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n engl j med 372;11 nejm.org March 12, 20151056
Pr esen tation of C a se
Dr. Naina Rastalsky (Medicine): A 68-year-old man with multiple
myeloma was seen in the rheumatology clinic of this hospital
because of increasing skin tightness, joint pain, and swelling of
the hands and feet.
The patient had been well until 2 years before this
presentation, when anemia was noted on routine examination at
another hospital. During the next 7 months, endoscopic and
colonoscopic screening examinations were negative. Pathological
examination of a bone marrowbiopsy specimen and aspirate revealed
30% plasma cells; flow-cytometric studies revealed an IgG lambda M
component. A diagnosis of multiple myeloma was made. Skeletal
radiographs reportedly revealed multiple lytic lesions.
Lenalidomide, bortezomib, and dexamethasone were administered,
followed by cyclophosphamide. Nine months before this presentation,
the patient was admitted to this hospital; melphalan hydrochloride
was administered, and autologous stem-cell transplantation was
performed. Results of follow-up studies were consistent with
complete remission.
Three months before this presentation, the patient was seen by
an orthopedist at this hospital for evaluation of low-back pain of
1 years duration. Magnetic reso-nance imaging (MRI) of the lumbar
spine, performed after the administration of intravenous
gadolinium, revealed multilevel degenerative changes, multiple
enhanc-ing lesions in the lumbar spine and left iliac bone, and
compression fractures of the first and second lumbar vertebrae,
findings consistent with the history of multiple myeloma.
Two months before this presentation, swelling and pain in the
hands occurred, followed by pedal edema, tightening of the skin of
the hands and feet, and diffuse hyperpigmentation on the trunk,
arms, and legs. Maintenance therapy with lenalido-mide was begun,
but it was stopped during the first cycle because of worsening
symptoms.
Diffuse joint pain occurred and hyperpigmentation increased. One
month before this presentation, on evaluation in the outpatient
cancer center of this hospital,
From the Department of Medicine, Johns Hopkins Hospital, and the
Department of Medicine, Johns Hopkins University School of Medicine
both in Baltimore (F.W.); and the Departments of Medicine (R.P.F.),
Radiology (J.-A.O.S.), and Pa-thology (R.M.N.), Massachusetts
Gener-al Hospital, and the Departments of Medicine (R.P.F.),
Radiology (J.-A.O.S.), and Pathology (R.M.N.), Harvard Medi-cal
School both in Boston.
N Engl J Med 2015;372:1056-67.DOI:
10.1056/NEJMcpc1409840Copyright 2015 Massachusetts Medical
Society.
Founded by Richard C. Cabot Eric S. Rosenberg, M.D., Editor
Nancy Lee Harris, M.D., Editor Jo-Anne O. Shepard, M.D., Associate
Editor Alice M. Cort, M.D., Associate Editor Sally H. Ebeling,
Assistant Editor Emily K. McDonald, Assistant Editor
Case 8-2015: A 68-Year-Old Man with Multiple Myeloma, Skin
Tightness,
Arthralgias, and EdemaFredrick Wigley, M.D., Robert P. Friday,
M.D., Ph.D., Jo-Anne O. Shepard, M.D.,
and Rosalynn M. Nazarian, M.D.
Case Records of the Massachusetts General Hospital
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other uses without permission.
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-
n engl j med 372;11 nejm.org March 12, 2015 1057
Case Records of the Massachusetts Gener al Hospital
the red-cell indexes and results of liver-function tests were
normal, as were blood levels of electro-lytes, calcium, phosphorus,
magnesium, glucose, thyrotropin, iron, iron-binding capacity,
ferritin, and folate; other test results are shown in Table 1.
Total urine protein was 90 mg per liter (reference range, 0 to
135). Fine-needle aspiration biopsy of a fat pad was performed, and
pathological ex-amination of the specimen revealed no evidence of
malignant cells or amyloid. A transthoracic echocardiogram showed
trace mitral regurgita-tion, trace tricuspid insufficiency, and a
left ven-tricular ejection fraction of 64% and showed that the
ascending aorta was 41 mm in diameter (refer-ence diameter,
-
n engl j med 372;11 nejm.org March 12, 20151058
T h e n e w e ngl a nd j o u r na l o f m e dic i n eTa
ble
1. L
abor
ator
y D
ata.
