Anemia NOT ALWAYS RELATED TO IRON DEFICIENCY, BLOOD LOSS, AND - - PowerPoint PPT Presentation

▶
anemia
SMART_READER_LITE
LIVE PREVIEW

Anemia NOT ALWAYS RELATED TO IRON DEFICIENCY, BLOOD LOSS, AND - - PowerPoint PPT Presentation

Mar 14, 2024 717 likes •1.38k views

Anemia NOT ALWAYS RELATED TO IRON DEFICIENCY, BLOOD LOSS, AND CHRONIC DISEASE Noon Conference James Phillips 8/6/19 1 Outline 1. Review Case 2. Discuss Disease Pathogenesis 3. Discuss Differential Diagnosis 4. Discuss Diagnostic Criteria

slide-1
SLIDE 1

Anemia

NOT ALWAYS RELATED TO IRON DEFICIENCY, BLOOD LOSS, AND CHRONIC DISEASE Noon Conference James Phillips 8/6/19

1

slide-2
SLIDE 2
  • 1. Review Case
  • 2. Discuss Disease Pathogenesis
  • 3. Discuss Differential Diagnosis
  • 4. Discuss Diagnostic Criteria
  • 5. Discuss Treatment
  • 6. Patient Update

Outline

2

slide-3
SLIDE 3

History of Present Illness

Presented from outside ED for 1-week history of shortness of breath which abruptly started, without inciting events. Started with one episode of chest pain that lasted for few minutes, however the dyspnea persisted without changing in severity. Patient endorses dyspnea on exertion but unable to specify the limit of exertion when she feels out of breath. Patient has orthopnea and sleeps on two

  • pillows. She denies PND. No Palpitations or lightheadedness/syncope.

Denies recent flu-like symptoms. Patient denies any significant cardiac history, has risk factors of hypertension, mixed hyperlipidemia, and previous tobacco abuse. She denies rheumatologic diseases but has multiple joints with "osteoarthritis". Patient lives with husband and has two sons.

3

slide-4
SLIDE 4

Medical History

  • HTN, HLP​
  • GERD with esophagitis​
  • Primary osteoarthritis involving

multiple joints, lumbosacral spondylosis​

  • Vitamin D deficiency​
  • Neuropathy​
  • Fibromyalgia, insomnia, depression

4

slide-5
SLIDE 5

Medications:

  • Vitamin D3 5000 units QD​
  • Biotin 5mg QD​
  • Fenofibrate 150mg QD​
  • Temazepam 30mg HS​
  • Lidocaine patch 5%​
  • Tizanidine 4mg Q6H
  • Pregabalin 75mg BID​
  • Meloxicam 15mg QD

5

  • Esomeprazole 10mg QD​
  • Calcium vitamin D​
  • Oxycodone/APAP 5-325mg Q8H​
  • Desonide cream​
  • Simvastatin 40mg HS​
  • Amlodipine 5mg QD​
  • Atenolol 100mg QD​
  • Alpha-methyldopa 500mg TID
slide-6
SLIDE 6

Past Surgical History

  • No pertinent history

6

slide-7
SLIDE 7

Family History

  • No pertinent history

7

slide-8
SLIDE 8

Social history

  • Smoking – Less than 20 pack year history, quit in the 1970s.
  • Alcohol – never drinker
  • Illicits – denies use
  • Living situation – lives with husband in safe environment
  • Occupation – retired, non-contributory

8

slide-9
SLIDE 9

Review of Systems

9

slide-10
SLIDE 10

Review of Systems

  • 10 point review of systems negative except for:

Positive shortness of breath, arthralgias, back pain

10

slide-11
SLIDE 11

Physical Exam

11

slide-12
SLIDE 12

Physical exam

  • Vitals: Temp 98.6 F, HR 76, RR 20, SpO2 98%, BP 113/52
  • HEENT: Negative
  • Neck: Negative
  • CV: Negative
  • Thorax: Decreased breath sounds
  • Abdomen: Negative
  • Extremities: Negative
  • Neuro: Negative
  • Integument Negative

