TRAVEL MEDICINE UPDATE/RHEUMATOLOGY CONSULTATION
| TRAVEL MEDICINE UPDATE —Steven S. Krotzer, MD, MPH, Instructor of Medicine, Mayo Clinic, Scottsdale, Arizona
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| General: most experience in clinical tropical disease and research comes from military, Peace Corps, and foreign service;
travelers to developing nations—commonly become ill; 5% seek medical care; 1 in 1000 medically evacuated (MedEvac
insurance for travelers)
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| Risk to travelers: cardiac events number one cause of death in American travelers; pulmonary decompensation (eg,
asthma attack) common reason for evacuation and hospitalization; trauma (eg, motor vehicle accident) number 2 cause of
death in American travelers (number one among all international travelers); infectious disease as cause of mortality at
bottom of list (mostly malaria); destination important; category of traveler important (host factors; risk behavior; epidemiologic
associations; expatriates); visiting friends and relatives (VFR)—large group of international travelers (40%);
few get travel advice; 80% of typhoid cases come from VFR group as does one third of imported malaria in United
States; most high-risk group of travelers
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| Infectious diseases among travelers to developing nations: traveler’s diarrhea and enterotoxigenic Escherichia coli top
list; influenza and hepatitis A compete for number one as most vaccine-preventable disease in travelers; chance of contracting
tuberculosis (TB) same as for hepatitis A during 1 mo of travel in developing nation (one third of humanity infected
with TB); vector-borne diseases—malaria (night-biting Anopheles mosquitos); dengue and yellow fever
(daytime biting Aedes aegypti); vector-borne diseases prevented by avoiding bites; N, N-diethyl-meta-toluamide
[DEET] on skin and permethrin on clothing highly effective; mosquitos attracted to dark clothing (wear white and cover
up), volatile compounds from sebum (adults more than children; men more than women), carbon dioxide, and heat
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| Traveler’s diarrhea: ≈45% enterotoxigenic E coli; ≈25% combinations of Campylobacter, Shigella, and Salmonella;
≈5% everything else; no pathogen identified in ≈25% (80% of these respond to antibiotics); instructions for self-
treatment—use of motility agents; low threshold for starting course of antibiotics (typically ciprofloxacin; one dose curative
in majority of cases); when to seek medical care; fluoroquinolone resistance—increasing; azithromycin (Zithromax)
recommended over ciprofloxacin in Southeast Asia; rifaximin new luminal agent (“currant jelly” stools if used in
invasive setting); primary prevention—peeling fruits, avoiding vegetables and ice cubes not proven overwhelmingly
effective; frequent handwashing works; beware of water fraud (encourage drinking of effervescent bottled beverages); water
too hot to touch from tap essentially pasteurized (95% bacterial kill); cholera vaccine (Dukoral)—oral vaccine; some effectiveness
for enterotoxigenic E coli; not recommended; not available in United States
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| Essential immunizations: diphtheria and tetanus booster (only one third of American adults up to date); hepatitis A; vaccines
required for entry into specific countries and those for diseases with epidemic potential; adult booster for measles and
polio (consider); influenza—prospective study of Swiss travelers showed 3% of travelers to developing nations got influenza;
India number one risk country; pattern of transmission unpredictable; vaccine often not available; role in high-risk
patients for course of standby oseltamivir (Tamiflu) to carry along (not substitute for immunization); transmission of respiratory
diseases on airplanes—influenza; studies show 1 in 1000 passengers on commercial aircraft have active TB;
severe acute respiratory syndrome (SARS; transmission well documented); pneumococcal disease; quality of air on
aircraft—air enters superheated and sterile from jet engine, comes in above head and collected below (at feet); 50% of air
recirculated through high efficiency particulate air (HEPA) filter; risk for aerosol transmission limited to seats around infected
passenger (2 rows, 2 seats); transmission via fomites; hepatitis A—significant case fatality rate; excellent vaccine;
2 shots confer lifelong immunity; Havrix potentially useful for imminent departures (evidence that post-exposure Havrix
effective in preventing hepatitis in contacts); yellow fever—mandatory vaccination for travelers; outbreaks still occur
(January, 2004 in Colombia); potential for urban epidemics; concern about 1 in 400,000 risk for viscerotropic disease in
people >60 yr of age (60% mortality; 14 deaths in past decade, half in patients with thymectomy or thymus disease; yellow
fever vaccine contraindicated in these patients); meningococcal vaccination—required if going on Haj, entering Saudi
Arabia or “meningitis belt”; old vaccine may continue as vaccine of choice due to problem with new vaccine; new meningococcal
vaccine—conjugate (may work in children <2 yr of age); lasts longer; eradicates or prevents nasal carriage;
possible cases of Guillain-Barré associated with vaccine; vaccination essential because 50 countries have had epidemics;
