JULY,
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SOFT
TISSUE CALCIFICATIONS LUPUS ERYTHEMATOSUS* By
JOEL
A.
BUDIN,
M.D., NEW
and
FRIEDA
YORK,
NEW
tissue calcification, a well known roentgen manifestation of connective tissue disorders, is commonly associated with scleroderma and dermatomyositis. Its occurrence in systemic lupus erythematosus (SLE), however, has been rarely appreciated and little emphasized. To the best of our knowledge only 8 cases have previously been documented in detail.3”’#{176} It is the purpose of this paper to present additional cases noted among 130 cases of SLE seen at the Columbia-Presbyterian Medical Center and to emphasize that such soft tissue calcification may be present in relation to the skin and deeper soft tissues, as well as in relation to the peripheral vasculature. The salient clinical and laboratory features of our 9 patients are summarized in Table i. The details of 3 representative cases follow. CLINICAL
bilateral
and
distributed
at the
Seventy-fifth
Annual
Meeting
OF
the
t Professor
Department
of Radiology,
CASES
3
in
of the American
Columbia-Presbyterian
find-
I. This 19 year old girl was first seen in with recurrent fever, arthralgias, a malar rash, and leukopenia. She had a positive LE cell preparation, a high anti-DNA titer, and a low serum complement. She was treated with prednisone and hydroxychloroquine. In 1968 she developed severe bilateral retinal vasculitis which responded well to massive doses of steroids. Because of a persistent rash on her face and arms, albuminuria, and steroid induced osteoporosis, azathioprine was begun. In 1969, renal biopsy revealed membranous and proliferative glomerulonephritis. In 1972, painless bilateral lower extremity nodules with surrounding areas of depigmentation were followed by the development of indolent ulcers and draining sinuses. Roentgenograms of her lower extremities in March 1973 revealed diffuse linear and nodular calcifications in the subcutaneous and deep tissues of both thighs and legs (Fig. I, ii and B) as well as extensive calcification of the femoral and popliteal arteries (Fig. 1, C and D). A similar pattern of calcification was subsequently demonstrated in both upper extremities, but without evidence of vascular calcifications (Fig. i, E and F).
CASE II. This 6o year old woman was first diagnosed as having SLE in 1958 with the advent of arthralgias, fever, and easy bruisability. Laboratory evaluation revealed leukopenia, thrombocytopenia, a positive LE cell test, positive direct Coomb’s test, elevated serum gamma globulin, and a negative latex fixation. In 1961 she developed bilateral pleural effusion s. Despite steroid therapy, progressive deforming arthritis of her hands and feet ensued, with metacarpal-phalangeal joint subluxations and flexion contractures. Multiple Roentgen
Ray
Society,
San
Francisco,
1974.
From
cutaneous
CASE
these patients, while had unilateral localized calcific deposits. One of these cases demonstrated diffuse calcifications of the upper as well as the lower extremities. Two patients showed premature vascular calcification involving the femoral and popliteal arteries. Periarticular calcifications of the hand were seen in i case. Three patients had calcific nodules at sites of previous or current cutaneous inflammation or ulceration. The remaining 6 Presented
M.D.t
1965
of
*
FELDMAN,
YORK
REPORT
FINDINGS
diffusely
SYSTEMIC
patients had no associated ings in the extremities.
The ages of our i male and 8 female patients ranged from 19 to 6o years. Subcutaneous calcification of the lower extremities was the most common manifestation, occurring in 7 of our cases. Calcifications were
IN
1975
Medical
of Radiology.
358
Center,
New
York,
New
York.
California,
September
24-27,
Voa.
114,
No.
Calcifications
3
in Systemic
Lupus
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Age,
Case I. (G.T.)
Sex
Location
OF
DATA
9
IN
CASES
Clinical
of Calcification
19
F
Diffuse: subcutaneous and deep Both thighs, legs, arms and forearms Femoral and popliteal arteries
Fever, retinal
359
I
TABLE SUMMARY
Erythematosus
Features
arthralgia, vasculitis,
Laboratory
nephritis, leg ulcers
rash,
Data
+LE prep, +antinuclear antibody, serum complement, leukopenia. Renal biopsy: membranous and proliferative glomerulonephritis
II.
(J.H.)
6o
F
Diffuse: subcutaneous and deep Both lower legs and thighs
Fever, arthritis, pleural effusions, multiple infections, leg ulcers
+LE prep, +direct Coomb’s, A serum gamma globulin, -latex fixation
III.
