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Clinical Problem Solving 12/16/08. Moderator: Stuart Cohen MD Discussant: Carlos Estrada MD. Case #1. 21 y/o Caucasian Male presents to clinic with 8 day h/o fever and malaise 2 days PTA developed sore throat Denies myalgias, cough, shortness of breath No nausea, vomiting or diarrhea

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Clinical problem solving 12 16 08 l.jpg

Clinical Problem Solving12/16/08

Moderator: Stuart Cohen MD

Discussant: Carlos Estrada MD


Case 1 l.jpg
Case #1

  • 21 y/o Caucasian Male presents to clinic with 8 day h/o fever and malaise

  • 2 days PTA developed sore throat

  • Denies myalgias, cough, shortness of breath

  • No nausea, vomiting or diarrhea

  • Denies nasal congestion, rhinorrhea

  • Denies headache, stiff neck, visual changes


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Case #1

  • No rash, joint pain

  • No dysuria, frequency or urgency

  • No sick contacts

  • No recent travel outside of country or hikes in the woods


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Case #1

  • PMH: None

  • MEDS: None

  • Fam Hx: non-contributory

  • Soc Hx:

    • Senior at University of Alabama Tuscaloosa

    • No tobacco or drug use

    • Social alcohol consumption

    • Not sexually active


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Case #1

  • PE: 120/60, 70, 12, 100.2

  • HEENT

    • Erythematous posterior pharynx with cobblestoning, large tonsils with exudate

    • Bilateral anterior cervical and posterior cervical adenopathy (tender)

  • CV: RRR with no M/R/G

  • Lungs: Clear bilaterally, ABD: soft, non-tender, non-distended, No hepatosplenomegaly

  • EXT: No C/C/E

  • Neuro: Non-focal


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Case #1

  • Data

    • Rapid Strep: Positive

    • WBC 13.3, HCT 39, Plts 244

      • 18% segs, 50% lymphs, 18% Monos,

      • 8% Atypical lymphs

    • Monospot: Positive

    • EBV VCA IgM: Positive

    • Throat Culture: No growth


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Mono/Strep both?

  • True co-infection with GAS and EBV is rare but reported in the literature

  • GAS colonization in patients with EBV is more likely (some reports suggest up to 30%)


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Centor Criteria

  • Tonsillar exudates

  • Tender anterior cervical adenopathy

  • Fever by history

  • Absence of cough

  • 0 or 1 positive  NPV of 80%

  • 3 or 4 positive  PPV of 50-60%


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Diagnostic testing for GAS

  • Rapid Streptococcal Antigen Test (RAST)

    • Sensitivity 80-90%

    • Specificity 90- 95%

  • Throat Culture

    • Sensitivity 90%

    • Specificity 95%


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Rationale for antibiotics

  • To prevent Rheumatic Fever

  • To prevent peritonsillar abscess

  • To prevent transmission

  • To relieve symptoms

    • For patients with severe pharyngitis, symptoms resolve 2.5 days earlier with antibiotics


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Antibiotics in patients with EBV

  • Macular-papular pruritic rash which is frequently prolonged

  • Offending Antibiotics

    • Amoxicillin

    • Penacillin

    • Azithromycin

    • Levofloxacin

    • Cephalexin

  • Not reported with Clindamycin

  • Mechanism of rash unknown

  • Rash does not presage true drug allergy


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Case #2

  • 44 y/o white male presents with 3 month h/o left upper extremity weakness

  • Developed abruptly with no associated pain

  • limited to distal hand muscles with numbness and paralysis of all finger movements


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Case #2

  • 1 yr PTA, developed abrupt onset right shoulder pain which lasted for 4 weeks

    • 1 month after being struck in the neck with water heater

  • Followed by slow progression of weakness and wasting of shoulder girdle muscles (unable to abduct his arm)

  • Partial return of function of right arm weakness over past 9 months


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Case #2

  • Evaluation at University of Michigan 1 yr ago:

    • MRI brain and c-spine – Normal study

    • Shoulder films- Normal

    • EMG: right brachial plexopathy


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Review of Systems

  • Denies recent trauma, vaccines or surgical procedures

  • No recent fevers, chills, night sweats

  • Denies chest pain, SOB, cough or dysphagia

  • Denies abdominal pain, nausea or vomiting

  • Reports 40# weigh loss over past 9 months

  • New onset left lower extremity weakness


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Case #2

  • PMH:

    • Severe depression with recent psychiatric hospitalization

    • Right upper extremity weakness (brachial plexopathy)

  • Meds: Risperdal, lexapro

  • FamHx: non-contributory

  • SocHx:

    • Separated from wife- living at his sister’s house

    • Past truck driver

    • Past tobacco use, no alcohol, no drugs


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Case #2

  • Physical Exam:

  • VS: AF, 94/60, 60, 12 (weight 115#)

  • Appearance: Cachectic but NAD

  • HEENT: OP clear, fundi-no papilledema, no lymphadenoapthy or thyromegaly

  • CV: RRR with no M/R/G

  • Lungs: Clear bilaterally

  • ABD: S/NT/ND/ pos bowel sounds, No hepatosplenomegaly

  • Ext: NO C/C/E


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Case #2

  • Neurological exam:

  • Mental status: normal memory, comprehension and cognition.

  • Cranial nerves II – XII: visual fields full; extraocular movements intact; facial/jaw strength normal; hearing normal; gag normal; tongue midline without atrophy; normal shrug.

  • Motor strength testing:

    • RUE- 3/5 grip, 4/5 wrist flexion and extension, 4+/5 biceps/triceps

    • LUE- 0/5 grip, 0/5 wrist flexion, 4/5 wrist extension, 4+/5 bic/triceps

    • RLE- 5/5 strength

    • LLE- 4/5 strength with foot drop


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Case #2

  • Neurological exam (cont’d):

  • Deep tendon reflexes: 2+ everywhere except absent left knee and ankle; toes –downgoing bilaterally.

  • Sensory examination: Proprioception intact. Vibration diminished in feet and hands. Pinprick diminished in C5/C6 dist on right upper extremity and C8/T1 distribution on left upper extremity.

  • Coordination: normal finger-to-nose and heel-to-shin testing.

  • Gait: normal station; normal heel, toe and tandem walking.


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Case #2

  • WBC 11, HCT 34, Plt 362

  • 138 109 22 89

    43 29 1.3

  • AST 24, ALT 34, AlkPhos 84, Bili 1.0

  • Tot protein 7.6, albumin 2.8

  • B12, Folate- normal

  • TFT’s- normal

  • HIV- negative, HCV- negative, HbsAg- negative

  • UA: 3+ blood, 2+ protein, >25 RBC’s

    • Urine Protein/Creatine: 730 mg/24hr


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Case #2

  • ESR 10, ANA < 1:80, RF (-)

  • C3,C4,CH50 - normal

  • SPEP, UPEP, IFE: Negative

  • P-ANCA (-), C-ANCA 1:320

  • Anti-MPO <13, Anti-PR3: 129


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Case #2

  • CXR- No acute disease

  • EMG/NCS

    • Left brachial plexopathy involving lower trunk (C8/T1)

    • Selective motor denervation in left femoral and posterior tibial innervated muscles (compatible with plexopathy)

  • Kidney biopsy

    • Focal necrotizing glomerulonephritis with crescents, pauci-immune

    • (consistent with ANCA associated vasculitis)



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Vasculitic neuropathies

  • Systemic Vasculitic Neuropathy

  • Nonsystemic Vasculitic Neuropathy

    • No associated systemic disease


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Systemic Vasculitic Neuroapthy

  • Pathogenesis

    • Immune complex deposition

      • Mixed cryoglobulinemia, Polyarteritis nodosa

    • Cell-mediated immunity

      • ANCA associated vasculitides

  • Patterns of nerve involvement

    • Ischemic lesions occur randomly along course of peripheral nerve  asymmetric, patchy involvement of both sensory and motor nerves

    • Longest nerves are affected first

      • typically lower extremity (sciatic nerve)- often present with foot drop


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Systemic Vasculitic Neuroapthy

  • Clinically present with pain, paresthesias, numbness and weakness

    • Mononeuritis multiplex

    • Polyneuropathy

    • radiculopathy and/or

      plexopathy

  • Non-neurologic symptoms of fever, malaise, weight loss and specific organ involvement


