A Rare case of jaundice with skin lesion

A CASE OF JAUNDICE WITH SKIN LESIONS : 

A CASE OF JAUNDICE WITH SKIN LESIONS Dr Mahesh R Varma 5th Nov 2008

32 y old House wife presented to us with…. : 

32 y old House wife presented to us with…. Fever for ~ 5 days two weeks back Jaundice 1 week Pruritus 1 week

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Fever - High grade with chills and rigor - Intermittent - Lasted for 4 days 2 wks back - Decreased in intensity on medications - Afebrile for the last 1 week. - No periodicity/drenching sweats - No arthralgia/myalgia/rash - No dysuria/hematuria

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Consulted a private physician who noticed Jaundice - No concomitant fever - Dark urine(+) ; No pale stools - Mild pruritus(+) - No waxing and waning of jaundice - No rash / bleeding tendencies - No h/o GI bleed

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Mild pruritus(+) Anorexia, aversion to food(+) No travel outside the state No h/o native medication intake No head ache or altered sensorium No photophobia/seizures

Past history.. : 

Past history.. Skin lesions in Feb 2007 Biopsy ? CTCL 46 cycles of Radiotherapy (Total body) (ADAYAR) Remission Reappearance of lesions on face ? BM Inv ? BM Bx ? Infiltration CHOP 8 cycles (Last in June 2008) Now on Methotrexate and 6MP(RCC)

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No past h/o jaundice No prior hospitalizations other than for CTCL No past blood transfusions Not a DM/HT/CLD/CKD

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H/o Total body irradiation from March – May 2007 Took Cyclophosphamide * 8 Cycles Doxorubicin * Feb-Jun’08 Vincristine Prednisolone On Mtx and 6 MP from June 2008

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Personal history - Sleep,Bowel,Bladder (N) - Mixed diet - No addictions/i.v.d.a - Lives with husband and 2 kids Family history - Eldest brother HBsAg(+) - 3 siblings; all healthy - Father mother alive - No other significant family history

Summary.. : 

Summary.. 32 y female diagnosed to have had CTCL with BM involvement and had underwent Chemoradiotherapy and presently on Mtx and 6 MP,now presenting with fever followed by jaundice for the last 2 weeks - C/c Hepatitis with Flare - Drug induced Hepatitis - Cholangitis - Acute viral hepatitis - Lymphomatous liver infiltration - Leptospirosis/Malaria

On Examination…. : 

On Examination…. Patient fully conscious , oriented , comfortable Co operative Mild Icterus(+) No P / Cy / Clb / Edm B/L Axillary , Epitrochlear , Cervical LN(+);significantly enlarged(2 x 2 cms; rubbery) HR 74 / min; BP 120/70 mmHg ;JVP (N) No stigmata of hepatocyte failure No K-F ring

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Multiple maculopapular lesions over the face and anterior chest wall Plaque like lesions over the (L) eyebrow Coarse dry skin with exfoliation and fissuring of skin No thyromegaly No acanthosis Nigricans No rashes or petechiae

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P/A - Not distended ; Umbilicus central, inverted - No scars / striae / Dil Veins / Mass - Soft , Non tender - Liver palpable 3 cms BCM(R) ; Firm , Not tender , smooth surface , span 16 cms - Splenomegaly 4 cms - No FF - No bruit / rub over the abdomen - DRE Normal

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RS - Trachea central - B/L AE equal; NVBS CVS s1s2 (N) ; No s3/ s4 / (m) CNS - HMF (N);No FND / Flap; Fundus Normal Musk sk system – No arthritis / deformity / pigmentation

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Differentials… CLD with flare Hepatic infiltration by lymphoma Drug induced Hepatitis Cholangitis Hemolytic anemia Non hepatotropic viral infection

Investigations : 

Investigations Hb 9.6 g/dl ; TC 7610 ; N25 L 60 E11; ESR 20 ; Plt 1,80,000 MCV 85.2;MCH 26.4 ; MCHC 31.6 ; PCV 31 Peripheral Smear - A few reactive lymphocytes ; MP Negative Retic count 0.5%;DCT Negative (Twice) RBS 110 ; B Urea/S Cr 20/1.1 Na/K 142/4.9