(V.G.)
23
F
Periarticular
Malar aseptic
‘Suspicious” LE prep A sedimentation rate, latex fixation
IV.
(F.W.)
52
F
Diffuse: deep Both lower legs
Rash, alopecia, Raynaud’s drome, venous insufficiency lower extremities
V.
(M.K.)
22
F
Localized: (R) lower
superficial
Numbness
of hands
leg
arthralgia,
nephritis,
tissues
of hand
rash, arthralgia, necrosis femoral
recurrent
VI. (E.J.)
VII. (A.F.)
VIII.
(M.C.)
IX.
(P.B.)
nephritis, heads
+LE prep, serum complement, Farr antibody per cent, +latex fixation. Skin biopsy: + antibody to basement membrane and nuclei
synof
and fingers,
+LE
pyoderma,
cence,
prep, +LE immuno-fluores+STS, +latex fixation
thrombophlebitis
40
F
Localized: (L) thigh
deep
Weakness,
arthralgia, fever, lymphadenopathy, nephritis
+LE
so
F
Localized: (R) thigh
deep
Athralgia,
+Anti-DNA, serum complement
3
M
Femoral
(L) popliteal
F
23
arteries-bilateral
nephritis, femoral
+Antinuclear antibody +direct Coomb’s +VDRL thrombocytopenia
heads
Arthralgia, rash, nephritis, aseptic necrosis (L) distal
antibody,
prep, +antinuclear serum complement. Renal biopsy: proliferative glomerulonephritis
rash, proteinuria
Rash, purpura, aseptic necrosis
fossa
x2,
+LE prep, +antinuclear +VDRL Renal biopsy:
femur
antibody, lobular
glomerulonephritis
episodes
of
infection,
diverticular
abscess,
including osteomyelitis ulna, and
distal radius and abdominal wall, but’ocks,
sitated tween
almost
continuous
a of abscesses
perforated the
ment
right of the
arms and feet, hospitalization
necesbe-
1961 and 1963. In 1965 and 1966 she was treated for recurrent leg ulcers. Roentgenograms of her lower extremities in 1972 (Fig. i, il-C) revealed diffuse nodular subcutaneous calcifications involving both distal thighs and lower legs.
with
Austin-Moore
investigation
of the
prostheses. persistent
In
albuminuria
1965,
and
edema revealed an erythrocyte sedimentation rate of I 14, two “suspicious” LE cell tests, and a negative latex fixation. A roentgenogram of the left hand taken for arthralgias and swelling showed calcifications in the periarticular soft tissues of the interphalangeal and metacarpalphalangeal joints (Fig. 3). Steroid dose adjustment afforded symptomatic relief. DISCUSSION
CASE
In.
A 23 year old woman
was first seen
in 1959, at age 17, for a malar rash which was aggravated by sunlight. In 1960, she developed malaise, progressive ankle edema, and arthralgias, and was found to have nephrotic syndrome.
In 1963
She
and
the femoral
responded well 1964, bilateral
heads
to dexamethasone. aseptic necrosis
necessitated
of
their replace-
Several noted i,
patterns
of
in this series. Three
n,
and
iv)
exhibited
calcification
were
patients
(Cases
diffuse,
linear,
streaky, or nodular calcific conglomerates or a combination of these in the subcutaneous
ties.
and
Case
deeper tissues of the lower i had the most extensive
extremiinvolve-
Joel
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360
FIG.
i.
(1 and
B) Anteroposterior
calcification in the superficial tional plaques of calcification,
year
A. Budin
and
Frieda
Feldman
JULY,
1975
views of the thighs and lower legs show multiple discrete nodular areas of and deeper soft tissues. (C and D) Lateral views of both knees show addias well as heavily calcified femoral and popliteal arteries (arrows) in this 19
old girl.
ment, with calcifications in the upper extremities as well. A similar pattern was noted in 2 previously reported cases.9”#{176} Only I of our 3 patients (Case Iv) had clinical evidence of venous insufficiency, but in addition, this patient had a severe diffuse
cutaneous
eruption
strable
antibodies
to
membrane
on
skin
nuclei
biopsy.
with and
Cases
demonbasement i and
II
had account
no evidence for
the
of venous roentgenographic
insufficiency
to
findings.
Both, however, had a history of recurrent indolent leg ulcers, a not uncommon cutaneous manifestation of SLE, occurring in 29 of 520 cases reported b Dubois.3 In certain instances, leg ulcers have preceded by months or years the typical picture of SLE.’ The etiology of these ulcers remains con-
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VOL.
