Transcript Infections in the Elderly

Resident as Teacher Series
Tuesday, December 17, 2013
Wednesday, December 18, 2013
Carl B. Lauter, MD, FACP
Section Head, Section of Allergy & Clinical Immunology
Member, Section of Infectious Diseases
Department of Medicine
William Beaumont Hospital – Royal Oak
Professor of Medicine
Oakland University William Beaumont School of Medicine
Clinical Professor of Medicine
Wayne State University School of Medicine
Governor, Michigan Chapter, American College of Physicians
A 53-year-old Caucasian man is admitted to the hospital
through the Emergency Center with fever, rigors,
sweats, cough, pleuritic chest pain and difficulty in
breathing. He has rusty sputum. His WBC is 15,000 with
a neutrophilia and left shift. The chest x-ray revealed
lobar consolidation the left lower lobe. Treatment is
initiated with IV ceftriaxone and azithromycin. On the
fourth hospital day, an infectious disease consultation is
requested because of “persistent fever on therapy.”
As you ramble on through life,
whatever be your goal
Keep your eye upon the donut
and not upon the hole!
The Optimist’s Creed
Author Unknown
A 21-year-old Caucasian USAF airman presents
himself to the Chanute Air Force Base Hospital
Emergency Center with the chief complaint of
alternate day itchy hives.
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Pity the physician who has seen a case
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Listen to the patient, doctor. He/she is trying to tell
you the diagnosis
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Learning medicine is like sailing:
 Seeing patients without reading is like sailing without a
chart
 Reading without seeing patients is like never having sailed
at all
A 35-year-old obstetrician sees an allergist because of a
three week history of itchy hives which began after
attending a medical meeting in Chicago. His overall
health is excellent, he takes no medications except
now, as needed, diphenhydramine for the hives. Other
than some epigastric discomfort and gassy symptoms,
somewhat more frequent bowel movements and a five
pound weight loss, the rest of the ROS is normal.
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OCCAM’s Razor vs Hickam’s Dictum
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No matter how hard you push and squeeze,
try to make it fit into one disease
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The patient can have as many diseases as
they damn well please
A 41-year-old Caucasian woman is transferred to a tertiary care infectious
disease center for evaluation and management of suspected Herpes Simplex,
type 1, viral encephalitis. She has a fever of 104⁰F, is obtunded and barely
rouseable but has no overt focal neurological findings. There has not been
any seizure activity clinically or on EEG. Initial head CT imaging with RCM
shows no focal abnormality. Her PMH is totally normal and she took no
medications prior to this illness. Her CSF revealed clear colorless fluid with an
OP of 200, WBC 33, all mononuclears, RBC 5, protein 88 and glucose 55
(blood glucose of 100). Investigational CSF and serum antibody tests (PHA)
for antibodies to HSV-1 are positive, but the technician is concerned because
the serum and CSF controls are also positive.
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People are down on what they are not up on
If you hear hoofbeats, think of horses, not zebras, unless you
are in Royal Oak.
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Are you (as a doctor) an FOB or SOB?
EFU
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Fever somewhere – fever nowhere, look under the diaphragm
Not all that wheezes is asthma
The clean plate sign
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Dress British, think Yiddish!
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Guideline process:
 Experts gather
 Evaluate the evidence
 Recommendations
 Decision process “codified” and displaced from the
individual patient and physician
 “Best” evidence is separated from the rest
▪ RCT
▪ Meta-analysis of RCTs
 Clinical experience and mechanistic reasoning are not
accepted as evidence or as tests of evidence.
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Randomized clinical trials (RCT) limits:
 Too much data
 Conflicting reports > difficult to interpret
 Not enough time
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For many clinical problems, there is no evidence e.g. RCT
 Example: antibiotic prophylaxis for endocarditis. Evidence did
not change but guidelines did after the evaluators changed
?biases?
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Meta-analyses may conflict with each other
Limits in applicability
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Selected populations: age, race, geography
Exclusions, “inclusion criteria”
Inadequate details
Participating physicians – skill, judgment, learning curve e.g.
what is of value elsewhere may not be of value everywhere
Generalizability of RCTs
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Standard of care?
Quality of care based on adherence
Exceptions: Modify above
 Individual patient circumstances
 Patient preferences
 Role of clinical expertise and mechanistic reasoning
 Brief statement; “fine print”
 Incompatible with the original criteria of guideline framing
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Limitations:
 Often incomplete, inconclusive, absent or
outdated
 Supplemented by lower levels of evidence
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How to estimate likelihood that an individual
patient will respond to, or be injured by the
tested therapy
Limitations based on guideline process:
people, societies, journals
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Disciplined, analytical, scientific approach
that integrates all the relevant information in
the search for the best diagnosis and therapy
approaches for individual patients.
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Contrast with
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A context-dependent way of thinking and
decision-making in professional practice to
guide practice actions.
Higgs, J. Jones, MA
Clinical Reasoning in The Health Professions
3rd Edition, pp 3-17, 2008
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Clinical Reasoning = Clinical Decision Making
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Intuitive mode of problem solving
 Rapid, generally subconscious approach, driven
by experience:
▪ Subject to considerable error = cognitive biases
▪ Indispensable = given the number decisions a clinician
