VIRAL INTRUDERS
| UPDATE ON HIV EMERGENCIES —Rachel L. Chin, MD, Associate Professor of Clinical Medicine, University of California,
San Francisco, School of Medicine
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| Introduction: Centers for Disease Control and Prevention (CDC) estimates almost 1 million US residents infected; 25%
unaware they carry disease; 40,000 new cases each year; treatment remains difficult, lifelong, and expensive; no cure or
vaccine
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| Case 1: HIV-positive man 28 yr of age who complains of dry cough and fever for 2 to 4 wk; no history of opportunistic infections,
takes no medications, and has normal vital signs; O2 saturation 95%; chest x-ray negative; patient diagnosed
with bronchitis and discharged; returned 10 days later with diffuse pneumonia; admitted to intensive care unit (ICU)
with diagnosis of Pneumocystis jiroveci (formerly carinii) pneumonia (PCP)
|
 | Discussion: checking CD4 count to determine stage of HIV infection could have changed management; early disease
>500 cells/mm3 , intermediate 200 to 500 cells/mm3, late <200 cells/mm3 , very late <50 cells/mm3
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| Viral load: not important to emergency physicians but extremely important to primary care physicians; primary physician
may check viral load every 4 to 6 wk, more often than CD4 count (checked every 4-6 mo); blip in viral load warns physician
that patient may not be taking his or her medication or may be having drug/drug interaction
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| CD4 count: important; if patient similar to case 1 has CD4 count <200 cells/mm3 and not taking PCP prophylaxis, all upper
respiratory infections (URIs) need close follow-up (next 1-2 days); if CD4 count >200 cells/mm3 and patient taking prophylaxis
and compliant with medications, bronchitis reasonable expectation
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| Pneumocystis jiroveci pneumonia: leading AIDS-defining condition; CD4 count <200 cells/mm3 ; fever; dyspnea on exertion
(eg, getting more and more difficult for patient to do normal daily activities); dry cough for weeks to months; if
CD4 count unknown, refer patient to primary care physician earlier rather than later; CD4 counts 3 to 6 mo old still
valid unless opportunistic infections present; signs and symptoms nonspecific (may have clear lungs, no rales)
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| Laboratory work: serum lactate dehydrogenase (LDH) can help determine if lung badly infected (severe infection if level
≈400 U/L); sputum induction first test if PCP suspected; if no sputum obtained and bronchoscopy unreasonable to perform,
use high-resolution computed tomography (CT) to look for cysts; on chest x-ray, PCP has bilateral symmetrical
interstitial ground-glass appearance; may see consolidation; cysts better seen on CT; chest x-ray normal in up to 10%
of patients; up to 30% of patients presenting for first time have pneumothorax
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| Treatment: trimethoprim–sulfamethoxazole (Bactrim); if patient allergic to sulfonamides, clindamycin plus primaquine
reasonable alternative (think of methemoglobinemia with primaquine therapy); atovaquone good alternative but extremely
expensive (pentamidine not as effective); treat for 21 days, followed by prophylaxis; start steroids if PaO 2 <70
mm Hg or O2 saturation <90%; start steroids within 72 hr
|
| Bacterial pneumonia: 10 times more common in HIV-positive patients than HIV-negative patients, even with CD4 count
of 800 cells/mm3 ; patients have fevers, shortness of breath, chest pain, purulent sputum, productive cough, acute duration
(3-5 days), and focal lung findings; white blood cell count may be elevated
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| Case 2: HIV-positive man 28 yr of age complaining of headache; taking no medications
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| Discussion: if CD4 count <100 cells/mm3 , need lumbar puncture (LP) to rule out cryptococcal meningitis; Cryptococcus
neoformans most common fungus responsible for infections in patients with AIDS; clinical presentation often very
late (ie, CD4 count <100 cells/mm3 ); symptoms are fever and headaches (fever may be absent); headache chronic
(weeks to months); disease not in patient’s head if serum cryptococcal antigen negative; if positive, must perform LP to
rule out; patients do not have meningeal signs, nuchal rigidity, Kernig’s or Brudzinski’s signs; CT negative; treatment
amphotericin with or without flucytosine for 2 wk, followed by oral long-term suppressive therapy; must manage increased
intracranial pressure to prevent hydrocephalus and seizures; poor prognosis if opening pressure on LP >250
mm Hg
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| Cerebral toxoplasmosis: most common parasite to cause focal brain lesion in patients with low CD4 counts (<200 cells/mm3 );
presents with headaches, fever, altered mental status, focal signs; seizures most common presentation seen in emergency
department (ED); obtain CT with contrast to look for toxoplasmosis (shows multiple ring-enhancing lesions);
consider lymphoma if only one lesion seen; toxoplasmosis disappears from CT when treated; if lesions do not disappear,
it is lymphoma (“that’s when the neurosurgeons will biopsy it”)
