PROF.DR.NOORUL AMEENPANDICHELVAN

M6

40 yrs old female came with c/o breathlessness -2 mon insidious onset progressive class 2 related with exertion h/o easy fatigability h/o arthralgia h/o tiredness h/o loss of weight

No h/o cough and sputum production palpitation orthopnea paroxysmal nocturnal dyspnea chest painPast history: Not know case of DM/HT/PTPersonal history: Not an Alcoholic/SmokerMenstrual history: Attained menarche @ 12 yrs of age Regular; once in 26 days Last for 4 days

General examination Conscious Oriented Pallor Hyperpigmentation seen Scar seen in left side neck Not Icteric No Cyanosis No Clubbing No Pedal edema No Lymph node enlargement

BP 90/60 mmhg Pulse rate 70/min

CVS : S1S2 heard P2 loud

RS : NVBS BAE No added sound

P/A: Soft

CNS: NFND

Provisional diagnosis Pulmonary hypertension ? Addison disease ? MCTD

INVESTIGATIONUrine examination Albumin- nil Sugar - nil Deposit- nilCBC Hb -9.2 TC -5700 DC - P60 L40 E0 PCV -33 ESR -6/15 PLC -1.6 lakh MCV -86BLOOD Urea 36 Sugar 106 Creatinine 0.8 Sodium 130 Potasium 3.9

ECG –normal

CXR - Cardiomegaly

Echocardiography

BLOOD IMMUNOLOGY ANA Positive 1:40 dilution

CRP Negative

ASO Negative

RF Negative

HypothyroidismPulmonary hypertensionAnemia? Cause

Patient treated withTab. Thyroxine 100 ug odTab. Deriphylline tds Tab. Bct tdsPatient advised to do ACTH stimulation test

After two months patient comes with c/o breathlessnessc/o abdominal painc/o athralgiac/o numbness in both lower limbsc/o hard of hearing

On examination

Conscious Oriented Pallor Not Icteric No Cyanosis No Clubbing B / L Pitting pedal edema No Lymphnode enlargement

CVS: S1S2 heard P2 loud

RS: NVBS BAE No Added sound

P/A: Abdomen distension Moves with respiration Flanks full Shifting dullness +

CNS: HMF Normal CN Normal TONE Normal

POWER RT LT UL 4 4 LL 4 4

DTR Present Present

B/L Plantar Flexor Sensory system – Vibration sensation lost in both lower limbs

Cerebellar and autonomic nervous system- Normal

HypothyroidismPulmonary hypertensionAscitiesPeriperal neuropathyAnemiaCause - ? MCTD ? Autoimmune polyglandular

syndrome

INVESTIGATIONSUrine Examinations Albumin-1+ Sugar-nil Deposit – 4 to 5 pus cells/hpfRenal lab values Glucose – ve Bilirubin neg Ketone neg Specific gravity 1.010 Blood 2+ ph 5.0 Protein 2+ Nitrogen neg Leucocytes neg

24 hr urine protein- 20mg/dayCOMPLETE BLOOD HAEMOGRAM HB-11.5 RBC-3MILLION/CUMM ESR-10/22 MCHC-30.1 MCV-79.4 MCH-28.4 PCV-31 PLT-1.2 TC-5200 DC-P69;L30;E1

BLOOD Sugar-105mg FBS-59MG/DL; PPBS-123MG/DL

Urea-71mg Creatinine-1.5mg Sodium-135 meq/l Potasium-5.1meq/l Chloride-108 meq/l LIVER FUNCTION TEST Total bilirubin-0.8 SGOT-18 SGPT-16 ALP-78 Total protein-5.9 Albumin-3.9

ABG ANALYSIS: ph-7.38 po2-85.4mmhg pco2-27.6mmhg hco3-16.2mmol/l h+-41.2nmol/l na-131.3mmol/l k-5.50mmol/l ag-18.9mmol/l

Absolute eosinophil count-80 cells/cumm

ASCITIC FLUID ANALYSIS Protein-4.4 Sugar-92 Aalbumin-1.2 SAAG -2.66 Cell count - 96%lymphocytes;4%mesothelial cells= Cytology- clusters of reactive mesothelial cells and few lymphocytes in a eosinophilic background-reactive effusion