must make daily
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The individual patient, who is real and not the
“average” patient, needs to be the main focus
of our clinical care.
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Skill sets:
 Synthesizing skills
 Recognizing prototypes
 Focusing on cues and clues
 Using community resources
 Dealing with uncertainty
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Does not supply generic answers for groups
Not the same as “expert opinion” (personal
experience or personal analysis)
Not a license to guess
Not a license to ignore RCTs = starting points(s)
of clinical reasoning
Accepts the probabilistic nature of decisions
and that decisions are often provisional
Pragmatic – based on analysis of the consequences
of acting or not acting and predictions of risk vs
benefit, outcomes
 Key features:
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 Complexity
 Imagination
Essential to integrate the knowledge from RCTs into
a specific clinical situation
 Knowledge, experience, open-minded “out of the
box” thinking
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Two main types of reasoning methods:
 Analytic = System 2 Thinking
▪ Deliberate - Involves generation and testing of multiple
hypotheses
 Non-Analytic = System 1 Thinking
▪ Pattern recognition
▪ Intuitive
▪ Automatic in nature
National Prescribing Centre: Med Rec Bulletin 2011;22(1)
Croskerry P. Acad Med 2003;8(8):775 - 780
In the area of patient safety, recent attention has focused on diagnostic error. The reduction of
diagnostic error is an important goal because of its associated morbidity and potential
preventability. A critical subset of diagnostic errors arises through cognitive errors, especially
those associated with failures in perception, failed heuristics, and biases; collectively, these
have been referred to as cognitive dispositions to respond (CDRs). Historically, models of
decision-making have given insufficient attention to the contribution of such biases, and there
has been a prevailing pessimism against improving cognitive performance through debiasing
techniques. Recent work has catalogued the major cognitive biases in medicine; the author
lists these and describes a number of strategies for reducing them (“cognitive debiasing”).
Principle among them is metacognition, a reflective approach to problem solving that involves
stepping back from the immediate problem to examine and reflect on the thinking process.
Further research effort should be directed at a full and complete description and analysis of
CDRs in the context of medicine and the development of techniques for avoiding their
associated adverse outcomes. Considerable potential exists for reducing cognitive diagnostic
errors with this approach. The author provides an extensive list of CDRs and a list of strategies
to reduce diagnostic errors.
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Aggregate bias: when physicians believe that aggregated data, such as those
used to develop clinical practice guidelines, do not apply to individual patients
(especially their own), they are invoking the aggregate fallacy. The belief that their
patients are atypical or somehow exceptional may lead to errors of commission, e.g.
ordering x-rays or other tests when guidelines indicate none are required.
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Anchoring: the tendency to perceptually lock onto salient features in the patient’s
initial presentation too early in the diagnostic process, and failing to adjust this initial
impression in the light of later information. This CDR may be severely compounded
by the confirmation bias.
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Ascertainment bias: occurs when a physician’s thinking is shaped by prior
expectation; stereotyping and gender bias are both good examples.
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Availability: the disposition to judge things as being more likely, or frequently
occurring, if they readily come to mind. Thus, recent experience with a disease
may inflate the likelihood of its being diagnosed. Conversely, if a disease has not
been seen for a long time (is less available), it may be underdiagnosed.
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Base-rate neglect : the tendency to ignore the true prevalence of a disease,
either inflating or reducing its base-rate, distorting Bayesian reasoning. However,
in some cases, clinicians may (consciously or otherwise) deliberately inflate the
likelihood of disease, such as in the strategy of “rule out worst-case scenario” to
avoid missing a rare but significant diagnosis.
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Feedback sanction: a form of ignorance trap and time-delay trap CDR.
Making a diagnostic error may carry no immediate consequences, as considerable
time may elapse before the error is discovered, if ever, or poor system feedback
processes prevent important information on decisions getting back to the decision
maker. The particular CDR that failed the patient persists because of these
temporal and systemic sanctions.
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Framing effect: how diagnosticians see things may be strong influenced by the
way in which the problem is framed, e.g. physicians’ perceptions of risk to the
patient may be strongly influenced by whether the outcome is expressed in terms
of the possibility that the patient might die or might live. In terms of diagnosis,
physicians should be aware of how patients, nurses and other physicians frame
potential outcomes and contingencies of the clinical problem to them.
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Commission bias: results from the obligation toward beneficence, in that harm
to the patient can only be prevented by active intervention. It is the tendency
toward action rather than inaction. It is more likely in over-confident physicians.
Commission bias is less common than omission bias.
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Confirmation bias: the tendency to look for confirming evidence to support a
diagnosis rather than look for disconfirming evidence to refute it, despite the latter
often being more persuasive and definitive.
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Diagnosis momentum: once diagnostic labels are attached to patients they
tend to become stickier and stickier. Through intermediaries (patients,
paramedics, nurses, physicians), what might have started as a possibility gathers
increasing momentum and it becomes definite, and all other possibilities are