*
Var
iabl
e
Ref
eren
ce
Ran
ge,
Adu
lts
This
Hos
pita
l, 1
Mo
befo
re
Pres
enta
tion
This
Hos
pita
l, 18
Day
s
befo
re
Pres
enta
tion
This
Hos
pita
l, 5
Wk
afte
r Pr
esen
tatio
n
Oth
er
Hos
pita
l,
6 W
k af
ter
Pres
enta
tion
This
Hos
pita
l,
6 W
k 3
Day
s af
ter
Pres
enta
tion
Oth
er
Hos
pita
l,
3 M
o af
ter
Pres
enta
tion
This
Hos
pita
l, 3.
5 M
o af
ter
Pres
enta
tion
This
Hos
pita
l, 3.
75 M
o af
ter
Pres
enta
tion
This
Hos
pita
l, 4
Mo
afte
r Pr
esen
tatio
n
Hem
atoc
rit (
%)
41.0
53.
038
.337
.829
.323
.830
.626
.029
.330
.725
.0
Hem
oglo
bin
(g/d
l)13
.51
7.5
12.6
12.5
9.4
7.6
9.7
7.8
9.4
9.9
8.1
Whi
te-c
ell c
ount
(p
er m
m3 )
4500
11,
000
7200
9100
9300
9600
13,1
0013
,300
9500
11,6
0074
00
Diff
eren
tial c
ount
(%
)
Neu
trop
hils
407
059
.169
.278
.075
.375
.577
.581
.483
.1
Lym
phoc
ytes
224
413
.016
.47.
97.
26.
58.
84.
55.
7
Mon
ocyt
es4
1115
.29.
611
.814
.416
.310
.912
.39.
1
Eosi
noph
ils0
811
.34.
012
.2.
10.
81.
71.
11.
1
Bas
ophi
ls0
30.
60.
60.
20.
20.
40.
40.
10.
1
Plat
elet
cou
nt (
per
mm
3 )15
0,00
040
0,00
032
5,00
028
5,00
036
4,00
027
7,00
032
1,00
045
6,00
032
4,00
022
4,00
088
,000
Ret
icul
ocyt
es (
%)
0.5
2.5
2.7
6.0
Eryt
hroc
yte
sedi
men
ta-
tion
rate
(m
m/h
r)
013
4338
Ure
a ni
trog
en (
mg/
dl)
825
1419
2018
1723
4286
Cre
atin
ine
(mg/
dl)
0.60
1.5
00.
840.
880.
80.
90.
821.
111.
874.
38
Estim
ated
GFR
(m
l/m
in/1
.73
m2 )
6
0>6
0>6
0>6
0>6
0>6
0>6
036
14
Prot
ein
(g/d
l)
Tota
l6.
08.
36.
16.
45.
45.
15.
75.
05.
25.
0
Alb
umin
3.3
5.0
3.4
4.0
3.4
3.1
3.4
2.6
2.5
Glo
bulin
2.3
4.1
2.7
2.4
2.3
2.6
2.5
Cal
cium
(m
g/dl
)8.
510
.58.
48.
88.
28.
08.
67.
87.
67.
2
Lact
ate
dehy
drog
enas
e (U
/lite
r)11
021
029
030
527
742
445
2
Vita
min
B12
(pg
/ml)
>250
172
328
609
Rhe
umat
oid
fact
or
(IU
/ml)
-
n engl j med 372;11 nejm.org March 12, 2015 1059
Case Records of the Massachusetts Gener al Hospital
Var
iabl
e
Ref
eren
ce
Ran
ge,
Adu
lts
This
Hos
pita
l, 1
Mo
befo
re
Pres
enta
tion
This
Hos
pita
l, 18
Day
s
befo
re
Pres
enta
tion
This
Hos
pita
l, 5
Wk
afte
r Pr
esen
tatio
n
Oth
er
Hos
pita
l,
6 W
k af
ter
Pres
enta
tion
This
Hos
pita
l,
6 W
k 3
Day
s af
ter
Pres
enta
tion
Oth
er
Hos
pita
l,
3 M
o af
ter
Pres
enta
tion
This
Hos
pita
l, 3.
5 M
o af
ter
Pres
enta
tion
This
Hos
pita
l, 3.
