Transcript Castle-POES disease successfully treated with Rituximab Nezam Torok , MD PGY2 History :   A 42 year old African American Man CC : Back pain , for.

Castle-POES disease
successfully treated with
Rituximab
Nezam Torok , MD
PGY2
History :
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A 42 year old African American Man
CC : Back pain , for 1 week
PMH :
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Nov 2008 : Pericardial
effusion
Dec 2008 : Suspecion of
sarcoidosis
Social history
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Smoker 30 PPY
sexual dysfunction
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Neurological : Motor function : power 4/5 lower
limb –leg flexor and extensors as well as foot ,
bilaterally with diminished DTR and decreased
sensation to touch , pain , and position , otherwise
negative .
More lab tests :
HIV , HHV 8 negative
 Normal or negative tests include : TFT ,
LH , FSH , testosterone ,ANA , ANCA ,
ACE ,RF , SS-A , SS-B , C3, C4, Hep B ,
Hep C ,PSA, vit B12 , APA .
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SPE :
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increase in IgG 1950 mg/dL(normal 590-1540 mg/dL)
mild increase in IgA 498 (normal 50-413mg/dL )
serum immunofixation polyclonal hypergammaglobulinemia
with slightly excess lambda chains , kappa chains 1040
mg/dL ( normal 539 -1320 mg/dL) , and Lambda chains
690mg/dL (normal 285-673mg/dL ) with kappa /lambda
ratio of 1,5 .
Normal architecture
Effaced architecture of the LN in
castlemans disease , HE stain 4 X
Normal architecture of LN
Atrophic germinal centers
, HE stain 40X
Normal germinal center, containing
larger lymphocytes undergoing
activation
Atrophic germinal center and
effaced architercture
Vascular proliferation ,10 X
Vascular proliferation 20 X
Vascular proliferation 40 X
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interleukin 6 level: 6 pg/ml (normal 0-5pg/ml)
plasma Vascular Endothelial Growth factor level
(VEGF): 130 pg/ml (normal 6-86 pg/ml)
normal interleukin 1.
Summary of findings
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Osteosclerotic lesions
Neuropathy motor and sensory
Skin changes
Lymphadenopathy
History of pericardial effusion
Castlemans disease
High IL-6 and VEGF
Diagnosis is
Multicentric Castleman’s
disease with features of
POEMS syndrome (CastlePOES)!
Treatment
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There is no standard treatment for this disorder and no
randomized or quasi-randomized controlled clinical
trials of treatment for POEMS syndrome exist in the
available literature*
* Treatment for POEMS (polyneuropathy, organomegaly, endocrinopathy, Mprotein, and skin changes) syndrome. Kuwabara S; Dispenzieri A; Arimura K;
Misawa S Cochrane Database Syst Rev. 2008 Oct 8;(4):CD006828
How did we treat the patient
Rituximab
375/m2 , weekly for 4
weeks , then once every
2-3 months
How did the patient respond
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Remarkable improvement in muscle power ,
able to function again
Fatigue resolved
Sexual function improved.
Dec PET scan activity at the scerotic bone
lesions
No lymphadenopathy
BUT
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VEGF was still at the same level .
no change in skin lesions.
SPEP and immunofixation the same pattern
Investigational model
differential scanning calorimeter (DSC)
differential scanning calorimeter
(DSC
Our Patient
Control
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The DST shows abnormal thermogram, which
means there is abnomal molecular species
present in the serum of the serum sample that
interact in a significant way with one or more of
the proteins in the serum
it is different from electrophoresis technique
that are sensitive to size and charge
What kind of protein , whats is the relation to
immunofixation ?
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“Thinking is more interesting
than knowing, but less interesting
than looking”.
References
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Bradwick PA, Zvaifler NJ, Gill GN, et al. Plasma celldyscrasia with polyneuropathy,
organomegaly,endocrinopathy, M protein and skin changes: the POEMSsyndrome.
Medicine 1980; 59: 311–322
Dispenzieri A, Kyle RA, Lacy MQ, et al. POEMS syndrome: definitions and long-term
outcome. Blood 2003;101:2496–506
Nakanishi T, Sobue I, Toyokura Y, et al. The Crow-Fukase syndrome: a study of 102
cases in Japan. Neurology 1984;34:712-20.
Shikama N, Isono A, Otsuka Y, Terano T, Hirai A.a case of POEMS syndrome with
high concentration of IL-6 in pericardial fluid . J Intern Med. 2001 Aug;250(2):170-3
Hashiguchi T, Arimura K, Matsumuro K, et al. Highly concentrated vascular
endothelial growth factor in plateletsin Crow-Fukase syndrome. Muscle Nerve.
2000;23:1051-1056.
Soubrier M, Dubost JJ, Serre AF, et al. Growth factors in POEMS syndrome: evidence
for a marked increase in circulating vascular endothelial growth factor. Arthritis
Rheum. 1997;40:786-787
Joanne Shirine Allam, Cassie C. Kennedy, Timothy R. Aksamit and Angela Dispenzieri
. Pulmonary Manifestations in Patients With POEMS Syndrome. Chest 2008;133;969974