excluded.
 Fundamental attribution error: the tendency to be judgmental and blame
patients for their illnesses (dispositional causes) rather than examine the
circumstances (situational factors) that might have been responsible. In particular,
psychiatric patients, minorities, and other marginalized groups tend to suffer from this
CDR. Cultural differences exist in terms of the respective weights attributed to
dispositional and situational causes.
 Gambler’s fallacy: attributed to gamblers, this fallacy is the belief that if a coin is
tossed ten times and is heads each time, the 11th toss has a greater chance of being
tails (even though a fair coin has no memory). An example would be a physician who
sees a series of patients with chest pain in clinic or the emergency department,
diagnoses all of them with an acute coronary syndrome, and assumes the sequence
will not continue. Thus, the patient probability that a patient will have a particular
diagnosis might be influenced by preceding but independent events.
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Gender bias: the tendency to believe that gender is a determining factor in the
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Hindsight bias: knowing the outcome may profoundly influence the perception
probability of diagnosis of a particular disease when no such pathophysiological
basis exists. Generally, it results in an over-diagnosis of the favored gender and
under-diagnosis of the neglected gender.
of past events and prevent a realistic appraisal of what actually occurred. In the
context of diagnostic error, it may compromise learning through either an underestimation (illusion of failure) or over-estimation (illusion of control) of the decision
maker’s abilities.
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Multiple alternatives bias: a multiplicity of options on a differential diagnosis
may lead to significant conflict and uncertainty. The process may be simplified by
reverting to a smaller subset with which the physicians is familiar but may result in
inadequate consideration of other possibilities. One such strategy is the threediagnosis differential. “It is probably A, but it might be B, or I don’t know C.”
Although this approach has some heuristic value. If the disease falls in the C
category and is not pursued adequately, it will minimize the chances that some
serious diagnosis can be made.
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Omission bias: the tendency toward inaction and rooted in the principle of nonmaleficence. In hindsight, events that have occurred through the natural
progression of a disease are more acceptable than those that may be attributed
directly to the action of the physician. The bias may be sustained by the
reinforcement often associated with not doing anything but it may prove disastrous.
Omission biases typically outnumber commission biases.
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Order effects: information transfer is a U-function: we tend to remember the
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Outcome bias: the tendency to opt for diagnostic decisions that will lead to good
beginning part (primacy effect) or the end (recency effect). Primacy effect may be
augmented by anchoring. In transitions of care, in which information transferred
from patients, nurses, or other physicians is being evaluated, care should be taken
to give due consideration to all information, regardless of the order in which it was
presented.
outcomes, rather than those associated with bad outcomes, thereby avoiding
chagrin associated with the latter. It is a form of value bias in that physicians may
express a stronger likelihood in their decision-making for what they hope will
happen rather than for what they really believe might happen. This may results in
serious diagnoses being minimized.
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Overconfidence bias: a universal tendency to believe we know more than we
do. Overconfidence reflects a tendency to act on incomplete information, intuitions
or hunches. Too much faith is placed in opinion instead of carefully gathered
evidence. The bias may be augmented by both anchoring and availability, and
catastrophic outcomes may result when there is a prevailing commission bias.
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Playing the odds: (also know as frequency gambling) is the tendency in
equivocal or ambiguous presentations to opt for a benign diagnosis on the basis that
it is significantly more likely than a serious one. It may be compounded by the fact
that the signs and symptoms of many common benign diseases are mimicked by
more serious and rare ones. The strategy may be unwitting or deliberate and is
diamaterically opposed to the rule out worst-case scenario strategy (see base-rate
neglect).
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Posterior probability error: occurs when a physician’s estimate for the
likelihood of disease is unduly influenced by what has gone on before for a particular
patient. It is the opposite of the gambler’s fallacy in that the physician is gambling on
the sequence continuing, e.g. if a patient presents to the office five times with a
headache that is correctly diagnosed as migraine on each visit, it is the tendency to
diagnose migraine on the sixth visit. Common things for most patients continue to be
common, and the potential for a non-benign headache being diagnosed is lowered
through poster probability.
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Premature closure: a powerful CDR accounting for a high proportion of missed
diagnoses. It is the tendency to apply premature closure to the decision-making
process, accepting a diagnosis before it has been fully verified. The consequences of
the bias are reflected in the maxim: “When the diagnosis is made, the thinking stops.”
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Psych-out error: psychiatric patients appear to be particularly vulnerable to the
CDRs described in this list and to other errors in their management, some of which
may exacerbate their condition. They appear especially vulnerable to fundamental
attribution error. In particular, comorbid medical conditions may be overlooked or
minimized. A variant of psych-out error occurs when serious medical conditions
(e.g., hypoxia, delirium, metabolic abnormalities, CNS infections, head injury) are
misdiagnosed as psychiatric conditions.
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Representativeness restraint: the representativeness heuristic drives the
