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Commentary case
By :
Prof. Dr.: Fawzy Megahed
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 marrow–
biopsy specimen and aspirate revealed 30%
plasma cells; flow-cytometric studies
revealed an IgG lambda M component.
Skeletal radiographs reportedly revealed
multiple lytic lesions.
He had hyperlipidemia, hypertension, lowback pain, and gastroesophageal reflux
disease; he had undergone colonic
polypectomies and had a history of prostate
cancer for which radical prostatectomy was
performed 11 years earlier.
Medications included rosuvastatin, and
omeprazole. He lived with his wife and
worked in an office. He had stopped smoking
20 years earlier, drank alcohol in moderation,
and did not use illicit drugs. His mother and
maternal uncle had rheumatoid arthritis.
?
A diagnosis of multiple myeloma was
made.
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.
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 lenalidomide 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, results
of liver-function tests were normal, as were
blood levels of electrolytes, thyrotropin, iron,
iron-binding capacity, ferritin, and folate .
What is your differential
diagnosis ?
Which of the following can explain
this new presentation ?
1- Multiple Myeloma and Systemic Amyloidosis
2- paraneoplastic syndrome
3- nephrogenic systemic fibrosis
4- Eosinophilic fasciitis (Shulman’s syndrome)
5- Lenalidomide toxicity
6- Scleroderma
7- Scleromyxedema
Total urine protein was 90 mg per liter . Fineneedle aspiration biopsy of a fat pad was
performed, and pathological examination of
the specimen revealed no evidence of
malignant cells or amyloid.
A TTE showed trace mitral regurgitation,
trace tricuspid insufficiency, and a left
ventricular ejection fraction of 64% and
showed that the ascending aorta was 41 mm
in diameter (reference diameter, <36 mm);.
Urinalysis was normal.
On presentation, the patient rated the
joint pain at 6 on a scale of 0 to 10, with 10
indicating the most severe pain.
On examination, the blood pressure was
112/63 mm Hg and the pulse 100 beats per
minute; the temperature, respiratory rate,
and oxygen saturation were normal. A
systolic murmur, grade 2/6, was heard at the
right and left upper sternal borders.
There was swelling and tenderness in the
MCP and proximal IP joints bilaterally and
swelling below the knees to the toes, without
erythema or warmth. The range of motion
was decreased in the MCP and ankle joints.
The skin on the MCP joints and legs below
the knees to the toes was hyperpigmented.
Testing for antibodies to Ro , La , Sm, RNP, Jo1, Scl-70 (topoisomerase I), and CCP was
negative, and the level of creatine kinase was
normal.
Can we review our diagnosis?
?
Which of the following is the the
most appropriate diagnosis ?
1- Sclerederma
2- paraneoplastic syndrome
3- nephrogenic systemic fibrosis
4- Eosinophilic fasciitis (Shulman’s syndrome)
5- Lenalidomide toxicity
6- Scleroderma
7- Scleromyxedema
8- other diagnosis to be pursued.
A tapering course of prednisone was
administered.
Five weeks later, after returning from a
vacation in Aruba, the patient was seen for
follow-up appointments at the hematology
clinic of the other hospital and the
rheumatology clinic of this hospital.
He reported severe fatigue, decreased
exercise tolerance, and weight loss of
approximately 3.5 kg. He rated the joint pain
at 2 out of 10, but substantial stiffness
persisted while he was taking prednisone.
On examination, the blood pressure was
110/70 mm Hg, the pulse 100 to 111 beats
per minute, and the oxygen saturation 96%
while he was breathing ambient air; the
temperature was normal.
The MCP and proximal IP joints remained
swollen but were less tender, and the wrists
were slightly full. There was 1+ pitting edema
below the knees; the skin was deeply tanned
and firm in a manner that was out of
proportion to the degree of pitting edema.
The stool was dark brown and positive (3+)
for blood. The administration of omeprazole
was increased to twice daily .
One week later (six weeks after this
presentation), the patient was admitted to
the other hospital because of worsening
anemia . The hematocrit rose to 27.9% after
leukocyte-reduced red cells were transfused.