124,
No.
Calcifications
3
in Systemic
jectural. Although a vasculitis has often been hypothesized, histopathologic support for this explanation is lacking, and indeed, clinical response to steroids has been inconsistent. Ofinterest in both Cases i and ii is the occurrence of soft tissue calcification in those areas involved with recurrent ulcerations. This association suggests that the calcification may have been precipitated by chronic inflammation and tissue necrosis. Case v had a palpable plaque-like calcific deposit along the anterior aspect of the lower leg without associated eruption or ulceration. This type of calcification was observed by Kabir and Malkinson.’ In i of their patients, calcinosis cutis developed 7 years prior to the onset of SLE, a situation reminiscent of the prior appearance and subsequent association of calcinosis universalis with dermatomyositis in childhood. After the onset of SLE in this case, however, many of the newly developing calcific nodules arose at sites of cutaneous inflammation, again suggesting local predisposing factors. In the second case of Kabir and Malkinson, sponded
the to
areas
calcific with
nodules skin
grene,
of
peripheral
thrombophlebi
arterial
tis,
of
occlusion,
livedo
FIG.
Erythematosus
361
(E and F) Anteroposterior demonstrate a similar
I.
arms
corre-
lesions
views pattern
of both foreof calcifica-
tions.
dis-
coid lupus. Calcifications of the arteries of the lower extremities were observed in Cases j and vIJI, ages 19 and 3 respectively. While in Case , diffuse subcutaneous calcifications were also present, arterial calcification was the only manifestation in Case viii. Neither of these patients was diabetic, and both had repeatedly normal serum calcium and phosphate determinations. Since Baehr et al.’s classic paper,2 SLE has been recognized as a diffuse disease in which inflammatory and degenerative changes may involve small vessels. Raynaud’s phenomenon has been frequently stressed as one of the manifestations which may precede the onset of SLE by many years. It is not well realized, however, that the same may also be true of other vascular complications. Only isolated reports
Lupus
gan-
reticularis
and
erythermalgia
have
appeared,
while
premature calcification of major peripheral vessels, particularly as detected on roentgenograms, has received even less attention. Alarcon-Segovia and Osmundso& in their report
of
Clinic,
cases
ii
indicate
manifestations
i.e.,
seen
at
the
peripheral
were
the
Mayo
vascular
initial
clinical
7, preceding the onset of better recognized signs and sympby many years. They also noted that vascular manifestations occurred, tended to be multiple and recurrent,
presentation
other toms when they
of SLE that
in
in
7
roentgen cification
of
ii
patients.
documentation was not alluded
Periarticular
as demonstrated observed in 2 tients.7 8 In the remainder
Unfortunately,
of to.
vascular
III
(Fig. 3) reported
calcifications
in Case previously of our
in
cases,
the
focal
calhand
were pacal-
Joel
362
A. Budin
and
Frieda
Feldman
necrosis areas
of of
onstrated
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the
soft
5975
JULY,
left
distal
tissue
in this
femur.
calcification
No
other
were
dem-
patient.
Although some cification described iniscent of those
the patterns of calin our series are remseen with hyperparathy-
roidism,
our
none
or laboratory secondary the frequent The of
of
association
in
several
with
eruptions
phic process, calcification
patients
had
clinical
evidence of either primary or hyperparathyroidism, despite presence of renal insufficiency.
calcification
taneous
of
of
our
ulcerations
points
more
patients and
to
cu-
a dystro-
rather than to the metastatic of normal tissues seen in hy-
perparathyroidism.
“Overlap” collagen described.
cific tissues
deposits of
were the
included in this focal plaque-like popliteal
fossa
noted
lower
in
the
deep
extremities.
during
treatment (Fig. , A and this occurred simultaneously
the
with been diag-
ix,
developed in the left
course
B).
in patients frequently with the
soft
Case
latter group, calcifications
syndromes disease have Thus, patients
of
her
Interestingly
with
aseptic
3. Note calcific conglomerates in the peri-articular soft tissues (arrows) with preservation of normal mineralization and joint architecture.
FIG.
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VOL.
No.
124,
Calcifications
3
in Systemic
Lupus
363
Erythematosus
4. (1 and B) Lateral views of left knee at ages i8 and 23. Note initial absence ment of calcifications in the soft tissues of the popliteal fossa. Aseptic necrosis present as evidenced by an osteochondral fragment (arrow).
