Download MODULE 5: Case Classification and Differential Diagnosis

MODULE 5: Case Classification and
Differential Diagnosis
Dengue Clinical Management
Acknowledgements
This curriculum was developed with technical assistance from the University of Malaya Medical Centre. Materials were contributed by the
Ministry of Health, Singapore, the United States Centers for Disease Control and Prevention, and the University of Malaya Medical Centre.
Dengue case classification by severity
Dengue has a wide spectrum of clinical presentations with often
unpredictable evolution:
• Self-limiting disease in most patients
• Severe disease in a small proportion of patients, characterized by
plasma leakage with/without haemorrhage
WHO proposed a dengue case classification system in 2009:
• Supported by set of clinical and/or laboratory parameters
• Aim to show clear-cut difference between patients with nonsevere versus severe dengue
• Classification levels would help clinicians in decision making
about intensity of treatment and observation
Dengue case classification (2009)
Dengue
Without
With
warning signs
Severe dengue
•
•
•
1. Severe plasma leakage
2. Severe haemorrhage
3. Severe organ impairment
Dengue case definition (2009)
Probable dengue
Live in and/or travelled to a dengue-endemic area
Fever and two of the following criteria:
•
Nausea, vomiting (new)
•
Rash
•
Aches and pains (combined)
•
Tourniquet test positive
•
Leucopenia
•
Any warning sign
Laboratory-confirmed dengue
(Important when there is no sign of plasma leakage)
Dengue case classification (2009)
Dengue ± warning signs
Without
With
warning signs
Criteria for dengue ± warning signs
Probable dengue
Live in or travelled to dengueendemic area. Fever and two of
the following criteria:
• Nausea, vomiting (new)
• Rash
• Aches and pains (combined)
• Tourniquet test positive
• Leucopenia
• Any warning sign
Laboratory-confirmed dengue
(important when no sign of plasma leakage)
Warning signs*
Severe dengue
•
•
•
1. Severe plasma leakage
2. Severe haemorrhage
3. Severe organ impairment
Criteria for severe dengue
1. Severe plasma leakage leading to:
•
Shock (DSS)
•
Fluid accumulation with respiratory
distress
Abdominal pain or tenderness
• Persistent vomiting
• Mucosal bleed
2. Severe bleeding
• Lethargy; restlessness
Bleeding that causes hemodynamic
• Liver enlargement >2 cm
instability and may require blood
• Clinical fluid accumulation
transfusion
• Increase in HCT with rapid decrease
in platelet count
3. Severe organ involvement
•
Liver: AST or ALT ≥1000
* Requiring strict observation and medical
•
CNS: Impaired consciousness
intervention
•
Impaired cardiac function
•
Dengue mimics many clinical syndromes
Flu-like illness
Clues to diagnose dengue:
Viral exanthem
Understanding the
dynamic and systemic
nature of dengue
Acute abdomen
Infections
Autoimmune
diseases
Haematological
disorders
Dengue
Knowing its various
manifestations as the
disease progresses from
febrile phase to critical
phase and evolves into
recovery phase
Conditions that mimic the febrile phase of dengue
Viral infections
Influenza, measles, rubella
Chikungunya, West Nile virus
Enterovirus
Other viral haemorrhagic fever
Infectious mononucleosis
Acute HIV seroconversion illness
Bacterial infections
Leptospirosis
Typhoid
Rickettsia infections (typhus, scrub typhus, etc.)
Parasitic infections
Malaria
Febrile illness with
a rash
Diarrhoeal diseases
Measles, rubella
Infectious mononucleosis, enterovirus
Chikungunya, West Nile virus,
Scarlet fever, meningococcal infection
Leptospirosis, typhoid
Rickettsia infections (typhus, scrub typhus, etc.)
