Educational Objectives

The goal of this activity is to discuss the emergence or resurgence of major viral diseases, and to review the most interesting literature in rheumatology over the past year. After hearing and assimilating this program, the clinician will be better able to:
1. Apply the components of “good respiratory etiquette” to clinical practice.
2. Recognize the most important lessons learned in clinical medicine and public health from the efforts to control major viral epidemics.
3. State why more funding is needed for developing antibiotics and vaccines.
4. Describe the latest evidence supporting the use of aspirin in the management of giant cell arteritis.
5. Explain the danger of using cyclophosphamide in the long-term management of ANCA-associated vasculitides.


From the Johns Hopkins University School of Medicine’s Topics in Clinical Medicine

WHAT HAPPENED LAST YEAR IN INFECTOUS DISEASE?—John G. Bartlett, MD, Professor and Chief, Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore
Respiratory etiquette: states that patients with cold should wear surgical mask in waiting room and stay 3 ft away from other patients; nurse also should wear mask; impetus was severe acute respiratory syndrome (SARS), but measures actually long overdue; may prevent transmission of influenza and other infectious respiratory illnesses, because droplet nuclei spread illness, either through direct contact or by aerosolization within 3 ft of other people
Severe acute respiratory syndrome: first diagnosed as atypical pneumonia in 2002 in China; subsequently spread by index patient, starting in February 2003 in Hong Kong; spread globally within 1 mo; virus sequenced within days due to international cooperation among 11 virologists; outbreak declared over in July 2003; 9 cases reported so far in 2004, almost all laboratory-related; most cases and deaths occurred in China; 33 probable cases, 8 confirmed cases, and 0 deaths in United States; cases occurred mostly at home or in hospital; health care workers accounted for up to 50% of cases
Coronavirus: normally causes minor cold in humans; strain responsible for SARS carries base-pair deletions that make it human pathogen; first patients probably contracted infection from civet cats
Lessons learned: importance of global response network; power of e-commerce for dissemination of medical information and communication among professionals; capacity for heroic response by medical professionals (Toronto good illustration); need for respiratory etiquette
Avian flu: influenza A H5N1; first seen in Hong Kong in 1987, with 28 cases and 6 deaths; first instance of direct flu transmission from bird to human; lack of person-to-person transmission prevented development of large epidemic, but millions of chickens culled in Hong Kong following realization that virus was “two mutations away” from being transmissible among humans; rampant epidemic among chickens in Asia in 2003; 33 human cases occurred (23 fatal); virus still not transmissible among humans, but epidemic possible if virus mutates spontaneously or mixes with human flu virus in person who has both
Other strains of avian flu: H9N2 (originated in China; causes mild symptoms); H7N7 (seen in Netherlands; mostly causes conjunctivitis, but did cause 1 fatal case of flu in veterinarian); H5N2 (United States; 1 mild human case); H7N3 (Canada; 1 case of conjunctivitis)
Vietnamese patients: 10 cases noted in patients with average age of 14 yr (age range 5-24 yr); mortality rate 80%
Lessons learned: timing of influenza impossible to predict; global surveillance essential; test under development for detecting unusual strain (available soon); method of rapid vaccine development necessary; consider universal vaccination; large supply of neuraminidase inhibitors important
Bovine spongioform encephalitis (BSE; prion disease): first cow tested positive for BSE in United States in December 2003 (animal was slaughtered “downer cow”); cow traced to Canada; 1 human case of variant Creuzfeldt- Jakob disease (vCJD) detected in United States (acquired in England); bone meal identified as source of infection in England, banned in United States; first human case seen in 1996; incubation period in human thought to be 6 to 10 yr; risk of contracting BSE from meat real but “vanishingly small”
Prions: infectious agents that lack DNA and RNA; name comes from proteinaceous infectious particle; actual infectious agent is prion protein (PRP); vCJD causes dementia, depression, myoclonus, and death; genetic predisposition identified in all victims so far; evidence for possible blood transmission; 17 people currently known to have received infected blood products
Lessons learned: prions are unique infectious agents that resist all attempts at killing, including autoclaving; resulting disease always progresses to death; PRP configuration dictates pathology; diagnosis made only by biopsy taken at autopsy; controversial issues include rigor and method of screening cows, transmissibility in blood, and relationship to chronic wasting disease afflicting elk and deer in United States
Monkeypox: started with shipment of Gambian rats into United States in April 2003; sick animal noted by veterinarian after it infected prairie dog given as pet, bit child and parents (all three subsequently became ill; first cases reported in United States)
Lessons learned: community-based clinicians will be first to detect bioterrorism; monkeypox may be endemic in United States; consider pet alternatives to African rodents
Community-acquired pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA): community-acquired strain different from strain found in hospitals; causes soft tissue infections (mainly furunculosis) and occasional case of invasive disease; sensitive to many other antibiotics, especially clindamycin and trimethoprim- sulfamethoxazole; derived from clone seen globally; cases may involve pulmonary necrosis and require respiratory assistance; of 4 cases seen by speaker, 3 developed acute respiratory distress syndrome; 2 patients developed shock, lost digits; 1 patient required bilateral, below-knee amputations; organisms from all 4 patients had Panton-Valentine leukocidin gene
Lessons learned: represents novel strain of MRSA; community prevalence 20% to 50%; causes pneumonia in relatively few patients (soft tissue infection more likely), but devastating; culture any suspected Staphylococcus infection, because they are resistant to beta-lactam drugs; control infection by covering skin lesions and using respiratory precautions when pneumonia present