FIG.
nostic features of SLE may have many characteristics of those with scleroderma or dermatomyositis. However, most patients in our series had classic manifestations of SLE. Although the marked joint involvement
in
Case
H
may
suggest
an
overlap with rheumatoid arthritis, extensive soft tissue calcifications are certainly not a typical finding in the latter disorder. It is tempting to regard the occurrence of calcinosis in the various connective tissue disorders as further evidence that they are merely individual expressions of the same pathologic spectrum. However, until the etiologic factors of these diseases are better understood, this concept would appear to bean oversimplification. In view of the fact that each of the connective tissue disorders usually possesses distinct histopathologic features, it is just as feasible to consider the process of dystrophic calcification as a nonspecific
tissue. Several mation been
response
to or result
mechanisms pathologic
of this proposed.4
Local
to
of damaged
explain calcification
factors
favoring
the
forhave soft
tissue
calcification
The increased predisposes
and
subsequent
of the distal
have
develop-
femur
been
suggested.
alkalinity of necrotic to precipitation of
salts. In addition, elevated phosphatase, which may cations, have often been necrotic
tissue.
released
by
This
damaged
is also
tissues calcium
levels of alkaline facilitate calcifidemonstrated in
phosphatase
may
lysosomes
within
be the
injured cells. Defective esterification of phosphate liberated by alkaline phosphatase may also lead to precipitation of calcium phosphate. Similarly, breakdown of substances able to bind calcium in a non-ionic form may be involved. In any event, the causes of tissue damage leading to calcinosis may differ in SLE and the other collagen diseases. Infection, vasculitis and ischemi a, autoimmune reaction at
the
cell
membrane
level,
and
fibrinoid
replacement may all represent separate pathways to tissue necrosis and subsequent dystrophic calcification. Although soft tissue calcifications were noted in 9 of 130 cases of SLE, the review was retrospective. The majority of cases had not had routine roentgenograms of the extremities. The actual incidence of soft
364
Joel A. Budin
tissue
calcinosis
ably
in SLE
higher
than
is,
that
therefore,
reflected
and
probin
this
Frieda 2.
re-
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Calcifications
tissues, mented gether
commonly
disorders,
with
much more preci ated,
discerned, date the of
rarely
This
premature
the peripheral
and, clinical
soft
with
been
docu-
association, calcific deposits
vasculature,
frequently may be
deeper
associated
have
SLE.
with
3.
in the skin and
although
collagen
probably
toin
4.
6.
may premanifesta-
10032
D.,
systemic 1965,
62,
vascular
lupus 907-919.
and
syndromes
erythematosus.
OSMUNDSON,
associated Ann. mt.
P. J. with Med.,
J.
NUCLEAR
New
Fourth
ROENTGENOL., MED.,
T.
Family
Suppl.,
edi-
cry-
THER-
938-943.
studies in systemic Acta med. scandinav., D.
ODONE,
SPLITTER,
Radiology,
1963,
M.
RAD.
86,
416.
C. D.,
E. P., and joint disease POWELL,
1961,
erythematosus.
with tion.
10.
Pathology
AM.
&
8. NOONAN,
Center
General
W.
LEONHARDT,
1964,
Medical
Lupus Erythematosus. Company, Inc.,
thematosus and calcinosis cutis. A.M.A. Arch. Dermat. & Syph., 1969, ZOO, 17-22. KEATS, T. E. Collagen diseases: demonstrations of nonspecificity of their extrapulmonary man-
lupus
REFERENCES
Peripheral
KABIR,
APY
7.
Editor. Book
W. B. Saunders Company, Philadelphia, pp. 435-444. D. I.,and MALKINSON, F. D. Lupus
ifestation.
9. ALARCON-SEGOVIA,
H.
FLOREY, 1970,
.
L.
1966.
tion.
ap-
the disease.
139-155.
E. McGraw-Hill
DuBols,
York,
occurs
than heretofore roentgenographically
in some instances, and laboratory
Joel A. Budin, M.D. Department of Radiology Columbia Presbyterian 622 West i68th Street New York, New York
I.
associated endocarditis).
1935,50,
SUMMARY
P., and SCHIFRIN, A. of peripheral circulation with lupus erythematosus Tr. A. Am. Physicians,
KLEMPERER,
disease
(usually
and
5975
JULY,
G.,
BAEHR,
Diffuse
port.
tions
Feldman
T.,
ENGLEMAN,
S. D. Manifestations in systemic lupus erythematosus. 8o,
of
837-843.
