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Lupus erythematosus and avascular bone necrosisA clinical study of three cases and review of the literature.

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Lupus Erythematosus and Avascular Bone Necrosis :
A Clinical Study of Three Cases and Review
of the Literature
Avascular necrosis of the femoral head
was observed in two patients with systemic lupus erythematosus and one patient with facial discoid lupus erythematosus and equivocal evidence of dissemination. Histologic studies in one
case suggested widespread vasculitis.
One of the patients had never received
corticosteroid treatment. Therefore, it
seems somewhat more likely that the
avascular necrosis is due to lupus erythematosus than to steroid-induced vasculitis.
Ha essite observate duo patientes con
lupus erythematose generalisate e un
con lupus erythematose discoide facial
e evidentia equivoc de dissemination,
omne le tres presentante necrosis avascular del capite femoral. Studios histologic de un caso suggereva vasculitis
disseminate. Un del patientes habeva
nunquam essite tractate con corticosteroides. Per consequente, il pare plus
probabile que le necrosis avascular es
causate per le lupus erythematose e
non per vasculitis inducite per steroides.
HE ASSOCIATION BETWEEN lupus erythematosus (LE) and avascular
bone necrosis (AN) had not been observed until recently when Dubois
and Cozen1 reported eleven cases of avascular necrosis of the femoral head
and condyle in a series of 400 patients with systemic lupus erythematosus.
Baganz and Bailey2 added another case to the literature.
It is the purpose of this paper to report three additional observations of
this combination. One of these cases is of particular interest (Case l),since
the patient had never received adrenocortical steroids, and since his disease
was manifested as discoid lupus erythematosus with only equivocal evidence
of dissemination.
Case 1. C . F., a 42 year old male Negro was admitted to Long Beach Veterans Administration Hospital on Mar. 3, 1961, because of pain in the right hip, shortening of the right
lower extremity, and a limp. The pain had started one year previously, was maximal on
arising, decreased with activity, and was intermittent. During the 6 months prior to admission, the pain became severe and shortening of the extremity appeared. Interestingly, the
patient had worked as a farm hand 3 to 4 years previously and had to sling bushels of
feed along the right hip.
About 5 years prior to admission, the patient had noted scaliness of the scalp, localized
areas of alopecia and a dry scaling rash on the cheeks and forehead. Skin biopsy at that
time revealed chronic discoid lupus; only local therapy was given. At no time had steroids
been used in the treatment of this lesion.
Physical examination on admission revealed a melanotic butterfly lesion of the face
(fig. 1) with leukoderma of both ears. The patient walked with a limp, favoring the
right leg, which was 2.5 inches shorter than the left. The range of motion about the right
hip was: flexion 90 plus 10 degrees; extension 180 degrees; external rotation 5 degrees;
abduction 10 degrees; adduction 5 degrees; internal rotation 0 degrees. The remainder of
the physical examination was not remarkable.
From the Medical Seruice, Veterans Administration Hospital, Long Bemh, California.
Fig. 1.-Case
1. ButterfIy rash of discoid lupus erythematosus.
Laboratory studies revealed proteinuria varying from 32 mg. to 2.8 Gm. in 24 hours.
PSP, blood urea nitrogen and creatinine clearance were normal. The sedimentation rate
(Wintrobe) varied from 32 to 58 mm. per hour. C-reactive protein, F-2-latex test, DNA
latex agglutination and serologic tests for syphilis as well as seven lupus preparations were
negative. The serum proteins were normal; electrophoretically, there was a slight elevation
of the beta and gamma globulins. A battery of liver function tests was normal. Hemoglobin
was type AA electrophoretically, and the Cr-51 red blood cell survival determination gave
a normal result. X-ray changes were compatible with aseptic necrosis of the right femoral
head (fig. 2 ) .
On May 2, 1961, a cup arthroplasty was performed on the right femoral head. An irregular dense bony necrotic area measuring 1 x 2% cm. in the superior portion of the
femoral head was noted with marked hyperemic hyperplastic villous synovial reaction.