75 M
o af
ter
Pres
enta
tion
This
Hos
pita
l, 4
Mo
afte
r Pr
esen
tatio
n
Ant
inuc
lear
ant
ibod
ies
Neg
ativ
e at
1:
40 a
nd
1:16
0 di
lu-
tions
Posi
tive
at
1:12
80 d
i-lu
tion,
sp
eckl
ed
patt
ern
Ant
ibod
ies
to d
oubl
e-st
rand
ed D
NA
Neg
ativ
e at
1:
10 d
ilu-
tion
Neg
ativ
e at
1:
10 d
ilu-
tion
2-
mic
rogl
obul
in
(g/
ml)
0.70
1.8
03.
003.
324.
467.
82
Imm
unog
lobu
lins
(m
g/dl
)
IgG
614
1295
887
1079
591
675
1196
1281
IgA
693
0962
6881
112
107
IgM
533
3467
5018
757
58
Seru
m p
rote
in e
lect
ro-
phor
esis
Nor
mal
pa
tter
nN
orm
al
patt
ern
Nor
mal
pa
tter
nN
orm
al
patt
ern
Nor
mal
pa
tter
n
Free
kap
pa li
ght c
hain
(m
g/lit
er)
3.3
19.4
24.5
16.5
17.3
40.2
34.4
38.0
Free
lam
bda
light
cha
in
(mg/
liter
)5.
726
.333
.526
.413
4.0
58.5
62.6
69.9
Free
kap
pa:la
mbd
a
ratio
0.
31.
70.
70.
60.
10.
687
0.5
0.5
Imm
unof
ixat
ion
No
M c
ompo
-ne
nt d
e-te
cted
No
M c
ompo
-ne
nt d
e-te
cted
C-r
eact
ive
prot
ein
(m
g/lit
er)
-
n engl j med 372;11 nejm.org March 12, 20151060
T h e n e w e ngl a nd j o u r na l o f m e dic i n e
stain revealed finely granular mucin deposits inter-spersed
between dermal collagen bundles (Fig. 1D). An elastic-tissue stain
revealed preservation of
dermal elastic fibers, with straightening and par-allel
arrangement (Fig. 1E).
Dr. Rastalsky: Three months after this presen-
Figure 1. Skin-Biopsy Specimen.
Hematoxylin and eosin staining of histologic sections of a
skin-biopsy specimen from the dorsum of the left hand revealed a
normal epidermis with dermal collagen expansion involving the
subcutaneous tissue (Panel A, asterisk); there is adnexal atrophy
with periadnexal fat loss (Panel A, arrow). A sparse
lymphoplasmacytic infiltrate was identi-fied at the junction of the
dermis and the subcutaneous fat (Panel B, arrow). There were areas
of reticular dermal fi-broblast hypocellularity (Panel C). An
immunohistochemical stain for CD34 shows a diffuse loss of CD34
expression in dermal spindle cells (Panel C, inset). A colloidal
iron stain shows interstitial mucin deposits (Panel D). An
elastic-tissue stain shows preservation of dermal elastic fibers,
with parallel arrangement and straightening (Panel E, arrow).
A B
DC
E
*
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Case Records of the Massachusetts Gener al Hospital
tation, prednisone was administered for persistent stiffness.
The patient reported extreme fatigue and increasing dyspnea on
exertion during the pre-ceding 3 months. Results of tests performed
at the other hospital are shown in Table 1. Chest imaging was
performed because of the worsen-ing shortness of breath.
Dr. Jo-Anne O. Shepard: Computed tomography (CT) of the chest
revealed reticulation in the sub-pleural region at the lung bases
and bronchiolec-tasis (Fig. 2A). There was no evidence of
pulmo-nary edema. These findings were suggestive of nonspecific
interstitial pneumonia. Soft-tissue windows showed a small pleural
effusion on the right side and minimal dilatation of the main
pulmonary artery that could be correlated with pulmonary
hypertension (Fig. 2B). The esopha-gus was diffusely dilated and
contained contrast material throughout. A representative sagittal
image showed generalized osteopenia, multiple lytic lesions
throughout the spine and ribs, and multiple healed fractures,
including one in the sternum (Fig. 2C). These skeletal findings
were consistent with the history of multiple myeloma.