B. Systemic
lupus erythematosus
widespread subcutaneous fat calcificaProc. Roy. Soc. Med., 1974, 67, 215-217. SAVIN, J. A. Systemic lupus erythematosus with ectopic calcification. Brit. 7. Dermat., 1971,
8,
191-192.
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SOFT
TISSUE CALCIFICATIONS LUPUS ERYTHEMATOSUS* By
JOEL
A.
BUDIN,
M.D., NEW
and
FRIEDA
YORK,
NEW
tissue calcification, a well known roentgen manifestation of connective tissue disorders, is commonly associated with scleroderma and dermatomyositis. Its occurrence in systemic lupus erythematosus (SLE), however, has been rarely appreciated and little emphasized. To the best of our knowledge only 8 cases have previously been documented in detail.3”’#{176} It is the purpose of this paper to present additional cases noted among 130 cases of SLE seen at the Columbia-Presbyterian Medical Center and to emphasize that such soft tissue calcification may be present in relation to the skin and deeper soft tissues, as well as in relation to the peripheral vasculature. The salient clinical and laboratory features of our 9 patients are summarized in Table i. The details of 3 representative cases follow. CLINICAL
bilateral
and
distributed
at the
Seventy-fifth
Annual
Meeting
OF
the
t Professor
Department
of Radiology,
CASES
3
in
of the American
Columbia-Presbyterian
find-
I. This 19 year old girl was first seen in with recurrent fever, arthralgias, a malar rash, and leukopenia. She had a positive LE cell preparation, a high anti-DNA titer, and a low serum complement. She was treated with prednisone and hydroxychloroquine. In 1968 she developed severe bilateral retinal vasculitis which responded well to massive doses of steroids. Because of a persistent rash on her face and arms, albuminuria, and steroid induced osteoporosis, azathioprine was begun. In 1969, renal biopsy revealed membranous and proliferative glomerulonephritis. In 1972, painless bilateral lower extremity nodules with surrounding areas of depigmentation were followed by the development of indolent ulcers and draining sinuses. Roentgenograms of her lower extremities in March 1973 revealed diffuse linear and nodular calcifications in the subcutaneous and deep tissues of both thighs and legs (Fig. I, ii and B) as well as extensive calcification of the femoral and popliteal arteries (Fig. 1, C and D). A similar pattern of calcification was subsequently demonstrated in both upper extremities, but without evidence of vascular calcifications (Fig. i, E and F).
CASE II. This 6o year old woman was first diagnosed as having SLE in 1958 with the advent of arthralgias, fever, and easy bruisability. Laboratory evaluation revealed leukopenia, thrombocytopenia, a positive LE cell test, positive direct Coomb’s test, elevated serum gamma globulin, and a negative latex fixation. In 1961 she developed bilateral pleural effusion s. Despite steroid therapy, progressive deforming arthritis of her hands and feet ensued, with metacarpal-phalangeal joint subluxations and flexion contractures. Multiple Roentgen
Ray
Society,
San
Francisco,
1974.
From
cutaneous
CASE
these patients, while had unilateral localized calcific deposits. One of these cases demonstrated diffuse calcifications of the upper as well as the lower extremities. Two patients showed premature vascular calcification involving the femoral and popliteal arteries. Periarticular calcifications of the hand were seen in i case. Three patients had calcific nodules at sites of previous or current cutaneous inflammation or ulceration. The remaining 6 Presented
M.D.t
1965
of
*
FELDMAN,
YORK
REPORT
FINDINGS
diffusely
SYSTEMIC
patients had no associated ings in the extremities.
The ages of our i male and 8 female patients ranged from 19 to 6o years. Subcutaneous calcification of the lower extremities was the most common manifestation, occurring in 7 of our cases. Calcifications were
IN
1975
Medical
of Radiology.
358
Center,
New
York,
New
York.
California,
September
24-27,
Voa.
114,
No.
Calcifications
3
in Systemic
Lupus
Downloaded from www.ajronline.org by 191.177.186.224 on 06/21/16 from IP address 191.177.186.224. Copyright ARRS. For personal use only; all rights reserved
Age,
Case I. (G.T.)
Sex
Location
OF
DATA
9
IN
CASES
Clinical
of Calcification
19
F
Diffuse: subcutaneous and deep Both thighs, legs, arms and forearms Femoral and popliteal arteries
Fever, retinal
359
I
TABLE SUMMARY
Erythematosus
Features
arthralgia, vasculitis,
Laboratory
nephritis, leg ulcers
rash,
Data
+LE prep, +antinuclear antibody, serum complement, leukopenia. Renal biopsy: membranous and proliferative glomerulonephritis
II.