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| Cytomegalovirus (CMV) retinitis: most common vision-threatening condition in people with AIDS; CD4 count often <50
cells/mm3 ; patients complain of blind spots, field loss, or floaters; call ophthalmologist; requires close follow-up or admission;
treat with valganciclovir (oral)
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| Medications and prophylaxis: if CD4 count increased to >200 cells/mm3 and stays there for >6 mo, can stop prophylaxis
for PCP, disseminated Mycobacterium avium complex (MAC), and treatment for CMV retinitis; give acyclovir prophylaxis
against herpes simplex virus; standard of care to use 3 medications, ie, nucleoside reverse transcriptase inhibitors, nonnucleoside
reverse transcriptase inhibitors, nucleotides, and protease inhibitors
|
| Case 3: 40-yr-old HIV-positive woman complaining of diffuse right upper quadrant pain; has anorexia, nausea, and malaise;
no history of gallstones or alcohol abuse; taking medications; recent CD4 count 400 cells/mm3 ; sodium bicarbonate
12 mmol/L; patient given diagnosis of pancreatitis because liver function tests (LFTs) mildly elevated and lipase
elevated; CT showed fatty liver; patient taking stavudine (d4T; commonly associated with lactic acidosis); patient
transferred to ICU; sodium bicarbonate continued to drop; lactate level >9 mmol/L; patient died in <3 days
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| Discussion: missed lactic acidosis with fatty liver associated with patient’s medication; onset may be sudden or gradual;
common with nucleoside medications and not associated with any other AIDS drugs; vague abdominal complaints and
right upper quadrant pain; primary care physicians frequently monitor LFTs in patients taking nucleosides, looking for
bump in LFTs (indicates time to stop medication); mortality 80% when lactate >8 mmol/L
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| Emergencies related to HIV therapy: pancreatitis, lactic acidosis, abacavir hypersensitivity reaction, indinavir-induced
kidney stones, rashes; <medscape.com> and <aidsmeds.com> good resources for drug reactions in AIDS patients
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| Abacavir (Ziagen; component of Trizivir) hypersensitivity: black box warning; hypersensitivity reaction often nondescript,
eg, fever, malaise; often occurs in first 4 wk of therapy; consult patient’s primary care physician before stopping
medication because once drug stopped, patient cannot ever take it again (anaphylactic shock occurs, and patient dies
within 24 hr)
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| Case 4: 28-yr-old man complaining of right flank pain; urinalysis shows 20 to 50 red blood cells (RBCs); renal CT protocol
demonstrated dilated ureters, no hydronephrosis, no stones; patient taking indinavir (Crixivan)
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| Discussion: common for patients on indinavir to get kidney stone-like symptoms and form crystals in their kidneys; up
to 22% of patients feel and look like they have kidney stones, but CT and x-rays negative; speaker has stopped ordering
imaging studies on these patients unless pain cannot be controlled; often can treat them through pain; do not stop
medication; administer IV hydration and give morphine or ketorolac (Toradol)
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| Rashes: associated with nonnucleoside reverse transcriptases; up to 37% of patients present with severe rashes (eg,
Stevens Johnson syndrome, toxic epidermal necrolysis) requiring admission to burn unit
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| Immune reconstitution syndrome: medication-induced boost in immune system leads to accentuated antigen-specific immune
response; CD4 count high, and patients have just started medications; patients appear to have MAC lymphadenitis,
CMV retinitis, or worsening tuberculosis (TB); emergency physicians do not have to make diagnosis; observation
indicated; usually do not stop patient’s medication but treat through complication; CMV retinitis must be closely
watched by ophthalmologist because of possibility of blindness
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| VIRUSES: FROM COLDS TO RABIES —Gregory J. Moran, MD, Professor of Medicine, the David Geffen School of
Medicine at the University of California, Los Angeles, Department of Emergency Medicine, and Division of Infectious Diseases,
Olive View-UCLA Medical Center
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| Colds: average child gets several colds per year; caused by viruses; antibiotics ineffective; can recommend decongestants
and alternative therapies, eg, vitamin C, zinc (some studies support benefit, some do not; probably will not hurt patients)
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| Influenza: different from cold; people sicker; onset more abrupt; tends to be accompanied by acute high fever; headaches
and myalgias prominent symptoms; usually have cough and upper respiratory infection (URI) symptoms and look sick;
may cause seizures or croup-like symptoms in children; children often get gastrointestinal (GI) symptoms as well; can
diagnose it reasonably well if in right season, if epidemic in community, and someone presents with this constellation
of symptoms (do not necessarily need to obtain rapid test)
