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Dengue fever
This month’s selected commentary
Dengue fever Warren R. Heymann, MD Based on the dialogue ‘‘Tropical diseases in nontropical areas’’ between Drs Theodore Rosen and Stuart Brown Dialogues in Dermatology, a monthly audio program from the American Academy of Dermatology contains discussions between dermatologists on timely topics. Commentaries from Dialogues Editorin-Chief Warren R. Heymann, MD, are provided after each discussion as a topic summary and are provided here as a special service to readers of the Journal of the American Academy of Dermatology. ( J Am Acad Dermatol 2009;60:306-7.)
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or dermatologists in the United States, tropical diseases are no longer just abstractions to be memorized for board examinations. International travel, urbanization, suburban sprawl into previously uninhabited land, and global climate change with its effect on vegetation and potential vectors are all factors that have led to the increasing number of tropical diseases that may be seen in our offices. In this dialogue, Dr Rosen discusses leishmaniasis in soldiers returning from Iraq, cutaneous larva migrans, myiasis, tungiasis, dengue fever, and venereal diseases including donovanosis (granuloma inguinale), chancroid, and lymphogranuloma venereum. This commentary will focus on dengue fever. Two and one half billion people now live in areas that put them at risk for the infection. This year alone, 50,000 people in Brazil have been infected with the dengue virus, resulting in 60 deaths.1 Halstead2 states that 50 million to 100 million individuals worldwide are infected every year, resulting in 500,000 hospitalizations. Indeed, dengue is the most prevalent arthropod-borne virus affecting humans. According to Kyle and Harris,3 ‘‘Due in part to population growth and uncontrolled urbanization in tropical and subtropical countries, breeding sites for the mosquitoes that transmit dengue virus have proliferated, and successful vector control has proven problematic. Dengue viruses have evolved rapidly as they have spread worldwide, and genotypes associated with increased virulence have expanded from South and Southeast Asia in to the Pacific and the Americas.’’
The statements and opinions expressed in this commentary are those of the Editor-in-Chief of Dialogues in Dermatology.
306
Dengue viruses belong to the family of Flaviviridae. Infections are transmitted by the bite of infected mosquitoes of the genus Aedes. There are 4 genotypes of dengue virus; infection may be asymptomatic or cause dengue fever, dengue hemorrhagic fever (DHF), or the dengue shock syndrome (DSS).4 According to Enserink,5 the mosquito Ae aegypti dines almost exclusively on humans, ‘‘which is why it has caused an explosive rise in dengue cases in the tropics the past 2 decades.’’ Ae albopictus, also known as the Asian tiger mosquito, is an aggressive biter that feeds on a variety of mammals, birds, and reptiles. When other host species are scarce, such as in urban environments, the mosquito may have little choice other than to bite humans. Ae albopictus appearing in the United States has been attributed to the international trade of secondhand tires, in which the mosquito travels as a stowaway, due to water content of these tires, which is ideal for the eggs and larvae of the mosquito. Additionally, the Lucky bamboo plant has been implicated in the transmission of the vector. Dengue outbreaks with Ae albopictus tend to be mild.5 Disease severity correlates with a panoply of cytokines, in concert with altered platelet, dendritic-cell, monocyte, and T-cell functions. This suggests that immunologic responses to components of dengue viruses could contribute to autoimmune processes leading to DHF or DSS.2 The pathogenesis of DHF/DSS remains to be elucidated, although it has been hypothesized that non-neutralizing levels of heterotypic antibodies from a prior dengue virus infection promotes increased viral replication within mononuclear leukocytes (known as the phenomenon of antibody-dependent enhancement of infection).4 This is consistent with
J AM ACAD DERMATOL
Dialogues in Dermatology 307
