Differentials
Rocky mountain spotted fever
SIGNS / SYMPTOMS
More severe illness usually with petechial rash rather than maculo-papular/papulo-vesicular rash.
Eschar at site of tick bite is rarely present.
INVESTIGATIONS
Serology: positive.
Polymerase chain reaction (PCR): positive for Rickettsia rickettsii DNA in blood or biopsy specimens.
Malaria infection
SIGNS / SYMPTOMS
Most common cause of non-specific febrile illness in returning travellers.
Residence in/travel from malaria-endemic region.
Inadequate or absence of malaria chemoprophylaxis.
INVESTIGATIONS
Giemsa-stained thick and thin blood smears: positive for Plasmodium species.
Rapid diagnostic tests: positive for Plasmodium species.
Dengue fever
SIGNS / SYMPTOMS
May be difficult to distinguish clinically.
Headache and retrobulbar pain that worsens with eye movements is typical.
A rash may be present in about one half of patients and may be petechial or otherwise haemorrhagic.
No eschar in viral infections.
INVESTIGATIONS
Specific serology. Viral multiplex polymerase chain reaction (PCR), if available. PCR may detect dengue virus in serum early in the illness. Isolation of virus by tissue culture is less common. Antibodies may be detected after resolution of the illness but are not helpful in the acute phase.
Non-structural protein 1 (NS1) detection: positive.
Chikungunya virus infection
SIGNS / SYMPTOMS
Residence in/travel from chikungunya-endemic region.
Prominent joint symptoms (e.g., polyarthritis and carpal tunnel syndrome are common).
Hyperpigmentation of skin and intertriginous lesions are common.
Ocular symptoms (e.g., photophobia, retro-ocular pain, conjunctival inflammation).
INVESTIGATIONS
Enzyme-linked immunosorbent assay (ELISA)/indirect fluorescent antibody: positive for chikungunya antibodies.
Reverse transcriptase-polymerase chain reaction (RT-PCR): positive for chikungunya viral RNA.
Zika virus infection
SIGNS / SYMPTOMS
Residence in/travel from Zika-endemic region or unprotected sexual contact with infected individual.
May be difficult to distinguish clinically. No eschar in viral infections.
Non-purulent conjunctivitis or conjunctival hyperaemia may be present.
INVESTIGATIONS
Reverse transcriptase-polymerase chain reaction (RT-PCR): positive for Zika.
Serology: positive for Zika.
West Nile virus
SIGNS / SYMPTOMS
Headache, myalgias, and weakness are more prominent. A diffuse erythematous maculopapular or morbilliform rash, which spares the palms and soles, is more common in children than adults. Neuroinvasive disease occurs in <1.0% of patients.[27]
INVESTIGATIONS
West Nile virus-specific IgM in serum or cerebrospinal fluid.
Lyme disease
SIGNS / SYMPTOMS
Residence in or travel to endemic area.
History of possible erythema migrans.
Sometimes has an area of central clearing within the erythema.
INVESTIGATIONS
Serological diagnosis is possible in convalescent period. Antibodies against Borrelia present.
Western immunoblotting: shows presence of Lyme-specific IgM and IgG.
Polymerase chain reaction: positive for Borrelia.
Typhoid fever
SIGNS / SYMPTOMS
The rash is far more extensive in rickettsial infections than in typhoid fever. No eschar in typhoid fever.
INVESTIGATIONS
Positive blood cultures grow Salmonella typhi in typhoid fever but not in rickettsial infection.
Meningococcal disease
SIGNS / SYMPTOMS
May be difficult to distinguish clinically.
Rash characteristically petechial and begins earlier than in rickettsial infections, starting centrally and spreading peripherally.
Septic shock, disseminated intravascular coagulation, and digital necrosis more likely.
INVESTIGATIONS
Blood cultures (and sometimes cerebrospinal fluid cultures): positive for Neisseria meningitidis.
Chickenpox
SIGNS / SYMPTOMS
Vesicular rash. Successive crops of lesions appear over several days on trunk, face, and oral mucosa. Typically, lesions are in different stages of evolution from vesicles to crusts. Haemorrhagic and bullous lesions rarely occur.
INVESTIGATIONS
Vesicle Tzanck smear: multinucleated giant cells.
Direct fluorescent antibody test: positive for varicella zoster virus (VZV).
Polymerase chain reaction: positive for VZV DNA.
Measles infection
SIGNS / SYMPTOMS
Erythematous or brownish morbilliform rash spreads from the head and neck downwards and persists for 3 to 7 days.
Coryza, cough, and conjunctivitis are usual.
A pathognomonic enanthem (Koplik's spots) occurs early in the disease.
INVESTIGATIONS
Positive serum measles anti-IgM antibody is the preferred test.
Significant rise in serum measles anti-IgG antibody in paired acute and convalescent specimens.
Isolation of measles virus from throat, nasopharynx, blood, or urine (usually processed by public health and reference laboratories only).
