11 patients with SLE, and ten patients with
RA. One patient with rhupus died of sepsis and the other
three patients were stable or improved. Nine patients with
RA with information regarding outcome were stable or
improved (90%); one was worse (10%). Five patients with
SLE were improved or stable (46%); two were worse (19%);
and four were dead (36%).
COMMENT
Patients sharing features of both RA and SLE have been
observed infrequently. It has not been clear whether they
represented a unique entity with particular clinical char¬
acteristics, immunologie features, course, and prognosis or
merely chance occurrence of RA and SLE together. Our
observations indicate that while rhupus probably reflects
coincidental concurrence of RA and SLE, it is nevertheless
sufficiently clinically different from either RA or SLE
alone to have therapeutic and prognostic implications.
Toone et al,10 in 1960, presented 15 patients with RA
with positive lupus erythematosus cell preparations. Seven
of these patients had classic RA without multisystem
disease or SLE, four patients had classic RA and developed
multisystem disease (pericarditis, pleuritis, leukopenia,
and nodules), and four patients had weakly positive or
negative RF tests with systemic disease (serositis, sto¬
matitis, leukopenia, and proteinuria). The latter patients
may have had SLE with mild arthritis or coexistent RA.
Kantor et al,2 in 1969, reported the case of a 41-year-old
woman with destructive, deforming arthritis, nodules,
ologic (from a kidney biopsy specimen) evidence of SLE.
Hahn et al,5 in 1970, presented six patients with SLE who
had periarticular subcutaneous nodules that were "rheu¬
matoid" on biopsy findings in three patients; three of these
patients were RF positive and three were transiently RF
positive. Rheumatoid nodules also have been reported in
other patients with SLE.2·6 In 1976, a 41-year-old patient,
RF negative, with reportedly false-positive Wassermann
test results, developed an erosive, deforming arthritis with
nodules, and renal insufficiency; results of a kidney biopsy
were consistent with lupus nephritis.11 In 1981, Fischman
et al3 described a patient with coexisting RA and SLE.
Saulsbury et al,12 in 1982, presented two children with
long-standing JRA who subsequently developed SLE with
positive ANA, anti-DS-DNA, hypocomplementemia, and
circulating immune complexes. Ragsdale et al13 noted ten
cases ofJRA evolving to SLE—five with rash and serositis,
six with glomerulonephritis, and three with Raynaud's
phenomenon. Linn et al7 found that patients who were both
ANA positive and RF negative were quite similar to
patients who were both ANA and RF positive, ANA and
RF negative, and ANA negative and RF positive. Others4
have noted ANA positivity in 20% to 40% of patients with
RA and associated it with severe disease.
We describe six patients with overlapping clinical and
serologie features of RA and SLE, termed rhupus. Our
patients tended to be young women. They had polyarthritis,
nodules, malar rash, DLE, photosensitivity, and nephritis,
as have reported patients with RA-SLE overlap.2-7·10-13 Our
patients were frequently anemic, leukopenic, thrombocy-
topenic, and had elevated ESRs. They had erosive arthritis,
met all or most diagnostic criteria for both RA and SLE,
were usually both ANA and RF positive, and occasionally
were hypocomplementemic. These features too are similar
to those reported.27·1013 Two of our patients with rhupus
may have represented evolution from JRA to SLE, as has
been appreciated.1112 The observed prevalence of rhupus
(0.09%) was much less than expected for the coexistence
of RA and SLE (1.2%) for our study population. This is
rather close to the 0.06% of Fischman et al3 and is consistent
with chance concurrence of SLE and RA. Our patients
with rhupus were treated with NSAIDs, steroids, and
antimalarial drugs. Only one received immunosuppres-
sives. None was treated with gold or penicillamine. This

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 may reflect conservatism on the part of individual physi¬
cians and/or a mild course of disease for patients. The
conditions of most patients with rhupus stabilized or
improved with therapy.
We conclude that rhupus is not common and that it
occurred less frequently than would be expected, based on
the prevalence of RA and SLE in our patient population.
Nevertheless, patients with rhupus were clinically distinct
References
1. Schur PH: Systemic lupus erythematosus, in Beeson PB, McDermott
W (eds): Cecil-Loeb Textbook ofMedicine, ed 13. Philadelphia, WB Saunders
Co, 1971, p 821.
2. Kantor GL, Bickel YB, Barnett EV: Coexistence of systemic lupus
erythematosus and rheumatoid arthritis: Report of a case and review of the
literature, with clinical, pathological, and serologic observations. Am J Med
1969:47:433-444.
3. Fischman AS, Abeles M, Zanetti M, et al: The coexistence of
rheumatoid arthritis and systemic lupus erythematosus: A case report and
review of the literature. J Rheumatol 1981;8:405-414.
4. Condemi JJ, Barnett EV, Atwater EC, et al: The significance of
antinuclear factors in rheumatoid arthritis. Arthritis Rheum 1965;8:1080\x=req-\
1093.
5. Hahn BH, Yardley JH, Stevens MB: 'Rheumatoid' nodules in systemic
lupus erythematosus. Ann Intern Med 1970;72:49-58.
6. Dubois EL, Frion GJ, Chandor S: Rheumatoid nodules and rheumatoid
granulomas in systemic lupus erythematosus. JAMA 1972;220:515-518.
Downloaded From: http://archinte.jamanetwork.com/ by a Western University User on 06/11/2015
from patients with either SLE or RA. Appreciation of
these patients with rhupus is important since their therapy
and outcome differ from those having RA or SLE alone.
This investigation was supported by the Florida Chapter Arthritis
Foundation, Bradenton, and the Veterans Administration, Washington, DC.
Barbara Gibbs and Elizabeth Stein assisted with preparation of the
manuscript.
7. Linn JE, Hardin JG, Halla JT: A controlled study of ANA+ RF\p=m-\
arthritis. Arthritis Rheum 1978;21:645-659.
8. Ropes MW Bennett GA, Cobbs S, et al: 1958 revision of diagnostic
criteria for rheumatoid arthritis. Bull Rheum Dis 1958;9:175-176.
9. Tan EM, Cohen AS, Fries JF, et al: The 1982 revised criteria for the
classification of systemic lupus erythematosus. Arthritis Rheum 1982;25:
1271-1276.
10. Toone EC, Irby R, Pierce EL: The LE cell in rheumatoid arthritis.
Am J Med Sci 1960;240:599-608.
11. Case 29-1976, Case records of the Massachusetts General Hospital:
Weekly clinicopathological exercises. N Engl J Med 1976;295:156-163.
12. Saulsbury FT, Kesler RW, Kennaugh JM, et al: Overlap syndrome of
juvenile rheumatoid arthritis and systemic lupus erythematosus. J Rheu-
matol 1982;9:610-612.
13. Ragsdale CG, Petty RE, Cassidy JT, et al: The clinical progression
of apparent juvenile rheumatoid arthritis to systemic lupus erythematosus.
J Rheumatol 1980;7:50-55.