VOLUME 60, NUMBER 2
the observation that a secondary infection with a different strain of the dengue virus increases the risk of DHF/DSS. While many patients may have an asymptomatic infection with the dengue virus, the clinical illness may be on a spectrum ranging from dengue fever, to DHF, to DSS. According to Pincus, Grossman, and Fox,6 the incubation period for dengue fever is 3 to 14 days. The characteristic exanthem of dengue fever is estimated to occur in 50% to 82% of patients. ‘‘The initial rash involves a flushing erythema of the face, neck, and chest that typically occurs within the first 24 to 48 hours of the onset of symptoms. . .The subsequent rash, seen 3 to 5 days later, is characterized by a generalized morbilliform eruption with petechiae and islands of sparing e ‘white islands in a sea of red’ e and is thought to be an immune response to the virus.’’ In some cases a petechial eruption is noted on the dorsa of the feet, legs, hands, and wrists. An enanthem of minute glistening vesicles on the soft palate may be seen within 12 hours of the onset of illness. Systemic features include fever, dizziness, headache, back pain, arthralgias (hence the term ‘‘breakbone fever’’), weakness, and eye pain.7 Pincus, Grossman, and Fox note that typical laboratory findings include leukopenia, thrombocytopenia, elevated transaminase levels, hemoconcentration, and hyponatremia. Up to 30% of patients with DHF may have disease progress to DSS. The diagnosis of dengue fever can be confirmed by viral isolation, polymerase chain reaction analysis, or the identification of dengue virusespecific antibodies. Treatment is supportive, with efforts to maintain intravascular volume with albumin and/or blood transfusions. Efforts are under way to develop a dengue vaccine; any successful vaccine will need to be tetravalent against all 4 strains of the dengue virus in order to prevent DHF/DSS.4 Erren and Erren8 note that a balanced combination of measures, including vector control and vaccine development will be necessary to curtail the dengue epidemic. The late Vice-President Hubert Humphrey stated, ‘‘Freedom is the most contagious virus known to man.’’ Until we have learned to temper our environment, control vectors, and learn
the intricacies of viral immunology, we will not experience freedom from tropical viruses such as dengue. Dermatologists in nontropical climates need to be aware that tropical diseases may present to them, especially in those patients with a travel history to endemic regions. REFERENCES 1. International action needed on dengue. Lancet 2008;371(9620): 1216. 2. Halstead SB. Dengue. Lancet 2007;370(9599):1644-52. 3. Kyle JL, Harris E. Global spread and persistence of dengue. Annu Rev Microbiol 2008 Apr 22 Epub ahead of print. 4. Radakovic-Fijan S, Graninger W, Mu¨ller C, Ho¨nigsmann H, Tanew A. Dengue hemorrhagic fever in a British travel guide. J Am Acad Dermatol 2002;46:430-3. 5. Enserink M. Entomology. A mosquito goes global. Science 2008; 320:864-6. 6. Pincus LB, Grossman ME, Fox LP. The exanthema of dengue fever: clinical features of two US tourists traveling abroad. J Am Acad Dermatol 2008;58:308-16. 7. Samlaska CP. Viral hemorrhagic fevers. In: James WD, editor. Military dermatology. Washington (DC): Office of the Surgeon General at TMM Publications; 1994. pp. 197-212. 8. Erren TC, Erren M. Defeating dengue; new mosquito genome, old promise? Bull World Health Organ 2008;86:A.
Additional topics from the January 2009 issue of the Dialogues in Dermatology: 1. Diet and acne With F. William Danby, MD, interviewed by Stephen Stone, MD 2. Pediatric alopecia With Amy J. McMichael, MD, interviewed by Gary Brauner, MD
Dialogues in Dermatology is published monthly by the American Academy of Dermatology in both audio cassette and CD formats. Corporate and editorial offices: 930 E. Woodfield Dr, Schaumburg, IL 60173-4729. 2009 subscription rates: $150 for individuals in the United States, Canada, and Mexico; $200 International. ª 2009 by the American Academy of Dermatology, Inc. Subscriptions are available by calling toll-free: 866-503-7546 or faxing 847-240-1859. Additional information is available in the Marketplace section of www.aad.org.