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Systemic Vasculitides

  • Primary systemic vasculitides

    • Microscopic polyangiitis

    • Polyarteritis Nodosa

    • Churg-Strauss syndrome

    • Wegener’s Vasculitis

  • Secondary systemic vasculitides

    • Rheumatoid Vasculitis

    • SLE, Sjogren’s

    • Hepatitis C and mixed cryoglobulinemia

    • HIV and CMV

    • Paraneoplastic vasculitic neuropathy


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Wegener’s Vasculitis

  • Wegener’s

    • c-ANCA (PR3) 75-90%

    • p-ANCA (MPO) 5-20%

  • Pulmonary disease in 70-85%

  • Glomerulonephritis in 70-80%

  • Arthralgias/Arthritis in 60-70%

  • Peripheral nerve involvement reported in up to 40% of cases and often occurs early in the disease course

  • Nerve involvement can be the first and sole symptom of a beginning systemic vasculitis

c-ANCA

p-ANCA


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Case #3

  • 54 y/o WM

    • seen in ED 2 weeks prior after falling - Left wrist fx

    • In ED, found to be anemic (HCT 24, MCV 74)

    • Presents to you for follow-up

  • ROS:

    • Diarrhea x many months, watery, yellow, 2-12 BM/day, frequent abd distention

    • Denies abdominal pain, BRBPR, melena

    • Arthritis- mostly large joints

    • Frequent Headaches (No photophobia, blurry vision)

    • ? Unsteady gait


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Case #3

  • Pmhx: arthritis

  • Meds: Naprosyn, Flexeril

  • Fhx: Non- contributory

  • Sochx: no tobacco, occ alcohol, No IVDA


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Case #3

  • PE: AF,135/69, 94, 20, 100% RA

    • Pale conjunctiva, OP- clear

    • CV: RRR no m/r/g

    • Lungs: clear

    • ABD: soft, mild distention, BS present, No hepatosplenomegaly or bruits

    • Ext: No C/C/E

    • Skin: No rashes

    • Rectal: heme negative

    • Neuro: normal except for mild decreased vibratory sense in bilateral lower extremities


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Case #3

  • Data:

    • Hct 24, MCV 74, WBC 4.5 (nl diff), plts 154

    • Chem 7: Normal

    • Retic 2.1%, LDH 168, ferritin <1

    • Fe 8, TIBC 318, B12 175

    • AST 54, ALT 48, Bili 0.9, AP 132, Alb 3.2,

    • Amylase 55, TSH 2.4, FT4 1.0

    • 25-OH Vit D 12


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Case #3

  • Work-up:

    • Head CT in ED: Normal

    • Colonoscopy: 2 tubular adenomas o/w Normal

    • EGD :gastropathy without acute bleed (CLO -)

      • Scalloped mucosa in duodenum

      • Biopsy: mucosal inflammation, crypt hypoplasia, villous atrophy

  • Anti-endomysial Ab: (+) 1: 160

  • DEXA Osteoporosis T score: – 3.3 spine


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Celiac disease

  • Epidemiology

    • Occurs primarily in whites of northern European ancestry

    • Based on classic symptoms of malabsorption

      • Prevalence 1:4000- 1:8000

    • subclinical or oligosymptomatic celiac diseae

      • Prevalence 1:250- 1:500


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Celiac disease

  • Pathogenesis

    • Immune disorder that is triggered by an a environmental agent (gliadin component of gluten) in genetically predisposed individuals

    • IgA antibodies to gliadin

    • Ig A antibodies to endomysium

      • (target antigen: tissue transglutaminase)


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Celiac disease

  • Clinical Manifestations

    • Diarrhea with steatorrhea

    • Consequences of malabsorption

      • Weight loss

      • Anemia (iron deficiency and b12)

      • Neurologic disorders from b12 deficiency

      • Osteopenia from vit D and calcium deficiency


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Celiac disease

  • Associated Conditions

    • Liver disease

    • Diabetes Mellitus

    • Thyroid disease

    • Myocarditis and cardiomyopathy

    • GI malignancies & non-Hodgkin's lymphoma

    • Dermatitis herpetiformis


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Celiac disease

  • Treatment

    • Gluten free diet

    • Calcium and Vitamin D replacement

    • IV Iron

    • Bisphosphonate




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