THE JOURNAL OF THE SOUTH DAKOTA STATE MEDICAL ASSOCIATION

Volume 70Number 7

July 2017

Volume 70 lNumber 7July 2017

The Journal of the South Dakota State Medical Association

ContentsPresident’s Comments291 A Productive Annual Leadership Conference – Robert E. Van Demark, Jr., MD

Editorial245 Pharmacogenomics and Mental Illness – Keith Hansen, MD

The Journal294 Atomoxetine Pharmacogenetics: Lessons Learned – David Ermer, MD;

Tamara Vik, MD

298 Brain Tuberculoma: A Case Report and Literature Review – Khalil Aloreidi, MD; Jamal Dodin, MD; Jeremy Berg, MD; Wendell Hoffman, MD

303 Physician Perceptions of Barriers to Advance Care Planning – Laura Fanta, MS II; Jill Tyler, PhD

311 A Rare Case of Lymphadenopathy: Kikuchi-Fujimoto Disease – Josh Rezkalla, MD; Douglas Lynch, MD

314 Treatment of Peritonsillar Abscess in Immunosuppressed Patients – Jed H. Assam, MS, MD; William C. Spanos, MD

319 Atrial Fibrillation Induced by Carbon Monoxide Poisoning and Successful Treatment with Hyperbaric Oxygen – Maheedhar Gedela, MD; Nathan Y. Weltman, MD, PhD; Naga Sushma Chavvakula, MBBS; Paul L. Carpenter, MD, FACC; and Tamera Sturm, DO

Pharmacology Focus322 Hepatitis C: Cured – Michael Lemon, PharmD

Extenuating Circumstances324 Clinical Ethics With All Her Matter-of-Fact – Ann Freeman Cook, PhD;

Jerome W. Freeman, MD, FACP

Special Features327 Quality Focus: The Appropriate Use of Antipsychotic Medicine

– Stephan D. Schroeder, MD

328 Board News – Margaret B. Hansen, PA-C, MPAS

331 Patient Education: Cancer and Keeping Your House in Order – Richard P. Holm, MD

Member News332 For Your Benefit: Shaping Your Profession

SDSMA Leaders Announced at Annual Leadership Conference

333 SDSMA Honors Members with Awards

334 Legal Brief Highlight: New Laws in Effect as of July 1

Scholarship Recipients Recognized at Annual Banquet

335 New Tool Helps Navigate MACRA

The Issue Is…Reducing the Opioid Epidemic

Advertisers In This Issue336 Physician Directory

Office of Publication2600 W. 49th Street, Suite 200Sioux Falls, SD 57105605.336.1965Fax 605.274.3274www.sdsma.org

EditorKeith Hansen, MD

SDSMA PresidentRobert E. Van Demark, Jr., MD

Chief Executive OfficerBarbara A. Smith

SDSMA Vice PresidentMark East, MS

Staff Editor Elizabeth Reiss, MS–ereiss@sdsma.org, 605.336.1965

Advertising RepresentativeElizabeth Reiss, MS–ereiss@sdsma.org, 605.336.1965

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291July 2017

President’s Comments

A Productive Annual Leadership Conference By Rob e r t E . Van D ema r k , J r . , MD

SDSMA P r e s i d e n t

Last month, I attended the South Dakota StateMedical Association (SDSMA) Annual LeadershipConference in Deadwood. Thanks to everyone whoattended the conference. I would also like to thank Dr.Tom Herman for his efforts as SDSMA president over thepast year. It has been a challenging year for ourAssociation. Tom’s leadership has been appreciated by allof us. A special thanks to the Executive Committee andnew Board of Directors. Congratulations to Dr. RobertMarciano, who was elected as policy council chair, andcongratulations to the newly elected at-large directors:Drs. Kara Dahl, Mark L. Harlow, and Lucio Margallo. Iwould also like to recognize the SDSMA staff. Theyalways do an exceptional job for our membership.

At our conference, we were honored to have theAmerican Medical Association (AMA) Chair-Elect Dr.Gerald E. Harmon as our guest and to hear what the AMAis doing on behalf of all physicians in our ever-changinghealth care environment. Dr. Harman spoke about theAMA positions on issues including the following: • The repeal and replacement of the Affordable Care Act (ACA);

• Physician burnout and what the AMA is doing to help; and

• The national opioid epidemic.

The University of South Dakota Sanford School ofMedicine Dean Dr. Mary Nettleman followed with anupdate on the medical school. This year’s graduating classhad a 100 percent residency match rate. Congratulationsto the new residents, and to the new incoming class.

Topics presented at our second annual membership openforum included contraception coverage, health care needsof people who are transgender, Maintenance ofCertification, physician training requirements, PhysicianOrders for Life-Sustaining Treatment (POLST), teen contraception, and Native American health care.

Following the open forum, a panel discussion focused onthe topic of physician burnout with panelists Drs. LaurieDrill-Mellum, Mark Harlow, Tad Jacobs, Tim Ridgway,and Craig Uthe. These experts provided advice on how wecan better understand and respond to burnout, reducesources of stress, and support physician wellbeing.

Dr. Drill-Mellum spoke at the SDSMA PAC luncheon.Her presentation was entitled “Clinical Health andWellbeing –Reducing the Cost of Impact of Physician

Burnout. Did you know that nearly 50 percent of physiciansexperience some type of professional burnout? One of thetop reasons for this is the increase in administrativeresponsibilities – increasing regulatory pressures andevolving payment and care delivery models – which reducethe amount of time physicians spend delivering directpatient care. Dr. Drill-Mellum is chief medical officer andvice president of patient safety solutions at MMIC. Wewere thrilled to welcome her at our annual conference toshare her expertise.

Following the luncheon, the Council of Physicians andthe Policy Council met. To those of you who have volun-teered your time serving on the Council of Physicians overthe years, I thank you. In 2016, our bylaws were changedand we have now entered our transition year. At the closeof our Council of Physicians meeting, our new PolicyCouncil was installed. The Council of Physicians and theExecutive Committee have now been replaced by the newPolicy Council and Board of Directors. The PolicyCouncil will meet twice a year and is charged with devel-oping and adopting policy. The Board of Directors will beinvolved with day-to-day management of the SDSMA.

Following the Policy Council meeting, the AwardsBanquet and Scholarship Recognition completed theConference day. Read more about the annual conferencein Member News on page 332.

It is an honor to be the president of the SDSMA. Ourorganization has a long and rich history. The first meetingof the then-named Dakota Medical Society was held June3, 1882 – 135 years ago. That meeting was held sevenyears before South Dakota became a state. That initialgathering was held in the parlor of the Grand CentralHotel in Milbank. Ten physicians attended the first meeting of the Society; attendance was limited because in1882 the railroad was still under construction betweenYankton (the Dakota Territory capital) and Aberdeen.One can only imagine the challenges of practicing medicine in Dakota Territory in 1882. What would thatgroup of pioneer physicians think about the practice ofmedicine in 2017?

As we enter this new year we face many challenges. Justlike past generations of physicians, I know we will worktogether to develop solutions that will promote the artand science of medicine and improve the health of ourpatients: the citizens of South Dakota.

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Iwould like to welcome our readers to this issue ofSouth Dakota Medicine and hope you will find the articles of interest. In this month’s edition we continuewith the point-counterpoint series evaluating personalizedmedicine through the use of pharmacogenetics in the useof the medication atomoxetine. The authors do an outstanding job of highlighting some of the controversiesthat surround the use of pharmacogenomics in mental illness. How does one use highly individual and specificinformation about the pharmacogenetics of a medicationto treat a heterogeneous group of diseases with commonpresentations? What is the effect of the blood-brain barrier? Is the medication or its metabolites even able toachieve therapeutic levels within the central nervous system? This manuscript highlights many of the challengesfacing the clinical application of pharmacogenomics.

Fanta and Tyler explore difficulties in advance care planning. The authors interviewed 19 physicians andqueried about difficulties they have encountered inadvance care planning.

This manuscript identifies a number of potential barriersto discussion of advance care planning with patients.Hopefully this manuscript can help raise awareness aboutthese complex challenges and improve physician-patientcommunication about end-of-life planning.

This month we also have a number of case reports andcase series. Assam and Spanos discuss peritonsillar abscesses developing in two immunocomprised individuals.The importance of diagnosis and appropriate treatment isemphasized. In this issue there is an article on an unusualcause of lymphadenopathy known as Kikuchi-Fujimotodisease. Kickuchi-Fujimoto disease can present with

concerning symptoms raising ones suspicion for lymphoma;however, it is a benign condition often treated withantipyretics and continued observation. This manuscriptreviews the management of lymphadenopathy and thisunusual condition. Gedela et al. also discuss an unusualpresentation of carbon monoxide poisoning, atrial fibrillation. The authors review the diagnosis and treatmentof this important condition. Aloreidi et al. discuss a caseof a patient presenting with brain tuberculoma and someof the challenges in making the diagnosis and treatingthese subjects. In this month’s edition of South DakotaMedicine, we have a number of thought-provoking casereports and manuscripts.

