Clinical rheumatology, 1987, 6, N ~ 3 439-445

Case Report

The coexistence of rheumatoid arthritis and systemic lupus

erythematosus

C. VENEGONI*, M. CHEVALLARD*, G. MELE*,

G. BANFI**, M. CARRABBA*

*Department of R h e u m a t o l o g y , University o f Milan, G. Pini Orthopaedic Insti-

tute, M i l a n ; **Division o f Nephrology and Dialysis, Maggiore Policlinico Hospi-
tal, Milan, Italy.

SUMMARY A 29-year-old white female with longstanding classical rheumatoid arthritis

(RA) developed clinical and serological manifestations o f systemic lupus erythematosus
(SLE) with prominent signs o f diffuse proliferative lupus nephritis. She fulfilled the A R A
criteria f o r the classification o f SLE as well as the A R A criteria f o r classical RA. The
concomitant presence o f these two affections in the same patient is rare and the discriminat-
ing features suggest that this coexistence may be coincidental. With respect to treatment, our
patient had good relief o f symptoms by a combined administration o f methylprednisolone
pulses and cyclophosphamide.

Key words: Rheumatoid Arthritis, Systemic Lupus Erythematosus, Lupus Nephritis.

INTRODUCTION diagnosis of RA, but who later were found

Although systemic lupus erythematosus
(SLE) and rheumatoid arthritis (RA) are dif-
ferent diseases, some of their features may
be found concomitantly in the same patient,
making the diagnosis and clinical manage-
ment of such cases difficult (1,2). In some
cases instead of appearing simultaneously as
an "overlap syndrome", the serological and
clinical signs of one disease (usually SLE)
develop subsequently and a few patients
have been described in the literature with an
initial presentation compatible with a
Received28 October 1986, Accepted 23 February 1987 presented an ESR of 100 mm (Westergren),
Correspondence to." MASSIMOCHEVALLARD,
Cattedra di Reumatologia,IstitutoOrtopedicoG. Pini, CRP markedly positive, mild anemia, RA-
Via G. Pini, 3, 20122 Milano, Italy.
to have typical manifestations of SLE (3-6).
We describe a young woman with classical
deforming and erosive RA, who after some
years developed SLE as defined by the 1982
revised ARA criteria (7), with biopsy-proven
diffuse proliferative lupus glomerulonephri-
tis.
CASE REPORT
A 29-year-old Caucasian woman devel-
oped classical RA at the age of 21 (1978).
She had typical symmetrical arthritis of the
wrists, metacarpophalangeal and proximal
interphalangeal joints of the hands and me-
tatarsophalangeal joints. At that time she
test 1/320, Waaler Rose 1/32. LE cell phe-
440 C. Venegoni, M. Chevallard, G. Mele et al.

nomenon and antinuclear antibodies (ANA) blood pressure was 170/110 mm Hg. Chest
were negative; renal and hepatic function X-rays showed bibasilar pleural effusion and
tests were normal. Radiological investi- cardiomegaly; marked typical and symme-
gations showed juxta-articular deminerali- t r i c a l erosions were noted in the hands,
zation and slight erosions o f the joints o f knees, ankles and feet (Fig. 1). ECG was
hands and feet. A diagnosis o f RA was normal and echocardiography showed slight
made and the patient started treatment with pericardial effusion. Laboratory investi-
nonsteroidal anti-inflammatory drugs and gations revealed : haemoglobin 8.8 g/dl ; he-
gold salts with good relief o f symptoms. matocrit 36070 ; erythrocytes 4,000.000/mm 3 ;
After 18 months she stopped gold therapy leukocytes 6,800/mm 3 ; platelets
(total dose 800 mg) and went on with 350,000/mm3; ESR 50 m m ; blood urea 48
NSAIDs and occasional low-dose cortico- m g / d l ; serum creatinine 1.1 mg/dl with
steroids. creatinine clearance of 39 ml/min. Total
In January 1985 during a new flare-up o f plasma proteins were 5.8 g/dl with albumin
arthritis, she developed progressive dyspnea 39.5070, alpha2 13.4070 and gammaglobulins
and was admitted to our Rheumatological 33.1 070. Urinary protein excretion was about
Department. At this time she showed mark- 3g/24h with a non-selective glomerular pat-
ed dyspnea, prominent signs o f disease ac- tern. Additional findings included: RA test
tivity, facial erythema and ankle oedema. In 1/640; Waaler Rose 1/64; ANA 1/128 (ho-
the months before this exacerbation of mogeneous) ; anti-Sin positive ; anti n-DNA
symptoms, she did not take medications antibodies strongly positive (Chritidia Lucil-
known to induce lupus erythematosus. Her iae); LE cell phenomenon positive; VDRL