Dr. Rastalsky: The patient was admitted to this hospital 3.5
months after this presentation. On examination, there were
bilateral bronchial breath sounds, crackles at the base of the left
lung, ex-tensive hardening of the skin from the hands to the elbows
and from the toes to above the knees, and deep bronze discoloration
on the trunk, arms, and legs. Joint motion was limited by skin
thick-ening. Test results are shown in Table 1. An en-doscopic
examination was performed.
Dr. Nazarian: During the endoscopy, a gastric-biopsy specimen
was obtained from the antrum; examination of the specimen revealed
expansion of the lamina propria and prominent fibromus-cular
hyperplasia. Other areas showed ectatic mu-cosal capillaries with
occasional fibrin thrombi (Fig. 3). This constellation of findings
was con-sistent with gastric antral vascular ectasia (which is also
referred to as watermelon stomach be-cause the condition is
characterized by the parallel arrangement of longitudinal folds
containing di-lated vessels that converge at the pylorus, and this
arrangement resembles the stripes on a water-melon).
Dr. Rastalsky: IVIG and bortezomib were ad-ministered. The
patient was discharged on the fourth day.
Five days later, the patient reported increased
discomfort and inability to bend his joints and was using a
wheelchair. Test results are shown in Table 1. During the next 4
days, confusion de-veloped and he had difficulty with word-finding.
Oral intake was poor. Four months after this presentation, he was
brought to the emergency department of this hospital; on
examination, he was alert, oriented to person only, and had
dif-ficulty with word-finding and verbal expression. The blood
pressure was 98/63 mm Hg, and there was periorbital and facial
edema; the remainder of the examination was unchanged. Test results
are shown in Table 1. The peripheral-blood smear showed 2 to 4
schistocytes per high-power field. Urinalysis showed 2+ albumin by
dipstick, a spe-cific gravity of 1.015, and a pH of 6.0; the
urinary sediment was packed with pigmented, coarsely granular casts
and had 10 nondysmorphic eryth-rocytes per high-power field and no
cellular casts. The ratio of total spot-urine protein to creatinine
was 4.0. CT of the head, performed without the administration of
contrast material, was negative. The patient was readmitted to this
hospital.
A diagnostic test result was received.
Differ en ti a l Di agnosis
Dr. Fredrick Wigley: This patient had multiple my-eloma that
appeared to be in remission, exposure to several drugs, bleeding
due to gastric antral vascular ectasia, interstitial pulmonary
fibrosis with a small pleural effusion, cognitive dysfunc-tion, and
acute renal failure with associated throm-botic microangiopathic
anemia. Although he had complications involving multiple organ
systems, I will focus my differential diagnosis on his rapidly
progressive skin thickening with hyper-pigmentation and associated
polyarthritis. In par-ticular, the features and distribution of the
skin disease and the degree of pigmentation are ma-jor clues in
this case.
Multiple Myeloma and Systemic Amyloidosis
Are the features of this patients illness a direct consequence
of multiple myeloma? The labora-tory data including the absence of
the mono-clonal protein, the serum free light-chain level of less
than 1500 mg per liter, and the kappa:lambda ratio of 0.26 to 1.65
strongly suggest that the myeloma was in remission. In addition,
skin le-sions associated with plasma-cell infiltration
(plas-macytoma) would appear as nodules rather than
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T h e n e w e ngl a nd j o u r na l o f m e dic i n e
as the diffuse skin involvement that was described in this case.
Likewise, evidence of systemic amy-loidosis was not seen on fat-pad
biopsy, echocar-diography, or skin biopsy. Patients with
amyloi-dosis usually have hemorrhagic lesions due to the fragility
of infiltrated cutaneous vessels, and the joint disease is not very
inflammatory and usu-
ally involves proximal joints; the skin and joint disease seen
in this case were not consistent with amyloidosis.
Toxic Effects
Is this patients disease a consequence of toxic effects
associated with medications or with the recent MRI examination?
During the course of this patients treatment, he received several
drugs that may have caused a secondary process. Le-nalidomide can
cause a diffuse rash, but the rash is usually an eczematous
eruption without clini-cally significant skin thickening.