Mantouex test : Negative

USG ABDOMEN Ascities B/L increased renal cortical echos Liver – normal size Spleen- normal sizeECHO- RA/RV dilated TR moderate pg 46mmhg Moderate pulmonary hypertension No RWMA Normal LT ven systolic function

ENDOCRINOLOGY STUDY

THYROID FUNCTION TEST

T3- 47.02ng/dl(80-200ng/dl) T4- 5.77ugm/dl(4.6-12ugm/dl) TSH-16.322miu/ml(0.27-4.20miu/ml)

Anti TPO antibodies -30.39 iu/ml(0-34iu/ml)

Serum Cortisol -8.32ugm/dl(6.2-19.4iu/ml)

ACTH stimulation test serum Cortisol-8.53ugm/dl

DHEA sulphate-21.60ugm/dl(80-560ugm/dl)

Parathyroid hormone – 77.82pg/ml (15-65pg/ml)

Patient treated with Tab.Prednisolone 5mg 6 tablets Tab.Fludrocortisone 50ugm Cap.Omeprazole 40mg bd Tab.Eltroxine 100 mg bd Tab. Calcium lactate tds

BLOOD IMMUNOLOGY ANA- Positive 1:100 dilution Ds-DNA ab Negative Scl 70 ab Negative Anti centromere ab Negative Sm antibody Negative U1 nrnp NegativeBlood HBsAG :Negative Anti hcv: Negative hiv elisa:Negative vdrl Negative

Pulmonary function test

Ct abdomen

Blood biochemistry Calcium-11.1 mg/dl then comes to

8.6 mg /dl Phosphorus -5.1mg/dl LDH-131u/l ALP-104.1 iu/l24 hr urine calcium 56mg/dl

Differential diagnosis for metastatic sclerotic leisonsThyroid carcinomaRenal cell carcinomaBreast carcinomaGastric carcinomaSkin carcinoma

Nerve conduction study

Results:Upper limb Right median and ulnar nerve CMAP

latency,amplitude and velocity –WNL Left side - AbsentLower limb both CMAP AND SNAP not obtainedImpression Both sensory motor neuropathy of both

lower limb and possible sensory motor neuropathy of upper limb

Meanwhile patient said c/o headache –B/L Diffuse Dullache

Patient developed lymphnode enlargement B/L inguinal B/L axillaryFNACRt inguinal LN: c/c lymphadenitisLeft inguinal LN:material inadequate for

definite opinionRight axilla LN: granulomatous lymphadenitisLeft axilla LN: c/c lymphadenitis

biopsy

Serum electrophoresis- normal protein 5.1 albumin 3.2Urine BJP NegativeSerum ACE 16.3 u/l(8-52)

Patients have hypothyroidism addison disease hyperparathyroidism pht severe restrictive lung disease papilledema glomerulonephritis ascities b/l pitting pedal edema polyneuropathy m protein elevation sensory neural hearing loss multipe osteosclerotic leison castle man disease-multicentricClinically diagnosed as poems syndrome

Haematology opinion:

Final diagnosis POEMS SYNDROMEP- polyneuropathyO-organomegalyE-endocrinopathyM-m protein componentS- skin changes

Patient treated with Tab.Prednisolone 5 mg 6 tab Tab.Fludrocortisone 50 ug Tab.Eltroxine 100 ug od Tab.Amitriptylline 2.5 mg bd Tab.Calcium lactate tds Cap.Omeprazole 40 mg bd

Poems syndromeDefined as the combination of plasma cell

proliferation disorder(typically myeloma) , polyneuropathy and effects on many other organ systems

Peak incidence around 5-6 th decade of life unlike myeloma which is common around 6-7th decade of life

Twice as common in menOther names: osteo sclerotic myeloma, pep

syndrome, crow fukase syndrome, takatsuki syndrome

DIAGNOSTIC CRITERIA

Polyneuropathy Monoclonal plasma cell disorder One or more of the following major criteria - Sclerotic bone lesion - Castleman’s disease - Elevated VEGF levels One or more of the following minor criteria Organomegaly ( enlarged spleen,liver or lymphnode) Extra vascular volume overload(pleural effusion,ascities,pedal edema)

endocrinopathy(adrenal,pitutary,gonadal,parathyroid)dm,hypothyroidism alone insufficient