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Br T/D 2.3/1.1?3.6/1.1 AST/ALT 53/31?44/29 ALP 145(<145)?336(<300) GGT 83(12-49) Prot T/Alb 7.1/3.4 Ca 9.2;PO4 3.5;UA 5.5;S Cortisol 19.22(N) T3 70(84-201);T4 8( 5-14);TSH 0.19(2-4.2) S LDH 955(<613) S Amylase 45;S Lipase 112

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PT T/C 12.3/12.3 INR 1.0 Serology - HBsAg(-) - Anti HCV (-) - Anti HAV IgM (-) - Anti HEV IgM (-) - Monospot(-);Enterochek (-) - PS for MP Negative - ANA (-) - Retro (-)

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Urine NAD Blood C/S - Coagulase negative staphylococci (MRSA ? Contaminant) Urine C/S Sterile

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Imaging - CXR (N) - USG – Liver span 14.7cms. - CBD (N) - No FL/IHBRD - Pancreas (N) - Spleen 14.2 x 5.5 cms - No e/o CLD/PHT - No FF - S.V.OGD - Normal

Liver biopsy result… : 

Liver biopsy result… Portal tracts contain medium to large sized lymphoid cells with pale cytoplasm and irregular hyperchromatic nuclei with mitotic activity and histiocytes. Interlobular bile ducts show nuclear atypia and proliferation Sinusoidal dilatation and macrovesicular steatosis seen. Lymphoid cells are CD 3 (+).Occasional CD 20 (+) lymphocytes are also seen. MIB index is 50-75 %

Liver infiltrate.. low power.. : 

Liver infiltrate.. low power..

High power view.. : 

High power view..

CD 3 Membrane positivity.. : 

CD 3 Membrane positivity..

Hepatic involvement in Hematological malignancies : 

Hepatic involvement in Hematological malignancies Liver is a major component of the RES Involvement common but rarely life threatening Many forms of involvement - Infiltration - Lymphomas - Toxicity - Drugs , Radiation - Opportunistic infections - Nonspecific - Steatosis, Hemosiderosis - Paraneoplastic - Granulomas, Cholestasis (Hodgkin's) - Amyloid ( Myeloma )

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Liver involvement - NHL>HD - The majority of infiltrative lesions are portal - Secondary Lymphomatous involvement is usually detected by HPE - Primary Invmt presents as mass lesions - Almost 100% Invmt with Hepatosplenic ?d T cell lymphoma ( Young males with HSM without lymphadenopathy; Trisomy 8, Isochromosome 7q) -Most common abnormality is elevated ALP

CTCL(Sezary Syndrome) : 

CTCL(Sezary Syndrome)

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Histologically there is a dense perivascular and superficial dermal atypical lymphoid infiltrate with minimal focal epidermotropism

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CTCL Diagnosis: The Problems Diagnosis may take months to years. Multiple skin biopsies often needed • Rare condition, many subtypes • Mistaken for more common skin problems - Eczema - Psoriasis - Allergic contact dermatitis - Drug allergy - Tinea

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Peripheral blood: - Romanowsky stained smears show large cells with slight cytoplasm containing PAS+, perinuclear vacuoles and large, cerebriform, hyperchromatic nuclei

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Positive stains: CD2, CD3, CD4, CD5 Negative stains: CD8 Molecular: clonal rearrangement of T cell receptor, but no specific chromosomal abnormalities

CTCL Staging : 

CTCL Staging IA Limited(<10% BSA) skin patches/plaques IB Generalized(>10%BSA) skin patches/plaques IIA Patch/plaque and nonspecific(<2cms) enlarged LNs IIB Tumors III Erythroderma IVA Any skin lesions & positive LNs IVB Any skin lesions & positive organ involvement

Treatment.. : 

Treatment.. Aimed at - Symptomatic relief - Countering sepsis( MRSA,PsA ) - Prevent Opportunistic infections - Specific treatment

Specific Treatment : 

Specific Treatment Photopheresis and biological response modifier therapy Increase TH 1 response….. IFN @ Intravenous Denileukin diftitox is a fusion toxin (DAB389 IL-2) in refractory CTCL Chemotherapy - Single agent - Pentostatin,Gemcitabine > Fludarabine - Combination chemotherapy - CHOP, CMED Total body irradiation Newer agents- Histone deacetylase inhibitor (Depsipeptide) - Purine nucleoside phosphorylase inhibitor ( Bcx 1777)

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Thank You