Biopsies from the synovia (fig. 3 ) and the muscle (fig. 4) and skin surrounding the hip
joint were also obtained and showed evidence of vasculitis in these tissues.
A renal needle biopsy (fig. 5) showed evidence of mild membranous glomerulitis. Needle
biopsies of the facial skin and finger pad revealed nonspecific chronic dermatitis. In July
1961, gradually increasing pain and limitation of motion developed in the left hip and
the patient was readmitted. X-ray films and planigrams (fig. 6 ) of the left femoral head
now showed changes typical of avascular necrosis on this side, as well.
Case 2. J. P., a 35 year old white man, was admitted to Long Beach Veterans Administration Hospital in December 1980. He had been in good health until 1946 when he devel-
Fig. %-Case 1. X-ray of pelvis, March 1961, irregular sclerosis and flattening
of right femoral head, consistent with avascular necrosis.
oped a red, scaling, pruritic rash of the face and neck which subsided after moving to a
cooler climate. From 1947 to 1948 he had migratory polyarthritis, thought to be rheumatoid, and was treated with salicylates. Intermittent arthralgia has persisted. In 1949, he
had a pleural effusion and fever. Since 1952, he has noted typical intermittent Raynaud's
phenomenon of varying severity. In 1954, a high remittent fever, diffuse erythematous
rash, facial and pedal edema, polyarthritis, pleural effusion and hematuria occurred and
were diagnosed as systemic lupus erythematosus on the basis of several positive lupus
erythematosus cell preparations. This episode responded dramatically to ACTH and cortisone, and he has been on corticosteroids ever since. The average daily maintenance dose
has been 20 mg. of prednisone; attempts at further reduction repeatedly led to flare-ups
of the facial rash, joint pains, malaise and fever. In 1955 and again in 1958, the daily dose
of steroids had to be increased to 40 mg. for short periods.
Pain in the right hip on walking appeared in 1957. X-ray films, a t that time, showed
evidence of aseptic necrosis. The symptoms were greatly relieved by reduction of weight
bearing for several months. Subsequently, he was able to ambulate moderately and to work.
In the fall of 1960, right hip pain increased, and thrombophlebitis of the left leg occurred.
On admission, he was noted to be a thin, well developed Caucasian male with a painful
right lower extremity. Adduction and abduction of the leg were reduced by about 50 per
cent, Rexion by 20 per cent. The spleen was palpable. Laboratory studies revealed no
significant abnormalities. Lupus erythematosus preparations were equivocal at this time.
X-ray examination of the right hip showed destructive changes in the femoral head consistent with aseptic necrosis. Comparison with X-ray films of 1957 disclosed slight progression. The patient was treated with strict bed rest followed by gradual ambulation,
with crutches and then with an ischial brace. He was discharged in February 1961, with
substantial improvement of his symptoms, while serial X-ray studies showed no significant
Fig. 3.-Case 1. Biopsy of synovial tissue, vasculitis and perivascular lymphocytic
infiltration (H& E stain, X 150).
Cms 3. C. B. was first admitted to Childrens Orthopedic Hospital, Los Angela, in October 1955, at the age of 11 years. For the previous year she had had an intermittent fever
and a progressive anemia requiring blood transfusions. On entry she had a temperature of
104 F., cardiomegaly with congestive failure, and hepatosplenomegaly. The hemoglobin
was 2.9 Gm. per cent. Serum bilirubin and urine urobilinogen were elevated, Coombs
test was positive, and several lupus erythematosus preparations were positive with both
bone marrow and peripheral blood. She improved dramatically on 60 mg. of prednisone
daily. From 1955 until 1957 she required u) mg. or more daily and was frequently readmitted to the hospital for episodes of hemolysis, pleural effusion, polyarthritis and intercurrent infections. Since 1958, her course has been smoother and presently she is doing
well on 10 to 15 mg. of prednisone daily. No evidence of kidney involvement other than
a moderate proteinuria has been present since 1955.