Editorial

Pharmacogenomics and Mental Illness B y K e i t h Han s e n , MD

Ed i t o r, S o u t h D a k o t a M e d i c i n e

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Atomoxetine Pharmacogenetics: Lessons Learned By Dav i d E rme r, MD ; and Tama r a Vi k , MD

Personalized medicine, also termed precision medicine,emphasizes treatments specific for individuals basedon their unique genetic characteristics. Becauseclinical traits represent a combination of genetic and non-genetic (environmental) factors, a major contributorto this approach is identifying an individual’s uniquegenetic make-up. Genetic factors can influence diseaserisk (risk of onset and/or rate of progression) as well as treat-ment response (efficacy and/or toxicity). Pharmacogeneticsis the study of genetic differences in treatment response.Some of these genetic factors can modify a drug’s mechanism of action (pharmacodynamics), whereas otherscan modify a drug’s metabolism (pharmacokinetics). Thecytochrome p450 (CYP450) enzymes are responsible formetabolizing more than 90 percent of medications.1 Whenstudying the CYP450 enzyme system variants, individualsare typically identified as poor, intermediate, extensive, orultrarapid metabolizers based on their genetic evaluation.2

Atomoxetine (Strattera) is one of the psychiatric medica-tions that is impacted by genetic variation in metabolism.

Atomoxetine is a potent norepinephrine reuptakeinhibitor (NRI) approved by the Food and DrugAdministration (FDA) for use in attention deficit-hyperactivity disorder (ADHD) in 2002.3 As the first nonstimulant medication approved for ADHD, it is animportant medication for the treatment of ADHD whenstimulant medications are contraindicated. However,most treatment algorithms list atomoxetine as a secondline agent as most studies show that stimulants havegreater efficacy. Atomoxetine has very clear weight baseddosing strategies, and it is also impacted by individualpharmacogenetic profiles. This paper explores characteristicsunique to atomoxetine, as well as discussing characteristicsof psychiatric medications in general.

One of the most pressing issues when studying psychiatricmedications is in defining mental illness. Psychiatric illnesses can be difficult to define with overlapping, subjective, and potentially unreliable symptom lists.

Psychiatric diseases are identified by having a collection ofsymptoms that do not necessarily correlate to measurableneurophysiologic processes. In other words, ADHD (alongwith most psychiatric illnesses such as depression andautism) is probably a heterogeneous group of diseases witha common clinical presentation. We are currently redefiningmental illness by studying measurable neuronal circuits,genes, and cells that correlate with emotional and behavioral disturbances.4 Once this paradigm shift occurs,it will be much easier to provide objective measures fordiagnosis and treatment response. Until then, we are leftto apply personalized precision medication to impreciseillness definition. The current state of psychiatric diagnosisdoes not allow for optimal study of pharmacogentic variables because we are dealing with a group of disorderswith a common clinical appearance. This would be akin tostudying malaise without looking at the underlying pathophysiology.

LandscapeInitially, atomoxetine was called tomoxetine and wasbeing developed as an antidepressant medication.5

Historically, however, the company never pursued thatindication for unclear reasons. The drug was later renamedatomoxetine to avoid confusion with the anticancer drugtamoxifen. Then in 2002 atomoxetine was approved foronce daily use to treat ADHD in children, adolescents,and adults by Eli Lilly and Company under the brand nameStrattera. The once a day dosing efficacy was surprisinggiven the short plasma half-life (approximately fourhours) of atomoxetine for most patients. This dosing paradigm was partly driven by the initial observation thatthe kinetics of atomoxetine metabolism varied widely inthe general population. According to Lilly ResearchLaboratories, “Perhaps the most striking finding of thisstudy is the evidence that despite the relatively short half-life of atomoxetine, once daily dosing in the morning wasassociated with effects that persisted into the evening.Factors other than time on receptor could be importantdeterminants of response or that pharmacokinetics in the

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central nervous system differ from those in the plasma.”6

Because atomoxetine is primarily metabolized through theCYP2D6 enzyme pathway, the manufacturer was requiredby the FDA to demonstrate that the drug was safe forCYP2D6 poor metabolizers. CYP2D6 is highly polymorphic;many gene variants exist, and it is common that patientsinherit an abnormal copy of this gene. Approximately onein ten patients (10% of the general population) inheritstwo nonfunctioning copies of CYP2D6.7 Currently, thepublished FDA guidelines for CYP2D6 is somewhat nonspecific. FDA recommends that for CYP2D6 poor metabolizers one should start at the normally recommendeddose and increase after 4 weeks if the “symptoms fail toimprove and the initial dose is well tolerated.” This is afairly routine clinical practice with or without pharmoco-genetic information. There are no FDA dosing strategyrecommendations for rapid metabolizers, and this mayvery well be a more important variant than poor metabo-lizers. Gene duplications are common and more than onein ten patients are rapid metabolizers for CYP2D6 (estimates vary from 10-30 percent depending upon country of origin and ancestry).

ImplementationAtomoxetine appears to have a very wide therapeuticwindow. A 2008 adverse drug reaction (ADR) studyshowed discontinuation rates of poor metabolizers at 6%vs 2% for extensive metabolizers which was not clinicallysignificant (p=.08), although statistical power was limitedand larger studies are needed.8 The response rate of poormetabolizers was higher than that of extensive metabolizers.Based on upon these potential differences in risk-benefitratio, early commercially available pharmacogenetic testreports had recommended using caution when an individualwas found to be a poor metabolizer. However, the evidencewould suggest that poor metabolizers may be better candidates for atomoxetine.

The studies have not been done, but there is speculationthat many of the nonresponders in atomoxetine studieswere extensive and ultra-rapid metabolizers who wereconsiderably under dosed. Atomoxetine follows linearkinetics so rapid metabolizers may have a 10-fold lowerplasma level than poor metabolizers. Ultra-rapid metabolizers may have a 20-fold lower plasma level.Unfortunately, studies linking plasma drug levels (therapeutic drug monitoring), pharmacogenetic status,and efficacy have not been done with atomoxetine. Foratomoxetine, pharmacogenetic studies may prove moreuseful in impacting dose strategies for rapid metabolizers

rather than avoiding side effects in individuals who arepoor metabolizers.9

In summary, no salient changes in dose strategies are recommended for atomoxetine poor metabolizers as atomoxetine has a fairly mild side effect profile even athigh levels. Extensive and ultrarapid atomoxetine metabolizers, on the other hand, may need higher dosing.At this time, studies have not been done to determinewhat those dosing strategies should be. Additionally, thedose strategies would more than likely recommend atomoxetine doses that are much higher than those currently approved by the FDA. Based on current information, it is not clear that pharmacogenetics studiesadd any valuable clinical information when prescribingatomoxetine. Furthermore, if clinicians had followed initial pharmacogenetics guidelines warning about usingatomoxetine in individuals with poor metabolizer status,they could have excluded a useful and important medicationfor their patients.

Future OutlookIt is a common misunderstanding that pharmacogeneticshas reached a point where one can use the informationgained to determine the effectiveness of a psychotropicmedication and not solely to understand how one metab-olizes the medication. Our experiences with atomoxetineprovide several valuable lessons as we move forward utilizing genetic studies of drug metabolism to personalizeprescribing and improve patient outcomes. Most impor-tantly, pharmacokinetic factors need to be taken into consideration when evaluating genetic information. Foratomoxetine and many other medications, plasma levelsof the medication do not always correlate to clinicalresponse. Therefore, other pharmacodynamic factors (andpharmacokinetic factors beyond metabolism) are involvedwith atomoxetine response. Given that serotonin reuptakeinhibitors increase serotonin levels immediately, whileoptimal clinical response can take weeks or months andbenefits of these antidepressants are realized even after themedications are stopped, genetic variation in mechanism(receptors, G-proteins and signal transduction) is likely tobe a strong contributor. Thus, the clinical efficacy of mostpsychiatric medication is quite complex, and absorptionand distribution appear to be just as important as metabolism and elimination.10 For example, the geneticsof blood-brain barrier function may prove to be just asimportant as (or even more important than) genetic studies of drug metabolism for psychiatry, because mostpsychiatric medications act at brain receptors.

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Atomoxetine has shown us that pharmacogenetics studiesneed to be evaluated in the context of therapeutic bloodmonitoring and efficacy studies. The utility of pharmaco-genetics studies with atomoxetine will be greatlyenhanced once metabolizer status is correlated with therapeutic drug monitoring and outcome. At the presenttime, we are only left to guess at dosing strategies in individuals who are rapid and ultrarapid metabolizers ofatomoxetine. If an optimal blood level is determined, itmay be more predictive to check a blood level of the drug(phenotype) rather than the pharmacogenetic status(genotype).

Pharmacogenetic studies may not be as useful for medica-tions with a wide therapeutic index like atomoxetine.Drugs that have more individual variations in responseand severe potentially life-threatening side effects may bebetter initial candidates for pharmacogenetics studies.Nonetheless, as our knowledge continues to grow and testing costs fall, pharmacogenetics studies will be utilizedmore and become an increasingly accessible tool in individualized patient care.

Acknowledgements: The authors thank Dr. Russell A. Wilke for helpful guidance and support during preparation of this manuscript.

REFERENCES1. Hicks JK, Bishop JR, Sangkuhl K, et al. Clinical Pharmacogenetics Implementation

Consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing ofselective serotonin reuptake inhibitors. Clin Pharmacol Ther. 2015;98(2):127-34.

2. Chen Q, Zhang T, Wang JF, et al. Advances in human cytochrome p450 and per-sonalized medicine. Curr Drug Metab. 2011;12(5):436-44.

3. Eli Lilly and Company. Package Insert, Strattera.4. Insel TR. The NIMH research domain criteria (RDOC) project. Precision medicine

for psychiatry. Am J Psychiatry. 2014; 171(4):395-7.5. Zerbe RL, Rowe H, Enas CG, et al. Clinical pharmacology of tomoxetine, a poten-

tial antidepressant. J Pharmaco Exp Ther. 1985;232:139-43.6. Michelson D, Allen AJ, Busner J, et al. Once-daily atomoxetine treatment for chil-

dren with adhd: a randomized, placebo-controlled study. Am J Psychiatry.2002;159(11):1896-901.