good practice to go to Centers for Disease Control and Prevention (CDC) website at traveler’s health and look under outbreaks
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| Important immunizations: typhoid—high risk in South Asia (highest in Indian subcontinent), North Africa, Peru, and
other parts of world, especially for VFR; fever in traveler from South Asia (India, Pakistan) has typhoid until proven otherwise
(fever in traveler from sub-Saharan Africa has malaria until proven otherwise); vaccine unchanged; difficult to
take oral vaccine correctly; hepatitis B—endemic in China, Africa, South America, and Central America; tattoos and
body piercing risky behavior (“not just where you go, but what you do”); 10% to 15% of travelers have high-risk behavior
for hepatitis B aquisition; booster vaccine helps protect those at risk (identify behavior); expatriates (live in endemic
area >3 mo) should have immunization; rabies—Mexico high-risk country for rabies; incidence of significant animal
bites in expatriates and travelers substantial; incidence of rabies in animals wandering around tourist destinations very
high; 5% of animals in Bangkok rabid; rabies essentially fatal in humans; 3-dose pre-exposure series and 2 injections following
exposure 100% effective (no need for immune globulin); Japanese encephalitis—high mortality; half of survivors
have neurologic sequelae; risk for infection same as risk for anaphylactic reaction from vaccine (must have
sufficient exposure history to justify vaccine); same vectors that transmit West Nile virus transmit Japanese encephalitis
(eg, Culex tritaeniorhynchus); traveler going to spend 1 mo in nocturnal setting with nocturnal mosquito exposure
would benefit from vaccine; manufacturer will probably stop providing vaccine in United States in 1 yr
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| Immunizations with possible utility: varicella—disease of adults in tropics; individuals who grew up in developing nations
probably naive to chickenpox; cholera—vaccine not recommended
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| Returning travelers from Iraq and Afghanistan: 1000 cases of leishmaniasis; 2 species (Leishmania major [majority];
Leishmania tropica [exotica]); mammalian reservoir (fat-tailed desert rat); vector sandfly Phlebotomus papatasi;
Leishmania major—typical wet ulcer painless, lasts 6 mo, and heals with scar; Leishmania tropica—“dry ulcers”
with other possible dermatologic manifestations (eg, hypersensitivity reaction); first Gulf war had 6 to 12 cases of Gulf
War syndrome that grew out Leishmania tropica from bone marrow
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| CURBSIDE CONSULTATIONS WITH A RHEUMATOLOGIST —Philip Seo, MD, Assitant Professor, Department of
Medicine, Johns Hopkins University School of Medicine, Baltimore
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| Patient with positive antinuclear antibody (ANA): patient with malar rash, glomerulonephritis, and erythrocyte sedimentation
rate (ESR) of 100 mm/hr, obvious to call rheumatologist; patient with ANA and no other suggestive signs or symptoms,
plan not so obvious; tests—lupus erythematosus (LE) cell found in patients with systemic lupus erythematosus
(SLE) exists because patients have antibodies to nuclear antigens; ANA test more specific than LE test because it analyzes
broader spectrum of autoantibodies, eg, Ro, La, Smith, ribonucleic protein [RNP]; ANA test relays intensity of autoantibody
response (reported with titers); staining pattern gives idea of diseases involved; ANA of 1:40 or 1:80 not
helpful; study of 125 normal (healthy, working full-time) people showed one third of patients have positive ANA (1:40),
13% have positive ANA (1:80); ANA of 1:160 or 1:320 less likely false-positive but not necessarily specific for rheumatic
disease; retrospective study—of 320 patients with positive ANA titers ≥1:640, 35% had rheumatic disease
(mainly SLE), but almost half of them had nothing wrong (unclear why ANA positive); follow-up of these patients
showed that most remained ANA-positive and only 3 developed rheumatic disease; study of military recruits—
diagnosed with SLE; looked back at serum sample to see timing of becoming antibody positive; showed that majority of
people who develop Smith and RNP antibodies do so in year preceding diagnosis of SLE; patients gradually accumulate
autoantibodies until diagnosed with SLE, at which point it stabilizes; other causes of positive ANA—thyroid disease
most common
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| Summary on ANA: patients with positive ANA at higher risk of developing SLE, but not certain; positive ANA seen in
many rheumatic and nonrheumatic illnesses; patients who accumulate multiple autoantibodies over time at increased risk,
but prophylactic treatment not indicated
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| Patient with swollen joint: important to make sure swelling actually in joint; young adult—hot red knee; gonococcal infection
most common form of acute monoarthritis, occurring in 2% of patients infected with Neisseria gonorrhoeae; female
predominance; cultures generally negative; 2 forms include acute monoarthritis (affects large joint, frequently knee) and
systemic illness involving tenosynovitis (tenderness proximal to joint; rash [difficult to see]); treatment—ceftriaxone intravenously