In November 1956, she complained of right hip pain on squatting. X-ray investigation at
that time was negative and the symptom subsided. In February 1958, at the age of 14,
the pain returned and was more severe. A limp with limitation of adduction and abduction
was noted. X-ray study (fig.7) showed typical findings of aseptic necrosis. Her symptoms
improved with restriction of activities, and the last X-ray film in December 1960, was
interpreted as showing slight improvement.
Aseptio necrosis of bone is generally thought to be due to impairment of
as indicated by the more modem term "avascular
necrosis." Details of this process are incompletely understood, particularly the
relationship of avascular necrosis to osteochondritis dissecans and to the more
common epiphyseal ischemic necrosis in children which is felt by some to be
the local blood supply:
Fig. 4.-Case 1. Biopsy of striated muscle, small blood vessel with dense mural
infiltration with polymorphonuclear cells (H & E stain, X 250).
genetically detem~ined.~
The disease seems to take a different course in different age group^.^ The vascular concept in general, however, is supported
by the following facts :
1. The histologic findings are those of an infarct;
2. Experimentally, avascular necrosis can be produced by injection of
particulate matter or air into the local circu1ation;e
3. Avascular necrosis occurs after traumatic disruption of major arteries7
or with conditions causing obstruction of smaller vessels by embolism, thrombosis or inflammation, such as caisson disease>O sickle cell anemia,'O Gaucher's
diseasell and irradiation;12
4. When tracer studies with P-32following dislocation or fracture indicate
poor perfusion of the femoral head, avascular necrosis will develop later.13J4
The femoral head is more prone to avascular necrosis than any other
osseous structure, because of the anatomy of its blood supply. Three groups
of arteries, the superior and inferior metaphyseal and the lateral epiphyseal,
derived from the medial femoral circumflex, penetrate the joint capsule and,
coursing within the joint along the surface of the neck and head, are exposed
to trauma.15 The medial epiphyseal artery, end branch of the medial femoral
circumflex, enters via the ligamentum teres. There are no anastomoses between
the epiphyseal and the metaphyseal circulations prior to closure of the epiphyseal line, and only small spiral communications develop thereafter.16
Fig. 5.-Case 1. Renal biopsy, increased cellularity of glomerulus, thickening of
basement membrane and partial obliteration of Bowman's capsule (PAS stain,
Xeither area has any anatomic vascular connection with the nutrient artery
of the femoral diaphysis. The relative lack of collaterals makes the arterial
vasculature of the femoral head very sensitive to interruption at any level.
The frequent widespread vasculitis in systemic lupus erythematosus, known
since the classic publication by Baehr, Klemperer and Schifrin in 1935," involves mainly smaller vessels.l@According to some authorsl8 it is found more
commonly in small veins, but arteries may be also a a c t e d and infarcts are
not uncommon, particularly in the pulmonary circulation.20 It seems likely
that inflammatory vascular obstruction may cause avascular necrosis in predisposed bone. While we were unable to find evidence of vasculitis in bone
removed at operation, it was demonstrable in the synovial tissue (fig. 3) and
in muscle (fig. 4 ) surrounding the involved hip. This would seem to lend
further support to this concept.
Corticosteroid treatment has been implicated in the development of avascular necrosis. Heimann and Freiberger2' described four patients with avascular
necrosis of the femoral and humeral heads following prolonged corticosteroid
administration. They postulate that corticosteroid-induced or -activated vasculitis might be the pathogenetic mechanism. Trimble22 in discussing their re-
Fig. d.-Case 1. Planigram left hip, irregular areas of sclerosis and radiolucency
suggesting avascular necrosis.