7. Pinto N, Dolan ME. Clinically relevant genetic variations in drug metabolizingenzymes. Current Drug Metab. 2011;12(5):487-97.

8. Trzepacz PT, Williams DW, Feldman PD, et al. CYP2D6 metabolizer status and ato-moxetine dosing in children and adolescents with ADHD. EurNeuropsychopharmacol. 2008;18:79-86.

9. De Leon J. Translating pharmacogenetics to clinical practice: Do cytochromeP450 2D6 ultrarapid metabolizers need higher atomoxetine doses? J Am AcadChild Adolesc Psychiatry. 2015;54(7)532-34.

10. Wilke RA, Reif DM, Moore JH. Combinatorial pharmacogenetics. Nature ReviewsDrug Discovery. 2005;4:911-8.

About the Authors:David Ermer, MD, Associate Professor, Department of Child and AdolescentPsychiatry, University of South Dakota Sanford School of Medicine; Sanford ClinicPsychiatry and Psychology, Sioux Falls, South Dakota.Tamara Vik, MD, Assistant Professor, Department of Child and Adolescent Psychiatry,University of South Dakota Sanford School of Medicine; Child and AdolescentPsychiatry Residency Director; Avera Medical Group University PsychiatryAssociates, Sioux Falls, South Dakota.

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IntroductionCentral nervous system (CNS) involvement is one of themost devastating clinical manifestations of tuberculosis(TB), is noted in 5-10 percent of extrapulmonary TB casesand accounts for approximately 1 percent of all TB cases.The World Health Organization has estimated that one-third of the world’s population is infected with TB.1 Themortality rate of TB is unacceptably high, but with a timelydiagnosis and correct treatment, a high percentage ofpatients with TB can be cured.

National reporting of TB cases in the U.S. began in 1953.Between 1993-2012, the annual incidence of reported TBcases was declining. Data for 2013-2015 indicate that aftertwo decades of declining incidence, progress toward TBelimination in the U.S. appears to have stalled. A total of9,421 TB cases (a rate of three cases per 100,000 persons)were reported in the U.S. in 2014.2 During the last 10years, the state of South Dakota has averaged 14 TBpatients per year, including one case of CNS TB.Seventeen cases total were reported in 2015.3

CNS TB manifests as meningitis, encephalopathy, vasculopathy, brain abscess, tuberculoma and vertebralspondylitis.4 In regions where the incidence rates are low,such as North America and Western Europe, extrapulmonarymanifestations of diseases are seen primarily in adults witha reactivation infection.5 A history of tuberculosis is

present in only approximately 10 percent of thesepatients.6 The presence of active pulmonary tuberculosison chest X-ray ranges from 30-50 percent.7

Case ReportA 44-year-old male who immigrated from Sudan to theU.S. 15 years ago developed a headache and low-gradefever for a week. His vital signs were normal except for atemperature of 100.2 degrees Fahrenheit. He was alert andoriented to place, person, and time. He had no focal neurological deficits or meningeal signs. A computerizedaxial tomography (CAT) scan of the head showed a rightfrontal hypodensity, which was concerning for infarctionor tumor. An MRI scan of his brain revealed two ring-enhancing lesions in the right temporoparietal region andthe posteromedial aspect of the right cerebellar hemisphere(Figures 1 and 2).

A cerebrospinal fluid (CSF) exam showed a glucose of 49(50-80 mg/dL), a protein level of 108.7 (12-60 mg/dL) andwhite blood cell count of 101 (0-5/uL) with 91% lympho-cytes. CSF microbiology workup was initially unrevealingwhich included a bacterial Gram stain and culture, acid-fast bacilli stain, and TB polymerase chain reaction. CSFcytology was negative for lymphoma. Syphilis, HIV, fun-gal, and viral studies were negative, as was the result of thecysticercosis serology.

The patient reported a history of latent TB which was

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Brain Tuberculoma: A Case Report and Literature Review By Kha l i l A l o r e i d i , MD ; J ama l Dod in , MD ; J e r emy Be r g , MD ; and

Wende l l Ho f fman , MD

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AbstractWe are reporting on a rare case of central nervous system tuberculosis (TB) in the state of South Dakota. Ourcase features one of the most infrequent forms of TB in the brain: multiple tuberculomas. A 44-year-oldimmunocompetent man was admitted complaining of a headache and fever for a week. His physical exam wasunremarkable. A magnetic resonance imaging scan of his brain showed two ring-enhancing lesions. The largestlesion was excised surgically and the histopathology exam was consistent with tuberculoma. We will discuss inthis report various aspects of this rare disease in term of epidemiology, diagnosis, and treatment.

treated with six months of isoniazid (INH) when he initially moved to the U.S. Given this fact, a chest X-raywas done looking for evidence of TB and it was normal buthis serum QuantiFERON test was strongly positive,greater than 10 (less than 0.35). As the workup so far wasinconclusive, a brain biopsy was planned. A right fron-toparietal craniotomy was performed and a 1.2 x 1.0 x 0.6cm circular mass was excised from the right parietal lobe.The mass was hard and fibrous, with a well-demarcatedborder. Histopathology of the mass demonstrated a largearea of central caseating necrosis ringed by chronic lymphocytic inflammation, epithelioid macrophages, andmultinucleated giant cells. Fungal stains with Gomorimethenamine silver were negative for organisms. The tissue was then stained with Auramine-O and examinedunder an ultraviolet laser microscope, which revealed rareacid-fast bacilli that were morphologically consistent withMycobacterium tuberculosis (Figures 3 and 4).

The patient was then started on an anti-TB regimen,which consists of two months of isoniazid (INH),rifampin, pyrazinamide, and levofloxacin, followed by 16months of INH and rifampin. He was also started on prednisone 60 mg/day for two weeks, followed by gradualtapering dose over the next six week for a total of eightweeks of steroid treatment. The patient did well after the

initiation of treatment in the hospital, experiencing a resolution of his symptoms. Ultimately, his CSF culturetest was positive for Mycobacterium tuberculosis (MTB)complex which was sensitive to the first line therapy. AnMRI brain scan a month after treatment initiation showedan interval decrease in the posteromedial right cerebellartuberculum. The patient continues to do well.

DiscussionApproximately one-third of the world’s population is currently infected with tuberculous bacillus, of whichapproximately 5-10 percent become sick or infectious atsome time during their life.1 Tuberculosis is among themost lethal infectious diseases worldwide, especially whenit comes to its rarest form, CNS TB. Tuberculous meningitis (TBM) is the most common form of CNS TB,followed by tuberculomas, which are granulomas formedby an interaction between the mycobacterial pathogenand the host’s immune response.

Intracranial tuberculomas manifest with features of aspace-occupying lesion of the brain including headache,vomiting, drowsiness, papilledema, focal or generalizedseizures, and focal neurological deficits or even hemiparesis.Symptoms of systemic illness and signs of meningealinflammation are rarely observed. CAT and MRI scans of

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Figure 1. Axial T1-weighted MRI showing an 11 mm ringenhancing lesion in the right temporoparietal region (arrow)

with surrounding edema.

Figure 2. Axial T1-weighted MRI showing an 8 mm enhancinglesion associated with a small amount of surrounding edema

in the right cerebellar hemisphere (arrow).

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Figure 3. Granuloma showing caseating necrosis (right side), lymphocytic inflammation (red arrow) and multinucleated giant cells (yellow arrows) (20x)

Figure 4. Fluorescent microscopy with Auramine-O stain shows an acid fast rod consistent with Mycobacterium tuberculosis (50x).

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tuberculomas demonstrate the typical features of contrast-enhancing ring lesions with surrounding edema. Theselesions can be multiple in up to 15-33 percent of the cases.8

Unlike CAT scan, MRI is better in demonstrating smalllesions and those in the posterior fossa and brainstem.9 Butneither of these imaging modalities is able to reliably distinguish tuberculoma from other causes of ring-enhancinglesions, in particular, pyogenic bacterial abscess, neurocys-ticercosis, toxoplasmosis, or neoplasia.10 In the early stagesof tuberculoma, the lesions are low density or isodense,often with edema out of proportion to the mass effect andlittle encapsulation. Later-stage tuberculomas are well-encapsulated, isodense or hyperdense, and have peripheralring enhancement.11

Maintaining a high degree of suspicion is vital in order toinitiate therapy promptly because the diagnosis of CNStuberculoma remains challenging, as granulomatousencasement may preclude MTB detection in serum orCSF samples. Typically, with TBM, the CSF picture showselevated protein and lowered glucose concentrations withlymphocyte pleocytosis.12 But with tuberculoma, the findingsare normal or nonspecific. Acid-fast bacilli are less commonly found in the CSF of patients with cerebraltuberculoma compared to those with TBM,13 and tissue

examination is usually required to confirm the diagnosis.

Treatment of TB should be started based on strong clinical suspicion, even before having culture proof, asdelaying therapy can result in devastating outcomes.Treatment include two months of four anti-tuberculosisagents with good CNS penetration, followed by a longerperiod of INH and rifampin. The four agents should notinclude ethambutol, as it does not reach a high enoughconcentration in the CSF.14 INH, pyrazinamide, andrifampin can be used, in addition to a fluoroquinolone oran injectable aminoglycoside.15 Eighteen months is recommended for the treatment of tuberculomas. In addition, glucocorticoid therapy of either dexamethasoneor prednisone should be added to the regimen for total ofeight weeks to prevent any potential neurological sequelaeof the treatment.