diagnostician toward looking for prototypcial manifestations of disease: “If it looks
like a duck, walks like a duck, quacks like a duck, then it is a duck.” Yet,
restraining decision-making along these pattern-recognition lines leads to atypical
variants being missed.
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Search satisfying: reflects the universal tendency to call off a search once
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Sutton’s slip: takes its name from the apocryphal story of the Brooklyn bank-robber
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Sunk costs: the more clinicians invest in a particular diagnosis, the less likely they
something is found. Comorbidities, second foreign bodies, other fractures, and coingestants in poisoning may all be missed. Also, if the search yields nothing,
diagnosticians should satisfy themselves that they have been looking in the right
place.
Willie Sutton who, when asked by the Judge why he robbed banks, is alleged to have
replies: “Because that’s where the money is!” The diagnostic strategy of going for the
obvious is referred to as Sutton’s law. The slip occurs when possibilities other than
the obvious are not given sufficient consideration.
may be to release it and consider alternatives. This is an entrapment form of CDR
more associated with investment and financial considerations. However, for the
diagnostician, the investment is time and mental energy and, for some, ego may be a
precious investment. Confirmation bias may be a manifestation of such an
unwillingness to let go of a failing diagnosis.
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Triage cueing: the triage process occurs throughout the health care system, from
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Unpacking principle: failure to elicit all relevant information (unpacking) in
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Vertical line failure: routine, repetitive tasks often lead to thinking in silos –
the self-triage of patients to the selection of a specialist by the referring physician. In
the Emergency Department, triage is a formal process that results in patients being
sent in particular directions, which cues their subsequent management. Many CDRs
are initiated at triage, leading to the maxim, “Geography is destiny.”
establishing a differential diagnosis may result in significant possibilities being missed.
The more specific a description of an illness that is received, the more likely the event
is judged to exist. If patients are allowed to limit their history-giving, or physicians
otherwise limit their history-taking, unspecified possibilities may be discounted.
predictable, orthodox styles that emphasize economy, efficacy, and utility. Though
often rewarded, the approach carries the inherent penalty of inflexibility. In contrast,
lateral thinking styles create opportunities for diagnosing the unexpected, rare or
esoteric. An effective lateral thinking strategy is simply to the post the question: “What
else might this be?”
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Visceral bias: the influence of affective sources of error on decision-making has
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Yin-Yang out: when patients have been subjected to exhaustive and unavailing
been widely underestimated. Visceral arousal leads to poor decisions.
Countertransference, both negative and positive feelings toward patients, may result in
diagnoses being missed. Some attribution phenomena (fundamental attribution error)
may have their origin in countertransference.
diagnostic investigations, they are said to have been worked up the Yin-Yang. The
Yin-Yang out is the tendency to believe that nothing further can be done to throw light
on the dark place, where, and if, any definitive diagnosis resides for the patient, i.e., the
physician is let out of further diagnostic effort. This may prove ultimately to be true, but
to adopt the strategy at the outset is fraught with the chance of a variety of errors.
Strategies
Knowledge
Data
Gathering
Data
Processing
Metacognition
Scaffolding
Direct
observation
with feedback
RIME
Diagnostic
timeout
Problem
representation
using semantic
qualifiers
Awareness of
cognitive
biases
SNAPPS
Reflection
Presentation to Hypothesisdiagnosis
driven physical
exam
Examples:
Acute
Chronic
Localized
Diffuse
Single
Multiple
Severe
Mild
Intermittent
Consistent
Previously healthy
History Significant For…
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Reporter – Describes data
Interpreter – Data processing
Manager – Plans what to do
Effective/Education – Goes beyond patient
care – educates others
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Summarize history and findings
Narrow the differential
Analyze the differential
Probe teacher about uncertainties
Plan management
Select case-related issues for self study
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Diagnostic time out
Awareness of cognitive biases
Reflection
“Thinking about thinking”
Three Forms:
 Making a plan before solving a problem
 Regulating thinking while thinking
 Reflecting on one’s thinking after a thinking episode to
assess and correct the future thinking
“I do my best thinking in the shower”
Strategy
Mechanism/Action
Develop insight/Awareness
Provide detailed descriptions and thorough characterizations
of known cognitive biases, together with multiple clinical
examples illustrating their adverse effects on decisionmaking and diagnosis formulation
Consider Alternatives
Establish forced consideration of alternative possibilities e.g.,
the generation and working through of a differential
diagnosis. Encourage routinely asking the question: What
else might this be?
Metacognition
Train for a reflective approach to problem solving: stepping
back from the immediate problem to examine and reflect on
the thinking process.
Decrease Reliance on
Memory
Improve the accuracy of judgments through cognitive aids:
mnemonics, clinical practice guidelines
Specific Training
Identify specific flaws and biases in thinking and provide
directed training to overcome them: e.g., instruction in
fundamental rules of probability, distinguishing correlation
from causation, basic Bayesian probability theory.
Strategy
Mechanism/Action
Simulation
Develop mental rehearsal, “cognitive walkthrough”
strategies for specific clinical scenarios to allow cognitive
biases to be made and their consequences to be observed.
Construct clinical training videos contrasting incorrect
(biased) approaches with the correct (debiased) approach
Cognitive Forcing Strategies
Develop generic and specific strategies to avoid predictable