Cyclophospha-mide or melphalan hydrochloride can induce a second
cancer, and thus it is possible that a para-neoplastic process such
as the palmar fasciitis and polyarthritis syndrome could explain
some of the features in this case. IVIG can cause renal toxic
effects that could in part account for the acute renal failure.
Could this patients rapidly progressive skin thickening and
hyperpigmentation be caused by exposure to gadolinium? In rare
cases, exposure to gadolinium during an MRI examination can result
in nephrogenic systemic fibrosis, a fibrotic process that mainly
affects the skin but also af-fects internal organs; lung fibrosis,
heart infiltra-tion, and neuropathy have been reported.1
Neph-rogenic systemic fibrosis typically occurs in patients with
severe impairment of renal function (with a glomerular filtration
rate of
-
n engl j med 372;11 nejm.org March 12, 2015 1063
Case Records of the Massachusetts Gener al Hospital
the arms and trunk, and spare the face. Severe flexion
contractures of joints result from fibrosis of deep soft tissue.
Dermal fibrosis and intersti-tial mucin deposition with little or
no inflam-matory infiltrate are seen on biopsy. This patient may
have an increased risk of gadolinium-induced renal disease because
of his older age and history of myeloma; however, he had relatively
normal results of renal-function tests at the time of the imaging
study, and furthermore, his inflamma-tory joint disease was not
consistent with neph-rogenic systemic fibrosis.
Myeloma-Related Skin Disorders
Scleredema is a disorder that is characterized by mucin
deposition in the dermis.2 It can be associ-ated with a previous
infection, diabetes, or mono-clonal gammopathy of undetermined
significance (MGUS); it has also been associated with multi-ple
myeloma. Scleredema is characterized by non-pitting doughy or woody
induration of skin of the neck, back (especially the middle of the
back), and shoulders, with sparing of the distal limbs. The
distribution of skin involvement in this pa-tient is not typical of
scleredema.
Scleromyxedema is a form of lichen myxede-matosus (papular
mucinosis) that is almost always associated with IgG MGUS. Several
cases of sclero-myxedema have been associated with multiple
myeloma.3 This rare disorder has four diagnostic criteria: a
generalized papular and sclerodermoid eruption, a triad of findings
on microscopic ex-amination of skin-biopsy specimens (mucin
de-position, fibroblast proliferation, and fibrosis), a monoclonal
gammopathy, and absence of a thy-roid disorder. Involvement of the
skin of the face, including papules on the neck, glabella, and
postauricular area, is almost always present; the limbs and back
can also be affected. Linear streaks of papules are characteristic
of scleromyx-edema, and hyperpigmentation is rare and mild. Unlike
patients with nephrogenic systemic fibro-sis, patients with
scleromyxedema can have a slight superficial, perivascular,
lymphoplasmacytic in-flammatory-cell infiltrate.4 Systemic disease
is common and can have neurologic, musculoskele-tal, cardiac,
gastrointestinal, pulmonary, and he-matologic manifestations
(including myeloma).5,6
Inflammatory polyarthritis may also occur. In addition, acute
renal crisis has been reported in patients with scleromyxedema; in
such cases, find-ings consistent with thrombotic
microangiopathic
anemia, including narrowed glomerular capillar-ies, endothelial
proliferation, and microthrombi, are seen.7-9 Many of the features
described in this case could be explained by scleromyxedema;
how-ever, the absence of skin papules, one of the four diagnostic
criteria, makes this diagnosis unlikely.
Eosinophilic fasciitis (Shulmans syndrome) should also be
considered because it has been associated with hematologic
diseases, including multiple myeloma. In patients with this
disorder, there is a rapid onset of skin changes on the arms and
legs and sometimes the trunk, with sparing of the face and hands.10
Fibrosis of deep soft tis-sue in the fascia leads to contractures;
dimpling of the skin (peau dorange), particularly of the upper
inner arms and forearms, is typical. Sys-temic disease is uncommon,
but an inflamma-tory rheumatoid-like arthritis can be seen.
Eosino-philia is present in approximately 80% of cases, and testing
for antinuclear antibodies is negative. The clinical features in
this case are not sugges-tive of eosinophilic fasciitis.
Scleroderma
Systemic sclerosis, or scleroderma, is an autoim-mune disease
associated with skin fibrosis and multisystem involvement.11
Obliterative vascular disease can lead to scleroderma renal crisis,
with manifestations such as thrombotic microangio-
Figure 3. Gastric-Biopsy Specimen (Hematoxylin and Eosin).