Next step!!!!!!!!
Endoscopy revealed severe acute gastritis
with marked erythema and friability. He was
discharged on the third day.
IVIG was administered monthly, with some
improvement in joint pain and stiffness.
Skin tightness persisted, and a skin biopsy
was performed.
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
lymphoplasmacyti
c infiltrate was
identified at the
junction of the
dermis and the
subcutaneous fat
(Panel B, arrow).
There were areas of
reticular dermal fibroblast
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).
Three months after this presentation,
prednisone was administered for persistent
stiffness. The patient reported extreme
fatigue and increasing dyspnea on exertion
during the preceding 3 months.
Chest imaging was performed because of the
worsening shortness of breath.
A CT scan of the chest with
lung windows, obtained
through the lung bases
with the patient in the
prone
position, shows subpleural
reticulation, ground-glass
opacities,
and
bronchiolectasis (Panel A).
A scan with soft-tissue
windows,
obtained
with the patient in the
supine position, shows
a small pleural effusion
on the right side,
diffuse distention of
the esophagus with air
and
liquid,
and
dilatation of the main
pulmonary artery
(measuring 3.5 cm in
diameter) (Panel B).
A scan with bone
windows,
obtained in the
sagittal
plane,
shows
diffuse
osteopenia,
multiple
lytic
lesions in the
spine,
and
a
healed fracture of
the body of the
sternum
(Panel C).
The patient was admitted 3.5 months after
this presentation. On examination, there
were bilateral bronchial breath sounds,
crackles at the base of the left lung, extensive
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 thickening.
An endoscopic examination was performed.
During the endoscopy, a gastric biopsy
specimen was obtained from the antrum.
Gastric-Biopsy
(Hematoxylin
Eosin).
Specimen
and
Examination of a gastricbiopsy specimen from the
antrum reveals expansion
of the lamina propria and
prominent fibromuscular
hyperplasia. There were
ectatic mucosal capillaries
with occasional fibrin
thrombi
(inset).
This
constellation of findings is
consistent with gastric
antral vascular ectasia
(“watermelon
stomach”).
IVIG and bortezomib were administered.
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. During the
next 4 days, confusion developed 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 difficulty
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.
Urinalysis showed 2+ albumin by dipstick, a
specific gravity of 1.015, and a pH of 6.0; the
urinary sediment was packed with
pigmented, coarsely granular casts and had
10 non dysmorphic erythrocytes /HPF and no
cellular casts. The ratio of total spot-urine
protein to creatinine was 4.0.
The peripheral blood smear showed 2 to 4
schistocytes /HPF . CT of the head, performed
without the administration of contrast
material, was negative. The patient was
readmitted to this hospital.
What is your final
diagnosis?
Which of the following is the the
most appropriate diagnosis ?
1- Sclerederma
2- paraneoplastic syndrome
3- nephrogenic systemic fibrosis
4- Eosinophilic fasciitis (Shulman’s syndrome)
5- Lenalidomide toxicity
6- Scleroderma
7- Scleromyxedema
8 – thrombotic thrombocytopenic purpura
The correct answer is
……………….
Scleroderma
Discussion
The differential diagnosis narrows to two
similar but discrete clinical syndromes:
scleroderma and scleromyxedema . The
finding of mucin deposition on examination
of the skin-biopsy specimen argues against a
diagnosis of scleroderma.
However, scleroderma is likely, given the
overall clinical features (including interstitial
lung disease, bleeding due to GAVE ,
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 scleroderma renal
crisis. Normotensive scleroderma renal crisis
has been reported, but this patient was
probably
dehydrated,
and
cardiac
dysfunction could have accounted in part for
his hypotension.
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 and are at high risk for
scleroderma renal crisis (20%).
They often have primary scleroderma-related
heart disease and are at increased risk for
concomitant cancer .
A positive test of anti-RNA polymerase III
antibodies would confirm the clinical
diagnosis of scleroderma.
TTP was considered as an explanation of the
patient’s central nervous system and renal
disease, but this diagnosis would not explain
the previous findings 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.
Thank you