Occam's razor need not
apply!
ID Case Conference
Wednesday March 28, 2007
David Fitzgerald, MD
HPI
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25 yo male immigrated from Guatemala 3 months ago now with
complaints of fever, rash, abdominal pain and diarrhea for the last 3
months since arriving in the US. These sxs have worsened over the
last 2 weeks prompting his presentation to the ER. Describes abd pain
as diffuse and crampy. Diarrhea is currently watery but had been
bloody initially.
Three months ago he walked across the desert border in Arizona and
spent 8 days in the desert short of water and food. After a few days he
began to have bloody BM's. No prior episodes of bloody BM's.
He saw a doctor recently and was given Aciphex for reflux and a
Medrol dose pack for the rash. He was also given an unknown
injection.
In ER pt had temp to 39.1, was tachycardiac and hypotensive. S/p 8 L
of fluid in ER and remained with tachycardia and borderline BP.
Increasing O2 requirement as well. Admitted to MICU.
► PMH
 Reports history of eye
surgery as a child
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SH
 Recent immigrant from
Guatamala as above.
Married, wife and 15 month
old son in Guatamala. Both
are well.
 Lives with his wife’s cousin
and several other friends
 Works at McDonalds
 Denies ETOH, tobacco or
illicit drugs
 Travel history across desert
southwest.
► FH
 NC
► Meds
 Acidphex
ROS
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Gen – fevers, chills, mild NS. 15 Lb wt loss over last 3 months
Neuro- No HA, neck stiffness, visual changes, focal weakness or
confusion. Friends with him confirm no change in mental status
HEENT – denies oral lesions, dysphagia/odynophagia, visual
disturbances
CV – no cp/palps
Pulm – mild cough, non productive. No SOB
GI- as above with diarrhea, abd pain. No vomiting, mild nausea.
Gu- no ulcers, discharge or dysuria
Skin – nonpruritic pink rash that started on his face, moved to his
trunk and stomach and then to his arms and legs.
Physical exam
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Temp : 39.1 Pulse:115 RR:20
BP 115/70, Sat: 95-98% 2 L
General: Pleasant interactive,
thin, Hispanic male, in mild
distress
HEENT – PERRLA, EOMI,
Anicteric, mild conj injection
bilaterally,
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 Confluent, non-tender, blanchable
macular erythema on the face
and upper trunk.
 Maculopapular, non-tender,
blanchable erythema,
proximal>distal extremities.
 MM dry. No oral lesions or thrush
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Neck – supple
Lymph – no cervical,
supraclavicular, axillary or
inguinal LAN noted
CV -Tachy, regular, no mrg
Lung – bronchial BS at bases
bilaterally. Mild crackles above
Abd – soft, mild ttp in R UQ and
RLQ, + BS, nondistended. No
RB/Guarding.
GU- no lesions or discharge
Ext – no c/c/e
Skin
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Neuro: A+O x 3, non focal
strength and sensation grossly,
CN2-12 intact
Data
WBC 14.0
 ANC 12.2
 ALC 0.4
► HGB 10.2 (decreased to 8.0 then to
7.3 over 12 hours)
 MCV 78
 RDW 16
 Retic count - 0.5% (low)
 Spherocytes noted
 Howell Jolly bodies noted
► PLT 395
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PT 19.4 INR 1.6 PTT 44
D dimer – 56,000
LDH – 20,000
Fibrinogen 303
AT III 82% low
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Direct Coombs
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Anti IgG - positive
Anti-complement negative
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Na 132
K 4.7
Cl 98
HCO3 20
BUN/Cr 18/1.1
Ca 6.0
Mg 1.9
PO4 4.4
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LFTS
Tbili 0.6
AST 580
ALT 106
Alk Phos 622
GGT 339
DATA
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CRP 17.6
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UA LE and Nit Neg, 2+ protein,
WBC 6, RBC 7
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Tox screen – negative
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CK 95
► CSF
 TNC 2
► 38%
PMNS
► 25% Lymphs
 RBC <1
 Protein 32
 Glucose 59
Radiology
► CT
chest and abdomen
 1. Patchy nodular
parenchymal
opacifications are
concerning for
infectious pneumonitis.
 2. Inflammatory change
of the ascending colon
with adjacent free fluid
suggests infectious
colitis.
► RUQ
US – negative for
cholecystitis. Nml liver,
spleen and kidneys
Peripheral smear
Diagnoses
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Fungal – Histo
 Peripheral blood smear –
intracellular and extracellular
yeast noted
 CSF cell count – intracellular
yeast noted
 Urine histo ag +
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Bacteremia
 Blood cx –
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► 2.