ConclusionTuberculoma of the brain can be challenging to diagnoseand treat. Maintaining a high degree of suspicion and initiating treatment early is crucial. Fortunately, CNStuberculoma prognosis has improved dramatically duringthe last several decades, from a nearly fatal diagnosis toover an 80 percent survival rate.16

REFERENCES

1. World Health Organization. Global Tuberculosis Report 2015. WHO; 2015.2. Reported tuberculosis in the United States, 2014. Atlanta, GA: US Department of

Health and Human Services, CDC;3. South Dakota Department of Health. Tuberculosis control program annual report,

2015.4. Cherian A, Thomas SV. Central nervous system tuberculosis. Afr Health Sci.

2011;11(1):116-27.5. al-Deeb SM, Yaqub BA, Sharif HS, Motaery KR. Neurotuberculosis: a review. Clin

Neurol Neurosurg. 1992;94 Suppl:S30-3.6. Sütlaş PN, Unal A, Forta H, Senol S, Kirbaş D. Tuberculous meningitis in adults:

review of 61 cases. Infection. 2003;31(6):387-91.7. Thwaites GE, Duc Bang N, Huy Dung N, et al. The influence of HIV infection on

clinical presentation, response to treatment, and outcome in adults with tubercu-lous meningitis. J Infect Dis. 2005;192(12):2134-41.

8. Hejazi N, Hassler W. Multiple intracranial tuberculomas with atypical response totuberculostatic chemotherapy: literature review and a case report. Infection.1997;25(4):233-9.

9. Sonmez G, Ozturk E, Sildiroglu HO, et al. MRI findings of intracranial tuberculomas.Clin Imaging. 2008;32(2):88-92.

10. Garg RK, Desai P, Kar M, Kar AM. Multiple ring enhancing brain lesions on com-puted tomography: an Indian perspective. J Neurol Sci. 2008;266(1-2):92-6.

11. Whelan MA, Stern J. Intracranial tuberculoma. Radiology. 1981;138(1):75-81.12. Karandanis D, Shulman JA. Recent survey of infectious meningitis in adults:

review of laboratory findings in bacterial, tuberculous, and aseptic meningitis.South Med J. 1976;69(4):449-57.

13. Baker CA, Cartwright CP, Williams DN, Nelson SM, Peterson PK. Early detectionof central nervous system tuberculosis with the gen-probe nucleic acid amplifica-tion assay: utility in an inner city hospital. Clin Infect Dis. 2002;35(3):339-42.

14. Blumberg HM, Burman WJ, Chaisson RE, et al. American ThoracicSociety/Centers for Disease Control and Prevention/Infectious Diseases Society ofAmerica: treatment of tuberculosis. Am J Respir Crit Care Med. 2003;167(4):603-62.

15. Chemotherapy and management of tuberculosis in the United Kingdom: recom-mendations 1998. Joint Tuberculosis Committee of the British Thoracic Society.Thorax. 1998;53(7):536-48.

16. Idris MNA, Sokrab TEO, Arbab MAR, et al. Tuberculoma of the brain: a series of16 cases treated with anti-tuberculosis drugs. Int J Tuberc Lung Dis.2007;11(1):91-5.

About the Authors:Khalil Aloreidi, MD, Resident, Department of Internal Medicine, University of South Dakota Sanford School of Medicine.Jamal Dodin, MD, Resident, Department of Internal Medicine, University of South Dakota Sanford School of Medicine.Jeremy Berg, MD, Resident, Department of Pathology, University of South Dakota Sanford School of Medicine.Wendell Hoffman, MD, Clinical Professor, Department of Infectious Disease, University of South Dakota Sanford School of Medicine.

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Physician Perceptions of Barriers to Advance Care Planning By L au r en F an t a , MS I I ; a nd J i l l Ty l e r, PhD

AbstractBackground: Numerous studies have confirmed the importance of advance care planning. Despite the benefits ofdirected end-of-life (EOL) discussions, a variety of barriers including discomfort with the topic, physician ideology, lack of time and reimbursement, delaying discussions, and lack of training impede physicians fromfacilitating these crucial conversations with their patients. This study aims to understand physicians’ perceptionsto additional barriers to advance care planning with patients and their families.

Methods: Interviews with 19 practicing physicians (seven women and 12 men). Their perceptions were noted ininterviews that were audiotaped, transcribed, and analyzed (n = 19).

Results: Physicians continue to face barriers to advance care planning as well as struggle with additional challenges such as difficulty with families, lack of patient education, inconsistencies and accessibility of advancedirective documents, and lack of physician-physician communication or agreement in care. Further analysisreveals contradictions regarding physician comfort level and the role of primary care. These results reveal thecomplexity of providing medical care and the continued need for improvements in physician-patient communication about EOL care.

Conclusions: Complex challenges in communication impede the delivery of successful EOL experiences forpatients and their families. With improvements in the practices of advance care planning, many of these challenges can be removed – enabling individuals to remain in control as they near the end of their lives andpreventing unnecessary pain and suffering on behalf of the patient and family.

IntroductionIn recent decades, there has been rising recognition of theshortfalls in end-of-life (EOL) care, including potentiallyunwanted or unwarranted interventions and lack of clinician knowledge regarding patient preferences.1,2 The2014 Institute of Medicine report, Dying in America,acknowledges the inadequacies in EOL care but is optimistic about the potential benefits of advance careplanning (ACP).3 ACP encompasses any discussion ofEOL care, such as discussion of values and goals of care,and should occur with the patient’s primary clinicianbefore the patient’s condition deteriorates.3,4 Patients whohave these EOL discussions with their doctors are morelikely to have their wishes known and respected and lesslikely to receive aggressive treatments than those without,

and family members report higher satisfaction and are lesslikely to develop major depressive disorder, experienceregret, or feel unprepared for the patient’s death.1,5 ACPenables patients and families to prepare mentally andemotionally for death, allows patients to stay involved andmaintain some control, and can alleviate the burden ofdecision-making on family members.6,7 Despite the apparent benefits, a review of the literature reveals thatphysicians are struggling to facilitate ACP conversationswith their patients. Barriers to discussion include physician and patient discomfort with the topic of death,8-11

physicians continuing to recommend curative treatmentsgiven the perception of death as a failure,12-14 a delay onthe part of the physician to initiate discussion due to difficulties prognosticating and reluctance to destroy the

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patient’s hope,15-17 a systemic shortage of time and reimbursement,3,18-20 and a failure to adequately addressthese topics in medical education.3,21-23 Due to the mountingevidence confirming the value of ACP, understandingadditional reasons that such conversations are not occurringis vital to the future well-being of physicians, patients, andtheir families. Only after barriers are identified and analyzed can potential ways to overcome, negotiate, andeven eliminate these barriers be initiated.

Accordingly, qualitative interviews were conducted toexplore the experiences and emotions of practicing physi-cians. Analysis reveals greater complexity, contradiction,and insight than has been previously described.

MethodsQualitative interviewing is used to gain an understandingfrom the participant’s point of view and is beneficial in thestudy of occurrences that are not easily observable.24 Thefact that these were self-reporting interviews allowedphysicians to use their own words to reflect upon EOL caresituations and to identify their own understandings of barriers to these discussions.

University of South Dakota Institutional Review Boardapproval (exempt) was obtained in March 2015. A snowball sampling method was used as recruitment emailswere sent to potential participants requesting first theirparticipation and then asking that they forward the emailon to other physicians who may be interested. Familypractice, internal medicine, and subspecialists in internalmedicine were targeted due to the likelihood that theyhad encountered and counseled patients at the EOL. Face-to-face interviews were scheduled at a time and locationconvenient for the participant. Interviews began in May2015 and continued through August 2015 upon identification of data saturation. All interviews were conducted by the student investigator.

Nineteen participants were included in this study. All 19were practicing physicians from South Dakota andNebraska. Eleven primary care physicians including sixfamily practice and five internal medicine doctors, andeight specialists including two hospitalists, two pulmonologists, and one each in nephrology, cardiology,oncology, and emergency medicine were interviewed. Theyears in practice ranged from two to 37 with a mean of 18.5years. There were seven female and 12 male physicians inthis study. Each physician was randomly assigned a pseudonym to preserve subject anonymity.

Interviews lasted approximately 20 minutes and wereaudio recorded. An informed consent document was usedto confirm that participants agreed to be recorded and thatparticipation was voluntary. The semi-structured interviewprotocol was designed to encourage physicians to speakopenly and spontaneously about physician-patient communication and EOL care. Interviews began with ageneral question about an experience involving EOL carecommunication followed by questions about what physicians perceived as successful and unsuccessful interactions. The interview became more focused as physicians were asked to identify additional barriers andpotential solutions to problems in EOL care. Further questions examined the use of advance directives, hospice,and palliative care.

Audio-recordings were transcribed following each interview. Grounded theory, “an analytical process thatculminates in the development of a formal, propositionaltheory,” was used in the analysis.24 After several carefulreadings of the transcripts, the textual data was labeledand unitized by the project director and the student investigator. Trends and common themes emerged whichwere grouped into comprehensive, carefully defined categories. Some of the data supported the previouslyidentified list of barriers while the unique perspectives ofpracticing physicians, rare in studies of this sort, revealednew barriers which were not present in prior reports.

ResultsThis study confirmed many of the barriers to advance careplanning identified in previous literature, including discomfort with the topic, physician ideology, lack of timeand reimbursement, delaying discussions, and lack oftraining, but also revealed additional challenges thatphysicians face when facilitating a successful EOL experi-ence for patients and their families. The results of theinterviews are reported according to the four prevalentthemes that emerged upon analysis. Physician contradictionsand solutions to problems in EOL care are also included.