Papilledema Thrombocytosis or Polycythemia Skin changes-hyperpigmentation,dermis

thickening,hirsutism,hyperhidrosis Glomerulonepritis Sensory neural hearing loss

These patients have only 5% or less than bone marrow plasma cell

Rarely have hypercalcemia or renal insufficiency

1/3rd to1/2 of pt have poly neuropathy where as in classic multiple myeloma only 1-8% of pts have polyneuropathy

EtiologyCaue is unknow

Anti body to HHV 8 seen 78% of cases with castleman disease and 22% of patients without castleman disease

Increased level VEGF, IL1BETA, IL6 and TNF alpha

VEGF targets the endothelial cells and promote angiogenesis

Both IL 1 beta and IL6 stimulate VEGF production

Elevated level of VEGF correlate with disease activity

Elevated VEGF accounts for organomegaly,edema and skin changes; but role in polyneuropathy uncertain

POLYNEUROPATHYThough resembles CIDP it is motor

predominanceMarked slowing of conduction velocity with

prolonged distal latencies and progressive dispersions of compound muscle action potentials with stimulation of motor nerves proximally

Nerve biopsy shows combination of axonal degeneration and demyelination

ORGANOMEGALY Hepatomegaly and Lymphnode enlargement

seen in 2/3rd of patientsSpleenomegaly seen in 1/3 rd of patientsBetween 11-30% patients have castleman’s

diseaseAssociation is not fully understood

MONOCLONAL PLASMA PROLIFERATIVE DISORDERMonoclonal protein is not large

May be missed on serum electrophoresis in 1/3 rd of patients

These patients require immunofixation electrophoresis of serum/urine

<10% patients have no circulating protein

They need biopsy proof of plasmocytoma

In general number of plasma cells are low and bone marrow shows hypercellular and reported as reactive or myeloproliferative disorder

SCLEROTIC BONE LESIONApproximately seen in 95% of patients

One half of patient have solitary sclerotic lesion

1/3 rd of patient have multiple sclerotic leisonPelvis ,spine, ribs and proximal extremites are

often involved

PULMONARY DYSFUNCTIONPulmonary hypertension,restrictive lung

disease and impaired diffusion capacity of carbon monoxide may occur

Improvement of PHT after therapy has been reported

Only 19% of poems syndrome initially presented with pulmonary hypertension

HAEMATOLOGY50% OF cases have thrombocytosis

20% of cases have mild erythrocytosis; anemia is not a feature of poems syndrome

May be arterial or venous thrombosis

TREATMENTCorticosteroid-15% patients shows clinical

improve ment and 7% of cases shows clinical stabilisation;should not be consider definite therapy rather temporizing therapy

Alkylating agents Cyclophosphamide-as a single agent or in

combination with prednisolone shows clinical improvement in 40% of cases

Melphalan- most effective agent against plasma cell disorder ; but there is risk of mds /acute leukemia

Thalidomide Has anti vascular endothelial growth

factor and anti tumour necrosis factor Cause peripheral neuropathy in 20%

patients receiving patients Worsen the pedal edema As a single agent no more effective

than oral alkylators

RADIATION patients with single or multiple sclerotic agent in

limited area –treated with radiation therapyWidespread sclerotic leison –systemic therapy

neededHigh dose chemotherapy and stem cell

transplantation have been triedIntravenous immunoglobulin and plasmapheresis

shows no clinical benefitBevacizumab – monoclonal antibody against vegf

have been triedAll trans retenoic acid has been used to suppress

the production of proinflammatory cytokines

PrognosisIf untreated often fatalOnly 60% of patients alive 5 yrs after onsetPrognosis is better for patient with single

sclerotic leisonsMultiple bone leison – intermediate prognosisCommon cause of death-cardiorespiratory

failure,infection and capillary leak syndrome

THANK YOUREF: HARRISON 17 EDI OTM E MEDICINE