Syphilis, acute HIV seroconversion illness
Autoimmune diseases (e.g. SLE)
Adverse drug reaction
Rotavirus
Salmonellosis
Other enteric infections
Conditions that mimic the critical phase of dengue
Acute abdomen
Acidotic breathing/
respiratory distress
Infections
Autoimmune diseases
Malignancies
Others
Acute appendicitis
Acute cholecystitis
Perforated viscus
Diabetic ketoacidosis
Diabetic ketoacidosis
Lactic acidosis
Renal failure
Acute respiratory distress syndrome (ARDS)
Sepsis, septic shock
Acute gastroenteritis
Leptospirosis, typhoid, typhus, malaria
Viral hepatitis
Acute HIV seroconversion illness
Systemic lupus erythematosus
Idiopathic thrombocytopenic purpura
Thrombotic thrombocytopenic purpura
Systemic vascultis
Acute leukaemia
Lymphoma
Other malignancies
Liver cirrhosis with portal hypertension
Adverse drug reaction
Differentiating dengue from leptospirosis
Causative organism
Dengue
Leptospirosis
Dengue virus
Leptospira spirochete
Mosquito bites
Contact with urinecontaminated water or soil
(e.g. flood water, puddles)
Source of infection
WHO case definitions Rash
Headache
Retro-orbital eye pain
Hemorrhagic manifestation
Arthralgia
Myalgia
Leukopenia
Rash
Menigeal irritation
Conjunctiva suffusion
Hemorrhagic manifestation
Cardiac arrhythmia or
failure
Cough/hemoptysis
Anuria/oliguria
Jaundice
Definitive therapy
Antibiotics (doxycycline,
penicillin, tetracycline,
erythromycin)
Early detection of warning
signs, supportive care and
judicious use of IVFs
Differentiating dengue from leptospirosis
Clinical features
Leptospirosis
Dengue
Fever (≥38°C)*
+++
+++
Myalgia
+++
+++
Headache
+++
+++
Rash
+
++
Jaundice
++
+/-
Hyperbilirubinemia (T.Bili >1.3)
++
+/-
Elevated blood urea nitrogen (BUN >25) or Creatinine >2
+
+/-
Leukocytosis (WBC >10 000)†
++
+/-
Positive tourniquet test
+
+++
+++
+
+
+++
Anaemia
Thrombocytopenia
*Mean frequency of symptoms from studies where the two diseases were directly compared among patient seeking care; +++ =
70%–100% of patients; ++ = 40%–69%; + = 10%–39%; +/- = <10%; - = 0%. Sources: Bruce MG et. al. Acta Tropica, 2005; Libraty DH et.
al. PLoS, 2007; LaRocque RC et al. EID, 2005; Ellis T et. al. VBZD, 2008.
**Leptospirosis cases may be more likely to have intermittent fever, but both infections may have biphasic fevers.
† Leptospirosis cases may be more likely to have a higher percentage of neutrophils and a higher absolute neutrophil count.
Differentiating dengue from malaria
Clinical features
P. falciparum
P. vivax
Dengue
+++
+++
+++
+
+
+++
Headache
+++
+++
+++
Rash
+/-
+/-
++
Jaundice
+
+/-
+/-
Vomiting
++
+
+
Abdominal pain
+
+
+/-
Hepatomegaly
+
+
+/-
Splenomegaly
+
+
+/-
Leukopenia
+/-
+/-
+++
Anaemia
++
++
+
Thrombocytopenia
++
++
+++
Fever (≥38°C)*
Myalgia
*Mean frequency of symptoms from studies where the two diseases were directly compared among patient seeking care; +++ = 70%–
100% of patients; ++ = 40%–69%; + = 10%–39%; +/- = <10%; - = 0%. Sources: Nimmannitya S et al. Am J Trop Med Hyg, 1969; 18:954–
971. Halstead SB et al. Am J Trop Med Hyg, 1969; 18:972–983. Beg et al. Int J Inf Dis, 2008; 12:37–42. Robinson et al. J Travel Med,
2001; 8(2):76– 81. Luxemburger et al. Tran R Soc Trop Med Hyg, 1998; 92:42-49.
Differentiating dengue from chikungunya
Clinical Features
Chikungunya virus infection
Dengue virus infection
+++
++
+
++
Arthalgias/arthritis
+++
+/-
Headache
++
++
Rash
++
+
Bleeding dyscrasias
+/-
++
-
+/-
Leukopenia
++
+++
Neutropenia
+
+++
Lymphopenia
+++
++
+
+++
Fever (>102°F)
Myalgia
Shock
Thrombocytopenia
*Mean frequency of symptoms from studies where the two diseases were directly compared among patient seeking care; +++ =
70%–100% of patients; ++ = 40%–69%; + = 10%–39%; +/- = <10%; - = 0%. Sources: Nimmannitya S et al. Am J Trop Med Hyg, 1969;
18:954–971. Halstead SB et al. Am J Trop Med Hyg, 1969; 18:972–983.
Differentiating dengue from surgical acute abdomen
Dengue-related acute abdomen
Surgical acute abdomen
Fever precedes pain and may
become afebrile
Fever may occur after onset of pain
Tender but not guarded
Guarded abdomen with rebound
tenderness in perforated viscus
May be distended in plasma leakage
May or may not be distended
Fluid resuscitation is imperative in
severe dengue
May require fluid resuscitation
Pain improves with fluid
resuscitation in severe dengue
Pain remains after fluid
resuscitation
Differentiating dengue shock from septic shock
Dengue shock
Temperature
- Occurs after defervescence
- Temperature is often subnormal or
normal
- Temperature may be high in those
with reactive haemophagocytic
syndrome
Septic shock
- Temperature is usually high
- But could be subnormal in late
stage of septic shock
(decompensation)
Pulse
- Small or weak pulse volume
- Narrowed pulse pressure
- Cold extremities
- Bounding pulse
- Widened pulse pressure with
warm extremities in the early stage
of septic shock
Full blood
count
- Usually leukopenic and
thrombocytopenic
- Leukocytosis maybe observed in
those with active bleeding
- Usually leukocytosis
- But could be leukopenic and/or
thrombocytopenic
C-reactive
protein
- Normal or mildly elevated CRP
- Markedly elevated CRP