Family Disagreement

The most frequently mentioned problems reported byphysicians involve the patients’ families. Almost all physi-cians mentioned some sort of turmoil that results due tofamily denial, grief, and disagreement.

Michael: And the problem usually arises, not with thepatient, but with the patient’s family. And frequently it’sin families that have a lot of conflict. Where parent and

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child have a problem that dates back 40 years…And thechild thinks if you can just make mom or dad live foranother week, we can get this sorted out.

Many physicians stated that families with previous conflict or feelings of guilt tend to experience the mostproblems. Furthermore, physicians indicated that often,the family members that cause the most difficulty arethose from farthest away geographically. These membersare most often removed from the situation and uninvolvedin the patient’s care until times of crisis.

Ian: The problem is the child that they have fromCalifornia, or who knows where, who hasn’t seen momor dad in six, seven years and now all of a sudden arehearing that mom or dad are near the end-of-life andthat can’t possibly be. ‘We need a better doctor. Weneed a Mayo Clinic. We need something more.’

However, family is not always a barrier as one physicianstated and many others implied through their reflectionson successful experiences involving family involvementand agreement.

Nathan: She had a very supportive family. And we spenta lot of time talking about her options and where wemove. We talked a lot about what her life goals were astime went on….She ended up passing away peacefully afew months later, but that overall went pretty smooth.

Lack of Patient Understanding and Education

Physicians reported trying to have EOL discussions withtheir patients; however, patients are often misinformedregarding the reality of their disease process and the capabilities of medicine. This makes facilitating appropriatecare difficult.

Heidi: It seems that when you talk about end-of-lifecare, to me the general public just thinks that they aregoing to live forever. And that you’re going to give memedications – we have technology and it’s going to getbetter.

Many physicians mentioned that it would be easier to helppatients at the end of their life if the general public weremore knowledgeable about their options for EOL care.

Paul: I think that’s probably where there is a lot of roomfor improvement…helping patients understand the disease process and how to manage symptoms and youknow, going to the emergency department or beingadmitted to the hospital when you have a chronic

terminal illness is not the best way to do that.

Physicians expressed the most frustration with patients’lack of understanding of hospice and palliative care.

Pamela: When talking about hospice or palliative carethey think, ‘Oh I’m just going to die,’ and it’s like, ‘No,that’s not what we’re saying.’

Difficulties in the Management of Advance Directives

Difficulties with the administrative practices associatedwith advance directives (AD) present another challengeto physicians. Although ADs are intended to grantpatients autonomy at the end of their lives, many physicians acknowledged that it doesn’t always work thatway. According to physicians, one difficulty with ADs isthat they are not standardized. Many physicians recalledsituations in which patients would go to a lawyer to fill-out an AD and return with a document that was notuseful.

Brian: And a lot of [ADs] are filled out by lawyers; nothing against lawyers, but it doesn’t often involvelanguage that is practically useful to a physician leadingtheir care.

Other physicians expressed frustration that, as the doctorsmanaging their patient’s care, even they have difficultyinterpreting ADs.

Ian: When I’m admitting a patient the last thing I dobefore I walk out of the room is I discuss code status.And I can’t tell you how many times I’ve gotten ‘I haveadvance directives,’ and uniformly nobody has a damnclue what that means! I don’t know what that means.It’s always somebody’s version of a six to 12 page document that I can’t understand.

In addition to the lack of standardization, many physiciansdiscussed other problems with ADs. Often, a written document is not present in an acute situation. They arealso not always followed despite the fact that they areunderstood to be a legal document.

Disagreement and Lack of Physician-PhysicianCommunication

Disagreement and lack of communication among physicians are additional barriers that physicians repeatedlyidentified. Physicians do not always agree with their colleagues on the best method of treatment for a patient,resulting in difficulty at the EOL.

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Pamela: I remember in residency a few instances whenphysicians did not always agree on things which made itharder. For example, somebody with a cancer diagnosiswhere they have been admitted multiple times and itseems like, okay, ‘is this somebody who we should be –or could be – considering looking more toward comfortor palliative care sort of situation versus aggressive treat-ment?’ And maybe the oncologist felt there’s still someother things that we can do, more that we can do. Andprimary felt, but how much is that really going to benefit them? And that’s where it can be a struggle, too.

Interestingly, several physicians specifically mentionedthat oncologists were more aggressive in continuing torecommend additional medications and treatments. Anoncologist also acknowledged that discussion of hospiceand palliative care does not always occur soon enough anddescribed the challenge faced by cancer specialists.

Sherry: Who’s going to be giving that conversation? Isit going to be the oncologist who’s going to talk aboutend-of-life care? Is it going to be the primary carebecause some primary care doctors bring it up and discuss it?

Clearly, there is disagreement among physicians as to thebest treatment plan for a given patient as well as whichprofessionals should be facilitating EOL discussions.

While the preceding factors were repeated throughout theinterviews and generally agreed upon among physicians,analysis reveals that physicians made statements that con-tradicted one another and even themselves.

Physician Contradictions

When asked if they were comfortable discussing EOL carewith their patients, all but one physician answered yes.Throughout the interviews, however, physicians madestatements that suggested otherwise. After stating thatthey felt comfortable having the discussion, one physicianlater admitted, “I’m not sure there is a comfortable” (Ian),and another disclosed, “So it’s uncomfortable to talk aboutdeath” (Michael). Physicians also conveyed the notionthat although they may be comfortable discussing EOLoptions, their colleagues are not. Furthermore, while mostphysicians said they were comfortable, many mentionedthe need for improvements in medical education on thesubject.

Another discrepancy expressed by physicians regards therole of primary care. Many doctors believed that it is the

duty of the primary care physician to address EOL issueswith their patients.

Natalie: I think it is really our responsibility as physi-cians – I’m not saying dermatologists and radiologists –but certainly as internists, family physicians, evenOBGYN people, people who are really doing primarycare, to address these issues with their patients.

Primary care physicians specifically addressed the pivotalrole that they play at the EOL.

Heidi: And then I think primary care probably has areally big role. Because I can see all the specialiststhey’ve seen, look at it all, and then present it to thepatient and say, ‘let’s take a step back.’

Physicians conveyed that patients are often much morereceptive to discussions about the EOL with someone theyknow and trust, and one primary care physician evenclaimed, “If you know the patient well, there really are nobarriers” (Nolan). Although physicians recognize theimportance of longstanding relationships and the trustthat primary care physicians are able to establish withtheir patients, many of these same physicians admittedthat they do not have enough time to discuss patient preferences for EOL care. One even suggested that the primary care physician is not the right person for the job.

Benjamin: I don’t know if the primary care physician isthe right person to do this or not. Because with all honesty primary care is over-burdened with too manythings.

These contradictions reveal some of the complexities thatcomplicate EOL care. While there are some aspects thatphysicians seem to agree upon, clearly there are othersthat they do not.

Doctors’ Solutions

When asked directly, physicians had many ideas for solu-tions to the problems associated with EOL care. Severalmentioned improvements in physician and patient educa-tion including more continuing medical education hoursfor physicians as well as seminars, public announcements,brochures, or television broadcasts for the public.

Floyd: I think one of the things is to educate patientsand the family more. Maybe if it’s through television. Ifthere are things we could have here at the clinic, youknow, little brochures or things in the room or havingthe nursing staff mention that to them sometimes when

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they check them in. Just things to bring it up for themat times.

Increasing the utilization of hospice and palliative carewas also recommended and several physicians suggestedcontinued improvements in communication.

Pamela: Trying to get as much of that discussion done asa routine thing on an outpatient basis is huge. I thinkthat is the biggest thing.

Some participants acknowledged the need for more systemic changes in the assumptions that are made regarding EOL care. One physician suggested that do notresuscitate (DNR) orders should be assumed for everypatient unless the patient specifically states otherwise.Another physician suggested that the Medicare paymentsystem should require patients to be responsible for a portion of the cost. While these later ideas represent adeparture from current medical practice, they reveal aglimpse into the minds of physicians who are struggling todeliver quality care to their patients. Clearly, the issuessurrounding communication at the EOL are complex andcannot be solved simply. As one physician put it, “it’sgoing to be a constant struggle” (Pamela).

DiscussionA major finding of this study is that significant and complex barriers prevent physicians from discussing EOLcare with their patients. Almost all physicians discusseddifficulty with family members who have unrealisticexpectations or have experienced previous family conflict.Some physicians described successful experiences inwhich family was engaged and supportive, demonstratingthe importance of family communication and involvementin EOL decision-making. In a multicenter survey of 1,256clinicians, family members’ or patients’ inability to accepta poor prognosis, family members’ or patients’ difficultyunderstanding the limitations and complications ofaggressive treatments, and disagreement among familyabout goals of care were identified among the most important barriers to goals of care discussions.25 This finding as well as the findings of this study suggest thatphysicians should encourage patients to communicatetheir EOL wishes to their family in an attempt to avoiddisagreements at the EOL.

Another obstacle physicians face concerns the lack ofpatient knowledge and understanding. Physicians voicedfrustration that in general, the public holds unrealisticexpectations of medicine and has considerable misunder-

standings of hospice and palliative care. In a survey conducted by the Center to Advance Palliative Care, 78percent of participants stated they did not have a basicunderstanding of palliative care, suggesting that manyAmericans lack knowledge about EOL care choices.26

Improving community awareness through programs sponsored by health care institutions in the community aswell as increasing the prevalence of both in-patient andout-patient palliative care teams could help to alleviatethis problem.