Rubella
SIGNS / SYMPTOMS
Typically a mild fever and generalised maculopapular rash improving in about 3 days. May also have non-tender lymphadenopathy of post-auricular, posterior cervical, and occipital lymph node groups; conjunctivitis; and arthralgias or arthritis.
INVESTIGATIONS
Rubella-specific IgM antibody or other specific test for rubella.
Parvovirus B19 infection
SIGNS / SYMPTOMS
Typically a mild illness, associated classically with rash initially presenting with 'slapped cheek' appearance, followed by lacy, reticular lesions. May have associated arthritis and/or anaemia.
Fever has usually subsided before rash develops.
INVESTIGATIONS
Parvovirus-specific antibody detection.
Roseola
SIGNS / SYMPTOMS
Rash appears after fever breaks.
INVESTIGATIONS
Specific test for human herpes virus 6 or human herpes virus 7.
Infectious mononucleosis
SIGNS / SYMPTOMS
Febrile illness that may involve sore throat, pharyngeal exudates, and hepatosplenomegaly.
INVESTIGATIONS
Specific test for Epstein-Barr virus (EBV) antibody.
Monospot for children over age 4 years.
Cutaneous drug reactions
SIGNS / SYMPTOMS
History of recent medication or drug ingestion. History of exposure to the drug, presence of oral lesions or ulcers, peri-orbital oedema, and low acute-phase markers.
INVESTIGATIONS
Diagnosis is made on clinical grounds, although acute-phase markers (such as erythrocyte sedimentation rate and CRP) in rickettsial disease are significantly higher than in an acute drug reaction.
Leptospirosis
SIGNS / SYMPTOMS
May be difficult to distinguish clinically. No eschar in leptospirosis.
The disease course may be bimodal, with fever, meningitis, and a rash (which may be haemorrhagic) developing several days after improvement in initial symptoms. Hepatitis, jaundice, interstitial nephritis, and myocarditis are common in severe Leptospira infections.
INVESTIGATIONS
Serological testing: confirms leptospirosis.
Anthrax
SIGNS / SYMPTOMS
Characteristic skin lesions of cutaneous anthrax begin as a pruritic, painless papule 2 to 5 days after exposure. The lesion becomes vesicular, evolving into a necrotic black eschar with massive surrounding oedema 24 to 36 hours later. The wound is typically painless.
INVESTIGATIONS
Wound Gram stain and culture: positive for Bacillus anthracis.
Scarlet fever
SIGNS / SYMPTOMS
Pharyngitis more pronounced.
INVESTIGATIONS
Throat culture or antigen detection test: positive for Streptococcus pyogenes.
Non-rickettsial bacterial sepsis
SIGNS / SYMPTOMS
May be difficult to distinguish clinically. No eschar in bacteraemia.
INVESTIGATIONS
Blood or other body fluid cultures diagnostic. No rickettsial species grows in normal blood cultures.
Toxic shock syndrome
SIGNS / SYMPTOMS
An acute febrile illness that is associated with vomiting, diarrhoea, myalgia, strawberry tongue, and erythematous rash with subsequent desquamation.
Many develop acute respiratory distress, hypotension, and shock.
The disease is caused by staphylococcal or group A streptococcal infections.
INVESTIGATIONS
Isolation of staphylococcus or group A streptococcus serotypes that produce TSS-1 toxin.
Mycoplasma pneumoniae pneumonia
SIGNS / SYMPTOMS
Dry, persistent cough. Bullous myringitis may be present.
Clinical response to appropriate antibiotic therapy.
INVESTIGATIONS
Serum cold agglutinins: may be positive in Mycoplasma infection.
Gastroenteritis
SIGNS / SYMPTOMS
Nausea, vomiting, and diarrhoea are more prominent.
INVESTIGATIONS
Direct examination of stool may demonstrate polymorphonuclear neutrophils and/or blood.
Stool cultures and antigen detection confirm diagnosis.
Thrombotic thrombocytopenic purpura
SIGNS / SYMPTOMS
Thrombocytopenia and a purpuric rash.
INVESTIGATIONS
Peripheral smears: show schistocytes.
Serum: shows elevated lactate dehydrogenase.
Kawasaki disease
SIGNS / SYMPTOMS
Occurs almost exclusively in children <8 years of age. Prominent features are a persistent high fever; bulbar conjunctivitis; erythematous changes of the mouth and pharynx; dry, cracked lips; swelling and pain of the hands and feet; and cervical lymphadenopathy.
Irritability, abdominal pain, diarrhoea, and vomiting are common. Periungual desquamation may be noted in the second week of the illness. Coronary and other arterial aneurysms may develop 1 to 4 weeks after the onset of illness.
INVESTIGATIONS
No specific diagnostic test is available.
Suggestive laboratory and diagnostic imaging findings include sterile pyuria, hepatitis, cerebrospinal fluid pleocytosis, pericardial effusion, gallbladder hydrops, and coronary artery abnormalities.
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