Differentials

Common

Viral syndromes

History

chills, headache, rhinorrhoea, sore throat, cough, nausea, vomiting, abdominal pain, myalgia, rash

Exam

generally normal except for non-specific rash

1st investigation
  • no initial test for most viruses:

    clinical diagnosis

    More
Other investigations

    Urinary tract infection

    History

    nausea, vomiting, dysuria, urinary frequency, abdominal or back pain, recent urinary incontinence, fever >24 hours, history of previous UTIs, non-black racial background

    Exam

    ill appearance, suprapubic or flank tenderness

    1st investigation
    • urine dipstick:

      positive for leukocyte esterase or nitrites

      More
    • urine microscopy:

      ≥5 WBC/HPF or any bacteria

      More
    • enhanced urinalysis:

      ≥10 WBC/mm³ or any bacteria on Gram stain

      More
    • urine culture:

      >100,000 colony forming units (CFU)/mL from clean-catch specimen; >10,000 CFU/mL from catheterised specimen; >1000 CFU/mL from suprapubic aspiration specimen

    Other investigations
    • procalcitonin:

      may be elevated

      More

    Pneumonia

    History

    cough, chest pain, abdominal pain

    Exam

    respiratory distress (retractions, grunting, nasal flaring), decreased breath sounds, tachypnoea, crackles

    1st investigation
    • CXR:

      infiltrates (focal or diffuse)

      More
    Other investigations
    • procalcitonin:

      may be elevated

      More

    Coronavirus disease 2019 (COVID-19)

    History

    typically asymptomatic or mild symptoms: brief and rapidly resolving fever, mild cough, sore throat, congestion, rhinorrhoea; moderate to severe illness can occur in children

    Exam

    fever and coryzal symptoms; may be inspiratory crackles, rales, and/or bronchial breathing in patients with pneumonia or respiratory distress.; patients with respiratory distress may have tachycardia, tachypnoea, or cyanosis accompanying hypoxia

    1st investigation
    • real-time reverse transcription polymerase chain reaction (RT-PCR):

      positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA

      More
    • rapid antigen test:

      positive for SARS-CoV-2 virus antigen

      More
    Other investigations

      Bronchiolitis

      History

      primarily a disease of infancy (rare in children age >1 year); usually starts with upper respiratory tract symptoms (e.g., rhinitis and cough); low-grade fever; increased severity of cough, wheeze, and laboured breathing

      Exam

      tachypnoea, retractions, wheezes, crackles; sometimes thoracoabdominal asynchrony; fever <40°C (<104°F); retractions, grunting, and nasal flaring

      1st investigation
      • no initial test:

        clinical diagnosis

      Other investigations
      • enzyme-linked immunosorbent assay (ELISA) rapid antigen detection:

        positive detection of viral antigen

        More
      • reverse transcriptase polymerase chain reaction (RT-PCR):

        positive detection of viral nucleic acid

        More
      • CXR:

        hyperinflation, interstitial inflammation, atelectasis

        More

      Acute otitis media

      History

      fever, pain, muffled sounds, post-auricular swelling if mastoid is involved, sleep disturbance, headache, diarrhoea, irritability in infants, poor appetite

      Exam

      bulging, erythematous, or opaque tympanic membrane

      1st investigation
      • no initial test:

        clinical diagnosis

      Other investigations

        Tonsillitis

        History

        sore throat, painful swallowing, headache, fever, chills, abdominal pain, nausea and vomiting, cough, rhinorrhoea

        Exam

        tonsillar erythema and enlargement, and enlarged tender cervical lymphadenopathy; purulent exudate may be present, especially if caused by group A beta-haemolytic streptococci

        1st investigation
        • throat culture:

          may be positive

          More
        • rapid streptococcal antigen test:

          identification of group A beta-haemolytic streptococci

          More
        Other investigations
        • serological testing for streptococci:

          considered positive if there is a four-fold rise in antibody titres

          More

        Rhinosinusitis

        History

        rhinorrhoea, nasal congestion, cough (frequently worse at night); symptoms lasting >10-14 days suggests bacterial (as opposed to viral) aetiology

