ID Fellows Case Conference

August 25, 2010

Lindley Barbee MD, MPH

A classic presentation of an uncommon disease …except among transplant patients.

An Uncommon Presentation of a Common Disease

Case

67 y M w/ small cell lymphocytic lymphoma/chronic lymphocytic leukemia presents to SCCA for evaluation for transplant

SLL/CLL dx’d in late 2006 with diffuse LAD TX course thus far: rituximab, pentostatine,

cyclophosphamide for three months in early 2007 Rituximab, solumedrol for relapse the following year Rituximab, cytoxan, prednisone in 2009 Since January 2010 – bendamustine, rituximab x 8 cycles July 2010 radiotherapy with gamma knife to abdomen

Background History

PMH Gout Benign adenoma of brain

s/p resection 2000 Pituitary adenoma Melanoma s/p excision TURP for BPH

Family History Father died of colon CA Mother died of liver CA

Medications Allopurinol Levothyroxine Cabergoline Dexamethasone 0.5mg Benadryl prn Marinol prn Compazine prn Ambien prn

Background History

Social History

Born Indiana, lives in Carson City NV

In the Marines lived in Japan and San Diego

Travel – Mexico, Kenya & Tanzania

Retired attorney, has a dog, no other animal exposures. Denies tob, etoh, illicit

Pre-transplant Serologies

HSV+, VZV +, CMV -, toxo -, HIV p24 -

Case

On 7/21 he had last XRT to abdominal mass On 7/23 he and his wife left Reno to drive to

Seattle for his pre-txp appt. During the drive suffered abdominal pain, nausea and vomiting.

On arrival to SCCA, July 27, he is weak and sweaty, c/o abdominal pain, n/v.

Labs reveal Na 120. Pt is admitted to UWMC.

Admission Data

VS: T 36.4 HR 80 BP 140/78 RR 18 100% RA

121 | 88 | 16 / AST 61 ALT 61 AlkPhos 121

4.0 | 21 | 0.8 \

2.99 \ / 54

Serum Osms 250 / 38 \

Una 53 75% polys

18% lymphs

Hospital Course: Days 2 - 4

Hyponatremia attributed to hypovolemia. Tx’d with NS and sodium slowly rises Cort stim is WNL GI is consulted for abdominal pain, now with

constipation – dx: Radiation Enteritis Pt is placed on bowel rest and given

parenteral nutrition and miralax

Hospital Course: Days 6 - 7

Pt develops rash on face on evening of HD6 In the morning, he syncopizes is found to be

hypotensive (SBP 80s) and bradycardic (50s) Started on broad spectrum abx –

Vanco, Imipenem and Cipro Transferred to the ICU; started on pressors

Exam

VS: T 37.4 HR 114 BP 105/60 RR 24 99% 2L GEN: wdwn man uncomfortable, rigoring HEENT: EOMI, small vesicular lesions scattered

on face and neck, neck supple LUNGS: tachypneic, CTAB CV: tachy, regular, no m/r/g EXT: cool extremities, trace edema SKIN: scattered vesicles on face, chest, back

upper arms, upper thighs

Example of Vesicles

Laboratory Data

3.84 33 AST 588 ALT 518

35 Alk Phos 197 T bili 2.4

142 118 35 Amylase 476 Lipase 413

4.1 20 1.4

Vesicle Swab FA: + VZV

Serum VZV PCR: 4 million copies

Diagnosis: Disseminated VZV

with Visceral Involvement

Varicella Zoster Virusin Immunocompromised Host

Primary VZV infection Herpes Zoster Multiple involvement of herpes zoster Disseminated VZV Visceral involvement CNS involvement Rare Triad: Hyponatremia, abdominal pain

and disseminated cutaneous VZV

Epidemiology

17-50% of BMT patients are expected to develop zoster in their post transplant course

Approx. 3.6% of those develop visceral VZV Disseminated zoster occurs in ~2.6% of