12

slide-13
SLIDE 13

Labs, Imaging, and Biopsies

13

slide-14
SLIDE 14

Labs

133 4.7 94 24 0.64 107 24 10.2 5.4 234 MCV: 88.3 RDW: 13.3

  • Troponin – 0.04​
  • Hb – 10.2, 8.8

(normal last time assessed as outpatient)

  • Haptoglobin – 246.4​
  • LDH - 164​
  • Retic count – 0.9
  • ​INR – 1.1
  • CRP – 222
  • ESR – 29
  • ANA – 1:160
  • Rheumatoid factor – 12

14

slide-15
SLIDE 15

Imaging CT images from outside ED not available – report did note large pericardial effusion Formal echo:

  • 1. Left ventricle: Systolic function is normal by the biplane method of disks. The estimated ejection

fraction is 59%.

  • 2. Right ventricle: Systolic function is normal.
  • 3. Pericardium, extra cardiac: A medium pericardial effusion is identified circumferential to the heart.

There is no significant mitral inflow respiratory variation. Tricuspid inflow Doppler is of poor quality. No systolic chamber collapse of the RA or diastolic collapse of RV. However, the IVC is dilated. Overall, there is not clear echocardiographic evidence for pericardial tamponade. Tamponade is a clinical diagnosis.

  • 4. Inferior vena cava: The vessel is dilated. The IVC collapses by less than 50% with inspiration.
  • 5. No significant valve disease.

15

slide-16
SLIDE 16

Imaging

16

slide-17
SLIDE 17

Disease case is based on

17

slide-18
SLIDE 18

Disease

  • The patient did in fact have a large pericardial effusion and was treated appropriately.
  • Incidentally, we noticed the patient had new onset normocytic anemia. On further

questioning, her PCP was also curious as to why she was suddenly anemic.​

  • What can we do to further clarify the cause of the patient's anemia?

18

slide-19
SLIDE 19

Differential

  • Anemia
  • Blood loss
  • Iron deficiency
  • Chronic Disease
  • Aplastic
  • Hemolytic anemia
  • Autoimmune
  • Drug induced
  • Intrinsic RBC defect
  • Laboratory error
  • Dilution effect

19

slide-20
SLIDE 20

Next steps

  • Suspicious of an underlying rheumatologic condition, we checked a direct combs ab

test – which was IgG positive

  • As we reviewed her medication list again, we noticed an agent that would turn out to

be a possible offender – alpha-methyl dopa.​

  • The drug was discontinued and the patient's anemia resolved.

20

slide-21
SLIDE 21

Pathogenesis

  • Anemia due to shortened survival time of RBCs due to premature destruction.
  • May be intrinsic or extrinsic​
  • Intrinsic abnormal property of RBC -> hereditary spherocytosis, G6PD deficiency​
  • Extrinsic, acquired defect in RBC -> drug induced hemolytic anemia
  • May be immune (auto-antibody destruction) vs non-immune (microangiopathic

hemolytic anemia)​

  • Further classified according to the temperature at which cell is destroyed -> warm vs

cold

  • May be intravascular (blood vessels) vs extravascular (live or spleen)

21

slide-22
SLIDE 22

Causes of hemolytic anemia

  • Hereditary spherocytosis​
  • G6PD deficiency​
  • Thalassemia​
  • Sickle Cell Disease​
  • Paroxysmal Nocturnal Hemoglobinuria​
  • Mycoplasma infection​
  • Autoimmune hemolytic anemia associated with SLE, RA, Hodgkin lymphoma, CML,
  • thers​
  • Hypersplenism
  • Lead poisoning​
  • Foot strike hemolysis
  • Microangiopathic hemolytic anemia

22

slide-23
SLIDE 23

General Mechanism of Hemolytic Anemia​

  • 1. Abnormal destruction of erythrocytes
  • 2. Increased breakdown of hemoglobin​
  • 1. Increased bilirubin, BUN​
  • 2. Increased fecal and urinary urobilinogen
  • 3. Bone marrow compensation
  • 1. Erythroid hyperplasia -> increased reticulocyte count, slight macrocytosis
  • 4. The balance between destruction and production determines severity of anemia