        Exam

        nasal drainage, cough, sinus tenderness, periorbital swelling

        1st investigation
        • no initial test:

          clinical diagnosis

        Other investigations
        • sinus x-rays:

          sinus opacification, mucosal thickening, air-fluid levels

          More
        • sinus CT:

          sinus opacification, mucosal thickening, air-fluid levels

          More
        • sinus aspiration:

          positive sinus cultures, most commonly Streptococcus pneumoniae, Haemophilus influenzae (non-typable), Moraxella catarrhalis

          More

        Meningitis

        History

        irritability, lethargy, seizures (focal seizures raise the concern for herpes meningoencephalitis), poor feeding, paradoxical irritability (cries more when held), nausea or vomiting, headache, neck pain, photophobia, back pain

        Exam

        pyrexia (or hypothermia), bulging fontanelle, papilloedema, meningismus, Kernig's and/or Brudzinski's sign may be positive although not commonly seen in infants, focal neurological deficits

        1st investigation
        • cerebrospinal fluid (CSF) cell count:

          >22 WBC/microlitre in term infant; >7 WBC/microlitre in older child

          More
        • CSF Gram stain and culture:

          identifies pathogen

          More
        • CSF protein and glucose:

          CSF protein ≥80 mg/dL; CSF glucose <50% of serum glucose

          More
        • serum polymerase chain reaction (PCR) for Neisseria meningitidis:

          molecular confirmation of specific pathogen

          More
        Other investigations
        • procalcitonin:

          may be elevated

          More
        • CSF PCR for N meningitidis and Streptococcus pneumoniae:

          N meningitidis or S pneumoniae DNA

        Bacteraemia (occult)

        History

        fever may be only symptom; malaise

        Exam

        may be normal examination apart from fever; important to evaluate for possible signs of sepsis (e.g., tachycardia, increased respiratory rate, behaviour change, delayed capillary return, rash)

        1st investigation
        • FBC:

          WBC ≥15,000/microlitre or ≤5000/microlitre; absolute neutrophil count (ANC) ≥10,000/microlitre

          More
        • blood culture:

          growth of bacteria; identifies pathogen

          More
        Other investigations
        • procalcitonin:

          may be elevated

          More

        Sepsis

        History

        may present with non-specific, non-localised symptoms (especially in younger children); fever, low body temperature or temperature instability; altered mental state or behaviour (e.g., drowsiness, delirium, lethargy, irritability, non-responsiveness, or apnoeas); may be history of risk factors (e.g., immunosuppression, and comorbidities); healthcare associated factors (e.g., indwelling vascular catheters, recent invasive procedures); in neonates, history of premature rupture of membranes, chorioamnionitis, or intrapartum maternal fever may be present; may present with circulatory shock; poor feeding, or emesis

        Exam

        tachycardia, tachypnoea, fever >38℃ (>100.4°F) or hypothermia <36℃ (<96.8°F); infants and young children may be hypotonic with normal or poor peripheral perfusion and hypotension; prolonged capillary refill, mottled or ashen skin, cyanosis, low oxygen saturation, reduced urine output; may be absence of bowel sounds; hypo- or hyperglycaemia may be present

        1st investigation
        • blood culture:

          may be positive for organism

          More
        • serum lactate:

          may be elevated

          More
        • FBC with differential:

          abnormal WBC count (i.e., above or below normal range for age or >10% immature white cells); low platelets

          More
        • CRP:

          elevated

        • blood urea and serum electrolytes:

          serum electrolytes may be deranged; blood urea may be elevated

        • serum creatinine:

          may be elevated

          More
        • LFTs:

          may show elevated bilirubin, alanine aminotransferase, aspartate aminotransferase

        • coagulation studies:

          may be abnormal

        • blood gases:

          may be hypoxaemia, hypercapnia, elevated anion gap, metabolic acidosis

        Other investigations
        • CXR:

          may show consolidation; demonstrates position of central venous catheter and tracheal tube