(J.H.)
6o
F
Diffuse: subcutaneous and deep Both lower legs and thighs
Fever, arthritis, pleural effusions, multiple infections, leg ulcers
+LE prep, +direct Coomb’s, A serum gamma globulin, -latex fixation
III.
(V.G.)
23
F
Periarticular
Malar aseptic
‘Suspicious” LE prep A sedimentation rate, latex fixation
IV.
(F.W.)
52
F
Diffuse: deep Both lower legs
Rash, alopecia, Raynaud’s drome, venous insufficiency lower extremities
V.
(M.K.)
22
F
Localized: (R) lower
superficial
Numbness
of hands
leg
arthralgia,
nephritis,
tissues
of hand
rash, arthralgia, necrosis femoral
recurrent
VI. (E.J.)
VII. (A.F.)
VIII.
(M.C.)
IX.
(P.B.)
nephritis, heads
+LE prep, serum complement, Farr antibody per cent, +latex fixation. Skin biopsy: + antibody to basement membrane and nuclei
synof
and fingers,
+LE
pyoderma,
cence,
prep, +LE immuno-fluores+STS, +latex fixation
thrombophlebitis
40
F
Localized: (L) thigh
deep
Weakness,
arthralgia, fever, lymphadenopathy, nephritis
+LE
so
F
Localized: (R) thigh
deep
Athralgia,
+Anti-DNA, serum complement
3
M
Femoral
(L) popliteal
F
23
arteries-bilateral
nephritis, femoral
+Antinuclear antibody +direct Coomb’s +VDRL thrombocytopenia
heads
Arthralgia, rash, nephritis, aseptic necrosis (L) distal
antibody,
prep, +antinuclear serum complement. Renal biopsy: proliferative glomerulonephritis
rash, proteinuria
Rash, purpura, aseptic necrosis
fossa
x2,
+LE prep, +antinuclear +VDRL Renal biopsy:
femur
antibody, lobular
glomerulonephritis
episodes
of
infection,
diverticular
abscess,
including osteomyelitis ulna, and
distal radius and abdominal wall, but’ocks,
sitated tween
almost
continuous
a of abscesses
perforated the
ment
right of the
arms and feet, hospitalization
necesbe-
1961 and 1963. In 1965 and 1966 she was treated for recurrent leg ulcers. Roentgenograms of her lower extremities in 1972 (Fig. i, il-C) revealed diffuse nodular subcutaneous calcifications involving both distal thighs and lower legs.
with
Austin-Moore
investigation
of the
prostheses. persistent
In
albuminuria
1965,
and
edema revealed an erythrocyte sedimentation rate of I 14, two “suspicious” LE cell tests, and a negative latex fixation. A roentgenogram of the left hand taken for arthralgias and swelling showed calcifications in the periarticular soft tissues of the interphalangeal and metacarpalphalangeal joints (Fig. 3). Steroid dose adjustment afforded symptomatic relief. DISCUSSION
CASE
In.
A 23 year old woman
was first seen
in 1959, at age 17, for a malar rash which was aggravated by sunlight. In 1960, she developed malaise, progressive ankle edema, and arthralgias, and was found to have nephrotic syndrome.
In 1963
She
and
the femoral
responded well 1964, bilateral
heads
to dexamethasone. aseptic necrosis
necessitated
of
their replace-
Several noted i,
patterns
of
in this series. Three
n,
and
iv)
exhibited
calcification
were
patients
(Cases
diffuse,
linear,
streaky, or nodular calcific conglomerates or a combination of these in the subcutaneous
ties.
and
Case
deeper tissues of the lower i had the most extensive
extremiinvolve-
Joel
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360
FIG.
i.
(1 and
B) Anteroposterior
calcification in the superficial tional plaques of calcification,
year
A. Budin
and
Frieda
Feldman
JULY,
1975
views of the thighs and lower legs show multiple discrete nodular areas of and deeper soft tissues. (C and D) Lateral views of both knees show addias well as heavily calcified femoral and popliteal arteries (arrows) in this 19
old girl.
ment, with calcifications in the upper extremities as well. A similar pattern was noted in 2 previously reported cases.9”#{176} Only I of our 3 patients (Case Iv) had clinical evidence of venous insufficiency, but in addition, this patient had a severe diffuse
cutaneous
eruption
strable
antibodies
to
membrane
on
skin
nuclei
biopsy.
with and
Cases
demonbasement i and
II
had account
no evidence for
the
of venous roentgenographic
insufficiency
to
findings.