23

slide-24
SLIDE 24

Autoimmune hemolytic anemia​

  • High suspicion for autoimmunity given polyarthropathy, elevated ESR/CRP
  • Ab binds to erythrocyte causing complement mediated destruction​
  • Warm (usually IgG)
  • Conditions include autoimmunity, lymphoproliferative (CML), drug induced​
  • Cold (usually IgM)​
  • Conditions include infectious, lymphoproliferative,

24

slide-25
SLIDE 25

Warm Autoimmune Hemolytic Anemia​

  • Optimal ab binding temperature 37 degree C (hence, warm)
  • IgG positive, C3 +/-
  • Peripheral smear may show spherocytes
  • Clinical manifestations – anemia, fatigue, dyspnea, jaundice, splenomegaly
  • Associated conditions – autoimmunity, lymphoproliferative disorders, drug-induced
  • Treatment – steroids, splenectomy, immunosuppression, treatment of underlying

condition

25

slide-26
SLIDE 26

Drugs associated with Warm Autoimmune Hemolytic Anemia​

  • Cephalosporins and penicillins (cefotetan, ceftriaxone, piperacillin)
  • NSAIDs
  • Many chemotherapeutic agents
  • Dapsone
  • Levofloxacin
  • Nitrofurantoin
  • Phenazopyridine
  • Quinidine
  • Alpha-methyl dopa

26

slide-27
SLIDE 27

Cold Agglutinin Disease​

  • Optimal ab binding temperature < 37 degree C (hence, cold)
  • IgM positive, C3 positive
  • Peripheral smear erythrocyte agglutination
  • Clinical manifestations – anemia, fatigue, dyspnea, jaundice,

acrocyanosis, splenomegaly

  • Associated conditions – Infectious, lymphoproliferative
  • Treatment – Cold avoidance, rituximab, plasmapheresis, treatment of underlying

condition

27

slide-28
SLIDE 28

Acknowledgements

  • Thank you to July CCU team

28

slide-29
SLIDE 29

References

  • MKSAP 18
  • Uptodate

29

slide-30
SLIDE 30

Questions?

30

slide-31
SLIDE 31

Thank you

31

slide-32
SLIDE 32

IgA Bullous Dermatosis Masquerading as SJS

PGY II Scholarly Activity Jonathan Burgei 08/06/19

32

slide-33
SLIDE 33
  • 1. Review Case
  • 2. Discuss Disease Pathogenesis
  • 3. Discuss Differential Diagnosis
  • 4. Discuss Diagnostic Criteria
  • 5. Discuss Treatment
  • 6. Patient Update

Outline

33

slide-34
SLIDE 34

History of Present Illness

34

slide-35
SLIDE 35

History of Present Illness

  • Recently admitted for 7 days for confusion/fevers/lethargy
  • Day 1
  • Erythema around dialysis port (R anterior chest wall)
  • Vanc + Zosyn
  • Day 3
  • Right tunneled HD cath removed
  • BC positive for MRSA + Enterococcus faecalis
  • Unasyn + Vancomycin
  • Day 4
  • Repeat BC
  • Day 7
  • Repeated BC negative
  • Placed new tunneled cath
  • Family refused SNF
  • Abx changed to daptomycin q 48 hrs x 2 weeks

35

slide-36
SLIDE 36

Continued

  • Returned to ER the next day
  • CC:
  • Burning in her eyes
  • blisters in mouth  arm, axilla, legs

36

slide-37
SLIDE 37

Medical History

37

slide-38
SLIDE 38

Past Medical History

  • Hypertension
  • Obesity
  • Diastolic Heart Failure
  • ESRD on HD (MWF)
  • DM
  • COPD
  • Atrial fibrillation
  • GERD
  • Hyperthyroidism
  • Dementia

38

slide-39
SLIDE 39

Past Surgical History

  • Tonsillectomy (Childhood)
  • Cholecystectomy (2017)
  • Total Abdominal Hysterectomy

39

slide-40
SLIDE 40

Family History

  • Mother
  • Heart Failure
  • HTN
  • DM
  • Stroke
  • Father
  • Heart Failure
  • HTN
  • DM

40

slide-41
SLIDE 41

Social history

  • Former Smoker, Quit 1988 (5 pack years)
  • Denied Alcohol
  • Denied Illicit drugs
  • Lives at home with daughter