Examination of a gastric-biopsy specimen from the antrum reveals
expansion of the lamina propria and prominent fibromuscular
hyperplasia. There were ec-tatic mucosal capillaries with
occasional fibrin throm-bi (inset). This constellation of findings
is consistent with gastric antral vascular ectasia (watermelon
stomach).
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n engl j med 372;11 nejm.org March 12, 20151064
T h e n e w e ngl a nd j o u r na l o f m e dic i n e
pathic anemia, pulmonary hypertension, cardiac disease, and
gastrointestinal bleeding due to gas-tric antral vascular ectasia;
all these features were seen in this case. Interstitial lung
disease is com-mon in patients with scleroderma, particularly in
those with antibodies to Scl-70 (topoisomerase I). There is an
increased risk of cancer among patients with scleroderma.12 Skin
disease associ-ated with scleroderma has a highly variable course,
but a subset of patients present with rapidly ad-vancing,
widespread disease that usually affects the distal limbs first,
spreads proximally to the trunk and face, and spares the back.
Scleroder-ma begins as an inflammatory process that is commonly
characterized by pitting edema and then transforms into a fibrotic
skin disease that is often associated with intense
hyperpigmenta-tion, inflammatory joint disease, and eventually,
joint contractures. Examination of skin-biopsy specimens often
reveals dermal fibrosis with dense extracellular matrix, a mild
perivascular inflam-matory infiltrate, and no excess mucin. This
patient had many features of scleroderma; however, the mucin
deposition that was seen on histopathologic examination would be
atypical of this diagnosis.
Summary
I think the differential diagnosis narrows to two similar but
discrete clinical syndromes: sclero-derma and scleromyxedema (Table
2). The find-ing of mucin deposition on examination of the
skin-biopsy specimen argues against a diagnosis of scleroderma.
However, I think scleroderma is likely, given the overall clinical
features (including interstitial lung disease, bleeding due to
gastric antral vascular ectasia, inflammatory joint disease with
limitations of motion, and rapidly emerging diffuse,
hyperpigmented, fibrotic skin disease without papules). The event
that led to his last presentation to the hospital was probably
sclero-derma renal crisis. Normotensive scleroderma re-nal crisis
has been reported, but this patient was probably dehydrated, and
cardiac dysfunction could have accounted in part for his
hypoten-sion. A subset of patients with scleroderma and anti-RNA
polymerase III antibodies present with rapid diffuse skin disease,
fibrosis of deep soft tissue, friction rubs, and joint
contractures. They are unlikely to have clinically significant
intersti-tial lung disease but are at high risk for sclero-derma
renal crisis (20%).22 They often have pri-
mary scleroderma-related heart disease and are at increased risk
for concomitant cancer and scleroderma.23
I suspect that a diagnostic test for the detec-tion of anti-RNA
polymerase III antibodies was performed in this case; a positive
test would con-firm the clinical diagnosis of scleroderma. It is
possible that examination of a tissue-biopsy spec-imen revealed the
presence of gadolinium, the cause of nephrogenic systemic fibrosis,
but this is doubtful. I considered thrombotic thrombocy-topenic
purpura as an explanation of the patients central nervous system
and renal disease, but this diagnosis would not explain the
previous find-ings of the skin, joints, and other organ systems. In
making a diagnosis of scleromyxedema, it would be necessary to
perform a kidney biopsy to look for mucin deposition in renal
vessels. My diagnosis in this patient with multiple myeloma that
has been previously treated and is in remis-sion is
scleroderma.
Dr. Eric S. Rosenberg (Pathology): Dr. Friday, what was your
impression when you evaluated this patient?