Inadequacies with ADs represent yet another barrier tosuccess given that ADs are not specific and are oftenworded in a way that makes them difficult to understand.This poses a significant problem in EOL care as physiciansare forced to infer what the patient may or may not havewanted. In addition, ADs are not always present whenneeded and are not always followed when they are present.While inadequacies with ADs can be found in the literature3, this study revealed the degree of frustrationthat many physicians feel when working with the documents and underscores the need for a standardizedand simplified advance directive.

Finally, physicians recalled that disagreement among doctors regarding patient care in conjunction with a lackof inter-professional communication are problematic. Thisdemonstrates that issues of responsibility for ACP havenot been negotiated at the policy level, or at institutionalor community levels.

This study also exposed some interesting contradictionsamong physicians. When asked, all but one physician saidthey were comfortable discussing EOL care with theirpatients. However, many physicians later described difficulties initiating and guiding these conversations,admitting their discomfort and allowing that even if it wasnot uncomfortable for them, it may be uncomfortable fortheir colleagues. Furthermore, the same physicians whoclaimed to be comfortable with EOL discussions still suggested the need for more education and training. Thisreveals that doctors are not as comfortable with the discussion as they may perceive themselves to be and needfurther training before they can become more effectiveand confident facilitating these discussions.

Ambivalence was also expressed in perceptions of the roleof primary care. Many doctors believed that primary carephysicians are best suited to have EOL care discussionswith patients. However, many also acknowledged that primary care doctors are overburdened and too busy to

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facilitate these long and potentially difficult discussions.Physicians seem to be pushing the conversation on totheir colleagues and failing to effectively communicatewith one another to establish responsibility for thisdimension of care. In addition, this finding suggests thatthe conversation ideally should occur with a patient’s primary care clinician, but without changes to the currentsystem, this may not be feasible.

This research also reflected physician perceptions of thecontinued need for improvements in EOL care. Physicianssuggested the need for more education directed at bothpatients and physicians as well as an increased presence ofhospice and palliative care. Physicians also proposed moresystemic solutions including changes to DNR orders andthe Medicare payment system.

An additional interpretation of the data concerns thedepth and breadth with which ACP was being conductedby the physicians in this study. While the physicians thatwere interviewed reported discussing patient preferencesat the EOL and were clearly empathetic and concernedabout the wishes and experiences of patients and families,they frequently described a brief conversation thatoccurred in the hospital or only after the patient’s conditionwas deteriorating. Rarely did physicians report conductingthorough conversations with both patients and their families throughout the patient’s lifetime. While physiciansmay have interpreted the phrase “end-of-life care discussion” as a conversation that occurs when the patientis near death, even this interpretation, as well as thesefindings suggest that the current facilitation of EOL carediscussions may not be the early and ongoing conversationsthat the best practice of ACP requires, hence the numerousproblems, including family disagreement, lack of patientunderstanding, difficulty with advance directives, and lackof physician communication. Advances in physicians’

understanding and utilization of ACP would have profound implications for improvements in the quality ofEOL care.

There are some limitations to this study. This study consisted of voluntary interviews, and as a result, physicians who were familiar with EOL care discussionsmay have been more willing to participate. The physicianswho participated in this study practiced in predominantlyrural areas and these findings may not be generalizable toall physicians. Furthermore, these interviews are self-reporting and rely upon the memory and integrity of participants.

The data produced in this study is unique in that it represents the perceptions, experiences, and insights ofpracticing physicians who daily deal with communicationat the EOL. These findings are particularly useful forresearchers attempting to improve quality and reduce thecost of care at the EOL. By identifying the most importantbarriers, this study can contribute to prioritizing futurework aimed at improving physician-patient communicationabout EOL care. Only after the barriers to success areidentified can researchers begin developing multifacetedinterventions to address these issues.

ConclusionThis study examined physicians’ perceptions and identifi-cation of the barriers to advance care planning discussionsbetween physicians and their patients. Complex challengesin communication impede the delivery of successful EOLexperiences for patients and their families. With improve-ments in the use of ACP, many of these barriers can beremoved — enabling individuals to remain in control asthey near the end of their life and preventing unnecessarypain and suffering on behalf of the patient, the family, andthe physician.

Table 1. Summary of Barriers to Advance Care Planning.

Traditional Barriers Barriers Identified

Discomfort with the Topic Family Disagreement

Physician Ideology Lack of Patient Education and Understanding

Lack of Reimbursement and Time Difficulties in Managing Advance Directives

Delayed Discussion Disagreement and Lack of Physician-Physician Communication

Lack of Medical Education

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REFERENCES

1. Detering KM, Hancock AD, Reade MC, et al. The impact of advance care planningon end of life care in elderly patients: randomised controlled trial. BMJ. 2010;340:c1345.

2. Rao JK, Anderson LA, and Smith SM. End of life: Is a public health issue. AM JPrev Med 2002;23(3):215-219.

3. Institute of Medicine (IOM). Dying in America: Improving Quality and HonoringIndividual Preferences Near the End of Life. Washington, DC: The NationalAcademies Press; 2014.

4. Detering K and Silveira MJ. 2014. Advance care planning and advance directives.UpToDate. Retrieved from http://uptodate.com.

5. Wright AA, Zhang B, Ray A, et al. Associations between end-of-life discussions,patient mental health, medical care near death, and caregiver bereavementadjustment. JAMA. 2008;300(14):1665-73.

6. Steinhauser KE, Christakis NA, Clipp EC, et al. Factors considered important at theend of life by patients, family, physicians, and other care providers. JAMA.2000;284(19):2476-82.

7. Billings JA. The need for safeguards in advance care planning. J Gen Intern Med.2012;27(5):595-600.

8. Moore C and Williamson J. The Universal Fear of Death and the CulturalResponse. In Handbook of Death & Dying. Thousand Oaks, CA: SAGEPublications, Inc; 2003.

9. Abel EK. The Inevitable Hour: A History of Caring for Dying Patients in America.Baltimore, MD: The Johns Hopkins University Press; 2013.

10. Freeman HE, Brim OG, and Williams G. New Dimensions of Dying. In OG Brim, HEFreeman, S Levine, NA Scotch ed. The Dying Patient. New York: Russell SageFoundation; 1970, pp. xiii-xxvi.

11. Black K. Health care professionals’ death attitudes, experiences, and advancedirective communication behavior. Death Studies. 2007;31:563-72.

12. Balaban RB. A physician’s guide to talking about end-of-life care. J Gen InternMed. 2000;15(3):195-200.

13. Swetz KM, Burkle CM, Berge KH, et al. Ten common questions (and theiranswers) on medical futility. Mayo Clin Proc. 2014;89(7):943-59.

14. Meier DE, Back AL, and Morrision S. The inner life of physicians and care of theseriously ill. JAMA. 2001;286(23):3007-14.

15. Doctors reluctant to discuss end-of-life care with heart failure patients. AmericanHeart Association Meeting Report Abstract 352. 2014. Retrieved fromhttp://newsroom.heart.org/news/doctors-reluctant-to-discuss-end-of-life-care-with-heart-failure-patients?preview=e794.

16. Old JL. Discussing end-of-life care with your patients. Fam Prac Manag.2008;15(3):18-22. Retrieved from www.aafp.org/fpm.

17. Christakis NA and Lamont EB. Extent and determinants of error in doctors’ prog-noses in terminally ill patients: prospective cohort study. BMJ.2000;320(7233):469-73.

About the Authors:Lauren Fanta, MS II, University of South Dakota Sanford School of Medicine. Jill Tyler, PhD, Chair, Department of Communication Studies, University of South Dakota.

Please note: Due to limited space, we are unable to list all references. You may contact South Dakota Medicine at 605.336.1965 for a complete listing.

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A Rare Case of Lymphadenopathy: Kikuchi-Fujimoto DiseaseBy J o s h R e z k a l l a , MD ; a n d Dou g l a s W. Lyn ch , MD

IntroductionThe causes of lymphadenopathy encompass a wide differential and can be alarming to physicians and patientsalike. Despite our best efforts, the evaluation of lymphadenopathy identifies a specific cause only 42 percent of the time.1 A lesser known cause of cervical lymphadenopathy is Kikuchi-Fujimoto disease. This is arare, benign condition of painful cervical lymphadenopathythat presents with some alarming “B” symptoms (fever,night sweats, or weight loss).2 The treatment for Kikuchidisease is antipyretics and observation; however, it is oftenconfused with lymphoma which leads to extensive work-up and evaluations.2,3 We present a case histologically consistent with Kikuchi disease as an opportunity toreview the best management of lymphadenopathy and togive providers insight to this rare disease.

