PGY4 Gastroenterology Fellow Mentor Maya BalakrishnanMD Case presentation 54 yo H ispanic female was brought in by her family after recurrent falls She felt p rogressively ID: 776899
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Slide1
Grand Rounds
4/16/15
Ashish Sharma
PGY-4 Gastroenterology Fellow
Mentor- Maya Balakrishnan,MD
Slide2Case presentation
54 y/o
H
ispanic
female
was brought in
by
her family
after
recurrent falls.
She felt
p
rogressively
feeling
weak
for at least 2
months.
She had persistent
nausea/vomiting
, post prandial fullness,
inability to tolerate
PO and a
30
lb. wt.
loss over 2 months.
Slide3Case presentation
She reported tingling
sensation of fingers and
tows, “felt
funny on the bottom of
foot”, “not
able to feel
pressure”, and “walked like a robot”.
She denied any hematochezia, hematemesis or melena.
Slide4Case presentation
PMH/PSH - None
Family history – thyroid disorder and lupus in her daughters
Social history – works as a cleaner, denied ETOH/smoking/illicit drugs
Medications - None
Slide5Case presentation - Exam
Vitals – Afebrile, P – 65,
BP- 86/47
, RR- 15, Pulse Ox – 99% on RA, BMI -22
Exam –
GEN
:
NAD
HEENT
:
mild icterus
,
OP
clear
CV
: RRR,
soft systolic murmur
CHEST
:
CTAB
ABD
: + BS, soft, mild periumbilical tenderness with no
guarding
or
rebound,
n
on distended
EXT
: No edema
NEURO
:
Rhomberg positive
, otherwise non focal and intact
Slide6Case presentation - Labs
CBC - WBC 3; Hb 5.6; PLT 96; MCV 115
CMP – Chemo 8 normal,
TB 4,
DB 0.8
, other LFTs normal
Coagulation profile – normal; TSH - normal
B12 – 187
, Folate – 15, Ferritin – 434, Iron Sat – 37%
Reticulocyte count – 1% (low)
LDH – 3670 (high), Haptoglobin < 32
Coomb’s test - negative
Homocysteine – 13.2 (ULN 10.7)
Methylmalonic acid (MMA) – 35437( ULN 378)
Intrinsic factor ab -
N
eg
Parietal cell ab - 48.7 (ULN 24.9)
Slide7Case presentation – Peripheral smear
Macrocytosis
, + tear drops, Dysmorphic
RBC,
+ hypersegmented neutrophil, early granulocyte progenitors, + platelet (normal morphology)
Slide8Case presentation - EGD
Normal stomach body
Atrophic stomach body
Slide9Case Presentation - Pathology
Atrophic stomach body
Normal stomach body
No H. pylori seen on immunohistochemical stains
Slide10Case Presentation - Pathology
Synaptophysin
staining
Intestinal Metaplasia
Slide11Diagnosis
Pernicious Anemia
-
Pernicious anemia (PA) is a macrocytic anemia that
is caused
by vitamin B12 deficiency, as a result of
intrinsic factor deficiency (which is caused by an autoimmune corpus restricted atrophic gastritis)
Slide12Clinical Questions
Background- Epidemiology, clinical presentation and diagnosis of PA
Is there a relationship between H pylori and PA?
Gastric cancer in PA - Incidence & role of surveillance
Slide13Epidemiology
PA is an uncommon disease
Primarily
a disease of the Caucasians, however there are recent reports of occurrence in
Blacks, Latin Americans and Asians
Incidence
- 9 cases/100k per year;
and about 0.13
% of population is
affected in high risk groups
Up to 1.9
% of persons > 60
years may have undiagnosed PAF: M- 2:1 per older data, but newer data shows no difference in gender distribution
Pedersen
AB. Morbidity
of pernicious anaemia.
Incidence, prevalence, and treatment in a Danish county.
Acta Med Scand 1969Carmel R. Prevalence of undiagnosed pernicious anemia in
the elderly. Arch Intern Med 1996
Slide14Clinical presentation
Mean age of
presentation
is 59-62
years
General symptoms - weakness, asthenia, decreased mental concentration, headache and with chest pain/palpitations in elderly.
Edith
Lahner
. Pernicious
anemia: New insights from a gastroenterological
point of
view.
World J
Gastroenterol
2009
Slide15Clinical presentation
GI symptoms – dyspepsia (
up to
28% patients)
Neurological symptoms - paresthesia, unsteady gait, clumsiness, and in some cases, spasticity (
up to
19% patients)
Association with other autoimmune disorders
Edith
Lahner
. Pernicious
anemia: New insights from a gastroenterological
point of view. World J Gastroenterol
2009
Slide16Diagnostic algorithm
Edith
Lahner
. Pernicious
anemia: New insights from a gastroenterological
point of
view.
World J
Gastroenterol
2009
Slide17Clinical Questions
Background- Epidemiology, clinical presentation and
diagnosis of PA
Is there a relationship between H pylori and PA?