Radiograph of both hands showingbilateral juxtaarticular osteoporosisand multiple erosions involving the
Fig. 1 :
metacarpophalangeal joints.
 The coexistence o f R A an S L E 441

negative with normal serum complement. inflammatory cell infiltrates were present in
HLA typing tissue showed A2, A9, B7, BI5, the interstitium, and a few segments of inter-
DR4 and DRW8 pattern. lobular arteries displayed moderate fibrotic
The patient was treated with prednisone intimal thickening.
(50 rag/day) and clonidine (450 mcg/day) Immunofluorescence showed diffuse
with remission of arthritis, pleural effusion glomerular deposits distributed segmentally
and dyspnea and good control of hyper- along the glomerular capillary walls, mainly
tension. In the following weeks blood urea subendothelial but also intramembranous
increased to 83 mg/dl, proteinuria to and subepithelial. Staining for IgM and Clq
9g/24h, while C 3 and C4 decreased to 56 and antisera was intense, but also IgA, IgG, C3
12 mg/dl respectively, therefore a percuta- and fibrinogen were present.
neous kidney biopsy was performed after a At electron microscopy severe and diffuse
pyelography (normal). fusion of pedicels and many virus-induced
Light microscopy showed segmental, par- tubular structures in endothelial cells were
tially :sclerotic formations in all glomeruli noted in the capillary loops. Subepithelial
and diffuse irregular hypercellularity of the and intramembranous osmiophilic deposits,
tuft (Fig. 2-3). The capillary walls were ir- some in the form of humps, were present.
regularly thickened with scattered and fre- The mesangial region was moderately en-
quently coarse protein deposits mostly in- larged with nuclear increase and many small
tramembranous, but sometimes also suben- osmiophilic deposits (Fig. 4). The histologi-
dothelial. Some rather large mononuclear cal picture was compatible with the

Fig. 2: Diffuse increase of tuft cellularity with numerous polinucleated and mononuclear cells, partially occluding
some loops ; fresh extracapillary proliferation is present circumferentially filling the urinary space. In some loops
double contour appearance (arrow) of the capillary wall is present (AFOG stain, 400X).
442 C. Venegoni, M. Chevallard, G. Mele et al.

Fig. 3 :Prominent segmental epithelial proliferation still accompanies diffuse intracapillary hypercellularity. Note
coarse protein deposits segmentally distributed along thickened capillary walls (arrows) (AFOG stain, 400X).

diagnosis of diffuse lupus glomerulonephri- DISCUSSION

tis "mixed form", i.e. Class IV-V of the
WHO classification of lupus nephritis. The symmetrical involvement of wrists
The patient was diagnosed as having asso- and small joints of the hands and feet to-
ciated SLE and was treated with I.V. me- gether the serological and radiological fea-
thylprednisolone pulses (lg/day) for three tures left no doubt about the diagnosis of
consecutive days, followed by an oral classical RA (8) made in 1978 in our patient,
maintenance dose of 0.5 mg/kg/day, plus although rheumatoid nodules were absent
cyclophosphamide (100 mg/day). Extrarenal and synovial histological studies were not
symptoms rapidly disappeared, while urina= performed. Moreover, the good response to
ry protein excretion and renal function im- the initial gold therapy and the progression
proved more slowly. of the erosive lesions after stopping therapy
At present, 12 months after discharge supported this diagnosis.
from hospital, the patient is well. She is still During an exacerbation of joint symptoms
on 10 rag/day of prednisolone. Proteinuria in 1985, the patient developed a clinical pic-
is about 1.5g/24h, serum creatinine 1.2 ture characteristic of SLE, ANA positive.
mg/dl, creatinine clearance 59 ml/min, ANA are not rare in patients with RA and
blood urea 43 mg/dl, ESR 42 mm, haemo- have been reported in about 5-15070 of cases
globin 12.1 g/dl, hematocrit 35%, serum to- (2,9,10). They are generally present from the
tal proteins 6.7 g/dl, ANA positive 1/128 , beginning of the disease and are thought to
anti n-DNA antibodies negative and comple- define a subset of patients with more
ment fractions in the normal range. pronounced articular and visceral involve-
 The coexistence o f R A an S L E 443