        • urine microscopy and culture:

          may be positive for nitrites, protein or blood; elevated leukocyte count; positive culture for organism

        • lumbar puncture:

          presence of organism on microscopy and positive culture

          More

        Septic arthritis

        History

        irritability, decreased joint mobility, limpness, inability to bear weight

        Exam

        joint swelling, redness, painful range of motion

        1st investigation
        • FBC:

          WBC >12,000/microlitre

        • ESR/CRP:

          elevated; ESR >40 mm/hour

        • blood culture:

          growth of bacteria; identifies pathogen

          More
        • plain x-ray:

          soft-tissue swelling, joint effusion

          More
        Other investigations
        • joint fluid FBC:

          >50,000 WBC/microlitre

          More
        • joint fluid Gram stain and culture:

          bacteria on Gram stain or growth on culture

          More
        • ultrasound:

          joint effusion

          More

        Osteomyelitis

        History

        irritability, pain, refusal to move extremity, limpness

        Exam

        limb tenderness, erythema

        1st investigation
        • ESR/CRP:

          elevated

          More
        • blood culture:

          growth of bacteria; identifies pathogen

          More
        • plain x-ray:

          soft-tissue swelling, lytic lesions, periosteal elevation

          More
        Other investigations
        • MRI limb:

          bone or soft-tissue involvement

          More

        Cat-scratch disease

        History

        exposure to cats (especially young cats), fever, blurred vision, confusion, arthralgia, myalgia

        Exam

        cutaneous lesion at site of inoculation, regional lymphadenopathy, hepatosplenomegaly, conjunctivitis, pre-auricular lymphadenopathy, retinitis, encephalopathy

        1st investigation
        • serology:

          positive for Bartonella henselae

          More
        Other investigations
        • biopsy:

          positive for B henselae

          More
        • blood or tissue culture:

          positive for B henselae

          More

        Infectious mononucleosis

        History

        sore throat, malaise, rash, jaundice, myalgias

        Exam

        rash, icterus, generalised (particularly posterior cervical) lymphadenopathy, hepatomegaly, splenomegaly, periorbital oedema, palatal petechiae

        1st investigation
        • FBC:

          lymphocytosis (especially with atypical lymphocytes)

          More
        • LFT:

          elevated AST and ALT

        • heterophile antibody:

          positive

          More
        Other investigations
        • Epstein-Barr antibodies:

          positive

          More

        Cytomegalovirus infection

        History

        fatigue, pharyngitis, nausea, vomiting, diarrhoea, malaise, rash, headache

        Exam

        hepatomegaly, splenomegaly, lymphadenopathy

        1st investigation
        • serology:

          CMV-IgM titre is indicative of acute infection; CMV-IgG titre suggests past infection; antibody avidity is low in recent infection

        • nucleic acid detection:

          positive

          More
        Other investigations

          Malaria infection

          History

          fever on alternate days (or every third day with Plasmodium malariae), chills, headache, myalgia, cough, nausea, abdominal pain, history of recent travel abroad​

          Exam

          high-grade pyrexia, splenomegaly, confusion

          1st investigation
          • peripheral blood smear:

            visible parasitaemia on microscopy

            More
          Other investigations
          • serology:

            positive

            More

          Lyme disease

          History

          headache, myalgia, fatigue, arthralgias, stiff neck, history of a tick bite​

          Exam

          erythema migrans (EM), meningismus, signs of carditis or myopericarditis, radiculoneuropathy, facial nerve palsy​

          1st investigation
          • no initial test:

            clinical diagnosis

            More
          Other investigations
          • serological testing:

            positive for Borrelia burgdorferi

            More

          Tuberculosis

          History

          night fever, sweating, cough, haemoptysis, poor appetite, weight loss, headache, history of recent travel abroad or contact with a person with the disease

          Exam

          lymphadenopathy, wheezing, abnormal breath sounds; altered mental status, seizures, focal neurological deficits; hepatomegaly, splenomegaly in severe cases; arthritis

          1st investigation
          • CXR:

            may demonstrate atelectasis from airway compression, pleural effusion, consolidation, pulmonary infiltrates, mediastinal or hilar lymphadenopathy, upper zone fibrosis.

