Clinical Case Presentation

Dwight Yin, M.D. Fellow Pediatric Infectious Diseases

History of Present Illness

19yo Latino male presenting in August 2009 8d prior to presentation
Fever to 104F, chills, myalgias Lightheadedness Back pain Symptoms waxed and waned every 3 hrs In Dominican Republic for weeks, where many rates and mice were noted constantly

History of Present Illness (2)

2d prior to admission
Admitted to hospital in Dominican Republic Thrombocytopenia Received IV Fluids and unspecified antibiotics Left against medical advice to return to U.S.

History of Present Illness (3)

On day of admission
Suprapubic abdominal pain, 8 out of 10 intensity Petechiae on bilateral legs Thrombocytopenia worsening, now platelets 23,000

Referred for admission by primary care physician

Other History
Past Medical History Age 2yo: peri-anal abscess Eczema Social History Lives with parents and 17yo brother in NC Travels regularly to Dominican Republic Immunizations up-to-date, including Menactra 3 yrs prior Medications: None Adverse Drug Reactions: Erythromycin-vomiting, diarrhea

Review of Systems
General: fever, chills, fatigue, 10 lbs. wt loss in 1 wk Skin: petechial rash on lower extremities, no jaundice Eyes: no conjunctivitis, icterus Neck: No stiffness Resp: No cough, dyspnea GI: Abdominal pain, nausea, anorexia. No vomiting, diarrhea, hematochezia. Ext: Myalgias. No edema GU: No hematuria Back: Back pain Neuro: No headache, confusion Heme: Thrombocytopenia

Physical Exam
Gen: Fatigued, uncomfortable but non-toxic VS: T 36.2 HR 64 RR 20 BP 125/63 Pulse Ox 99% RA HEENT: Conjunctivae clear, non-icteric, not injected Neck: Supple, +posterior cervical LAN Chest: CTA B, no retractions CVS: RRR and well-audible, no murmurs, rubs, or gallops Abd: Bowel sounds present, soft, non-distended, mild tenderness to palpation suprapubic. No hepatosplenomegaly. Ext: No edema or cyanosis, FROM of all joints. Skin: Petechiae from soles of feet to just below knees, nonblanching. Eczema over antecubital fossa and on neck.

His Feet

Laboratory Studies
WBC 6.6 Hb 14.8 Hct 41 Plt 80 Differential: 5% Bands, 42% Segmented Neutrophils, 26% Lymphocytes, 13% Monocytes, 8% Eosinophils, 6% Variably Lymphocytes INR 1.0 PT 11.9 PTT 34.9 Electrolytes normal AST 302 516 ALT 157 377 Total Bilirubin 0.9, Alkaline Phosphatase 95 Urinalysis unremarkable Stool Hemoccult positive

WHAT IS YOUR DIFFERENTIAL DIAGNOSIS?

Differential Diagnosis
Dengue Fever Salmonella Typhi Leptospirosis Enterovirus Malaria

Laboratory Studies
Dengue Fever Antibody Panel
IgM 10.91 (normal <0.9) IgG 0.28 (normal <0.9)

Epidemiology
Endemic and epidemic in tropical regions of Asia and the Americas Worldwide >100 million infections per year Over 2.5 billion at risk for infection

Dengue Worldwide Distribution

http://www.cdc.gov/dengue/epidemiology

Dengue Increasing in the Americas

http://www.cdc.gov/dengue/epidemiology

Cases in U.S.
1977 to 2004: 3,806 suspected cases of dengue imported to the United States July 2005: Case reported of confirmed dengue hemorrhagic fever in a resident of Brownsville, Texas, without travel August 2005: 1,251 dengue fever cases in Tamaulipas, Mexico August-November 2005: 24 additional cases in Texas, including 2 more infections not associated with travel

Seroprevalence 2004
2% of Brownsville residents and 7.3% of Matamoros residents were IgM-positive for dengue 40% of Brownsville residents and 78% of Matamoros residents had a past dengue infection Relevant mosquito larvae in 30% of households in both cities

http://borderhealth.cr.usgs.gov/staticmaplib.html

Microbiology
Flavivirus Transmitted by Aedes (Stegomyia) mosquitos
Ae. aegypti Ae. albopictus
gis.fem-environment.eu