bias in particular clinical situations
Make Task Easier
Provide more information about the specific problem to
reduce task difficulty and ambiguity. Make available rapid
access to concise, clear, well-organized information.
Minimize Time Pressures
Provide adequate time for quality decision-making.
Accountability
Establish clear accountability and follow-up for decisions
made.
Feedback
Provide as rapid and reliable feedback as possible to decision
makers so that errors are immediately appreciated,
understood, and corrected, resulting in better calibration of
decision makers.
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61 yo M presented to ER w/ 5 year h/o
unexplained intoxication
BAC = 371mg/dl (.37%)
Pt and wife stated he had not been drinking
H/O hypertension and hyperlipidemia but no
other health problems
All systems WNL
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After treating the pt for alcohol poisoning,
what would you do next?
a. Recommend AA meetings
b. Search the literature for rare syndromes
c. Do a complete GI workup
d. Refer the pt for psychiatric disorder
40% got it wrong
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Breath tests for lactose and fructose
intolerance
Hydrogen
Glucose tolerance
EGD and colonoscopy
Stool cultures
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Breath tests all negative
Glucose tolerance negative
EGD and colonoscopy negative
H. pylori isolated from stomach
Stool culture: Saccharomyces cerevisiae
(brewer’s yeast) and rare budding yeast
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Pt admitted to hospital for 24-hour
observation
 Belongings searched
 No visitors allowed
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Glucose challenge and high carbohydrate diet
 BAC and blood glucose drawn q.2 hours
 BAC registered 120 mg/dl at hour 20
 Verified by DPS breathalyzer
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Revealed a few possible clues
 MEDLINE®, EBSCOhost
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A few cases of gut fermentation and/or autobrewery had been reported
Possible tests and antifungal treatments
mentioned in literature
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3-week course of fluconazole (Diflucan)
100mg/day
Followed by a 3-week course of nystatin
500,000 IU 4/day
Acidophilus tablets q day
No sugar, no alcohol, no carbohydrates
during treatment
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Alcohol levels tested QID for 10 weeks w/
readings of 0.00
Repeated stool cultures were negative
Treated for H. pylori w/ tetracycline
No recurrent symptoms after one year
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Dx of gut fermentation or auto-brewery
syndrome
S. cerevisiae as probable causative agent
Success of treatment supports hypothesis
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1970s: A few cases of auto-brewery reported
in Japan in two articles
1980s: Several articles on gut/colon
fermentation
1990s: 2 discussion articles on diagnosis
2000s: Reports of S. cerevisiae as a pathogen
in immunocompromised pts
2001 & 2006: Auto-brewery in 2 children w/
short bowel syndrome
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Listen to intoxicated pts who deny ingesting
alcohol
Additional investigation needed to determine
definitive tests
Research into how overgrowth of a gut
commensal occurs
Additional research on microbiome
A 54-year-old woman was seen
for an outpatient allergy
consultation because of new
onset hives
Two weeks prior to evaluation, she
developed an intermittent mildly
pruritic rash.
 It was described as multiple small
red dots, cleared spontaneously in
45-60 minutes
 Recurred 1-2 times daily
 Subsequently, it looked more like
hives with increased pruritus.
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The rash became more severe.
It was associated with lightheadedness and
orthostatic unsteadiness.
One week later, she experienced wheezing,
dyspnea accompanying the rash.
On ONE occasion, her tongue swelled and
puffy hands were noted.
Her visiting out-of-town daughter (an EMT) took
her to the EC where she was evaluated by her
brother (a cardiologist).
 A single oral diphenhydramine capsule en route
rapidly cleared her symptoms in about 30 minutes.
 BP of 191/111 was noted in the EC
 Follow-up diphenhydramine prn and albuterol MDI
prn rapidly cleared her symptoms, but multiple
events continued to occur.
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Paroxysmal hypertension
Fibroid uterus
Abnormal PAP test, remote past
Acute food poisoning 4-5 wks
earlier after eating a hamburger in a
restaurant
Post infectious irritable bowel
syndrome
T&A, age 5
 Appendectomy and partial right colon
resection for intussusception by a
benign appendiceal tumor 18 years
earlier
 Repeated D&C’s, cervical biopsies
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Fall SAR, SAC as a child
Allergen immunotherapy for 5-6 years as
a teen (college years), mild as adult
Rare throat itch in fall
Childhood eczema
No asthma or hives
Pruritic skin rash with perfumes and soaps
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Married
Owner of a large local furniture store chain
Frequent traveler to Boulder, CO and NYC
Traveled to Italy one year prior to onset
Has one dog at home of 11 years duration
No cigarette or drug use
Drinks 3-4 glasses of wine weekly
Exercises vigorously
Rarely eats meat
Father – nasal allergies, Crohn’s Disease
1 of 2 brothers has severe nasal
allergies, possible asthma
 Maternal grandmother had colon
cancer
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Intermittent loose bowel
movements, bloating since the
food poisoning
 Occasional tension headaches
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Multivitamin
Niacin 500mg/daily
Advil® prn, no more than six per month
Losartan potassium- hydrochlorothiazide
– new prescription since EC visit
Diphenhydramine prn (as in HPI)
Albuterol MDI prn (as in HPI)
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Healthy appearing Caucasian woman in no acute distress
129#, 36.5°C, 140/96, 12-14, 68-70
HEENT:
Neck:
Lungs:
Heart:
Abdomen:
Normal mucosa, no edema
Thyroid not enlarged or tender
Clear
RR, murmur
soft, non-tender, no organomegaly,
hyperactive BS, well healed RLQ surgical scar
Skin:
no rash or hives, no edema, no
dermatographism, mild lichenification and
thickening in the antecubital fossae
Lymph nodes: none enlarged
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CBC, platelets, differential – within
normal limits
TSH
1.0 (0.5-5.20)
ANA
negative
CMP
within normal limits
WSR
16