Norovirus: responsible for globally endemic gastroenteritis; former names are “winter vomiting disease” and Norwalk agent; highly infectious (10 virions sufficient for infection); remains stable for several days, even after symptoms end (can persist on tables and other surfaces); prevalence has surged recently due to advent of unique genotype; symptoms include vomiting and diarrhea; lasts 10 to 60 hr; mortality low (except in elderly); patients do well at home, but are “miserable” while symptoms occur; treatment symptomatic; prevent through good hygiene; of 3714 outbreaks of gastroenteritis investigated in England, Norovirus responsible for 80%
Lessons learned: most common cause of gastroenteritis epidemics, especially aboard cruise ships and in health-care facilities; main concern for elderly patients; control by preventing contact, especially through good hand hygiene; treat with antiemetic agents
West Nile virus: first reported in Uganda in 1937; found to be neurovirus in 1990; cases reported in Eastern Europe and Israel; first Western hemisphere cases reported in 1999 in Bronx; now moving across the United States and causing fatalities; most patients asymptomatic, but flu-like symptoms in approximately 20% of cases; most serious cases those with neurologic symptoms (seen in approximately 1% of patients; include encephalitis, polio-like syndrome, myoclonus, and Parkinson’s disease); virus may be transmitted through blood (new screening method has detected >1000 contaminated units); transmission through organ transplants also detected (good screening test now available); transmission occurs from birds to mosquitoes to people; best preventive measures are using DEET (N, N-diethyl-m-toluamide) and eliminating standing water; patients immune after disease resolves; major risk factor for developing neurologic symptoms is age >50 yr; immunosuppression also risk factor; diagnosis made through serology (IgM); hyperimmune intravenous IgG (IVIG) now being tested as treatment
How it all fits together: devastating infections often affect economics as well as health; can cost countries many billions of dollars; many infections are zoonoses; demonstrates that epidemics unpredictable; Internet important positive and negative factor in dissemination of information (stay with reliable sources); remaining needs include rapid, targeted, and adequately funded development of antibiotics and vaccines that can be made rapidly available during a crisis
MRSA that presents as cellulitis: patients with furunculosis usually do well with drainage (choice of antibiotic less important); think of this organism and culture for it in all patients who have furunculosis or necrotizing pneumonia; speaker’s first choices for empiric therapy are trimethoprim-sulfamethoxazole or clindamycin
UPDATES IN RHEUMATOLOGY—David B. Hellmann, MD, Professor of Medicine, Johns Hopkins University School of Medicine, and Chairman, Department of Medicine, Johns Hopkins Bayview Medical Center, Baltimore
Aspirin and complications of giant cell arteritis (GCA): aim of study was to evaluate effect of low-dose aspirin in preventing cranial ischemic complications (blindness or stroke); GCA also a common cause of systemic vasculitis; investigators conducted retrospective chart review of 175 Israeli patients with GCA; 57 patients (33%) experienced stroke or visual loss; investigators studied association (if any) between use of aspirin and incidence of cranial ischemic complications; some patients took aspirin, 100 mg/day, for cardiovascular indications; 8% of those patients experienced cranial ischemic complications, compared with 29% of patients who did not take aspirin; patients taking aspirin were 5-fold less likely to develop visual loss or stroke at presentation of GCA; during follow-up, 13% of control patients developed cranial ischemic complications, compared with 3% of aspirin group (another 5-fold difference); patients’ smoking history not measured; crude measurement of other risk factors; in speaker’s opinion, results “mpressive
Possible mechanisms of aspirin action: inhibition of inflammatory cytokines (eg, aspirin better inhibitor of gamma-interferon than prednisone), or inhibition of thromboses through antiplatelet effect
Impact on internal medicine: make aspirin, along with prednisone, standard part of therapy for GCA; keep patient on aspirin for “quite some time”; main risk associated with aspirin is bleeding (in 65-yr-old, risk 1 in 100 to 1 in 500); however, since risk with GCA is stroke or permanent blindness, and provided patient had no history of recent gastrointestinal bleeding, speaker would treat with aspirin plus prednisone for at least 1 mo,
Warfarin for treatment of antiphospholipid antibody syndrome (APS): study aim to compare moderate-intensity anticoagulation (international normalized ratio [INR] 2-3) to high-intensity anticoagulation (INR 3.1-4.0) in preventing recurrent clotting from APS
Thrombosis risk with APS: associated with arterial and venous thrombosis; risk for recurrence even higher among patients with APS; some retrospective evidence that high-intensity warfarin may lower risk, but no prospective study done (until this one)
Study: included 114 patients with APS and history of arterial or venous thrombosis; study randomized, controlled, and double-blinded; major outcomes recurrent thrombosis and bleeding
Results: new clots developed in 6 patients in high-intensity group and in 2 patients in mild-intensity group (difference not significant); also, no difference in toxicity between groups; most patients experienced venous thromboses (easier to treat); patient compliance variable; no one entered study during first 3 mo after thrombosis (when risk of recurrence highest); investigators concluded that high-intensity warfarin not better than moderate- intensity warfarin for preventing thromboses in patients with APS; only 7% of patients developed recurrence with either form of anticoagulation
Impact on internal medicine: treat APS patients with moderate-intensity warfarin (INR 2-3)
Azathioprine or cyclophosphamide as maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies (ANCA): cyclophosphamide effective treatment for ANCA vasculitis, but highly toxic and associated with risk for malignancy; investigators treated all patients with Wegener’s or similar vasculitis with cyclophosphamide and prednisone for 3 mo, then randomized them so one group received azathioprine instead of cyclophosphamide; no difference between groups in risk for relapse or end-stage renal disease; also no difference in rate of toxicity; means duration of cyclophosphamide exposure can be reduced safely
Impact on internal medicine: for patients with Wegener’s vasculitis or other ANCA-associated vasculitides, standard treatment is to limit cyclophosphamide exposure to 3 mo after remission achieved, then substitute with something else; azathioprine and methotrexate both effective