Dengue fever Warren R. Heymann, MD Based on the dialogue ‘‘Tropical diseases in nontropical areas’’ between Drs Theodore Rosen and Stuart Brown Dialogues in Dermatology, a monthly audio program from the American Academy of Dermatology contains discussions between dermatologists on timely topics. Commentaries from Dialogues Editorin-Chief Warren R. Heymann, MD, are provided after each discussion as a topic summary and are provided here as a special service to readers of the Journal of the American Academy of Dermatology. ( J Am Acad Dermatol 2009;60:306-7.)
F
or dermatologists in the United States, tropical diseases are no longer just abstractions to be memorized for board examinations. International travel, urbanization, suburban sprawl into previously uninhabited land, and global climate change with its effect on vegetation and potential vectors are all factors that have led to the increasing number of tropical diseases that may be seen in our offices. In this dialogue, Dr Rosen discusses leishmaniasis in soldiers returning from Iraq, cutaneous larva migrans, myiasis, tungiasis, dengue fever, and venereal diseases including donovanosis (granuloma inguinale), chancroid, and lymphogranuloma venereum. This commentary will focus on dengue fever. Two and one half billion people now live in areas that put them at risk for the infection. This year alone, 50,000 people in Brazil have been infected with the dengue virus, resulting in 60 deaths.1 Halstead2 states that 50 million to 100 million individuals worldwide are infected every year, resulting in 500,000 hospitalizations. Indeed, dengue is the most prevalent arthropod-borne virus affecting humans. According to Kyle and Harris,3 ‘‘Due in part to population growth and uncontrolled urbanization in tropical and subtropical countries, breeding sites for the mosquitoes that transmit dengue virus have proliferated, and successful vector control has proven problematic. Dengue viruses have evolved rapidly as they have spread worldwide, and genotypes associated with increased virulence have expanded from South and Southeast Asia in to the Pacific and the Americas.’’
The statements and opinions expressed in this commentary are those of the Editor-in-Chief of Dialogues in Dermatology.
306
Dengue viruses belong to the family of Flaviviridae. Infections are transmitted by the bite of infected mosquitoes of the genus Aedes. There are 4 genotypes of dengue virus; infection may be asymptomatic or cause dengue fever, dengue hemorrhagic fever (DHF), or the dengue shock syndrome (DSS).4 According to Enserink,5 the mosquito Ae aegypti dines almost exclusively on humans, ‘‘which is why it has caused an explosive rise in dengue cases in the tropics the past 2 decades.’’ Ae albopictus, also known as the Asian tiger mosquito, is an aggressive biter that feeds on a variety of mammals, birds, and reptiles. When other host species are scarce, such as in urban environments, the mosquito may have little choice other than to bite humans. Ae albopictus appearing in the United States has been attributed to the international trade of secondhand tires, in which the mosquito travels as a stowaway, due to water content of these tires, which is ideal for the eggs and larvae of the mosquito. Additionally, the Lucky bamboo plant has been implicated in the transmission of the vector. Dengue outbreaks with Ae albopictus tend to be mild.5 Disease severity correlates with a panoply of cytokines, in concert with altered platelet, dendritic-cell, monocyte, and T-cell functions. This suggests that immunologic responses to components of dengue viruses could contribute to autoimmune processes leading to DHF or DSS.2 The pathogenesis of DHF/DSS remains to be elucidated, although it has been hypothesized that non-neutralizing levels of heterotypic antibodies from a prior dengue virus infection promotes increased viral replication within mononuclear leukocytes (known as the phenomenon of antibody-dependent enhancement of infection).4 This is consistent with
J AM ACAD DERMATOL
Dialogues in Dermatology 307
VOLUME 60, NUMBER 2