port, follows the same line of thought. However, the corticosteroid doses employed in Heimann and Freiberger’s cases were unusually large and one of
their patients had thrombotic thrombocytopenic purpura, a disease which in
itself leads to obstruction of small blood vessels. Sweetnam and coworkers28
reported four cases of “steroid arthropathy of the hip” developing after varying doses and periods of corticosteroid treatment. They point to painlessness
with increased weight bearing as the probable mechanism. There is some
doubt that their cases represent avascular necrosis, since 2 of their patients
had rheumatoid arthritis of the hip prior to treatment and the X-ray views
shown suggest severe progressive jcint disease rather than primarily osseous
avascular necrosis. Osteoporosis was also suggested as an explanation for
steroid-induced avascular necrosisz4 bur seems most unlikely, since the compensatory “osteoporosis” surrounding necrotic bone in avascular necrosis is
a sequel rather than a pathogenetic factor in avascular necrosis. The instances
of “Charcot joints” following intraarticular corticosteroid administration ob-
Fig. ‘I.-case
3. X-ray of pelvis, advanced avascular necrosis of right femoral
served by Chandlerz6 are also, presumably, pathogenetically quite different
from avascular necrosis.
One of our patients (Case 1) and one of Dubois and Cozen’s patients did
not receive steroids at any time prior to discovery of the avascular necrosis.
Five of Dubois and Cozen’s patients had not been receiving steroids for many
months to several years prior to the onset of symptoms of bone necrosis. In
all cases reported corticosteroid doses were moderate, far less than in the
series of Heimann and Freiberger. Good improvement of avascular necrosis
was observed under continued corticosteroid treatment in our cases 2 and 3
and in 2 cases of Dubois and Cozen’s.
These limited observations on the possible pathogenetic role of systemic
lupus erythematosus versus that of corticosteroid treatment in avascular
necrosis do not provide a conclusive sinswer. The situation is quite reminiscent
of the controversial role of corticosteroid treatment in the development of
vascular lesions in rheumatoid arthriti~.~~-~*
One of our patients (Case 1) had definite facial discoid lupus erythematosus (fig. l ) ,but a diagnosis of systemic lupus erythematosus could not be
h l y established. The early membranous glomerulitis (fig.5) and the vasculitis in various tissues suggest disseminakd disease. While the relationship be-
tween discoid lupus erythematosus and systemic lupus erythematosus remains
conversion from discoid to systemic lupus erythematosus is
not u11common~Oand most authorities feel that the two conditions are expressions of the same underlying p r o c e s ~If. ~
~ ~ ~ ~ necrosis is to be accepted
as a manifestation of systemic lupus erythematosus, its occurrence in a case
of discoid lupus provides a further interesting link between the two disorders.
Avascular necrosis of the femoral head was observed in 2 cases of systemic
lupus erythematosus and in one case of discoid facial lupus erythematosus
with possible early dissemination. The possible pathogenetic relationships
between avascular necrosis and systemic lupus erythematosus or avascular
necrosis and prolonged corticosteroid treatment were discussed.
We wish to thank Dr. Donald Polhemus and Dr. Robert Ward, Childrens Orthopedic
Hospital, Los Angeles, for permission to include Case 3 in this report; Dr. I. M. Reingold,
Veterans Administration Hospital, Long Beach, for help in evaluation of the biopsies; and
Mr. Tim Dodge, Veterans Administration Hospital, Long Beach, for taking the photographs.
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Jan K . Siemen, M.D., Chief Resident in Medicine, Medical
Service, Veterans Administration Hospital, Long B e d ,
lack Brook, M.D., Chief,Hematolugy Section, Medical Seruice,
Veterans Administration Hospitul, Long Beach, California;
Instructor in Medicine, University of Southern California
School of Medicine.
Lester Meister, M.D., Chief, Metabolism and Arthritis Section,
M e d i d Service, Veterans Administration Hospital, Long
Beach, California; Associate Professor of Clinical Medicine,
University of California, Los Angeles, Medical School.
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necrosis, lupus, literatury, clinical, avascular, stud, erythematosus, three, case, review, bones
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