Transcript MR-AC9

A case of pain…
And pain…
And pain…
Alan Chan, MD
Med-peds PGY4
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Chief Complaint: abd pain
• 18 yo previously healthy Caucasian female reports to local ED for
abdominal pain.
• Had had prior visit to PCP clinic for similar situation, but had
unremarkable history and exam thought was constipation and sent
home with miralax.
• A couple months later, repeat episode of abdominal pain, more
severe. Presents to the local ER with nausea, emesis.
• Had CT abd/pelvis scan with read demonstrating some colitis
throughout colon. Stool studies not done. Labs were normal.
• Sent home for supportive care and antibiotics.
• On PCP office follow up, normal exam.
• Referred to GI for further evaluation – had colonoscopy with biopsy –
inflammation, colitis.
• ?concern for IBD
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Several months and 5 visits later…
• Now in college presents again to local ED with extreme
abdominal pain. Now 19 years old.
• Similar to prior presentations.
• Diffuse mild to moderate achy abdominal pain with mild
guarding. Constant with “waves of increased pain” that
self resolve. Has not taken any medications at home.
• Acute onset, shortly after exercising. Subjective fever at
dorm. No chills. Moderate nausea with food anorexia.
No emesis. Mild dysphagia. “Mouth feels sticky.”
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PMH: none
PSH: none
ROS: No chills, fatigue, night sweats.
No trauma, vision changes
No rhinorrhea, sneezing; No dyspnea on exertion,
edema, no shortness of breath, wheeze
No recent illness. No throat pain, no odynophagia. NO
weight changes.
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Medications
• Ocella (drospirenone/ethinyl
estradiol 3 mg/30 mcg) –
class I monophasic OCP
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Allergies
NKDA
SH: College freshman. Never tried smoking.
Tried EtOH. Patient denies other drug use or
abuse.
FH: remote hx of DM and HTN in 2nd degree
relatives
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VS in ER: Temp 100.1, Resp 18, BP 115/61, Pulse
105. 98% on RA
General: Alert female appears stated age in mild
distress due to pain. Thin but not anorexic.
HEENT: EOMI, PERRL, no scleral changes. OP
clear with intact good dentition and braces, mildly
dry mucus membranes. Lips are full. Red mildly
large appearing tongue.
Neck: soft, supple, no LAP.
Chest: CTA bilat, no wheezing.
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CVS: tachy regular rhythm S1, S2, no murmur
Abd: BS +, TTP diffusely, non-localized.
Holding abdomen at midline. Neg psoas or
obturator sign. Able to walk to bathroom gingerly.
Ext: no edema, 2+ pulses
Neuro: CN 2-12 intact, no gross deficits.
Skin: no rashes, lips red appearing.
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Differential Diagnosis
CC: abd pain
HPI: 19 year old with
repeated abd pain
PMH:
none
Exam Findings
Abd exam with TTP.
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Laboratory Data
CBC
BMP
Urinalysis
Cardiac Enzymes
Liver Function Tests
Coagulation
Endocrinology
Serology
Immunologic Studies
Other Serology
Body Fluid Analysis
Cytology
Pathology
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Microbiology
CXR
EKG
Ultrasound
CT Scan
MRI
Other Studies
Other Imaging
Clinical Course
Differential Diagnosis
Discussion
Please Press to Return
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CBC
13.9
304
16.4
42.1
Seg Neutro 85, Lymph 3, Mono 4
MCV 84 (80-99)
RDW 13.1 (<14.5)
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BMP
134
107
11
3.9
19
0.7
AG 8 (3-15)
Ca 9.1 (8.8-10.5)
Mg 1.9 (1.8-2.5)
PO4 xx (2.4-4.7)
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128
Urine Analysis
color
sp gr
pH
Hgb
ketone
glu
prot
LE
nitrite
urobil
bili
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yellow
1.025
6.0
neg
neg
neg
neg
neg
neg
neg
neg
Microscopic
0 wbc
0 rbc
UDS
• Negative for anything
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Cardiac Enzymes
1st – actually not done
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Liver Function Tests
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AST
ALT
Alk Phos
Albumin
T Bilirubin
D Bilirubin
Protein
18 (15-41)
25 (7-35)
65 (32-91)
3.6 (3.5-4.8)
1.3 (0.3-1.2)
xx (0.1-0.5)
6.6 (6.1-7.9)
Lipase
< 10 (18-51)
Coagulation
PTT
PT
INR
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24.5 (21-33)
11.4 (10.3-13.0)
1.0
Endocrinology
TSH
Free T4
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2.5 (0.34-5.6)
X (0.6-1.6)
Serology
C4 9 (14-40)
C1 inhibitor antigenic protein 15 (19-37)
C1 inhibitor functional level 60 (nl is >=60)
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Studies
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Cytology
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Other Serology
• Inflammatory markers – would have been elevated
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Body Fluid Analysis
• nada
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Microbiology
• UCx neg
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Chest X-ray
• No acute cardiopulmonary process
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• nada
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CT abd/pelvis
Findings: The appendix is poorly visualized with a small amount of
thickened, enhancing appendiceal wall. There is no evidence of bowel
obstruction or free air.