            More
          • sputum, gastric aspirate or bronchoalveolar lavage acid-fast bacilli smear and culture:

            presence of acid-fast bacilli (Ziehl-Neelsen stain) in specimen​

            More
          • acid-fast bacilli smear and culture of extrapulmonary biopsy specimen:

            positive

            More
          • nucleic acid amplification tests (NAAT):

            positive for M tuberculosis

            More
          Other investigations
          • lateral flow urine lipoarabinomannan (LF-LAM) assay:

            positive

            More

          Kawasaki disease

          History

          fever, arthralgias, abdominal pain, irritability

          Exam

          changes in extremities (acute erythema of palms or soles, or oedema of hands and feet; periungual peeling of digits); polymorphous exanthema; bilateral bulbar conjunctival injection without exudates; changes in lips and oral cavity (erythema, cracked lips, strawberry tongue, diffuse injection of oral and pharyngeal mucosa); cervical lymphadenopathy (>1.5 cm diameter), usually unilateral

          1st investigation
          • FBC:

            WBC count >15,000/microlitre, anaemia, thrombocytosis (platelets 500,000/microlitre to >1,000,000/microlitre)

            More
          • ESR/CRP:

            ESR >40 mm/hour; CRP >285.7 nanomol/L (>3.0 mg/dL or 30 mg/L)

            More
          • echocardiogram:

            coronary artery aneurysms, myocardial dysfunction

            More
          Other investigations
          • LFT:

            elevated aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase (gamma-GT)

            More
          • urine analysis:

            mild to moderate sterile pyuria

            More

          Juvenile idiopathic arthritis (JIA)

          History

          pain in ≥1 joint lasting ≥6 weeks (pauciarticular arthritis involves ≤4 joints, polyarticular disease involves ≥5 joints); low-grade fever usually of longer duration (e.g., 2 weeks); morning stiffness; myalgias

          Exam

          joint swelling, warmth, tenderness; certain subtypes of JIA preferentially involve larger joints, iridocyclitis

          1st investigation
          • FBC:

            elevated WBC count

            More
          • ESR/CRP:

            elevated

            More
          • rheumatoid factor:

            positive

            More
          • antinuclear antibody:

            positive

            More
          Other investigations

            Systemic lupus erythematosus

            History

            malar rash, arthralgias, malaise, chest pain, seizures, photosensitivity, psychosis​

            Exam

            weight loss, hypertension, oedema, hepatomegaly, splenomegaly, lymphadenopathy, arthritis, cranial nerve abnormalities, malar rash, discoid rash, oral ulcer, arthritis, serositis (pleuritis or pericarditis)

            1st investigation
            • FBC:

              haemolytic anaemia with reticulocytosis, leukopenia, lymphopenia, thrombocytopenia

              More
            • urinalysis:

              proteinuria, cellular casts

              More
            • immune testing:

              positive antiphospholipid antibody or anti-DNA antibody; or anti-Sm antibody

            • antinuclear antibody:

              elevated titre

              More
            Other investigations

              Rheumatic fever

              History

              prolonged fever, history of sore throat, joint pains, rash, chest pain, dyspnoea, involuntary movements

              Exam

              arthritis (typically migratory and involving large joints), subcutaneous nodules (typically firm and painless), erythema marginatum (fleeting pink rash typically involving trunk and proximal arms and legs), murmur, pericardial rub, Sydenham's chorea

              1st investigation
              • rapid streptococcal antigen test or throat culture:

                positive rapid test or growth of group A beta-haemolytic streptococcus on culture

                More
              • streptococcal antibody titre:

                elevated or rising on serial measurements

                More
              • ESR/CRP:

                elevated

              • ECG:

                prolonged PR interval, heart block

              • CXR:

                cardiomegaly

              Other investigations
              • echocardiography:

                evidence of carditis, valvular defects

              Crohn's disease

              History

              nausea, vomiting, diarrhoea (sometimes bloody), abdominal pain, weight loss, arthralgia

