Clinical Problem Solving 11309

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Clinical Problem Solving1/13/09

• Moderator Stuart Cohen MD
• Discussant Bill Curry MD

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Case 1

• 53 y/o white female presents to ED with several
  week h/o progressive mental status decline
• h/o well compensated cirrhosis due to past
  alcohol (none in 7 yrs), mild short term memory
  loss and diarrhea predominant IBS
• Now with
• difficulty finding words and unable to speak
• Agitation, weakness and lightheadedness

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Case 1

• Seen in ED 5 days PTA with c/o shortness of
  breath, dizziness, weakness and memory loss
• Workup including head CT, chest x-ray,
  urinalysis, electrolytes, Liver function tests,
  Ammonia level was unrevealing and pt discharged
  home
• Progressive decline leading to ED visit
• After checking in but prior to being seen, pt
  loses consciousness and has witnessed
  tonic-clinic activity (in waiting room)

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Case 1

• PMH
• Alcoholic Cirrhosis (well compensted)
• Esophageal varices (s/p banding)
• COPD
• IBS (diarrhea predominant)
• Short term memory loss (? Secondary to cirrhosis)
• Depression
• MEDS
• Nadolol, lasix, aldactone, protonix, zoloft,
  ambien
• Recently prescribed compazine for nausea

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Physical Exam

• T 101.5, HR 50, BP 70/palp, RR 26
• HEENT cyanotic lips, PERRL, No gag reflex,
  Dolls eye reflex absent
• CV bradycardic but regular, NO murmurs, rubs
• Lungs CTA, no wheezes, crackles
• ABD S/ND/pos BS/ No HSM
• Ext NO C/C/E
• Neuro Unconscious, responds to painful stimulus,
  increased tone, DTR 3 throughout with bilateral
  down going toes

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Data

• WBC 12 (31 segs/64 lymphs/3 monos) HCT 39, Plt
  172
• 134 108 7 92
• 3.5 21 1
• AST 27, ALT 11, Bili 1.0, Alk phos 82
• Ammonia 29, CK 101, LDH 165
• UDS negative, ETOH negative
• CSF RBC 3, WBC 3, glucose 59, protein 44, VDRL
  neg,
• CSF HSV ,West Nile, Crypto, bacterial cultures
  all negative
• CXR- No infiltrate, no pulmonary edema
• Blood, Urine cultures- Negative

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Data

• Head CT- No acute process
• MRI (stroke protocol)- No evidence of acute
  infarction, no vacular stenosis, scattered
  microangiopathic changes
• Abdominal U/S- cirrhotic appearing liver, no
  ascites, no masses
• Echo- LVH, normal LV/RF function, small
  pericardial effusion, mild TR, PR, trivial AI
• EEG- diffuse slowing. No seizure activity

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Neuroleptic Malignant Syndrome (NMS)

• Idiosyncratic, life threatening reaction to
  antipsychotic medications
• Characterized by
• Mental status changes
• Initial symptom in 82 of pts
• Often agitated delirium with confusion
• Catatonic signs and mutism can be prominent
• Muscular rigidity
• Fever
• Autonomic instability

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Neuroleptic Malignant Syndrome

• There is substantial variability in the
  presentation of NMS
• Atypical cases described forme fruste with
  minimal muscular rigidity, only low grade fever,
  and no significant CK elevation
• Pathogenesis
• Precise mechanism is unknown
• Dopamine receptor blockade thought to play
  pivotal role in triggering condition

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(No Transcript)
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Drugs that can cause Neuroleptic Malignant
Syndrome

• Neuroleptic agents
• Aripiprazole
• Chlorpromazine
• Clozapine
• Fluphenazine
• Haloperidol
• Olanzapine
• Paliperidone
• Perphenazine
• Quetiapine
• Risperidone
• Thioridazine
• Ziprasidone

• Antiemetic agents
• Domperidone
• Droperidol
• Metoclopromide
• Prochlorperazine
• Promethazine

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Treatment for NMS

• Stop causative agent
• Supportive care
• Common complications include
• Dehydration, electrolyte disturbances, ARF with
  rhabdo, cardiac arrhythmias, respiratory failure,
  DIC, seizures
• Specific treatments
• Dantrolene
• Direct skeletal muscle relaxant used to treat
  malignant hyperthermia
• Bromocriptine
• Dopamine agonist used to restore lost
  Dopaminergic tone
• Amantadine
• Dopaminergic and anticholinergic effects often
  used as alternative to Bromocriptine

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Prognosis in NMS

• Most episodes resolve within 2 weeks
• Most patients recover without neurological
  sequelae except in cases with severe hypoxemia or
  prolonged hyperthermia
• Cases persisting for 6 months with residual
  catatonia and motor signs reported
• Mortality rate of 10-20

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Case 2

• 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 2

• Sochx
• Current tobacco
• Past alcohol
• No IVDA or recreational drug use
• On disability
• Famhx
• Non-contributory
• Allergies NKDA

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Case 2

• Pmhx arthritis
• Meds Naprosyn, Flexeril
• Fhx Non- contributory
• Sochx no tobacco, occ alcohol, No IVDA

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Case 2 Physical Exam

• 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 2

• Data
• Hct 24, MCV 74, WBC 4.5 (nl diff), plts 154
• Chem 7 Normal
• Retic 2.1, LDH 168, ferritin lt1
• Fe 8, TIBC 318, B12 175
• AST 64, ALT 58, 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 2