There is a tiny amount of free fluid in the pelvis, mostly on the right.
Pelvic structures are, otherwise, unremarkable.
The lung bases are clear. The liver, spleen, pancreas, adrenal glands,
kidneys, and gallbladder are normal. The bile ducts are not dilated. No
enlarged lymph nodes are identified in the abdomen and pelvis.
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Impression: The appendix is visualized with changes possibly
consistent with, but not confirmatory for acute appendicitis. There is
small amount of free fluid in the pelvis that is thought not to be
CD clinically significant. Clinical correlation is suggested.
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MRI – none
• nada
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2-D Echocardiogram
none
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Other Imaging
• HIDA - negative
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Clinical Course
• Worried about acute appendicitis.
• Taken to the OR the next day.
• Pathology back in a couple days with normal
appendix without signs of appendicits.
• Patient is making recovery as expected on post
op day 1 with some resolving pain.
• Still with some mild sticky swallowing. On further
exam, oral exam is somewhat unchanged and pt
notes this as well.
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• Screening for hereditary angioedema positive for
low complement levels.
• Underwent fresh frozen plasma infusion with
resolution of symptoms.
• Diagnosed with Hereditary Angioedema type I, not
started on therapy due to patient preference
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Discussion - Goals
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Complications
Diagnosis and Initial Treatment
Disease Background
Pathophys
Treatment
New stuff
MKSAP Q?
Definition
• Angioedema – self limited local swelling of the skin
• Urticaria or hives – flushing, generalized itching, near
syncope, hypotension with mast cell activation –
typically < 24 hrs
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History
• First described and Autosomal Dominant inheritance
pattern realized by Sir William Osler in 1888.
• Protein defect described in 1963 by Donaldson and
Evans.
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Types of familial angioedema
• Type I – absence of one allele with resulting
decreased expression of C1-inh in plasma – most
cases (85%) – labs shows low antigenic protein
and functional activity
• Type II – expression of a dysfunctional protein –
normal level, but low function
• Suggested type III – normal levels and function,
estrogen dependent
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Acquired type of Angioedema
• typically older
• Type I - may be from B cell malignancies, and
rheumatologic disorders, autoimmune
– Immune complexes that are formed more in these
diseases thought to consume C1 esterase inh
• Type II – autoAb (IgG, IgA, or IgM) against C1 INH
produced, bind and inactivate it.
– Can result in inactivation of C1-INH
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Idiopathic Angioedema
• Defined as >= 3 episodes of recurrent angioedema in
1 yr period with no apparent cause
• Estimated to effect up to 20% of people at some
point in life.
• Up to ½ have urticaria – not seen in other types
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ACE inhibitor induced AE
• Also seen in antibiotics, narcotics, NSAIDs, ARBs
(losartan)
• Class effect
• Hapten hypothesis from allergic standpoint may
explain the urticaria more than the angioedema.
• ACE substrate on angiotensin I and BK; excess of
latter causes effect
• Usually onset within 1st week, and can be a few
years out from 1st use.
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Background
• Incidence is about 1/50,000
• Typically symptoms begin in childhood, although
diagnosis delayed average of 10 years.
• As many as 20-25% are spontaneous mutation
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Bottom line for definition as of 2004
• Clinical criteria – angioedema, abdominal pain, or
largyngeal edema
• +
• Lab criteria – low C1 inh Ag level x2, low C1 inh fxn
level x2, or C1 inh mutation (only tested in kids < 1
yo)
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Onset
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• Typically in childhood, worsen in puberty, and
unpredictable severity
• Attacks typically have a prodrome, like a “tingling”
sensation
• Skin - Erythematous rash, nonpruritic
• Random swelling – hands, arms, feet, abdomen,
face
• Usually no fever, or leukocytosis
• Shift of fluids in abdominal attacks can cause
hypotension
• Involvement of airways – risk of asphyxiation
Risks
• Typically attacks occur without trigger, but some
may be local trauma such as dental work and
stress
• Pregnancy seems to have decreased attack
frequency – total circulating C1-INH increases.
• Attacks reported associated with oral
contraceptive use and menstruation.