The patient called a few days after her
initial visit.
She experienced another episode.
Diphenhydramine shortened the attack
and the Albuterol MDI helped with the
wheezing.
BP during the episode was 106/70.






Recurrent anaphylaxis, etiology
unclear
Allergic rhinitis
Allergic conjunctivitis
Atopic dermatitis
Mild post infectious IBS
Paroxysmal hypertension







Loratidine 10mg daily
Epipen®
Albuterol MDI
Diphenhydramine prn, albuterol MDI prn
Avoid ASA and NSAIDS
Continue losartan potassiumhydrochlorothiazide, niacin, vitamins
Lab tests


Total IgE, complement C3, C4, CH50 –
WNL
Stool studies:
 Ova and parasites – negative x 2
 Giardia antigen – negative
 Stool culture - positive for Campylobacter
jejuni
SUBSEQUENT THERAPY
Azithromycin “Z- pak”



Severe allergic reaction after first dose:
continued azithromycin
Allergic symptoms cleared over 2-3
weeks
“IBS” symptoms cleared over < 1 week

Lopez-jBrea, M, Fontelos PM, Baquero M, et. Al. Urticaria
associated with Campylobacter enteritis. Lancet
1984;1(8390):1354

Bretag AH, Archer RS, Atkinson, HM, et. al. Circadian
urticaria: another campylobacter association. Lancet
1984;1(8383):954.

Di Campli C, Gasbarrini A, Nucera E, et. al. Beneficial effects
of Helicobacter pylori eradication on idiopathic chronic
urticaria. Digestive Diseases and Sciences 1998;43(6):12261229.

Campylobacter Fetus Bacterin-Ovine, for
sheep (veterinary vaccine use only)

CAUTION:
“Anaphylactic reaction sometimes follows
administration of products of this nature”








Drugs
Foods
Infections
Internal Diseases
Inhalants
Bites/Stings
Contactants
Psychogenic
Immunologic
Processes
 Genetic
 Physical Agents

 Dermatographism
 Pressure urticaria
 Cholinergic urticaria
 Cold urticaria
 Solar urticaria
 Heat urticaria

A 38-year-old Asian Indian male had recent travel to
India 3 weeks ago, presents with bilateral generalized
joint pains

Also complained of bilateral severe calf pain

Low grade fevers 99.5-100 degrees F with profuse
sweating and chills for 4 days PTA

Patient took analgesics with no relief

No history of recent trauma

Presented with sore throat/high fevers, 3-4 days
after arrival

Diagnosed with viral syndrome and mild ear
infection at outside institution, treated
conservatively, no antibiotics

One week later, presented to outside institution
with left sided chest pain, no SOB--- negative
cardiac work up

3 weeks after travel, presented to WBH EC for persistent
arthralgias, low grade fevers, chills and difficulty ambulating

Review of history:
 No History of cough or flu like symptoms
 History of mosquito bites in India
 No History of rashes, skin lesions
 Denies Nausea/vomiting/abdominal pain
 No Urinary complaints/Diarrhea
 Sick family members in India

PMH: HTN, Diabetes, Anxiety

PSH: Sebaceous cyst removal


Social History:
-Works as software engineer in a private firm
-Smoking: 10 PY, quit 2 yrs ago
-Alcohol: social drinker
-Married with 2 kids, sexually active with single partner, No
H/O STD’s
-No IVDA
Travel to India-two occasions: Jan 08 and March 08

Allergies: NKDA

Home meds:
 Atenolol, lisinopril, simvastation, metformin, lorazepam,
acetaminophen and ibuprofen

ROS: Per HPI, mild headache, no urethral discharge

Family History: Father-CAD, Mother-Diabetes, History
Arthritis-not sure about the details