              Exam

              pallor, abdominal distension and tenderness, arthritis, anal involvement and oral lesions, erythema nodosum, uveitis

              1st investigation
              • FBC:

                anaemia, elevated or low WBC and platelet counts

                More
              • serum albumin:

                <30 g/L (<3.0 g/dL)

                More
              • ESR/CRP:

                elevated

                More
              • abdominal x-rays:

                bowel obstruction, pneumoperitoneum, toxic megacolon

              • complete metabolic panel:

                elevated liver enzymes

              Other investigations
              • faecal calprotectin:

                may be elevated

                More
              • endoscopy and biopsy:

                inflammatory lesions in the small intestine or colon

                More

              Ulcerative colitis

              History

              nausea, vomiting, diarrhoea (sometimes bloody), abdominal pain, weight loss, joint pains

              Exam

              pallor, abdominal distension and tenderness, skin rashes, arthritis, lack of anal involvement

              1st investigation
              • FBC:

                anaemia, elevated or low WBC and platelet count

                More
              • faecal calprotectin:

                elevated

                More
              • ESR/CRP:

                elevated

                More
              • abdominal x-rays:

                bowel obstruction, pneumoperitoneum, toxic megacolon

              • complete metabolic panel:

                elevated liver enzymes

              Other investigations
              • endoscopy:

                inflammatory lesions generally restricted to the mucosa of the colon and rectum

              Leukaemia

              History

              weight loss, poor appetite, petechiae, fatigue, pallor, bone pains, easy bruising, headache[9]

              Exam

              petechiae or purpura, testicular pain, lymphadenopathy, hepatomegaly, splenomegaly

              1st investigation
              • FBC with peripheral smear:

                abnormally low or high WBC count, anaemia, thrombocytopenia; abnormal cells on peripheral smear

              • CXR:

                mediastinal mass

              • lactate dehydrogenase:

                elevated

                More
              Other investigations
              • bone marrow biopsy:

                bone marrow hypercellularity and infiltration by leukaemic lymphoblasts; ≥20% lymphoblasts in the bone marrow; negative myeloperoxidase stain

              Non-Hodgkin's lymphoma

              History

              night sweats, poor appetite, weight loss, dyspnoea, cough, generalised pruritus

              Exam

              lymphadenopathy, hepatomegaly, splenomegaly, jaw or orbital mass

              1st investigation
              • FBC with peripheral smear:

                abnormally low or high WBC count, anaemia, thrombocytopenia; abnormal cells on peripheral smear

              • CXR:

                mediastinal mass

              • lactate dehydrogenase:

                elevated

                More
              Other investigations
              • bone marrow/lymph node biopsy:

                malignant cells

              Drug-related fever

              History

              history of new medications and/or a change in dosage, seizures, altered mental status

              Exam

              tachycardia; tachypnoea; hypertension; mydriasis; hot, flushed, dry skin (e.g., anticholinergics); diaphoresis (e.g., cocaine, amphetamines)

              1st investigation
              • no initial test:

                clinical diagnosis

              Other investigations
              • serum salicylate level:

                positive

                More
              • ECG:

                sinus tachycardia, conduction abnormalities, terminal R wave in lead aVR

                More
              • blood gas:

                acidaemia/alkalaemia; metabolic and respiratory acidosis/alkalosis

                More
              • other drugs screen:

                positive

                More

              Vaccine reaction

              History

              history of vaccinations, injection site pain, agitation, pruritus, vomiting, headache

              Exam

              injection site hypersensitivity, oedema, local mass; urticarial rash; myalgia; vasodilatation

              1st investigation
              • no initial test:

                clinical diagnosis

              Other investigations

                Scarlet fever

                History

                scarlatiniform rash, fever, sore throat, headache, nausea and vomiting, abdominal pain, skin or soft tissue infection including impetigo, surgical wound infection, absence of cough or other viral symptoms; scarlatiniform rash may present prior to or independent of symptoms of pharyngitis, especially in children <5 years