Dr. Robert P. Friday: The patient had a history of multiple
myeloma and had multisystem disease with prominent and rapidly
progressive skin fibro-sis, and these factors guided the initial
decision to administer IVIG for suspected scleromyxedema. However,
there were a number of competing di-agnostic considerations. The
detection of intersti-tial fibrosis on lung imaging in a patient
with progressive dyspnea and bleeding due to gastric antral
vascular ectasia increased our suspicion for scleroderma. At the
time of admission, the findings in the urinary sediment and the
relative hypotension in the presence of altered mental status and
acute kidney injury supported a diag-nosis of acute tubular
necrosis, but the presence of schistocytes and thrombocytopenia on
the peripheral-blood smear raised concerns about scleroderma renal
crisis. The patient had also received prednisone, and the
administration of prednisone is a known risk factor for
scleroder-ma renal crisis, including normotensive scleroder-ma
renal crisis.24
Clinic a l Di agnosis
Diffuse systemic sclerosis (scleroderma), with scleroderma renal
crisis.
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n engl j med 372;11 nejm.org March 12, 2015 1065
Case Records of the Massachusetts Gener al Hospital
Dr . Fr edr ick W igle y s Di agnosis
Systemic sclerosis (scleroderma) in a patient with multiple
myeloma that has been treated and is in remission.
Pathol o gic a l Discussion
Dr. Nazarian: Fibrosing dermopathies are a group of diseases
with overlapping clinicopathological features.10,13-15,25-27
Assessment of subcutaneous involvement and dermal fibroblast
cellularity on routine histologic examination can help to
dif-ferentiate among these conditions. Useful ancil-lary studies
(which were performed in this case) include colloidal iron staining
to assess for mu-cin deposition, elastic-tissue staining to
assess
the quality and quantity of elastic fibers, and
immunohistochemical staining to assess for CD34 expression in
dermal spindle cells.16,17
In this case, serologic studies were remarkable for the presence
of a high titer of antinuclear antibodies (1:1280), a positive
titer of anti-RNA polymerase III antibodies (>80; normal
titer,
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n engl j med 372;11 nejm.org March 12, 20151066
T h e n e w e ngl a nd j o u r na l o f m e dic i n e
Raynauds phenomenon or nailfold capillary ab-normalities, led to
some diagnostic confusion and underscored the multidisciplinary
diagnos-tic challenge in this case. Ultimately, correlation of the
histopathological features with clinical his-tory and laboratory
findings established the fi-nal anatomical diagnosis of
scleroderma.
Discussion of M a nagemen t a nd Foll ow-up
Dr. Rosenberg: Dr. Friday, would you tell us what happened with
this patient?
Dr. Friday: The patient was initially treated with intravenous
fluids. Renal biopsy was con-sidered, but it was decided that the
results would probably not influence therapy and the proce-dure
would expose this critically ill patient to unnecessary risk.
Hemodialysis was initiated, and low doses of enalapril were
administered. The patients mental status improved dramatically with
hemodialysis, but over a period of several days there was no
meaningful recovery of renal function. Despite having clearer
mentation, the patient had severe swallowing difficulties; on video
fluoroscopic evaluation, marked pharyngeal dys-function was
present, and thus a gastric tube was placed. He was transferred to
a rehabilitation fa-cility for further care. Four days after
discharge,
the patient was found unresponsive and pulseless. No
resuscitation efforts were pursued, in accor-dance with the
patients wishes.
Dr. John H. Stone (Medicine): Why did pharyn-geal dysfunction
develop very late in the course of this patients disease?
Dr. Wigley: Swallowing difficulties can be seen in a subset of
patients with scleroderma with very rapid, diffuse involvement of
the head, neck, and face. There are two problems: one is difficulty
with initiation of swallowing, and the other is dyspha-gia due to
esophageal dysfunction. Patients who have trouble with initiation
of swallowing have pharyngeal involvement due to either
inflamma-tory myositis or fibrosis of soft tissue.
Fina l Di agnosis
Scleroderma.This case was presented at the Medical Case
Conference.Dr. Wigley reports receiving consulting fees from Eiger
Bio-
pharmaceuticals and grant support from Actelion
Pharmaceuti-cals, MedImmune, Novartis, United Therapeutics, CSL
Behring, Sanofi Aventis, and HoffmannLa Roche; and Dr. Shepard,
re-ceiving consulting fees for providing expert testimony in a
legal case regarding thoracic imaging. No other potential conflict
of interest relevant to this article was reported.
Disclosure forms provided by the authors are available with the
full text of this article at NEJM.org.
We thank Dr. John H. Stone for his help in organizing this
conference and with the preparation and editing of the case
history.
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383-93.Copyright 2015 Massachusetts Medical Society.
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