Both, however, had a history of recurrent indolent leg ulcers, a not uncommon cutaneous manifestation of SLE, occurring in 29 of 520 cases reported b Dubois.3 In certain instances, leg ulcers have preceded by months or years the typical picture of SLE.’ The etiology of these ulcers remains con-
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VOL.
124,
No.
Calcifications
3
in Systemic
jectural. Although a vasculitis has often been hypothesized, histopathologic support for this explanation is lacking, and indeed, clinical response to steroids has been inconsistent. Ofinterest in both Cases i and ii is the occurrence of soft tissue calcification in those areas involved with recurrent ulcerations. This association suggests that the calcification may have been precipitated by chronic inflammation and tissue necrosis. Case v had a palpable plaque-like calcific deposit along the anterior aspect of the lower leg without associated eruption or ulceration. This type of calcification was observed by Kabir and Malkinson.’ In i of their patients, calcinosis cutis developed 7 years prior to the onset of SLE, a situation reminiscent of the prior appearance and subsequent association of calcinosis universalis with dermatomyositis in childhood. After the onset of SLE in this case, however, many of the newly developing calcific nodules arose at sites of cutaneous inflammation, again suggesting local predisposing factors. In the second case of Kabir and Malkinson, sponded
the to
areas
calcific with
nodules skin
grene,
of
peripheral
thrombophlebi
arterial
tis,
of
occlusion,
livedo
FIG.
Erythematosus
361
(E and F) Anteroposterior demonstrate a similar
I.
arms
corre-
lesions
views pattern
of both foreof calcifica-
tions.
dis-
coid lupus. Calcifications of the arteries of the lower extremities were observed in Cases j and vIJI, ages 19 and 3 respectively. While in Case , diffuse subcutaneous calcifications were also present, arterial calcification was the only manifestation in Case viii. Neither of these patients was diabetic, and both had repeatedly normal serum calcium and phosphate determinations. Since Baehr et al.’s classic paper,2 SLE has been recognized as a diffuse disease in which inflammatory and degenerative changes may involve small vessels. Raynaud’s phenomenon has been frequently stressed as one of the manifestations which may precede the onset of SLE by many years. It is not well realized, however, that the same may also be true of other vascular complications. Only isolated reports
Lupus
gan-
reticularis
and
erythermalgia
have
appeared,
while
premature calcification of major peripheral vessels, particularly as detected on roentgenograms, has received even less attention. Alarcon-Segovia and Osmundso& in their report
of
Clinic,
cases
ii
indicate
manifestations
i.e.,
seen
at
the
peripheral
were
the
Mayo
vascular
initial
clinical
7, preceding the onset of better recognized signs and sympby many years. They also noted that vascular manifestations occurred, tended to be multiple and recurrent,
presentation
other toms when they
of SLE that
in
in
7
roentgen cification
of
ii
patients.
documentation was not alluded
Periarticular
as demonstrated observed in 2 tients.7 8 In the remainder
Unfortunately,
of to.
vascular
III
(Fig. 3) reported
calcifications
in Case previously of our
in
cases,
the
focal
calhand
were pacal-
Joel
362
A. Budin
and
Frieda
Feldman
necrosis areas
of of
onstrated
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the
soft
5975
JULY,
left
distal
tissue
in this
femur.
calcification
No
other
were
dem-
patient.
Although some cification described iniscent of those
the patterns of calin our series are remseen with hyperparathy-
roidism,
our
none
or laboratory secondary the frequent The of
of
association
in
several
with
eruptions
phic process, calcification
patients
had
clinical
evidence of either primary or hyperparathyroidism, despite presence of renal insufficiency.
calcification
taneous
of
of
our
ulcerations
points
more
patients and
to
cu-
a dystro-
rather than to the metastatic of normal tissues seen in hy-
perparathyroidism.
“Overlap” collagen described.
cific tissues
deposits of
were the
included in this focal plaque-like popliteal
fossa
noted
lower
in
the
deep
extremities.
during
treatment (Fig. , A and this occurred simultaneously
the
with been diag-
ix,
developed in the left
course
B).
in patients frequently with the
soft
Case
latter group, calcifications
syndromes disease have Thus, patients
of
her
Interestingly
with
aseptic
3. Note calcific conglomerates in the peri-articular soft tissues (arrows) with preservation of normal mineralization and joint architecture.