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| Zanamivir (Relenza): inhaled neuraminidase inhibitor; sometimes causes irritation in airways; use with caution in patients
with underlying lung disease (“exactly the kind of people that tend to get into trouble when they get influenza”)
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| Oseltamivir (Tamiflu): also neuraminidase inhibitor; more popular because of simple oral twice-daily dosing for 5 days;
active against influenza A and B; if started during first 30 to 36 hr of illness, shortens length of illness by 1.0 to 1.5
days; also approved for prophylaxis; costs ≈$70 for 5-day course
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| Amantadine: costs ≈$5; treats influenza A only; high incidence of central nervous system (CNS) side effects, especially
in elderly population
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| Rimantadine: little more expensive (costs ≈$20); has fewer CNS side effects
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| Management: reasonable to make clinical diagnosis during flu season if disease in community; rapid test can confirm diagnosis
(costs ≈$15); reasonable to consider antiviral treatment for people at high risk who are within window of benefit;
vaccination every season key to control (especially in high-risk people)
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| Vaccine: new live attenuated vaccine; intranasal spray; gives subclinical mild infection; relatively contraindicated in immunosuppressed
patients; approved only for healthy people ages 5 to 49 yr (usually those who do not need flu vaccine);
recommended for teachers and health care workers; do not give with other antiviral drugs; costs ≈$50 (more
expensive than other vaccines)
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| Varicella (chicken pox): not seen as much as before; speaker sees it at his facility because of immigrants from Central
America and South America who are not routinely vaccinated; acyclovir works on patients with symptoms; reasonable
to give acyclovir to patients presenting within first 2 days of illness; American Academy of Pediatrics recommends
acyclovir for adolescents and those with chronic diseases or on long-term aspirin therapy; no clear guidelines for
adults, although reasonable to treat pregnant women, smokers, and severely immunocompromised patients
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| Varicella immune globulin: rare indications; must consider exposure, susceptibility, and likelihood of complications;
only definite indication is for immunocompromised neonates; consider in high-risk pregnant patients with high risk exposure
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| Zoster: presents with pain and blisters; usually not life-threatening or dangerous; patients can develop postherpetic neuralgia;
evidence for steroids and acyclovir alone and in combination; antiviral drugs shown to shorten duration of pain
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| Rabies: human rabies rare in United States but 100% fatal; 100% preventable with postexposure prophylaxis (expensive;
≈$1500); treat patients with real rabies exposure
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| Indications for postexposure prophylaxis: vary widely, depending on geographic location; indications— exposure to
skunk, bat, raccoon, or fox (wild carnivores; highest risk) unless animal proven negative; dogs, cats, and ferrets can be
observed for 10 days; if animal unavailable, consult local public health department
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| In United States: was problem in humans until rabies eliminated in dogs; big increase among wild animals over last 2 decades,
mostly in raccoons along east coast; all cases of human rabies over last few decades caused by bats; people can
be exposed to bats without knowing it; sleeping child in room with bat needs rabies prophylaxis; study of postexposure
prophylaxis found wide variations, eg, locations with higher incidence of rabies, such as Philadelphia and New York,
gave prophylaxis in 28% of animal bites, whereas areas with low or rare incidence, like Los Angeles and Albuquerque,
gave prophylaxis in <1% of animal bites
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| Treatment: cleaning wound reduces risk (virus must replicate locally before entering nervous system); give vaccine in
deltoid on days 0, 3, 7, 14, and 21; give immune globulin as well, 20 units/kg (try to infiltrate full dose at wound site);
know local epidemiology
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Educational Objectives
| The goal of this program is to educate the listener about viral infections. After hearing and assimilating this program,
the clinician will be better able to:
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| 1. Explain the significance of viral load and CD4 counts in HIV-infected patients and which is more important to
know in the emergency department.
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| 2. Recognize subtle complaints that may indicate life-threatening opportunistic infections in patients with AIDS.
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| 3. Detect and manage adverse effects of new AIDS drugs, including metabolic changes and immune reconstitution
syndrome.
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| 4. Illustrate how influenza differs from a cold in presentation and treatment.
