Resident as Teacher SeriesTuesday, December 17, 2013Wednesday, December 18, 2013

Carl B. Lauter, MD, FACPSection Head, Section of Allergy & Clinical Immunology

Member, Section of Infectious DiseasesDepartment of Medicine

William Beaumont Hospital – Royal Oak

Professor of MedicineOakland University William Beaumont School of Medicine

Clinical Professor of MedicineWayne 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 donutand not upon the hole!

The Optimist’s CreedAuthor 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.

Pity the physician who has seen a case

Listen to the patient, doctor. He/she is trying to tell you the diagnosis

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.

OCCAM’s Razor vs Hickam’s Dictum

No matter how hard you push and squeeze, try to make it fit into one disease

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.

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.

Are you (as a doctor) an FOB or SOB? EFU

Fever somewhere – fever nowhere, look under the diaphragm

Not all that wheezes is asthma The clean plate sign

Dress British, think Yiddish!

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.

Randomized clinical trials (RCT) limits: Too much data Conflicting reports > difficult to

interpret Not enough time

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?

Meta-analyses may conflict with each other Limits in applicability

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

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

Limitations: Often incomplete, inconclusive, absent or

outdated Supplemented by lower levels of evidence

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

Disciplined, analytical, scientific approach that integrates all the relevant information in the search for the best diagnosis and therapy approaches for individual patients.

Contrast with

A context-dependent way of thinking and decision-making in professional practice to guide practice actions.

Higgs, J. Jones, MAClinical Reasoning in The Health Professions3rd Edition, pp 3-17, 2008

Clinical Reasoning = Clinical Decision Making

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

The individual patient, who is real and not the “average” patient, needs to be the main focus of our clinical care.

Skill sets: Synthesizing skills Recognizing prototypes Focusing on cues and

clues Using community

resources Dealing with uncertainty

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: Complexity Imagination

Essential to integrate the knowledge from RCTs into a specific clinical situation

Knowledge, experience, open-minded “out of the box” thinking

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)

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.

Croskerry P. Acad Med 2003;8(8):775 - 780

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.

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.

Ascertainment bias: occurs when a physician’s thinking is shaped by prior expectation; stereotyping and gender bias are both good examples.

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.

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.

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.

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.

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.

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.

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.

Gender bias: the tendency to believe that gender is a determining factor in the 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.

Hindsight bias: knowing the outcome may profoundly influence the perception 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 under-estimation (illusion of failure) or over-estimation (illusion of control) of the decision maker’s abilities.

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 three-diagnosis 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.

Omission bias: the tendency toward inaction and rooted in the principle of non-maleficence. 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.

Order effects: information transfer is a U-function: we tend to remember the 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.

Outcome bias: the tendency to opt for diagnostic decisions that will lead to good 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.

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.

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).

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.

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.”

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.

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.

Search satisfying: reflects the universal tendency to call off a search once something is found. Comorbidities, second foreign bodies, other fractures, and co-ingestants 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.

Sutton’s slip: takes its name from the apocryphal story of the Brooklyn bank-robber 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.

Sunk costs: the more clinicians invest in a particular diagnosis, the less likely they 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.

Triage cueing: the triage process occurs throughout the health care system, from 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.”

Unpacking principle: failure to elicit all relevant information (unpacking) in 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.

Vertical line failure: routine, repetitive tasks often lead to thinking in silos – 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?”

Visceral bias: the influence of affective sources of error on decision-making has 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.

Yin-Yang out: when patients have been subjected to exhaustive and unavailing 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.

Knowledge Data Gathering

Data Processing

Metacognition

Scaffolding Direct observation with feedback

RIME Diagnostic timeout

Strategies Presentation to diagnosis

Hypothesis-driven physical exam

Problem representation using semantic qualifiers

Awareness of cognitive biases

SNAPPS Reflection

Acute Chronic

Localized Diffuse

Single Multiple

Severe Mild

Intermittent Consistent

Previously healthy History Significant For…

Examples:

Reporter – Describes data Interpreter – Data processingManager – Plans what to doEffective/Education – Goes beyond

patient care – educates others

Summarize history and findingsNarrow the differentialAnalyze the differentialProbe teacher about uncertaintiesPlan managementSelect case-related issues for self study

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 decision-making 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.