Strep Pneumonia
E coli
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Viral – HIV, EBV, CMV
 HIV Elisa +
 EBV VL - 32,308
 CMV VL – 3876
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Parasitic
 Fecal cx – 4+ PMNs
 Fecal O+P –Entamoeba
histolytica
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Negative studies
 Hepatitis serologies negative
 Bronch – PCP DFA negative
 CSF –
► HSV PCR neg
► Crypto ag neg
Final diagnosis
► Disseminated
histoplasmosis with meningitis
► HIV (CD4<10)
► CMV viremia (? Colitis)
► EBV viremia (? Underlying lymphoma)
► Entamoeba histolytica
► Strep Pna and E coli bacteremia
► Hemolytic anemia
Warm antibody autoimmune
hemolytic anemia (AIHA)
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Autoimmune hemolytic
anemia (AIHA) due to the
presence of warm
agglutinins is due to IgG
antibodies that react with
protein antigens on the
red blood cell (RBC)
surface at body
temperature.
For this reason, they are
called "warm agglutinins"
even though they seldom
directly agglutinate the
RBCs.
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Various etiologies –
 Drugs (penicillin, methyldopa, huge list)
Infectious agents – usually
viral
► Neoplasms (NHL and CLL)
► autoimmune disease (esp
SLE)
► Idiopathic (majority)
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AIHA – extravascular hemolysis
► Results
in extravascular hemolysis in spleen
as deformed RBC (spherocytes) are unable
to fit through the slits in the walls of the
blind channels in the cords of Billroth
Diagnosis
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Hemoglobin usually in the range
of 7 to 10 g/dL
Positive Direct Coombs test –
detects the presence of IgG or
complement bound to
erythrocyte mebranes
Retic count usually elevated
above 4 to 5 percent
LDH elevated
Indirect Bilirubin elevated
Haptoglobin decreased
Peripheral blood smear usually
shows the presence of
spherocytosis
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The combination of an increased
serum LDH and reduced
haptoglobin is 90 percent
specific for diagnosing
hemolysis, while the
combination of a normal serum
LDH and a serum haptoglobin
greater than 25 mg/dL is 92
percent sensitive for ruling out
hemolysis
Diff dx is that of hemolytic
anemia due to drugs and AIHA
due to the presence of cold
agglutinins (IgM)
Complications
► Lymphoproliferative
disorder
 In one series of 108
patients (not HIV) 18%
developed a
lymphoproliferative
disorder after a median
time of 2 years
► Venous
thromboembolism
 Reported in both NonHIV and HIV patients
AIHA in HIV/AIDS
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Direct Coombs test is positive in 20-40% of AIDS patients
but overt hemolysis is rare
Not well studied area due to small numbers of cases
reported
Pathophysiology of AIHA in AIDS may be related to
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Hypergammaglobulinemia related to B-Cell dysregulation
Direct activation of B cells by HIV
Coinfection with EBV or CMV
Other infectious agents associated with AIDS may also be
associated with production of auto-antibodies
► MAI,
CMV, EBV, PCP, M TB, Histoplasma capsulatium
 AIDS related malignancies
Reticulocytopenia
► Reticulocytopenia
in AIHA is more common in HIV
patients than in the general population
► May lead to underdiagnosis of AIHA in HIV
patients
► Theories
 May be due to antibodies that preferentially destroy
reticulocyte precursors
 May be related to abnormal microenvironment in bone
marrow caused by other infections (MAI, Histo, CMV),
lymphoma or drugs (ZDV)
Treatment
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No great data on the efficacy of various modalities
Patients with + Coombs, stable HGB and only mild
hemolysis can be monitored
Transfusions – may be difficult to cross match
Corticosteroids – mainstay of treatment.
 Prednisone 1 mg/kg daily
 Quickly slows or stops hemolysis in up to 2/3 of patients and
results in increase in HGB within one week
 Once stabilized can start taper
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IVIG – best used with steroids.
 Used in severe cases when a rapid response is desired
 1 g/kg per day for 2 days
 May decrease infectious complications of steroids
Treatment
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Splenectomy
 75% success rate in HIV patients with AIHA
 Removes the major site of RBC destruction
 Recommended in patients who do not respond to steroids or cannot be
tapered off them
 Can increase the number of circulating CD4 cells, but not alter the ratio
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Immunosuppressives
 Not universally accepted, even in those who fail to respond to above
treatments
 Can lead to worsening of anemia by BM suppression
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Plasmapheresis
 Controversial
 Due to the large extravascular distribution of IgG and continued AB
production
Search PubMed
► Autoimmune
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Hemolytic Anemia (AHIA)
Case Reports
Reviews
Differential Diagnosis
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