Gastric cancer in PA - Incidence & role of surveillance
Slide18PA and H pylori
PA
was primarily understood as an autoimmune condition occurring in a genetically predisposed individual – clustering with other autoimmune conditions, presence of auto-antibodies, HLA- DR restriction
In
recent years, H
pylori (infectious etiology)
is thought to be implicated in the pathogenesis of
PA
Mechanism ? -Molecular mimicry between H+/K+-ATPase and H pylori antigens likely
resulting
in loss of immunological tolerance in a genetically predisposed individual
Amedei
A. Molecular
mimicry between Helicobacter pylori antigens
and H+, K+ --adenosine
triphosphatase
in human gastric
autoimmunity. J Exp Med
2003
Slide19PA and H pylori
Reasons for this association –
- H pylori serology positive in upto 50% of PA patients
- H pylori found in upto 30% of stomach biopsies of PA patients
- PA (initially defined as corpus restricted atrophic gastritis), also involves antrum in upto 50% cases, with atrophic antrum gastritis seen in upto 30% cases
- Serology positive for H pylori antigens - Cag A and
Vac
A in upto 50% patients
Annibale
B.
CagA
and
VacA
are
immunoblot
markers of past Helicobacter
pylori
infection
in atrophic
body gastritis.
Helicobacter
2007
Fong
TL
.
Helicobacter pylori
infection in pernicious anemia: a prospective controlled
study.
Gastroenterology
1991
Slide20PA and H pylori
Edith
Lahner
. Pernicious
anemia: New insights from a gastroenterological
point of
view.
World J
Gastroenterol
2009
Slide21PA and H pylori
Therefore, pathogenesis of PA may be a autoimmune and/or infectious (H pylori related)
Slide22PA and H pylori
Importance of H pylori association with PA?
- May be a prognostic factor in gastric neoplasia in PA
Study by Rugge et al. 4/562 PA confirmed patients had gastric neoplastic epithelial lesions (all were OLGA stage III or IV, and all had H pylori association).
116/562 PA patients (9/10 PA patients treated for H pylori) studied prospectively with EGD/biopsy over a mean of 54 months developed NO gastric epithelial neoplasia.
Rugge et al. Autoimmune
gastritis: histology
phenotype
and
OLGA
staging.
Aliment
Pharmacol
Ther
2012
Slide23Clinical Questions
Background- Epidemiology, clinical presentation
and
diagnosis of PA
Is there a relationship between H pylori and PA?
Gastric cancer in PA - Incidence & role of surveillance
Slide24Gastric cancer and PA
There is a 7 fold increase in RR of gastric cancer in PA patients
Vannella et al. Systematic
review: gastric cancer incidence in pernicious
Anaemia.
Aliment
Pharmacol
Ther
2013;
Slide25Gastric cancer and PA - ASGE guidelines 2006
ASGE states that risk for gastric cancer in PA patients in US population is low (about 1.2%, close to average population risk)
Recommends at least one EGD after diagnosis of PA (risk is highest within 1
st
yr
of diagnosis)
Guidelines for gastric cancer surveillance in intestinal metaplasia/dysplasia should probably be applicable to PA patients as well
ASGE guideline: the role of endoscopy in the
surveillance of
premalignant
conditions
of the upper GI
tract GASTROINTESTINAL
ENDOSCOPY Volume
63
Slide26Gastric cancer and PA
Given that there are no guidelines for surveillance, an individualized approach needs to be adopted.
In patients with
gastric symptoms, pre-neoplastic lesions (on index EGD), age >50
yr
at diagnosis, family h/o gastric cancer, high risk ethnicity (Asian/
H
ispanic) and H pylori associated PA
may be considered for gastric cancer surveillance
Slide27Back to our patient
Patient had remarkable improvement in her fatigue and asthenia with Vitamin B12 injections.
Hb
and B12 levels improved. LDH and MMA decreased, and reticulocyte index increased
Neurological symptoms did not reverse
Repeat EGD done with mapping biopsies in 3 months, showed
e
xtensive intestinal metaplasia. Will repeat EGD in 4 years with mapping biopsies for reasons mentioned before
Will monitor for iron deficiency
Will obtain H pylori IgG for prognostication
Slide28Take home points
PA is an uncommon cause of anemia resulting from autoimmune atrophic body gastritis; presents in 5
th
or 6
th
decade of
life,
mostly commonly with general anemia symptoms
H pylori plays role in pathogenesis of PA via mechanism of molecular mimicry. This relationship may have prognostic significance for gastric neoplasia in PA
From the data shown, there is increased risk of gastric cancer in PA patients compared to average population. However there are no guidelines yet to support surveillance.
Slide29Take home points
Per ASGE at least one EGD is warranted after diagnosis of PA (preferably within 1
yr
), to screen for neoplastic or pre-neoplastic lesions. Thereafter, surveillance should be individualized.
Slide30Thankyou!