• 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 14000- 18000
• subclinical or oligosymptomatic celiac diseae
• Prevalence 1250- 1500

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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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Case 3

• 81 y/o AA male presents to ED with chest pain x 5
  hrs
• Location is mid sternal with no radiation
• Denies SOB, diaphoresis, palpitations, nausea or
  vomiting
• No cough, fevers, abdominal pain or back pain
• No relief with ASA, nitroglycerin or morphine
• Also c/o bilateral thigh pain

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Case 3

• PMH
• HTN
• DJD
• COPD
• BPH (s/p TURP)
• h/o right shoulder osteonecrosis
• Sickle cell disease
• MEDS
• Amlodipine, Tylenol 3, Alb/Atrovent ,MVI

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Physical Exam

• 96.5, 80, 148/80, 20, 100 RA sats
• HEENT PERRL, OP clear, No lymphadenopathy, NO
  JVD
• CV RRR with no m/r/g, No S3, S4
• Lungs clear bilaterally
• ABD S/NT/ND/ BS, No Hepatosplenomegaly
• Back No CVA or spinal tenderness
• EXT No C/C/E- bilateral thighs painful to touch

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DATA

• EKG NSR, LVH, No ST/T-wave changes
• CXR mild cardiomegaly, no infiltrates, no edema
• CPK 59, CK-MB 4.1, Troponin lt 0.1
• Chem 7 Normal
• WBC 8.1, Hgb 10/HCT 30, PLT 125K
• MCV 78, RDW 17.5

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Peripheral Smear
Smear anisocytosis, microcytosis, polychromasia,
target cells, poikilocytosis, macrocytosis,
hyperchromasia, and sickle cells
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Data

• Hemoglobin electrophoresis
• Hgb S 63.3, Hgb A 24.9, Hgb F 11.8
• Diagnosis
• Sickle Beta Thalassemia with persistent fetal
  hemoglobinemia

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Variant Sickle Cell Syndromes

• Sickle Cell Trait (Hb AS)
• Benign carrier condition- No hematologic
  manifestations
• 8-10 prevalence in African Americans
• Complications
• Hematuria, increased risk VTE (2-4x)

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Electrophoretic patterns in common
hemoglobinopathies
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Hb SC Disease

• Hb SC Disease
• Mixture of HbS trait and HbC trait
• Paradoxically, the combination of HbS and HbC
  causes significant disease
• HbC increases a KCL co-transporter that induces
  loss of K and water thus dehydrating the cell
  leading to polymerization
• Phenotypic expression is a disease which is more
  severe than sickle cell trait but less severe
  than SCD
• Target cells predominate the peripheral smear
  with sickle cells relatively uncommon

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Electrophoretic patterns in common
hemoglobinopathies
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Hemaglobin SC Disease
Hemaglobin SC Disease
Normal Peripheral smear
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Sickle-Beta Thalassemia

• Beta Thalassemia
• impaired production of beta globin chains which
  leads to relative excess of alpha globin chains.
  These excess chains are unstable and precipitate
  within the cell
• Sickle-Beta Thalassemia
• Sickle cell-beta (0) thalassemia
• Sickle cell-beta () thalassemia

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Electrophoretic patterns in common
hemoglobinopathies
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Sickle-Beta Thalassemia

• The hematologic and clinical severity of the
  disease is inversely related to the quantity of
  HbA
• In African Americans, 80 of the beta thalassemia
  mutations result in the milder phenotype in which
  HbA accounts for 18-25 total hemoglobin
• Disease is usually less severe than Sickle Cell
  Disease and Hb SC disease

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Benefits of Fetal HB

• Physiologic switch from fetal HB to adult HB is
  usually complete by age 2
• As HbF levels increase, disease complications and
  mortality decrease
• Sickle-Hereditary Persistence of HbF
• a condition in which each red cell has high
  concentrations of HbS, no HbA, and 20 to 30
  percent HbF,
• usually not anemic and do not suffer from
  vaso-occlusive manifestations
• Hydroxyurea increases HbF levels by 5-15
• decreases the incidence of acute chest syndrome
  by half

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The End
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Cerebrovascular accidents in sickle cell disease
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Clinical Severity in Variant Sickle Syndromes
Sickle Cell Disease
HgB SC disease
Sickle beta(0) thal
Sickle beta() thal
Sickle Cell Trait
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Clinical Severity in Variant Sickle Syndromes
symptoms
Sickle Cell Disease
HgB SC disease
Sickle beta(0) thal
Sickle beta() thal
Sickle Cell Trait
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Hgb hemoglobin Thal thalassemia.Numbers
indicate the percent of total hemoglobin for an
untransfused adult patient. Ranges are
approximate and may vary depending upon the
particular laboratory and method of
determination. Percent Hgb S can be as low as
21 percent in patients with sickle cell trait in
conjunction with alpha thalassemia.
Electrophoretic patterns in common
hemoglobinopathies
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Sickle Beta Thalassemia with persistent fetal
hemoglobinemia
Sickle Cell Disease
Normal Peripheral smear
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Sickle Cell-beta () Thalassemia

• The hematologic and clinical severity of the
  disease is inversely related to the quantity of
  HbA
• 80 of African American beta thalassemia
  mutations result in milder phenotype in which HbA
  accounts for 18-25 total hemoglobin
• Disease is usually less severe than Sickle Cell
  Disease and Hb SC disease