Case DetailsWe present a case of a 33-year-old Thai female with a pastmedical history of ankylosing spondylitis and hypothyroidismwith a complaint of a painful neck lump. Upon initialevaluation, she denied any trauma or recent infections.There was definite isolated left sided anterior and posterior cervical lymphadenopathy, but there was nosupraclavicular adenopathy or erythema/drainage of the

affected area. The enlarged nodes were mobile, firm, andtender. She was treated with corticosteroids, but theadenopathy persisted for the next two weeks. Upon follow-up, she developed fevers in addition to theadenopathy, but denied weight loss or night sweats. Shementioned that she has had right sided lymphadenopathyin the past that resolved with antibiotics in a few months.Given this new history, she was felt to have reactive lymphadenopathy secondary to an infection and wastreated with an antibiotic, but the node remained tenderand continued to enlarge over the next two weeks. Theconcern for malignancy continued to grow and initial labwork was pursued. Complete blood count and comprehen-sive metabolic panel were within normal limits.Ultrasound of the neck showed a palpable left neck softtissue mass due to lymphadenopathy. Computed tomography (CT) scan of the neck and soft tissues showedasymmetric enlarged lymph nodes in the posterior triangleof the neck with the largest node measuring 2.1 x 1 cm(Figure 1). An excisional biopsy was then performedrevealing a soft, normal appearing node about 1.3 cm insize. Pathologic examination revealed that the lymphnode architecture was partially maintained with focalareas demonstrating a histiocytic proliferation of palestaining cells (Figure 2). In addition, areas with increased

Journal

AbstractA relatively unknown cause of cervical lymphadenopathy is Kikuchi-Fujimoto disease, also known as histiocyticnecrotizing lymphadenitis. This is a rare and benign condition that presents with painful cervical lymphadenopathy,fevers, night sweats, and weight loss. This disease is most prevalent in Asian women between the age of 20-35years. The diagnosis of Kikuchi disease is made histologically and is characterized by paracortical areas of necrosis and a notable complete absence of neutrophils. The painful lymphadenopathy can be simply treatedwith antipyretics, but due to its presenting symptoms of Kikuchi disease, it is often mistaken for malignant lymphoma. As such, accurate diagnosis is required to avoid unnecessary testing. The evaluation of lymphadenopathy without an obvious cause can be quite challenging. When patients present with relapsingremitting lymphadenopathy, Kikuchi disease may warrant consideration.

karyorrhexis/apoptotic bodies with the notable absence ofneutrophils and eosinophils were identified (Figure 3).The main differential diagnosis included Kikuchi-Fujimoto disease or systemic lupus lymphadentitis. Thepatient was treated with analgesics and a short course of corticosteroids given her history of recurrent lymphadenopathy. She experienced resolution of the lymphadenopathy within 1 month, but she was scheduledwith rheumatology for further management given herautoimmune history and recurrences of lymphadenopathy.

DiscussionThe evaluation of lymphadenopathy should begin with athorough history and physical examination. The historyidentifies the patient age, duration of the lymphadenopathy,associated symptoms, and patient exposures such as recentinfections or insect bites.6 The physical exam starts bydetermining the anatomic location of the nodes andwhether the lymphadenopathy is regional or generalized.Node location such as the epitrochlear nodes of the elboware always pathologic, whereas supraclavicular nodal location has up to an 80% chance of malignancy.1,4 Thenext step of the physical exam serves to distinguishbetween node size, node consistency, and the presence ofskin ulceration or fixation.4 Normal nodes are usually less

than 1 cm.1 In fact, lymph node size less than 1 cm squaredessentially rules out a cancer diagnosis.1 Only three factorshave been proven to correlate well with the need for biopsy: lymph node size greater than 2 cm, node location,or serum levels of thymidine kinase.5

If clinical suspicion of malignancy is high after history andphysical exam, the best option is to proceed directly to anopen lymph node biopsy.1,6 Unfortunately, fine needleaspiration is often misused as a screening test and has lowvalue in the initial diagnosis of malignancy.6,7 However, ifthe goal is to avoid unnecessary biopsy, the patient can beobserved for three to four weeks for resolution.6,8 This is

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Figure 1. CT scan of the head and neck shows clustered asymmetrically prominent lymph nodes at left level 5.

The largest node measures 2.1 x 1 cm.

Figure 2. Histiocytic proliferation of pale staining cells (arrows) within the lymph node (hematoxylin and eosin, 20x).

Figure 3. Focus demonstrating increased karyorrhexis/apoptotic bodies (circles) with the absence of neutrophils and eosinophils

(hematoxylin and eosin, 40x)

safe to do as the prevalence of lymphadenopathy due tomalignancy has been estimated to be as low as 1.1 percentin the primary care setting.6 Using other factors or scoringsystems to determine the need for excisional biopsy havenot been validated.6 Evaluations using imaging or laboratory tests have not been in agreement and are largelyunproven.5

Kikuchi-Fujimoto disease, also known as histiocyticnecrotizing lymphadenitis, is a benign self-limiting diseaseof unknown etiology but has been associated with otherautoimmune disorders.9 Kikuchi disease presents withpainful cervical lymphadenopathy, fevers, weight loss,night sweats, and lymphocytopenia.9 Kikuchi disease ismost prevalent in young Asian women between the age of20-35 years. The disease is diagnosed histologically and ischaracterized by paracortical areas of necrosis with a predominance of CD8+ T cells and histiocytes around theareas of necrosis.9 Most notably, eosinophils and neutrophilsare rare or completely absent.9 Kikuchi-Fujimoto diseasehas a very favorable outcome and is usually treated simplywith antipyretics. The lymphadenopathy caused by thisdisease usually resolves in one to four months, but therecan be recurrences. However, the disease is often mistakenfor malignant lymphoma. As such, accurate diagnosis isrequired to avoid unnecessary testing.

Kikuchi disease differs from lymphoma in that it generallyaffects women of Asian descent between the ages of 20-35years whereas lymphomas tend to have a bimodal age distribution (first peak around 20 years of age and a secondpeak around 55 years of age).2,7 Kikuchi disease and lymphoma are both diagnosed histologically, which meansthe best way to reach the diagnosis of either disease is froman excisional node biopsy.6,7 Immunohistochemical analysis on the node can also be used to distinguishbetween Kikuchi disease or malignant lymphoma.9 Foreither disease, treating unclear lymphadenopathy withcorticosteroids may hinder or delay diagnosis.6 Pursuingthe diagnosis with other imaging studies may also complicate the diagnosis. For example, if fluorodeoxyglucosepositron emission tomography/computed tomography(FDG PET/CT) is performed, the maximum standardizeduptake value in patients with Kikuchi disease is actuallyhigher than patients with non-Hodgkin lymphoma.2,10

This has been a big factor of misdiagnosis.2

When the diagnosis of Kikuchi disease is made, it is usuallytreated simply with analgesics and antipyretics.2,9 Withthis treatment, 87-95 percent of patients will have

resolution of the lymphadenopathy within one to fourmonths.9 However, there can be recurrences in up to 20percent of these patients.2,9 In the case of recurrence,short-duration corticosteroids may be used. In complicatedKikuchi-Fujimoto disease with many recurrences, hydroxychloroquine has been used with success.9 Lastly,regardless of recurrences, Kikuchi-Fujimoto disease has anassociation with systemic lupus erythematosus in 13-28percent of the cases, and follow-up with rheumatology maybe warranted.2,10

ConclusionThe evaluation of lymphadenopathy without an obviouscause can be quite challenging. When patients presentwith relapsing remitting lymphadenopathy, Kikuchi disease may warrant consideration. If clinical suspicion formalignancy is high after history and physical exam, anexcisional biopsy should be performed. However, if clinical suspicion is low, the patient can be safely observedfor one month.

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REFERENCES1. Vassilakopoulos TP, Pangalis GA. Application of a prediction rule to select which

patients presenting with lymphadenopathy should undergo a lymph node biopsy.Medicine. 2000;79(5):338-47.

2. Deaver D, Horna P, Cualing H, et al. Pathogenesis, diagnosis, and management ofKikuchi Fujimoto disease. Cancer Control. 2014;21(4):313-21.

3. Mathew LM, Kapila R, Schwartz RA. Kikuchi-Fujimoto disease: a diagnostic dilemma. International Journal of Dermatology. 2016;55(10):1069-75.

4. Cunnane M, Cheung L, Moore A, Palma SD, Mccombe A, Pitkin L. Level 5 lym-phadenopathy warrants heightened suspicion for clinically significant pathology.Head and Neck Pathol. 2016 Dec; 10(4): 509-12.

5. Tsuji T, Satoh K, Nakano H, et al. Predictors of the necessity for lymph node biopsy of cervical lymphadenopathy. J Cranio Maxill Surg. 2015;43(10):2200-4.

6. Bazemore A, Smucker D. Lymphadenopathy and malignancy. Am Fam Physician.2002;66(11):2103-10.

7. Matsumoto F, Itoh S, Ohba S-I, Yokoi H, Furukawa M, Ikeda K. Biopsy of cervicallymph node. Auris Nasus Larynx. 2009;36(1):71-4.

8. Orita Y, Nose S, Sato Y, et al. Cervical lymph node extirpation for the diagnosis ofmalignant lymphoma. Surgery Today. 2012;43(1):67-72.

9. Dumas G, Prendki V, Haroche J, et al. Kikuchi-Fujimoto disease. Medicine.2014;93(24):372-382.

10. Błasiak P, Jeleń M, Rzechonek A, et al. Histiocytic necrotising lymphadenitis inmediastinum mimicking thymoma or lymphoma – case presentation and literaturereview of Kikuchi Fujimoto disease. Polish Journal of Pathology. 2016;1:91-5.

About the Authors:Josh Rezkalla, MD, University of South Dakota Sanford School of Medicine.Douglas W. Lynch, MD, Pathologist, Sanford Health Pathology Clinic; AssistantProfessor, Pathology, University of South Dakota Sanford School of Medicine.

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BackgroundPeritonsillar abscess (PTA) is a common deep cervical tissue pathology constituting an otolaryngology emergency.1-4

If not treated promptly it can progress to have fatal consequences. Complications of PTA have includedcarotid artery erosion, airway obstruction, spread to themediastinum, and septicemia.2,5

While a common otolaryngology emergency, the annualincidence of PTA is relatively rare in the U.S. (approxi-mately 30 out of 100,000 cases per year).6 Incidence ishighest in children and young adults with the majority ofcases occurring between the ages of 10-40 years old.3,7-9

Several studies have reported estimated rates of older(greater than 40 years old) patients within the overallpool of PTA cases to be less than 25 percent.8,10,11 Such discrepancy has consequently made information on disease presentation and treatment strategy in olderpatients with PTA quite limited.

