The Patient's CryThe Patient's CryCase Conference 1/15/13

Presented by Sophia Cenac, MD

• CC: “My fingers are blue.”

History of Present Illness• 47 yo woman with PMH of HCV and mononeuritis multiplex.• 4 months ago:

• Complained of pain in her hands and legs x 3-4 wks. • Described progressively worsening 10/10 burning pain in her

bilateral extremities • Fingertips to her wrists and from her toes to mid-shins bilaterally.

• Also complained of weakness, numbness, and tingling sensations in same distribution• Caused unsteadiness and difficulty walking • Experienced 3-4 falls.

• Denied injury or trauma to her hands or feet.

History of Present Illness• 3 months ago

• She presented to outside hospital for these complaints • Diagnosed with Hepatitis C• Given a prescription of Gabapentin 300 mg TID (did not fill)

• 2 months ago• Continued neuropathic pains• Was taking extra strength acetaminophen 2-3 tabs daily without

symptom relief. • Endorsed nausea with 2 episodes of non-bilious, non-bloody

emesis. • She was admitted for to UH for acetaminophen toxicity.

• Treated with n-acetylcysteine

History of Present Illness•Diagnosed with Mononeuritis multiplex after:

▫Extensive lab work-up found to be unremarkable B12, RPR, Utox, HbA1C, TSH, ANA, and HIV

▫NCS/EMG 8/12 Normal right sural nerve study. Left sural nerve had slowing in conduction velocity and

increased latency. The right and left peroneal and tibial nerves had no motor

response.

▫Sural nerve biopsyaxonal degen with myelin breakdowndecreased no. of myelinated fibers

Additional Findings

• Peripheral smear (8/12)

• Blood sample was clumping

• Decreased with heating

History of Present Illness•Additional work-up

▫Bone Marrow performed▫Flow Cytometry

Monoclonal mature B cells (6%) Two small bands of IgM Kappa specificity

(8/2012)IgM 838 (47-188)IgG 749 (680-1530)IgA 375 (75-374)IgE 72 (<100)

History of Present Illness

•Patient was discharged with:▫Pain control▫Pending studies

BM biopsy results Cryocrit SPEP/UPEP

▫Follow up with: GI Neuro PCP

History of Presenting Illness•Since discharge from UH

▫ Persistent lower extremity ulcerations and neuropathic pain

▫ Did not follow up with appointments

•2-3 days prior to admit▫ Ran out of her medications▫ Complained of sensory changes and weakness of

her finger (unable to bend finger)

•DOA▫ Change of color of her left 2nd digit▫ Experienced SOB and an episode of emesis

History of Presenting Illness• PMH:

▫ Hepatitis C (genotype 1a, viral load 275,999 IU/ml 8/2012)

▫ Mononeuritis multiplex▫ Presumed

cryoglobulinemia• PSH:

▫ Cholecystectomy (2000)▫ Sural Nerve biopsy

(8/12)▫ Bone marrow biopsy

(8/12)

• Medications:▫ Carbamazepine 200mg

PO BID▫ Gabapentin 1,200mg PO

TID▫ Lisinopril 40mg PO Daily▫ Morphine sulfate 15mg

PO TID • Allergies:

▫ NKDA

History of Presenting Illness

•Social: ▫ Lives with her niece in Marrero▫ Hx of ½ ppd tobacco for 5 yrs; quit 3 months ago.▫ Hx of 6 pack of beer/wk x 8 yrs; quit 3 months ago.▫ Crack cocaine use; quit 10 yrs ago. Denies IVDA.▫ Currently sexually active with one partner▫ Multiple tattoos

•Family: ▫ Mom deceased at 68 y/o secondary to CVA▫ Dad deceased at unknown age secondary with asthma and CHF.

•Health Maintenance: ▫ No PCP ▫ Not UTD on vaccines/screening studies.

Review of Systems• Constitutional: No f/c, no hair loss, weight stable• HEENT: No HA; no visual changes; no oral ulcers• Eyes: Negative for visual disturbance. • Respiratory: Increased SOB attributed to pain, no

cough• Cardiovascular: No CP, no palpitations• Gastrointestinal: (+) Nausea, emesis x1 (non-bloody);

no abdominal pain; no diarrhea, no melena, no BRBPR• Genitourinary: Negative for dysuria, urgency or

frequency• Musculoskeletal: No myalgias, no arthralgias• Neurological: (+) weakness of hands

Physical Exam

• Triage Vitals: ▫ BP:140/111 P:144 R: 26 T: 98°.0 F O2: 93% on RA

• Exam: ▫ BP:162/112 P: 98 R: 28 T: 98 F O2: 91% on 2L NC Ht: 5’4” Wt: 196 lbs BMI:

33.6 • Gen:

▫ Uncomfortable, sitting up with labored breathing• HEENT:

▫ NC/AT, EOMI, PERRLA, no scleral icterus, conjunctiva wnl, no LAD• CV:

▫ Tachycardic, regular rhythm, no m/r/g, no JVD noted at 45 degrees• Resp:

▫ Tachypneic with retractions, expiratory rhonchi throughout sparing b/l upper lung fields, +bibasilar crackles

Physical Exam cont.• Abd:

▫ Soft, NT/ND, +BS x 4, no HSM• Ext/skin:

▫ B/l hands cold to the touch, +cyanosis of index finger, without ROM of L index finger, non-tender to touch, 3 R calf lateral ulcers with some granulation tissue without erythema, warmth, or drainage, and L calf with lateral non-draining ulcer