PBSCT The triad of hyponatremia, abdominal pain,

and disseminated zoster has been reported in 8 cases, mostly among BMT patients

Case Reports

Ref Age/SexPrimary Disease

TX Clinical sx Day TX Outcome

1 57/M CML Allo BMT Abd pain/Ileus /

low Na9

Acyclovir/ valacyclovir

recovered

2 61/F NHL Auto SCTAbd pain/

low NA10 Acyclovir died day 10

3 38/M CMLAllo unrelated

SCTLow Na/abd pain/ileus

10 Acyclovir/ IVIG recovered

3 32/F ALL Allo sib SCTabd pain/ileus,

low Na7 Acyclovir/ IVIG recovered

4 19/F ALL Allo unrelatedLow Na/Abd

pain/hepatitis/ pancreatitis

13 Acyclovir recovered

7 65/F NHL CHOP/XRTAbd pain/

hyponatremia6 Acyclovir recovered

8 ? NHL Chemo/XRTIleus/abd pain/ hyponatremia

? None recovered

9 50/F AML Auto SCTAbd pain/vomit/ low Na/ hepatitis

7 Acyclovir recovered

Case: Therapy and Outcome

Pt was started on high dose acyclovir at 10mg/kg IV q8H

He was treated for 12 days IV and then transitioned to PO valacyclovir

Lesions have scabbed over, Na is corrected, no further abdominal pain.

Still with fevers and mild elevation of transaminases.

VZV PCR Copies and Log10

PCR LOG10 HD6: 4,000,000 6.6 HD12: 1,500,000 6.2 HD18: 8400 3.9 HD22: 4300 3.6 HD26: 7600 3.9

Summary

VZV is a common infection in transplant patients

Its manifestations vary from shingles to fulminant hepatic failure

Think VZV with hyponatremia and abdominal pain in the right immunocompromised host

References

1. Szabo, Horvath, Seimon and Hughes. Inappropriate antidiuretic hormone secretion, abodminal pain and disseminated varicella zoster virus infection: an unusual triad in a patient 6 months post mini-allogeneic peripheral stem cell tranplant for chronic myeloid leukemia. BMT 2000;26:231-3.

2.McIlwaine, Fitzsimons and Soutar. Inappropriate antidiuretic hormone secretion, abdominal pain and disseminated varicella zoster virus infection: an unusual and fatal triad in a patient 13 months post Rituximab and autologous SCT. Clin. Lab Haem 2001;23:253-254.

3. Au, Ma, Cheng, Ooi, and Lie. Disseminated zoster, hyponatremia, severe abdominal pain and leukemia relapse: recognition of a new clinical quartet after BMT. British J of Dermatology 2003; 149: 862-5.

4. Rau et al. Triad of severe abdominal pain, inappropriate antidiuretic hormone secretion, and disseminated varicella-zoster virus infection preceeding cutaneous manifestations after hematopoietic stem cell transplantation: Utility of PCR for early recognition and therapy. Ped Infect Dis J 2008; 27(3):265-8.

5. Kim et al. Factors influencing varicella zoster virus infection after allogeneic peripheral blood stem cell transplantation: low-dose acyclovir prophylaxis and pre-transplant diagnosis of lymphoproliferative disorders. Trans Infectious Disease 2008; 10: 90-98.

6. Shiley and Blumberg. Herpes viruses in Transplant recipients: HSV, VZV, Human herpes viruses and EBV. Infect Dis Clin N Am 2010; 24: 373-93.

7. Ohara et al. Abdominal pain and syndrome of inappropriate antidiuretic hormone secretion as a manifestation of visceral varicella zoster virus infection in a patient with Non Hodgkins Lymphoma. Am J Hematology 2006.

8. Ingraham, Estes, Bern, DeGirolami. Disseminated varicella-zoster infection with the syndrome of inappropriate antidiuretic hormone. Arch Intern Med 1983; 143(6):1270-1.

9. Vinzio et al. Severe abdominal pain and inappropriate antidiuretic hormone secretion preceeding varicella-zoster virus reactivation 10 months after autologous stem cell transplanation for acute myeloid leukaemia. BMT 2005; 35:525-7