Vitals: T max 38.2, 124/84, 86, 18, 98% RA

Gen: Mild distress due to pain

HEENT: MMM, no Icterus, PERLA

Neck: No LNs , No Thyromegaly

Heart: RRR, S1S2 heard, no M/R/G

Lungs: CTA B/L

Abdomen: Soft NT, ND, BS +, No organomegaly

Extremities : Upper extremity exam is normal

Lower ext:
 Hips:  ROM, Tenderness + B/L
 Knees: B/L joint /calf tenderness
 Ankles: B/L Achilles tendon tenderness
 No obvious synovitis

Skin: No rashes, nodules, petechiae

Neuro: normal

WBC: 15.6, Hb: 12.4, platelets: 169
Diff PMNs 7.3, L 6.2, M 1.1, Eos 0.2

Bun/Creatinine: 10/0.7

Blood cultures x2 neg, UA neg, Urine Cx neg

Imaging:
 B/l Hip x rays : Normal
 MRI hip : negative

Hip Aspiration:
 Wbc: 10 /microL, No PMNs
 Rbc: 1200/ microL
 Gluc: 26mg/dl
 No crystals
 Gram stain and culture: negative

EKG: NSR, no acute changes

TTE- mild MR, TR. No valve abnormality, EF >60%









Chikungunya fever/ viral arthropathy
Malaria/Dengue fever
Acute Rheumatic fever
Septic arthritis
Enteric fever
Infective endocarditis
Reactive arthropathy
Connective tissue disease/auto-immune
Gout and pseudo gout
ANA: negative
Rheumatoid factor: negative
C3/C4: negative
SS A/SS B: normal
Serum protein electrophoresis: chronic active
inflammation
 Uric acid: WNL
 CRP: 14.5, ESR: 95
 HIV negative
 Malaria smear negative






Young Asian Indian male, recent travel,
with sore throat, generalized arthralgias,
fever, pleuritic chest pain

High CRP and ESR

Rapid Strep test negative

Acute Rheumatic Fever

Strep culture: Positive

Streptococcal Antibodies Profile:
ASO: 1540 (<300)
Anti DNAse B: 1250 U/ml (<300)

Did well on high dose ASA and 10 day course of oral
PenVK®

24 hours later, improvement noted

Prophylaxis provided monthly (ongoing)

Chikungunya serolgies: negative at CDC
Commonly affected- knees, ankles, wrists, usually L.
ext joints first
 About 5-15 joints involved, inflamed < 1 week
 Latent period between strep infection and ARF is 2-3
weeks
 Synovial fluid is sterile but may find  WBCs
 Dramatic improvement with ASA/ NSAID’s
 No residual joint deformities
 May relapse 5-6 weeks post treatment

Major Criteria
 Carditis
 Polyarthritis (migratory)
 Chorea
 Erythema Marginatum
 Subcutaneous nodules
Minor Criteria
 Arthralgias
 Fever
 Elevated ESR, or CRP
 Prolonged PR interval on EKG
AND
 Elevated ASO titers / positive throat culture

Definition:
 To walk bent over. Swahili or Makonde. It refers
to the effect of incapacitating arthralgia.

A viral disease transmitted by Aedes
mosquitoes. Typically it is an acute illness
with fever, skin rash & severe arthralgia.
Persistent Arthralgia Associated with Chikungunya Virus: A Study
of 88 Adult Patients on Reunion Island
Gianandrea Borgherini,1 Patrice Poubeau,1 Annie Jossaume,1 Arnaud Gouix,1 Liliane Cotte,2 Alain Michault,3 Claude Arvin‐Berod,1 and Fabrice Paganin1
1Service de Pneumologie et Maladies Infectieuses, 2Centre d’Investigation Clinique, and 3Laboratoire de Virologie, Groupe Hospitalier Sud Reunion, Saint Pierre, La
Réunion, France
Background
An outbreak of chikungunya virus infection occurred on Reunion Island during the period 2005–2006.
Persistent arthralgia after chikungunya virus infection has been reported, but few studies have treated this
aspect of the disease.
Results.
Eighty eight patients (mean age, 58.3 years; male‐to‐female ratio, 1.1:1.0) were included in this study.
Fifty eight patients (65.9%) had been hospitalized for acute chikungunya virus infection, and
a history of arthralgia before chikungunya virus infection was reported by 39 patients
(44%). Fifty six patients (63.6%) reported persistent arthralgia related to chikungunya virus
infection, and in almost one‐half of the patients, the joint pain had a negative impact on everyday
activities. Arthralgia was polyarticular in all cases, and pain was continuous in 31 patients (55.4%).
Overall, 35 patients (39.7%) had test results positive for IgM antibodies to chikungunya virus.
Conclusions.
Persistent and disabling arthralgia was a frequent concern in this cohort of patients who had experienced
severe chikungunya virus infection 18 months earlier. Further studies are needed to evaluate the
prevalence of persist arthralgia in the general population to determine the real burden of the disease.
CID 2008;47:469-475.
Philip M. Gold, M.D. MACP
Chief Division of Pulmonary and Critical Care Medicine
Loma Linda University
Southern California