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C1 Inhibitor function, a serine protease
(like a1 antitrypsin, antithrombin)
• Inactivation of Factors
XIIa (Hageman) , XIIf,
and XIa
• Direct ininhibition of
activated kallikrein
• Prevention of C1
complement
autoactivation in
classical cascade
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Contact system
• C1 inhibitor suggested to inactivated 90% of factor
XIIa and its metabolite XIIf, and almost half of
kallikrein
• Kallikrein cleaves HMW kininogens and bradykinin
release
• Also cleaves plasminogen to active plasmin, which
cleaves factor XII
• Factor XII undergoes some autoactivation
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Short term treatment
• use C1 inh replacement, FFP. Latter is
controversial because it has contact proteins that
could promote bradykinin release
• Prophylaxis (prior to dental work) – C1 inh, or
androgen (takes days), or FFP 1-12 hr before
• C1 inh replacement (Cinryze and Berinert P) –
very expensive!
• Antifibrinolytics (EACA, TA) – thought to inhibit
plasmin activation – sparing effect. Not FDA
approved.
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Long term Tx
• Avoid triggers including drugs, estrogen meds,
tamoxifen, ACEI
• 17a – androgens (danazol and stanozolol), to
increase C1 INH, C4, and C2 levels – thought to
increase aminopeptidase P (inactivates kinins),
increase hepatic production of C1 INH.
• Doses can be adjusted to as low as danazol 200 mg
3 days a week.
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Androgens
• These attenuated androgens contraindicated
in pregnancy, childhood.
• Risk of hepatic involvement – cases of
hepatocellular carcinoma in patients taking over 10
years. Also abnormal liver enzymes, lipid
abnormalities.
• Common – weight gain, virilization, acne, muscle
pains, constipation, HTN
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Antifibrinolytic agents
• Used in pediatrics (before Tanner V puberty), but
not as affective.
• Only EACA (E-aminocaprioic acid) available in US.
• Also used in acquired angioedema.
• Common side effects - muscle cramps, myalgia,
elevated CK
• New agents – Bradykinin receptor blocker
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• 25 yo man wants a 2nd opinion for evaluation of episodes of
large, raised red welts and intense itching all over his body. The
lesions usually last 24 h + and then disappear. He has >= 2-3
episodes / wk, and he cannot identify any specific trigger for the
attacks. He was told his condition was hives and was given
hydroxyzine and then fexofenadine, neither of which significantly
controlled his symptoms. He reports no mouth or lip swelling, no
difficulty breathing, and no GI symptoms. His weight has been
stable.
• Temp 38.1 °C. Discrete dark wheal and flare lesions consistent
with urticaria on both arms and legs and the trunk and back.
Some lesions look like purpura. UA shows rbc and rbc casts
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• Which of the following is most likely to help establish the
diagnosis?
• A C1 esterase inhibitor measurement
• B Urine eosinophil count
• C Skin biopsy
• D Antigenic skin testing
• E Thyroid-stimulating hormone measurement
• Urticaria that does not respond to usual treatment should prompt a
workup for urticarial vasculitis, including esr, cbc, skin biopsy from
the edge of the wheal.
• Histopathologic evidence of vascular damage, nuclear debris, or
erythrocyte extravasation is diagnostic. This form of leukocytoclastic
vasculitis is often limited to the skin, but, occasionally, there is organ
involvement or systemic signs, such as fever, abdominal pain, or
nephritis.
• Most cases are idiopathic, but they can also be drug-induced (ACE
inhibitors, penicillin, and sulfonamide), related to rheumatic diseases
such as lupus, or caused by viral disease, including hepatitis B and
C infection, and infectious mono.
• Treatment is dictated by the underlying cause, if one is found. If not,
a trial of anti-inflammatory or immunomodulating medications is
indicated. Often, more than one agent must be tried before there is
long-term relief.
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Key point
Urticaria that does not respond to usual
treatment should prompt a workup for
urticarial vasculitis, including erythrocyte
sedimentation rate, complete blood
count, and skin biopsy from the edge of
the wheal.
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References
• MKSAP 14
• Weis M. Clinical Review of HAE: Diagnosis and Management.
Postgraduate Medicine 2009; 121(6): 113-120.
• Nzeako UC, Frigas E, Tremaine WJ. Hereditary Angioedema.
Arch Intern Med. 2001; 161: 2417-2429.
• Zuraw B. Hereditary Angioedema. NEJM. 2008; 359: 1027-36.
• Bowen T, Cicardi M, Frank M. Hereditary angiodema: a current
state-of-the-art review, VII: Canadian Hungarian 2007
International Consensus Algorithm for the Diagnosis, Therapy,
and Management of Hereditary Angioedema. Ann Allergy
Asthma Immunol. 2008; 100(Suppl 2): S30-40.
• Frank MM, Jiang H. New therapies for hereditary angioedema:
Disease outlook changes dramatically. J Allergy Clin Immunol.
2008; 121(1); 272-80.
• Uptodate articles accessed 10/2/2010. Diagnosis of hereditary
and acquired angioedema (C1 inhibitor disorders)
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"Worst case of pedal edema I've ever
seen."