• Neuro: ▫ Alert and oriented to person, place, time, and situation, speech normal in

context and clarity, 4/5 hand grip in RUE and 3/5 hand grip in LUE with decreased ROM of Left 2nd digit, moving all extremities, 2+ reflexes throughout, decreased sensation to light touch distal to R knee and distal to L mid-shin

LABS (11/12)WBC 11.3Hgb 10 1(5-25) 12 (8/12)Hct 29 (35-45) 37 (8/12)PLT 467 (130-400)MCV 89Diff N-92, L-7, M-1

Coags normalLactic acid 2.5 (0.3-2.4) 2.3 (8/12)

Trop 3.5 (peak 8.2) (<0.04)CK 2000 (peak=15,230) (<190)

Na 135K 2.8 (3.5-4.5)Cl 102CO2 18BUN 17Cr 0.7Tprot 6.9Alb 2.6 (3.4-5.0)Tbili 1.0AST 44ALK 74ALT 15

CRP 6.1 (<0.9) 16 (8/12)ESR 87 (0-20) 72 (8/12)

UA protein noneRBC 3-5WBC 3-5

UDS +THC+opiates

After RTX:Acute hep +Hep C Ab (8/12)T. Spot negANA negENA 6 negp/cANCA negC3 35 (83-180)C4 <5 (18-55)RF 95 (<20 – 8/12)

Additional Labs (8/12)

•BM results▫Small population of monoclonal B cells

(6%). Positive for CD19, CD20, AND CD22. Kappa light-chain restricted

•SPEP▫Mild increase of alpha1 and alpha 2

globulins with borderling low gamma fractions and without M spike.

•UPEP▫No protein bands

Additional Labs

•8/2012: ▫Cryoglob: 4%▫Immunofixation electrophoresis reveals Type II

cryoglobulin (monoclonal globulin with activity against polyclonal immunoglobulin)

(11/2012)IgM 299 (47-188)IgG 651 (680-1530)IgA not doneIgE 180 (<100)

(8/2012)IgM 838 (47-188)IgG 749 (680-1530)IgA 375 (75-374)IgE 72 (<100)

Hospital Course• Day # 1

▫ Sent to the MICU NSTEMI

LHC with no significant CAD Intubated and placed on vasopressors secondary to pulmonary

edema and hypotension Spiking temperatures

Placed on broad spectrum antibiotics • Days # 2 -4

▫ Plasma exchange initiated along with pulse steroids (80mg solumedrol daily)

▫ After 4 days plasma exchange Rituximab given and steroids tapered

▫ Continued spiking temperatures▫ Weaned from pressors

Hospital Coarse

•Day # 5-13▫Repeat Rheumatologic work-up▫Fevers resolved

Initial cultures negative▫Worsening cyanosis of digits

Necrosis of digits noted▫Extubated ▫Stepped down to the floor

Additional Lab Values• ENA 6 negative• Anti-MPO Ab <9.0• c-ANCA <1:20• p-ANCA <1:20• C3: 35-160 (83-180)

▫ 8/9/12 – 12/13/12• C4: 5-27 (18-55)

▫ 8/9/12 - 12/13/12• Repeat Cryoprecipitant : 5%

(nml is negative)• RF level: 2400 (<20)• Occult blood negative

• Repeat SPEP: ▫ Alpha 1 globulin 0.3▫ Alpha 2 globulin 0.8▫ Beta globulin 0.6▫ Gamma globulin 0.5▫ M spike +2 bands of 0.04

g/dL▫ SPEP 5.1 (6-8)

Hospital Conference

•Day # 13-20▫BM biopsy▫Began spiking temperatures

Coag neg staph line infection tx with Vanc▫Seen by Vascular Surgery

Anticipate autoamputation of necrotic digits

BM biopsy (11/12)

BM biopsy (11/12)

BM biopsy (11/12)

BM biopsy (11/12)

BM biopsy (11/12)

•11/2012:

▫BM biopsy with flow: Small monoclonal mature B cell population (3%

of population) CD19+ & kappa light chain restricted CD20 neg (s/p RTX) plasma cells present <1% T cells nl and nl CD4:CD8 ratio Consider lymphoplasmacytic lymphoma

Hospital Coarse

•Day #21 – 24▫Concern for gangrenous extremities

Surgery/Ortho consulted▫Re-started spiking temperatures

Rituximab held Piperacillin-tazobactam added to Vancomycin

▫Prednisone taper finished

Hospital Coarse

•Day #25-34▫Taken to OR for debridement of

gangrenous lower extremities. Found dead tissue Taken back for B/L BKA with additional

revision▫Development of RUE DVT on POD#3

Started on Plaquenil Discontinued on day 34 secondary to

persistentfevers

Surgical path/LE amputation

Surgical path/LE amputation

Right/Left Leg amputation

•Right leg▫ Large muscular vessels with vasculitis

(predominantly chronic inflammation)•Left leg

▫Vasculitis of medium sized blood vessels. Large muscular vessels with vasculitis (predominantly chronic inflammation)

Surgical path

Surgical path

Right and Left Disarticulation

•Left▫Vasculitis involving medium and large sized

arteries. Benign skin with underlying scattered hemosiderin laden macrophages.

•Right▫ Skin, underlying dermis and subcutaneous

adipose tissue with vasculitis, mixed inflammation and areas of necrosis, Skeletal muscle with inflammation and vasculitis; and bone marrow with fat necrosis.

•Day # 35-56▫Intermittent fevers persist

Coag neg staph 2/4 bottles Treated with Vancomycin

▫3rd dose of Rituximab administered▫Discharged to Touro Rehab

Outpatient Hepatitis C treatment planned

Thanks.