41

slide-42
SLIDE 42

Review of Systems

42

slide-43
SLIDE 43

Review of Systems

  • Constitutional: Positive for fatigue and chills. Negative for fever.
  • HENT: Positive for lip swelling. Negative for congestion, postnasal drip, sinus pain, sinus pressure and sore throat.
  • Eyes: Positive for burning. Negative for photophobia and visual disturbance.
  • Respiratory: Negative for cough, shortness of breath and wheezing.
  • Cardiovascular: Negative for chest pain, palpitations and leg swelling.
  • Gastrointestinal: Negative for abdominal pain, blood in stool, constipation, diarrhea, nausea and vomiting.
  • Musculoskeletal: Negative for arthralgias, back pain and myalgias.
  • Skin: Positive for blisters on mouth, arms, legs, axilla, inguinal folds
  • Neurological: Negative for dizziness, syncope, weakness, light-headedness and headaches.
  • Psychiatric/Behavioral: Negative for confusion and dysphoric mood. The patient is not nervous/anxious.

43

slide-44
SLIDE 44

Physical Exam

44

slide-45
SLIDE 45

Physical exam

  • Vitals: Temp 98.3 F, HR 84, RR 20, SpO2 98% RA, BP 155/74
  • HEENT: Normocephalic, mild facial fullness, lip swelling, mucosal ulcers present.
  • Neck: Normal range of motion, neck supple, no thyromegaly
  • Eyes: PERRL, EOM normal, no discharge noted
  • CV: RRR, no murmurs or rubs
  • Pulmonary: CTAB, normal effort and breath sounds. No respiratory distress
  • Abdomen: Soft, BS x 4, non-tender, no guarding.
  • Extremities: blisters noted to arms and legs
  • Neuro: A&O x 3, no cranial nerve deficit, normal muscle tone
  • Integument: Bullous rash noted to back, arms, legs, inguinal folds, axilla

45

slide-46
SLIDE 46
slide-47
SLIDE 47
slide-48
SLIDE 48
slide-49
SLIDE 49

Labs

137 3.4 105 10 1.86 79 28 9.5 29.4 6.3 321 MCV: 92.4 RDW: 15.9

49

Lactic Acid: 0.6

slide-50
SLIDE 50

Hospital Course

  • Day 1
  • SJS vs Allergic reaction: Benadryl (25mg), Epinephrine (0.3mg), Solumedrol (125 mg), Morphine (4mg)
  • Consults: ICU, nephrology, Gyn, Plastics, Wound care, ID, ophthalmology
  • Stop all Abx
  • NPO: concern for airway protection issues
  • Supportive care
  • SJS likely from Daptomycin
  • Day 2
  • Ophthalmology: Aggressive lubrication
  • Plastics: Lesions suggestive of SJS. Monitor for progression of lesions, otherwise treatment will be symptomatic
  • SLP: Recommended puree solid / nectar thick liquids
  • ID: SJS likely from daptomycin, drug holiday

50

slide-51
SLIDE 51

Hospital Course

  • Day 3
  • Vancomycin Restarted today
  • Blisters worsened throughout the day
  • Day 4/5
  • Skin very painful
  • Blisters continue to worsen
  • Day 6/7/8
  • Skin starts sloughing off
  • Severe burst blisters throughout body
  • Transferred to GMF

51

slide-52
SLIDE 52

52

slide-53
SLIDE 53

Hospital Course

  • Day 9
  • Blisters continue to worsen
  • 70% of blisters now open
  • Requiring transfer to burn unit
  • Requires biopsy for direct immunofluorescence

53

slide-54
SLIDE 54

Biopsy Result

  • Subepidermal vesicles and areas of complete skin sloughing and ulcerations
  • Epidermis appears viable without evidence of significant necrosis
  • Direct antibody localization demonstrates linear immunoreactivity for IgA at the basement membrane suggestive of

linear IgA dermatosis

54

slide-55
SLIDE 55

Vancomycin-Induced Linear IgA Bullous Dermatosis

55

slide-56
SLIDE 56

Vancomycin-Induced Linear IgA Bullous Dermatosis

  • First described in 1981
  • LABD incidence 0.5 per 1 million
  • Drug induced less common
  • Presentation
  • Drugs: Vancomycin, amiodaron, diclofenac, captopril, ceftriaxone, naproxen, piroxicam, phenytoin
  • Duration of drug administration: 1-29 days
  • Not dose dependent
  • Tense blisters on extensor surfaces, trunk, buttocks, face