Microbiology and Immunity

Serotypes
DENV-1 DENV-2 DENV-3 DENV-4

Immunity is type-specific
Single person can acquire 4 separate dengue infections during a lifetime

Clinical Manifestations
Incubation period 4 to 7 days (range 2-15 days) Majority of infections in children are asymptomatic or a mild systemic illness

Clinical Syndromes
Classic Dengue Fever Dengue Hemorrhagic Fever (DHF) Dengue Shock Syndrome (DSS)

Classic Dengue Fever

Acute onset of fever and headache (often retro-orbital) Commonly associated symptoms
Myalgia Arthralgia Vomiting Andominal pain Maculopapular rash

May be indistinguishable from many other viral illnesses

Classic Dengue Fever

Some may develop hemorrhagic manifestations
Epistaxis Petechial rash GI bleeding Positive Tourniquet Test
>20 petechiae in a square patch of skin following inflation of BP cuff

Classic Dengue Fever

Following 1-3 day remission, may have recurrent fever and rash Laboratory abnormalities may include
Leukopenia Thrombocytopenia Elevated transaminases

DHF and DSS

Rarely occurs with first infection More common with 2nd or 3rd dengue infection Progression to DHF occurs around day 3 to 7 of illness Progression to DSS often occurs suddenly with defervescence

Dengue Hemorrhagic Fever (DHF)

apps.who.int

ci.vbi.vt.edu

Tourniquet Test

WHO DHF Case Definition

The following (4) must all be met: Fever, or history of acute fever, lasting 2-7 days, occasionally biphasic Hemorrhagic tendencies, evidenced by at least one of the following:
A positive tourniquet test Petechiae, ecchymoses, or purpura Bleeding from the mucosa, gastrointestinal tract, injection sites, or other locations Melena or hematemesis

WHO DHF Case Definition (2)

Thrombocytopenia 100,000/mm3 Evidence of plasma leakage because of increased vascular permeability, manifested by at least one of the following
An increase in the hematocrit 20% above average for age, sex, and population. A decrease in the hematocrit following volume replacement treatment 20% of baseline. Signs of plasma leakage such as pleural effusion, ascites, and hypoproteinemia

Dengue Shock Syndrome Case Definition

All criteria of DHF plus circulatory failure as evidenced by:
Rapid and weak pulse and narrow pulse pressure ( 20 mmHg) Age-specific hypotension and cold, clammy skin and restlessness

Dengue Shock Syndrome (DSS)

Possible preceding symptoms
Sustained intense abdominal pain Restlessness or lethargy Sudden diaphoretic hypothermia Persistent vomiting

Diagnosis
Primarily clinical Hemagglutination Inhibition (HI)
Acute and convalescent titers for 4-fold rise Primary infection
Antibodies develop later than 5th day of illness Titers in convalescent phase < 1:1250

Secondary infection
Rise earlier Titers in convalescent phase > 1:1250, often > 1:10,240

ELISA
IgG 99% sensitivity, 96% specificity (acute/convalescent) IgM sensitivity and specificity much lower than HI

Management: Classic Dengue Fever

Rest Close observation Attention to hydration Pain management with acetaminophen Avoid aspirin due to interference with platelet function

Classic Dengue Fever: Disposition

Consider hospitalization if
Hematocrit elevated Platelet count low

Outpatient signs to watch for

Bleeding Petechial rash Severe abdomninal pain Agitation Restlessness Lethargy Respiratory difficulty

DHF and DSS: Intravenous Fluids!

bucksvets.com

DHF/DSS Treatment
Fluid Management
DHF: Isotonic fluids to support adequate circulating volume DSS: Intensive fluid therapy

Fatality rate
Untreated = 50% Early diagnosis and appropriate management = <1%

Take-Home Points
Remember to consider dengue fever, both imported and endemic cases Early detection and management with IV fluids significantly impacts mortality

References
CDC. Dengue Hemorrhagic Fever U.S.-Mexico Border. MMWR 2007;56:785-9. Emerg. Infect. Dis. 2007;13:1477-83 Hayes EB. Flaviviruses. Prin Inf Dis 2008: 1082-1087. Rothman AL. Clinical presentation and diagnosis of dengue virus infections. UpToDate 18.1, Jan. 2010. World Health Organization. Dengue hemorrhagic fever: diagnosis, treatment, prevention, and control. 2nd ed. Geneva, Switzerland: WHO, 1997.