A previously healthy 75-year-old woman
was found to be anemic with a hemoglobin
of 10 Gm
Her primary care physician referred her to a
hematologist who performed a bone
marrow aspiration which revealed 18%
myeloblasts in a hyper- plastic marrow

A diagnosis of aplastic anemia was made

The patient refused further medical
evaluation but maintained an active schedule

Over a period of 18 months she had periodic
pains, fevers and chills which she dismissed
as “a bug”



Approximately 17 months following the
diagnosis of anemia she was admitted to
the hospital with vaginal bleeding
Her hemoglobin was 8 Gm and her white
count and platelet counts were low
A repeat bone marrow was hypocellular



She received 2 units of blood and had a
transfusion reaction
Aside from the transfusion reaction she
was afebrile
She resumed her busy schedule but 7
months later with a Hgb of 7.9 and
platelets of 87000 she was started on 20
mg. of prednisone


She required periodic transfusions over the
ensuing 4 months and then developed fever
to 40.5º C
She was readmitted and history revealed
several days of fever, chills, night sweats
and several weeks of dry cough


Admitting radiograph showed old scars but
no active pulmonary disease
Blood cultures were negative, a repeat bone
marrow showed no change and patient
received penicillin and streptomycin
empirically



Patient was felt to have a fever related to
aplastic anemia and prednisone was
increased to 25 mg daily
She was discharged but continued to decline
at home
She developed melena and was admitted a
month later with a Hgb of 5 Gm



At the time of readmission an ill-defined
diffuse nodularity was noted on lung
radiographs
A diagnosis of Fever of Unknown Origin was
made
Miliary tuberculosis was considered and bone
marrow smear and culture were performed



Bone marrow smears were negative but INH
and Streptomycin were started empirically
She continued to receive these two drugs for
the remaining 6 weeks of her life
She suffered continuing fevers and GI
bleeding persisted



She was unhappy in the hospital and
requested discharge to home
She continued anti-tuberculous medications
and 60 mg prednisone at home
Her primary physician urged aggressive
treatment and doubled her INH dose but she
and her family discouraged additional heroic
measures
17 days following discharge she had a major
stroke and became comatose
 She died three days later at age 78
 An autopsy was performed
 After hospital discharge, bone marrow cultures
grew Mycobacterium tuberculosis
 The past history included an episode of pleurisy
at age 19





A CPC was conducted in the month
following death
Mycobacteria were present in the lungs,
liver, spleen, kidneys and bone marrow
There were no granulomata suggesting lack
of an immune response
They called the condition disseminated
Tuberculosis acutissima

Mycobacteria recovered from the bone
marrow were tested for drug sensitivity and
were resistant to INH and streptomycin



Did the patient have reactivation tuberculosis
or reinfection?
Did the patient have aplastic anemia and TB
or TB alone with myelopthisis or leukemoid
reaction?
Did medical error occur?
Four presidents attended her funeral
Details of her illness were held close
Although the family was pleased with her care, a
general sense that error contributed to her death
prevailed
 The reputation of Columbia Presbyterian Hospital
was severely tarnished
 NEJM CPC on 2/14/63 rumored to be that of
Eleanor Roosevelt
 Medical records opened by Roosevelt Library in
1990



Lerner, BH. Int J Tuberc Lung Dis 2001: 5:1080
Pray of what disease did
Mr.Badman die? He was
dropsical, he was consumptive,
he was surfeited, was gouty,
and, as some say, he had a tang
of the pox in his bowels. Yet the
captain of all these men of
death that came against him to
take him away, was the
consumption, for it was that
that brought him down to the
grave.
John Bunyan
1628-1688
The Life and Death of Mr. Badman. 1680








Tuberculosis
Phthisis
The King’s Evil
Consumption
The White Plague
Lupus vulgaris
Scrofula
Pott’s disease
Henry IV of France Touching
André de Laurens, 1609
Andrew Jackson
James Monroe
Ulysses S. Grant
Thomas Mann
Eugene O’Neill
Albert Camus
Robert Koch
Wilhelm Roentgen
Marie Curie
Selman Waksman
Nelson Mandela
Paul Ehrlich
Anders Celsius
Louis Braille
Alexander Graham Bell
Frédéric Auguste Bartholdi
Wolfgang von Goethe
Dylan Thomas
Elizabeth Barrett Browning
Charlotte Brontë
Emily Brontë
Anne Brontë
Robert Burns
Maxim Gorky
Robert Louis Stevenson
Molière
Henry David Thoreau
Sir Walter Scott
Immanuel Kant
Voltaire
Baruch Spinoza
Red Schoendeinst
Christy Mathewson
Vivian Leigh
Sarah Bernhardt
W.C. Fields
John Keats
Friedrich Schiller
René Laennec
Florence Nightingale
E.L Trudeau





TB present in humans since antiquity
Found in remains of bison dated 18,000
years ago
One third of world’s population affected
New cases occur at rate of one per second
2007: 13.7 million chronic cases world
wide, 9.7 million new cases and1.8 million
deaths