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| 5. Discuss the indications for postexposure prophylaxis for rabies.
|
Discussed on This Program
Abacavir sulfate [Ziagen]
Acyclovir (acycloguanosine) [Zovirax]
Amantadine HCl [Symmetrel]
Atovaquone [Mepron]
Clindamycin (many trade names)
Dapsone (DDS) [Aczone]
Flucytosine (5-FC; 5-fluorocytosine [Ancobon]
Indinavir sulfate [Crixivan]
Ketorolac tromethamine [Acular, Toradol]
Morphine sulfate (many trade names)
Oseltamivir phosphate [Tamiflu]
Penciclovir [Denavir]
Pentamidine isethionate [NebuPent, Pentacarinat, Pentam 300]
Primaquine phosphate
Rimantadine HCl [Flumadine]
Stavudine (d4T) [Zerit]
Trimethoprim–sulfamethoxazole (co-trimoxazole; TMP–SMZ) [Bactrim, Cotrim, Septra, Sulfatrim]
Valganciclovir [Valcyte]
Zanamivir [Relenza]
Programs of Related Interest
Eppes S, Zaoutis T: The changing face of pediatric viral infection. Audio-Digest Pediatrics 51:03(Feb 7), 2005;
Frazee B: Antibiotic use. Audio-Digest Emergency Medicine 20:07(Apr 7), 2003; Jaffe HW, Scott RC: Current perspectives
on HIV/AIDS. Audio-Digest Internal Medicine 52:05(Mar 7), 2005; Millis MR, Smith C: Serious viral infections.
Audio-Digest Family Practice 53:15(Apr 21), 2005; Moran GJ, Coates TJ: AIDS. Audio-Digest Emergency
Medicine 21:07(Apr 7), 2004; Sulak PJ: Viral STD update. Audio-Digest Obstetrics/Gynecology 51:17(Sep 7), 2004.
To Order, Contact Subscriber Service (1-800-423-2308)
Suggested Reading
Corden TE et al: Rabies prevention. WMJ 99:47, 2000; Galai N et al: Prognostic factors for survival differ according
to CD4+ cell count among HIV-infected injection drug users: pre-HAART and HAART eras. J Acquir Immune Defic
Syndr 38:74, 2005; Gibbons RV et al: Knowledge of bat rabies and human exposure among United States cavers.
Emerg Infect Dis 8:532, 2002; Haukoos JS et al: Emergency department triage of patients infected with HIV. Acad
Emerg Med 9:880, 2002; Lee GM et al: Misconceptions about colds and predictors of health service utilization. Pediatrics
111:231, 2003; Marco CA: Presentations and emergency department evaluation of HIV infection. Emerg Med
Clin North Am 13:61, 1995; Moran GJ et al: Appropriateness of rabies postexposure prophylaxis treatment for animal
exposures. Emergency ID Net Study Group. JAMA 284:1001, 2000; Rowland RW et al: Painful gingivitis may
be an early sign of infection with the human immunodeficiency virus. Clin Infect Dis 16:233, 1993; Rupprecht CE et
al: Clinical practice. Prophylaxis against rabies. N Engl J Med 351:2626, 2004; Rupprecht CE et al: Oral vaccination
of wildlife against rabies: opportunities and challenges in prevention and control. Dev Biol 119:173, 2004; Sokolove
PE et al: The emergency department presentation of patients with active pulmonary tuberculosis. Acad Emerg Med
7:1056, 2000; Stone S et al: Antibiotic prescribing for patients with colds, upper respiratory tract infections, and
bronchitis: A national study of hospital-based emergency departments. Ann Emerg Med 36:320, 2000; Tso EL et al:
Cranial computed tomography in the emergency department evaluation of HIV-infected patients with neurologic
complaints. Ann Emerg Med 22:1169, 1993; Yoshida D et al: Abdominal pain in the HIV infected patient. J Emerg
Med 23:111, 2002.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. For this issue,
the speakers reported no conflict.
Dr. Chin was recorded May 13, 2005, in San Francisco, at High Risk Emergency Medicine, sponsored by the University
of California, San Francisco, School of Medicine, Department of Emergency Medicine, and Division of Emergency
Services, San Francisco General Hospital; Dr. Moran, on April 22, 2005, in Coronado, California, at Advances
in Emergency Medicine and Primary Care, sponsored by Olive View Medical Center Department of Emergency
Medicine, the David Geffen School of Medicine at the University of California, Los Angeles, and the American College
of Emergency Physicians, State Chapter of California, Inc. The Audio-Digest Foundation thanks the speakers
and the sponsors for their cooperation in the production of this program.
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