FIG.
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VOL.
No.
124,
Calcifications
3
in Systemic
Lupus
363
Erythematosus
4. (1 and B) Lateral views of left knee at ages i8 and 23. Note initial absence ment of calcifications in the soft tissues of the popliteal fossa. Aseptic necrosis present as evidenced by an osteochondral fragment (arrow).
FIG.
nostic features of SLE may have many characteristics of those with scleroderma or dermatomyositis. However, most patients in our series had classic manifestations of SLE. Although the marked joint involvement
in
Case
H
may
suggest
an
overlap with rheumatoid arthritis, extensive soft tissue calcifications are certainly not a typical finding in the latter disorder. It is tempting to regard the occurrence of calcinosis in the various connective tissue disorders as further evidence that they are merely individual expressions of the same pathologic spectrum. However, until the etiologic factors of these diseases are better understood, this concept would appear to bean oversimplification. In view of the fact that each of the connective tissue disorders usually possesses distinct histopathologic features, it is just as feasible to consider the process of dystrophic calcification as a nonspecific
tissue. Several mation been
response
to or result
mechanisms pathologic
of this proposed.4
Local
to
of damaged
explain calcification
factors
favoring
the
forhave soft
tissue
calcification
The increased predisposes
and
subsequent
of the distal
have
develop-
femur
been
suggested.
alkalinity of necrotic to precipitation of
salts. In addition, elevated phosphatase, which may cations, have often been necrotic
tissue.
released
by
This
damaged
is also
tissues calcium
levels of alkaline facilitate calcifidemonstrated in
phosphatase
may
lysosomes
within
be the
injured cells. Defective esterification of phosphate liberated by alkaline phosphatase may also lead to precipitation of calcium phosphate. Similarly, breakdown of substances able to bind calcium in a non-ionic form may be involved. In any event, the causes of tissue damage leading to calcinosis may differ in SLE and the other collagen diseases. Infection, vasculitis and ischemi a, autoimmune reaction at
the
cell
membrane
level,
and
fibrinoid
replacement may all represent separate pathways to tissue necrosis and subsequent dystrophic calcification. Although soft tissue calcifications were noted in 9 of 130 cases of SLE, the review was retrospective. The majority of cases had not had routine roentgenograms of the extremities. The actual incidence of soft
364
Joel A. Budin
tissue
calcinosis
ably
in SLE
higher
than
is,
that
therefore,
reflected
and
probin
this
Frieda 2.
re-
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Calcifications
tissues, mented gether
commonly
disorders,
with
much more preci ated,
discerned, date the of
rarely
This
premature
the peripheral
and, clinical
soft
with
been
docu-
association, calcific deposits
vasculature,
frequently may be
deeper
associated
have
SLE.
with
3.
in the skin and
although
collagen
probably
toin
4.
6.
may premanifesta-
10032
D.,
systemic 1965,
62,
vascular
lupus 907-919.
and
syndromes
erythematosus.
OSMUNDSON,
associated Ann. mt.
P. J. with Med.,
J.
NUCLEAR
New
Fourth
ROENTGENOL., MED.,
T.
Family
Suppl.,
edi-
cry-
THER-
938-943.
studies in systemic Acta med. scandinav., D.
ODONE,
SPLITTER,
Radiology,
1963,
M.
RAD.
86,
416.
C. D.,
E. P., and joint disease POWELL,
1961,
erythematosus.
with tion.
10.
Pathology
AM.
&
8. NOONAN,
Center
General
W.
LEONHARDT,
1964,
Medical
Lupus Erythematosus. Company, Inc.,
thematosus and calcinosis cutis. A.M.A. Arch. Dermat. & Syph., 1969, ZOO, 17-22. KEATS, T. E. Collagen diseases: demonstrations of nonspecificity of their extrapulmonary man-
lupus
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APY
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W. B. Saunders Company, Philadelphia, pp. 435-444. D. I.,and MALKINSON, F. D. Lupus
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H.
FLOREY, 1970,
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ap-
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in some instances, and laboratory
Joel A. Budin, M.D. Department of Radiology Columbia Presbyterian 622 West i68th Street New York, New York
I.
associated endocarditis).
1935,50,
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P., and SCHIFRIN, A. of peripheral circulation with lupus erythematosus Tr. A. Am. Physicians,
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