(IV) or intramuscularly (IM), and treat for Chlamydia with doxycycline; fluoroquinolones alternative to ceftriaxone,
but keep in mind resistance increasing; response to therapy in 24 to 48 hr; slightly older patients—gout (especially
in man with family history of gout and recently started on diuretic for hypertension); uric acid not reliable for diagnosis
(may not be elevated); elevated uric acid levels by themselves do not demand therapy; may mimic acute septic arthritis or
cellulitis (area of skin that looks red, hot, and tender, with atypical distribution just over ankle or knee and spongy pitting
edema); treatment—not everyone needs long-term therapy; treat flares with indomethacin (Indocin) or colchicine; treat
chronic gout with allopurinol (can precipitate flare); allopurinol dose increased to keep uric acid level down; older
patients—septic arthritis; 80% monoarticular, of which 50% in knee; Staphylococcus aureus most common pathogen,
but need to look for atypical organisms (eg, gram-negative bacteria); more difficult to treat because of methicillin-resistant
Staphylococcus aureus (MRSA); septic arthritis not responding to antibiotics—Lyme disease; atypical mycobacteria
(eg, Mycobacterium marinum); crystalline arthritis may co-occur with infection
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| Summary on joint pain: make sure pain actually in joint (not bursitis or tendinitis); tap joints at least once; septic joints
need repeated taps (podagra [inflammation of first metatarsophalangeal joint] does not require tapping); send even few
drops of fluid for culture
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| Leukocytoclastic vasculitis (LCV): small-vessel vasculitis; palpable purpura—cutaneous manifestation of LCV; commonly
seen in lower extremities; generally asymptomatic, but discomfort or burning may be present; initially, lesions
look reddish, then fade into purplish-grayish color that lasts for several months; chronic lesions possibly accompanied by
bullae (biopsy shows nonspecific inflammatory infiltrate); erythrocyte extravasation; differential diagnosis—long; history
and physical (H and P) direct evaluation; idiopathic LCV (self-limiting in many patients) with no significant H and P
findings, but can treat with colchicine; 10% of cases caused by drugs (antibiotics and nonsteroidal anti-inflammatory
drugs [NSAIDs] big offenders); consider discontinuing any drugs started within 2 wk of onset of rash; propylthiouracil
(PTU)—associated with drug-induced antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis; generally
remains limited to skin but has potential to develop into something more serious; nonrheumatic causes of LCV—
cholesterol emboli (especially in hospitalized patient who recently underwent catheterization); endocarditis; other infections;
rheumatic causes—cryoglobulinemia; ANCA-associated vasculitis; SLE; Sjögren’s syndrome; rheumatoid arthritis;
rules for biopsy—biopsy fresh lesion to perform immunofluorescence; IgM and C3 deposition, think
cryoglobulinemia; much antibody deposition, think about SLE; if nothing seen, think ANCA-associated vasculitis; IgA
deposition specific for Henoch-Schönlein purpura; basics for evaluation—careful H and P; most forms of purpura get
worse with exercise; stop potentially offending drugs; serologic evaluation—blood cultures; test for rheumatoid factor,
rather than serum cryoglobulinemia; serum protein electrophoresis and urine protein electrophoresis to rule out plasma
dyscrasia; ANA; ANCA and inflammatory markers; test for hepatitis B and C; HIV; urinalysis (to detect glomerulonephritis)
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| Summary: by itself, positive ANA not worrisome; many patients with highly positive ANA never develop rheumatic disease;
dsDNA, RNP, Smith, and collections of multiple autoantibodies concerning for SLE, but just watch and wait; acute
monoarthritis considered septic until proven otherwise; septic arthritis considered emergency (treat with IV antibiotics);
younger patients more likely to have gonococcal arthritis; repeated arthrocentesis part of therapy for septic arthritis; palpable
purpura does not always indicate rheumatic disease; in patient with LCV, look for signs or symptoms of systemic disease
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| Questions and answers: colchicine dosage—rules for vasculitis similar to those for gout; taking into account age and renal
insufficiency, start on 0.6 mg qd or bid and watch tolerance; indication for long-term therapy for gout—3 to 4 attacks
per year on regular basis; punch biopsy for LCV—sufficient for simple LCV; however, to detect medium-vessel
vasculitis, need deeper biopsy; renal disease associated with hyperuricemia—controversial; uric acid 20 mg/dL merits
empiric therapy; incidence of renal disease with lower uric acid not clearly demonstrated; uric acid target level—
kept <5 mg/dL with allopurinol, lower if patient continues to flare; slight risk for hypersensitivity reactions, so start slow
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Educational Objectives
| The goal of this program is to provide the listener with information on travel medicine and commonly encountered issues in
rheumatology. After hearing and assimilating this program, the clinician will be better able to:
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 | 1. Provide vaccines that are essential for travelers to developing nations.