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

drinkingH/O hypertension and hyperlipidemia

but no other health problemsAll systems WNL

After treating the pt for alcohol poisoning, what would you do next?a. Recommend AA meetingsb. Search the literature for rare

syndromesc. Do a complete GI workupd. Refer the pt for psychiatric disorder40% got it wrong

Breath tests for lactose and fructose intolerance

HydrogenGlucose toleranceEGD and colonoscopyStool cultures

Breath tests all negativeGlucose tolerance negativeEGD and colonoscopy negativeH. pylori isolated from stomachStool culture: Saccharomyces

cerevisiae (brewer’s yeast) and rare budding yeast

Pt admitted to hospital for 24-hour observation Belongings searched No visitors allowed

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

Revealed a few possible clues MEDLINE®, EBSCOhost

A few cases of gut fermentation and/or auto-brewery had been reported

Possible tests and antifungal treatments mentioned in literature

3-week course of fluconazole (Diflucan) 100mg/day

Followed by a 3-week course of nystatin 500,000 IU 4/day

Acidophilus tablets q dayNo sugar, no alcohol, no

carbohydrates during treatment

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

Dx of gut fermentation or auto-brewery syndrome

S. cerevisiae as probable causative agent

Success of treatment supports hypothesis

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

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 dailySubsequently, it looked more

like hives with increased pruritus.

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.

Paroxysmal hypertensionFibroid uterusAbnormal PAP test, remote pastAcute food poisoning 4-5 wks

earlier after eating a hamburger in a restaurant

Post infectious irritable bowel syndrome

T&A, age 5Appendectomy and partial right

colon resection for intussusception by a benign appendiceal tumor 18 years earlier

Repeated D&C’s, cervical biopsies

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

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

Intermittent loose bowel movements, bloating since the food poisoning

Occasional tension headaches

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)

Healthy appearing Caucasian woman in no acute distress

129#, 36.5°C, 140/96, 12-14, 68-70

HEENT: Normal mucosa, no edema Neck: Thyroid not enlarged or tender Lungs: Clear Heart: RR, murmur Abdomen: 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

CBC, platelets, differential – within normal limits

TSH 1.0 (0.5-5.20) ANAnegative CMPwithin 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 potassium-

hydrochlorothiazide, 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

Severe allergic reaction after first dose: continued azithromycin

Allergic symptoms cleared over 2-3 weeks

“IBS” symptoms cleared over < 1 week

SUBSEQUENT THERAPYSUBSEQUENT THERAPY

Azithromycin “Z- pak”Azithromycin “Z- pak”

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):1226-1229.

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: 169Diff 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 EKGAND 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 IslandGianandrea 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. MACPChief Division of Pulmonary and Critical Care MedicineLoma Linda UniversitySouthern 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 Bunyan1628-1688The Life and Death of Mr. Badman. 1680

TuberculosisPhthisisThe King’s EvilConsumptionThe White

PlagueLupus vulgarisScrofulaPott’s disease

Henry IV of France TouchingAndré de Laurens, 1609

Andrew Jackson James MonroeUlysses S. Grant

Thomas MannEugene O’Neill Albert Camus

Robert Koch Wilhelm RoentgenMarie Curie

Selman Waksman Nelson Mandela Paul Ehrlich

Anders Celsius Louis Braille Alexander Graham Bell

Frédéric Auguste Bartholdi

Dylan Thomas

Elizabeth Barrett Browning

Wolfgang von Goethe

Charlotte Brontë Anne BrontëEmily Brontë

Robert Burns

Maxim Gorky

Robert Louis Stevenson

Molière Henry David ThoreauSir Walter Scott

Immanuel Kant Baruch Spinoza

Voltaire

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