56

slide-57
SLIDE 57

Differential

Diagnostic Criteria LAD Bullous Pemphigoid Pemphigus vulgaris SJS / TEN Clinical Tense bullae or

  • vesicles. Mucosal

lesions typically present Tense blisters, erosions, or crusts. Mucosal lesions typically spared. Flaccid blisters SJS < 10%, TEN >30%. Occur 1-3 weeks after exposure. Pain is prominent. Vesicles, bullae, and Nikolsky positive. Histological Subepithelial bulla with predominant neutrophils along the basement membrane Subepithelial bulla with predominant eosinophil predominance Intraepithelial cleavage with acantholysis. Necrosis and detachment of the epidermis. Immunofluorescence IgA deposition at the basement

  • membrane. Some

may show both IgA, IgG, and C3. IgG and C3 in a linear deposition at the basement membrane Intercellular deposition of IgG. Direct immunofluorescence is always negative

57

slide-58
SLIDE 58

Pathogenesis

  • IgA production against the basement membrane  Complement activation  recruitment of inflammatory cells 

Proteolytic enzyme release  basement membrane destruction and blister formation

  • Drug-specific T cells release cytokines  stimulate IgA autoantibodies
  • Drugs cross-react with auto-antigens of the basement membrane by changing their conformational structure

58

slide-59
SLIDE 59

Diagnostic Criteria

  • Clinical
  • Tense vesicles or bullae
  • Histopathologic
  • Subepithelial blister
  • Predominant neutrophilic infiltrate in the upper epidermis
  • Immunologic
  • Verify IgA autoantibodies with Direct Immunofluorescence (DIF)
  • IgA deposits along the basement membrane in a linear pattern

59

slide-60
SLIDE 60

Disease monitoring

  • Ocular LAD: chronic conjunctivitis  fibrosis/scarring  blindness
  • Airway obstruction
  • Esophageal strictures
  • Cutaneous and visceral infectious complications and septic shock

60

slide-61
SLIDE 61

Treatment

  • Stop the offending drug
  • Moisturizing ointment and topical betamethasone
  • Standard therapy
  • Dapsone (<0.5 mg/kg)
  • G6PD deficiency
  • Alternative
  • Sulfapyridine (15-60 mg/kg)
  • Dapsone and Sulfonamides may be combined
  • Corticosteroids may help
  • Median time to healing  20 days

61

slide-62
SLIDE 62

Update on patient

  • Day 11
  • Vancomycin stopped
  • Approximately 90% of blisters now open
  • MetroHealth accepts patient and is transferred
  • MetroHealth
  • Consulted: ID, Derm, Burn Unit, Nephro
  • Initially started on PO prednisone 40 mg and then on dapsone (once G6PD level returned)
  • ID started ampicillin and ceftaroline
  • Burn surgery: Aquafor

62

slide-63
SLIDE 63

References

  • Chanal, J., et al “Linear IgA Bullous Dermatosis: Comparison between the Drug-Induced and Spontaneous Forms.”

British Journal of Dermatology , 24 June 2013.

  • Fortuna, Giulio, and M. Peter Marinkovich. “Linear Immunoglobulin A Bullous Dermatosis.” Clinics in Dermatology,
  • vol. 30, no. 1, 2012, pp. 38–50., doi:10.1016/j.clindermatol.2011.03.008.
  • Guide, Shireen V., and M.peter Marinkovich. “Linear IgA Bullous Dermatosis.” Clinics in Dermatology, vol. 19, no. 6,

2001, pp. 719–727., doi:10.1016/s0738-081x(00)00185-1.

  • Up-to-date, Linear IgA bullous dermatosis.

63

slide-64
SLIDE 64

Questions?

64

slide-65
SLIDE 65

Thank you

65