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| 2. Prepare patients for protection against vector-mediated infections and self-treatment of traveler’s diarrhea.
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| 3. Discuss role of antinuclear antibodies.
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| 4. Evaluate the patient with a swollen joint.
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| 5. Discuss management of leukocytoclastic vasculitis.
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Discussed on This Program
Allopurinol [Aloprim, Zyloprim]
Atovaquone and proguanil HCl (A-P) [Malarone, Malarone Pediatric]
Azithromycin [Zithromax, Zmax]
Ceftriaxone sodium [Rocephin]
Cholera vaccine [Dukoral] (not available in United States)
Ciprofloxacin [Ciloxan, Cipro, Cipro I.V., Cipro XR, Proquin XR]
Colchicine
Doxycycline [several trade names]
Hepatitis A vaccine, inactivated [Havrix, Vaqta]
Indomethacin [Indocin, Indocin SR, Indomethacin SR, Indomethacin Extended-Release]
Mefloquine HCl [Lariam]
N, N-diethyl-meta-toluamide [DEET]
Oseltamivir phosphate [Tamiflu]
Permethrin clothing spray [Permanone Tick Repellent]
Propylthiouracil (PTU)
Rifaximin [Normix, Xifaxan]
Suggested Reading
Anandacoomarasamy A, et al: Cutaneous vasculitis associated with infliximab in the treatment of rheumatoid arthritis.
Intern Med J 35:638, 2005; Cannella AC, Mikuls TR: Understanding treatments for gout. Am J Manag Care 11:S451,
2005; Connor BA: Hepatitis A vaccine in the last-minute traveler. Am J Med 118:58S, 2005; Dinman S: Healthy information
for a safe and uneventful trip. Plast Surg Nurs 25:156, 2005; Hill DR: The burden of illness in international travelers.
N Engl J Med 354:115, 2006; Horvath LL, et al: Effect of Maximizing a Travel Medicine Clinic’s Prevention Strategies.
J Travel Med 12:332, 2005; Keysone JS: Travel-related hepatitis B: risk factors and prevention using an accelerated vaccination
schedule. Am J Med 118:63S, 2005; Labelle C, Macpherson DW: Evaluation of yellow fever vaccination centers
in Canada. J Travel Med 12:180, 2005; Mackell S: Traveler’s diarrhea in the pediatric population: etiology and impact.
Clin Infect Dis 41:S547, 2005; Masseoud D, et al: Overview of hyperuricemia and gout. Curr Pharm Des 11:4117, 2005;
Ponce De Souza E, Usatine RP: Palpable purpura and a visible sock line. J Fam Pract 54:520, 2005; Rack J, et al: Risk
and spectrum of diseases in travelers to popular tourist destinations. J Travel Med 12:248, 2005; Rice PA: Gonococcal arthritis
(disseminated gonococcal infection). Infect Dis Clin North Am 19:853, 2005; Soylu A, et al: Multisystemic leukocytoclastic
vasculitis affecting the central nervous system. Pediatr Neurol 33:289, 2005; Spira A: Yellow Fever vaccine as
a vehicle to better travel medicine. J Travel Med 12:303, 2005; Sunderkotter C, et al: Management of leukocytoclastic
vasculitis. J Dermatolog Treat 16:193, 2005; Waldon J: Travel immunizations: benefits and precautions. Am Fam Physician
71:2254, 2005.
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 faculty reports
nothing to disclose.
Dr. Krotzer was recorded at The 8th Annual Mayo Clinic Update: Sedona, 2005, held October 6-9, 2005 and October 20-
23, 2005, in Sedona, Arizona. Dr. Seo was recorded at the 50th Annual Topics in Clinical Medicine, held May 2-6, 2005,
in Baltimore and sponsored by Johns Hopkins University School of Medicine, Department of Medicine. The Audio-Digest
Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.
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