Classic signs and symptoms of PTA include presentationof a muffled, “hot potato” voice with severe pain, fever,soft palate swelling, and tonsillar asymmetry. An important “red flag” sign of PTA includes the identificationof trismus. Under any circumstance, when evidence ofeither a lack of swallowing or diminished airway patency

are present an immediate consult with an otolaryngologistis warranted. It is noteworthy to mention, however, thatin elderly patients or cases with immunosuppression theseclassic signs may be less obvious making clinical suspicionof critical importance for early detection of PTA.

The treatment of PTA involves decompression of theabscess through needle or bedside incision and drainageversus tonsillectomy. Systemic antibiotics are used in combination with drainage, but not instead of surgicaldecompression. Practice preferences for surgical manage-ment and postoperative care have been noted in multiplestudies to be variable at geographical and institutional levels.2,7,12

Antibiotic selection tends to be driven by considerationfor penicillin allergy and providing broad spectrum cover-age since mixed infections involving aerobes and anaerobesare most commonly encountered. The most commonanaerobic organisms isolated include Prevotella,Porphyromonas, Fusobacterium, and Peptostreptococcusspecies. Aerobic species typically identified includeStreptococcus pyogenes, Staphylococcus aureus, andHaemophilus influenzae.5 Initial antibiotic preferences tendto be driven by institution specific protocol.2 This usuallyincludes a penicillin agent covered for beta-lactamase

Treatment of Peritonsillar Abscess inImmunosuppressed PatientsBy J e d H . A s s am , MS , MD ; a n d Wi l l i am C . S p ano s , MD

AbstractPeritonsillar abscess (PTA) is a common pathology in otolaryngology emergency. The treatment of PTA is usually bedside drainage or surgical removal of the tonsils (Quincy tonsillectomy) in combination with antibiotic treatment. However, patients with immune suppression might have a more difficult treatment course.Such difficulties may be further magnified within older patients. This case report will describe successful multi-modality treatment of two separate incidents of PTA developing in the context of immunosuppression.Two separate incidents of PTA occurring in immunosuppressed, thrombocytopenic, cancer patients after recentchemotherapy are presented. Early utilization of incision and drainage, antibiotics, and granulocyte colony stimulating factor (G-CSF, filgrastim) for PTA presenting in the setting of chemotherapy related neutropeniaappears to be a viable option in patients with immunosuppression. Review of the current literature also demonstrates that reporting of PTA in older patients is important for future research efforts.

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which may be combined with metronidazole to improvecoverage. In cases of penicillin allergy, lincosamide (clarithromycin) and macrolide (clindamycin) derivativeshave been preferred.2,5,7 As an example, the use of amoxicillin-sulbactam (intravenous) transitioning toamoxicillin-clavulanate (oral) in patients without penicillin allergy is a common and appropriate regimen.

The standard treatment options assume a functionalimmune system as cases of PTA in the context of immuno-suppression have not been well described. Patients receivingchemotherapy may present with neutropenia and thrombocytopenia that may create increased risk associatedwith surgical intervention as well as possible treatmentfailure due to lack of a robust immune response to theinfection. Such risk may be further magnified in olderpatients. In this case study, we present the treatment strategy employed for two separate incidents of unilateralPTA developing after chemotherapy in immunosuppressed,thrombocytopenic, cancer patients.

Case ReportsCase 1A 58-year-old female on chemotherapy (nab-palcitaxel,bevacizumab, and gemcitabine regimen) for stage IIIatriple negative breast carcinoma presented to the emergency department with complaints of throat pain forthree days. Associated symptoms included left-sided retromandibular neck pain, left otalgia, and dysphagia.There was no accompanying fever. Pertinent patient med-ications included acetaminophen with propoxyphene aswell as ibuprofen for the throat pain. A course ofazithromycin initiated at the onset of her condition failedto prevent progression of her symptoms. Medical historywas significant for administered chemotherapy 10 daysprior to her presentation. The patient had no prior history of tobacco use or recurrent group A streptococcalpharyngitis.

Physical examination revealed a mild peritonsillarswelling and bulging of the soft palate. Left-sided necktenderness with level II and III non-fluctuant lym-phadenopathy without crepitus was identified. There wasno trismus and no pharyngeal exudates with good dentition observed. Vitals signs demonstrated tachycardia(105 bpm). Labs presented a white blood cell (WBC)count of 2.1 K/μL (Abs. Neutrophils were 693), hemoglo-bin of 13.5 g/dL, hematocrit of 38.5 percent, and plateletsof 178 K/μL. A rapid strep screen performed was negative. The patient underwent a bedside incision and drainage(I&D) procedure with incision entry made along the anterior tonsillar pillar and blunt dissection to the abscesspocket using a hemostat. A total of 5 cc’s of purulent

material was evacuated during the procedure. Microbialculture performed on the purulent material was negativefor β-strep isolates. The patient tolerated the I&D procedure well with minimal bleeding. Postoperative I.V.piperacillin-tazobactam was used until discharge, two dayslater, after stabilization of WBC counts with filgrastim andimprovement to a solid food diet. At discharge, a 10-dayregimen of amoxicillin-clavulanate 875-124 mg tabletswas prescribed with oxycodone-acetaminophen 5-325 mgtablets for pain as needed. The patient continuedchemotherapy one day thereafter with no recurrence ofPTA documented through to death from succumbing toher metastatic comorbidity 18 months later.

Case 2A 56-year-old female on chemotherapy (bendamustine)for chronic lymphocytic leukemia (CLL) presented to theemergency department with four days of sore throat.Associated symptoms included neck swelling, dysphagia,voice changes, difficulty opening her mouth (trismus),and fever. Pertinent medication history included a courseof azithromycin as well as ibuprofen and acetaminophenwith codeine. The patient’s past medical history was significant for administered chemotherapy 17 days prior topresentation. Additional significant history included a 30-pack-year smoking history and surgical history of tonsillectomy.

Physical exam revealed a swollen, tender, and non-fluctuantleft-side cervical lymph node chain without crepitus. Oralexamination demonstrated moderately-poor dentitionwith asymmetric swelling of the left pharyngeal area.Trismus was observed with a 2.5 cm interincisor oral opening. Oropharyngeal mucosa was non-erythematousand without exudates or plaques. Patient vitals were significant for a temperature of 103 degrees Fahrenheitand tachycardia (104 beats per minute). Patient labsshowed pancytopenia with a white blood cell count of 1.3K/μL (absolute neutrophils were 300), hemoglobin of 8.2g/dL, hematocrit of 26 percent, and platelets of 25 K/μL.A computed tomography (CT) scan revealed a 1.3 cm rim-enhancing fluid-filled pocket located in the left pharyngeal area.

Flexible fiberoptic endoscopy was performed to ensure air-way patency followed by an I&D procedure with incisionentry along the left anterior tonsillar pillar and blunt dis-section to the abscess pocket using a hemostat. A total of5 cc’s of purulent material was evacuated during the pro-cedure. Microbial culture and gram stain of purulent mate-rial demonstrated normal oral flora. The patient toleratedthe I&D procedure well with minimal bleeding and wasplaced on intravenous (IV) clindamycin. No additional

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blood product transfusions were used prior to the proce-dure or during recovery. Despite a low platelet count, thelimited bleeding encountered through the small incisionperformed was characteristic of this type of I&D proceduremaking the need for platelet and blood products lessessential when weighed against the risk of transfusion.The patient was discharged 13 days later after hematolog-ic stabilization with filgrastim, darbepoetin alfa, and irondextran. Chemotherapy was continued one month later.There was no recurrence of PTA documented for thispatient through to death from succumbing to their neo-plastic comorbidity 22 months later.

DiscussionWhile PTA is a common emergency pathology withinotolaryngology, the low incidence in the general population and high diversity in its presentation has madeelucidation of the pathophysiology for this disease a complex problem.1,4,5 There is controversy in literature foruniformly agreed upon guidelines for disease treatment.2,12,13

Such controversy exists for both the medical and surgicalmanagement of this disease.7,13 Appropriate treatmentstrategies for PTA have been debated for almost twodecades without consensus.12

With neutropenia and thrombocytopenia, the patients ofthis study present several unique challenges to surgicaltherapy and postoperative management of PTAintractable to initial antibiotic therapy. Patient immunod-eficiency presents questions about how traditional antibiotic approaches2,5,8 with abscess drainage may needto be augmented to ensure successful recovery. The use ofgranulocyte colony stimulating factor (G-CSF) therapy, aswas used in this study, to boost immune response has beenwell documented as an effective modality in instances ofimmunosuppression by chemotherapy.14 An apparent concern with coexistence of thrombocytopenia is theintraoperative bleeding risk.

One other study discussing PTA formation in a 20-year-old thrombocytopenic patient with chronic myelogenousleukemia raised similar concerns.15 The authors of this casedescribed delaying initial abscess drainage due to concernsof bleeding risk. Yet, the initial thrombocyte resuscitativemeasures undertaken were noted to fail due to coexistingalloimmunization complications and thereby delayeddefinitive treatment with I&D for another several daysallowing the infection to spread further into the deep neckspace. As a result of infection spread, incision drainagewas performed with coexisting thrombocytopenia (51K/μL) and described to have experienced no postoperativebleeding complications.

A question that is raised by this study’s comparison with

our own is whether undertaking I&D early in PTA treatment despite the bleeding risks outweighs the potential sequela of infection spread risked by attemptingto resuscitate platelet count prior to surgical inter