Fig. 4: Electron microscopy showing : A. Peripheral glomerular basement membrane with subepithelial deposits of
different size covered by activated podocytes (EM 17,000X); B. Parts of mesangial taille and mesangium with
numerous osmiophilic deposits along the mesangial basement membrane and within the mesangial matrix (EM
15,000X).
444 C. Venegoni, M. Chevallard, G. Mele et al.

ment (9,11,12,15), however, some authors gold (800 mg) over a period o f 18 months
found no correlation between A N A and sev- before developing nephropathy. Gold neph-
erity o f RA (13,14). ropathy (24-26) is usually characterized by
In A N A positive-RA patients the renal proteinuria and histological changes very
lesions are those generally found in classical s i m i l a r to those observed in idiopathic
RA, such as amyloidosis or chronic intersti- membranous nephropathy and generally de-
tial nephritis (16-19). Although glomerular velops during gold therapy and not subse-
proliferative changes with parietal deposits quently.
of immunoglobulins and complement have Finally, tissue typing studies have shown a
been reported in some patients with long- predominance o f H L A - D W 4 and DR4 in
standing and malignant RA (20,21), their RA (27) and DR3 and DR2 in SLE (28). The
patterns clearly differ from any o f the types study performed in our case revealed an RA
o f SLE nephritis (22). Concomitant cases pattern - DR4 positive - whereas B cell
with clinical and serological features o f these alioantigens which seem to be helpful in dif-
two diseases are not rare : they generally de- ferentiating between the two diseases were
velop the "overlap syndrome" at presen- not investigated (29).
tation and cause problems o f correct The appearance o f SLE nephritis and lu-
diagnosis since recently erosive lesions have pus serology after so many years o f RA can
been reported also in sporadic SLE patients be considered, in our opinion, either a
(23). simple random event as proposed by Fisch-
Recently, Fischman et al. (5) described a man et al. (5), or a turning o f RA into a
44-year-old white female who developed connective tissue disease as S L E .
proteinuria and biopsy-proven diffuse proli- As far as treatment is concerned, we gave
ferative lupus nephritis after an 18-year his- our patient three pulses o f I g each o f me-
tory o f classical RA, showing that SLE may thylprednisolone followed by a maintenance
have developed late in the course o f RA. In dose o f 0 . 5 m g / k g / d a y combined with cyclo-
addition to clinical and radiological find- phosphamide (100 m g / d a y orally) since SLE
ings, the diagnosis o f RA was supported also features were predominant and life threaten-
by histological evidence o f chronic synovitis ing. The favourable course of the renal dis-
and rheumatoid nodules in a tendon sheat. ease and o f the general clinical picture at
SerologiCal tests for syphilis were false-posi- least for the time being, is that observed in
tive for this patient since the onset o f RA most cases o f lupus flare-up with diffuse
and the authors wonder if this was the first proliferative glomerulonephritis (30-31).
sign o f SLE. Furthermore, also the articular lesions have
After 7 years o f classical RA our patient shown no progression on steroid and cyclo-
developed 5 o f 11 A R A 1982 revised criteria phosphamide therapy during the 12 months
.for SLE (7), among which renal involvement of follow-up. Whether the clinical features
was prominent. It consisted of diffuse proli- of SLE or RA will predominante in this
ferative glomerulonephritis with many his- patient, will only be visible on longstanding
tological features typical o f lupus nephritis observation.
(22). She had received a certain amount o f

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