the observation that a secondary infection with a different strain of the dengue virus increases the risk of DHF/DSS. While many patients may have an asymptomatic infection with the dengue virus, the clinical illness may be on a spectrum ranging from dengue fever, to DHF, to DSS. According to Pincus, Grossman, and Fox,6 the incubation period for dengue fever is 3 to 14 days. The characteristic exanthem of dengue fever is estimated to occur in 50% to 82% of patients. ‘‘The initial rash involves a flushing erythema of the face, neck, and chest that typically occurs within the first 24 to 48 hours of the onset of symptoms. . .The subsequent rash, seen 3 to 5 days later, is characterized by a generalized morbilliform eruption with petechiae and islands of sparing e ‘white islands in a sea of red’ e and is thought to be an immune response to the virus.’’ In some cases a petechial eruption is noted on the dorsa of the feet, legs, hands, and wrists. An enanthem of minute glistening vesicles on the soft palate may be seen within 12 hours of the onset of illness. Systemic features include fever, dizziness, headache, back pain, arthralgias (hence the term ‘‘breakbone fever’’), weakness, and eye pain.7 Pincus, Grossman, and Fox note that typical laboratory findings include leukopenia, thrombocytopenia, elevated transaminase levels, hemoconcentration, and hyponatremia. Up to 30% of patients with DHF may have disease progress to DSS. The diagnosis of dengue fever can be confirmed by viral isolation, polymerase chain reaction analysis, or the identification of dengue virusespecific antibodies. Treatment is supportive, with efforts to maintain intravascular volume with albumin and/or blood transfusions. Efforts are under way to develop a dengue vaccine; any successful vaccine will need to be tetravalent against all 4 strains of the dengue virus in order to prevent DHF/DSS.4 Erren and Erren8 note that a balanced combination of measures, including vector control and vaccine development will be necessary to curtail the dengue epidemic. The late Vice-President Hubert Humphrey stated, ‘‘Freedom is the most contagious virus known to man.’’ Until we have learned to temper our environment, control vectors, and learn
the intricacies of viral immunology, we will not experience freedom from tropical viruses such as dengue. Dermatologists in nontropical climates need to be aware that tropical diseases may present to them, especially in those patients with a travel history to endemic regions. REFERENCES 1. International action needed on dengue. Lancet 2008;371(9620): 1216. 2. Halstead SB. Dengue. Lancet 2007;370(9599):1644-52. 3. Kyle JL, Harris E. Global spread and persistence of dengue. Annu Rev Microbiol 2008 Apr 22 Epub ahead of print. 4. Radakovic-Fijan S, Graninger W, Mu¨ller C, Ho¨nigsmann H, Tanew A. Dengue hemorrhagic fever in a British travel guide. J Am Acad Dermatol 2002;46:430-3. 5. Enserink M. Entomology. A mosquito goes global. Science 2008; 320:864-6. 6. Pincus LB, Grossman ME, Fox LP. The exanthema of dengue fever: clinical features of two US tourists traveling abroad. J Am Acad Dermatol 2008;58:308-16. 7. Samlaska CP. Viral hemorrhagic fevers. In: James WD, editor. Military dermatology. Washington (DC): Office of the Surgeon General at TMM Publications; 1994. pp. 197-212. 8. Erren TC, Erren M. Defeating dengue; new mosquito genome, old promise? Bull World Health Organ 2008;86:A.
Additional topics from the January 2009 issue of the Dialogues in Dermatology: 1. Diet and acne With F. William Danby, MD, interviewed by Stephen Stone, MD 2. Pediatric alopecia With Amy J. McMichael, MD, interviewed by Gary Brauner, MD
Dialogues in Dermatology is published monthly by the American Academy of Dermatology in both audio cassette and CD formats. Corporate and editorial offices: 930 E. Woodfield Dr, Schaumburg, IL 60173-4729. 2009 subscription rates: $150 for individuals in the United States, Canada, and Mexico; $200 International. ª 2009 by the American Academy of Dermatology, Inc. Subscriptions are available by calling toll-free: 866-503-7546 or faxing 847-240-1859. Additional information is available in the Marketplace section of www.aad.org.