                Exam

                scarlatiniform rash: diffuse, finely papular (sandpaper-like), erythematous rash that blanches with pressure, accentuated in flexor creases producing red streaks known as Pastia's lines, flushed 'scarlet' bilateral cheeks with circumoral pallor, in patients with darker skin, may appear as though sunburnt; inflamed tongue with a white coating and prominent papillae ('strawberry tongue'); tonsillopharyngeal inflammation, patchy tonsillopharyngeal exudates, palatal petechiae, tender and enlarged anterior cervical lymph nodes; skin desquamation is a late finding (3 to 4 days after scarlatiniform rash); pyoderma

                1st investigation
                • clinical diagnosis:

                  diagnosis is mainly clinical

                  More
                Other investigations
                • rapid antigen detection test:

                  positive

                  More
                • bacterial culture:

                  positive for GAS

                  More

                Uncommon

                Typhoid (enteric fever)

                History

                malaise, vomiting, headache, abdominal pain, diarrhoea, cough, history of recent travel abroad, exposure to contaminated food products (commonly poultry and eggs)

                Exam

                bradycardia, rose spots (maculopapular rash typically on trunk and abdomen), hepatomegaly, splenomegaly

                1st investigation
                • blood culture:

                  positive growth of Salmonella typhi (or S paratyphi)

                  More
                • stool culture:

                  positive growth of S typhi (or S paratyphi)

                  More
                • urine culture:

                  positive growth of S typhi (or S paratyphi)

                  More
                Other investigations
                • bone marrow culture:

                  positive growth of S typhi (or S paratyphi)

                  More
                • Widal test:

                  detection of O and H antigens of S typhi

                  More

                Infective endocarditis

                History

                fever, malaise, symptoms due to septic emboli (e.g., stroke)

                Exam

                heart murmur, Janeway lesion (painless maculopapular lesions on palms and soles), Osler nodes (painful nodules on tips of fingers), Roth spots (haemorrhagic retinal lesions)

                1st investigation
                • blood culture:

                  bacterial growth (commonly Staphylococcus aureus, Enterococcus,Streptococcus bovis, Streptococcus viridans), HACEK (Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella species) organisms

                  More
                • echocardiography:

                  detection of vegetations, valvular dysfunction, perivalvular extension.

                Other investigations

                  Liver abscess

                  History

                  malaise, nausea, vomiting, jaundice, right upper quadrant abdominal pain, chest pain (may be confused with chest infection), poor appetite

                  Exam

                  icterus, hepatomegaly, right upper quadrant abdominal pain, hepatic mass, weight loss

                  1st investigation
                  • ultrasound or CT abdomen:

                    abscesses are most commonly found in the right lobe​

                    More
                  • LFTs:

                    elevated aspartate aminotransferase, alanine aminotransferase, and bilirubin

                    More
                  Other investigations

                    Brain abscess

                    History

                    irritability, lethargy, seizures, poor feeding, paradoxical irritability (cries more when held), nausea or vomiting, headache

                    Exam

                    pyrexia or hypothermia, focal neurological deficits, bulging fontanelle, papilloedema

                    1st investigation
                    • CT head with contrast:

                      rim-enhancing brain lesion in a well-defined abscess; hypodense area in early infection

                      More
                    • MRI with gadolinium contrast:

                      abscesses, cerebritis

                      More
                    Other investigations

                      Streptococcal toxic shock syndrome

                      History

                      high-grade fever, confusion, malaise, rash, diarrhoea, vomiting, respiratory distress, recent/current chickenpox

                      Exam

                      hypotension (<5th percentile for age for children <16 years of age), signs of pneumonia, jaundice, signs of prerenal failure, bleeding (due to coagulopathy), generalised rash that may desquamate, soft-tissue necrosis including necrotising fasciitis, myositis, or gangrene

                      1st investigation
                      • serum creatinine:

                        elevated ≥2 times upper limit of normal for age

                        More
                      • platelet count:

                        <100,000/microlitre

                        More
                      • LFT:

                        elevated ≥2 times upper limit of normal for age (aspartate aminotransferase, alanine aminotransferase, bilirubin)

                        More
                      • blood, cerebrospinal fluid (CSF), or aspirate culture:

                        isolation of group A Streptococcus

                        More
                      Other investigations
                      • CXR:

                        diffuse pulmonary infiltrates

                        More

                      Staphylococcal toxic shock syndrome

                      History

                      high-grade fever, confusion, malaise, rash, diarrhoea, vomiting, severe myalgia, disorientation or alterations in consciousness, menstruation and tampon use, distal limb injury especially paronychia or burn

                      Exam

                      hypotension (<5 percentile by age for children <16 years of age); orthostatic drop in diastolic BP ≥15 mmHg), orthostatic syncope or dizziness, diffuse macular erythroderma with desquamation 1-2 weeks after onset of illness particularly involving palms and soles; mucous membrane (vagina, oropharyngeal, or conjunctival) hyperaemia

                      1st investigation
                      • creatine kinase:

                        elevated >2 times normal limit

                      • blood urea nitrogen or serum creatinine:

                        >2 times normal upper limit

                      • platelet count:

                        <100,000/microlitre

                      • blood, throat, or cerebrospinal fluid culture:

                        no growth of pathogen

                        More
                      Other investigations
                      • Staphylococcus aureus antibody testing:

                        presence of S aureus in the absence of an acute-phase antibody

                      Tularaemia

                      History

                      ulceroglandular form: lymphadenopathy with (papule or ulcer developing into eschar at skin lesion of inoculation) or without skin changes, sore throat, abdominal pain, vomiting, diarrhoea, cough, shortness of breath; typhoid form: fever but no skin or lymph node involvement; chills, headache, anorexia, myalgias

                      Exam

                      hepatosplenomegaly, lymphadenopathy, conjunctivitis, skin lesion, exudative pharyngitis, abdominal tenderness, rales

                      1st investigation
                      • tube agglutination:

                        elevated titre >1:160, or 4-fold increase in acute and convalescent titres

                        More
                      Other investigations
                      • body fluid culture:

                        positive for Francisella tularensis

                        More

                      Brucellosis

                      History

                      malaise, fatigue, depression, recent travel, exposure to animals or animal products (especially of unpasteurised cheese), lethargy, orthopaedic complaints, scrotal pain, abdominal pain, headache, arthralgia, weight loss

                      Exam

                      scrotal or abdominal tenderness, hepatosplenomegaly

                      1st investigation
                      • serum agglutination:

                        positive titres >1:160

                      • enzyme-linked immunosorbent assay:

                        positive

                        More
                      Other investigations
                      • blood culture:

                        positive growth

                        More

                      Leptospirosis

                      History

                      exposure to environmental sources (e.g., animal waste, contaminated soil or water), myalgias, rigors, headache, cough, nausea, vomiting, diarrhoea, abdominal pain

                      Exam

                      conjunctival suffusion, uveitis, evidence of haemorrhage, hepatosplenomegaly, muscle tenderness

                      1st investigation
                      • blood, cerebrospinal fluid, or urine culture:

                        positive for growth of Leptospira

                        More
                      • enzyme-linked immunosorbent assay:

                        positive for Leptospira

                      Other investigations
                      • microscopic agglutination test:

                        positive for Leptospira

                        More

                      Encephalitis

                      History

                      headache, seizures, altered mental status

                      Exam

                      non-specific rash, focal neurological deficits, meningismus

                      1st investigation
                      • cerebrospinal fluid (CSF) polymerase chain reaction:

                        positive for pathogen

                        More
                      • CSF Gram stain and culture:

                        pleocytosis; positive for pathogen

                        More
                      • MRI brain:

                        abnormal

                        More
                      Other investigations

                        Myocarditis

                        History

                        rhinorrhoea, cough, chest pain, palpitations, dyspnoea, orthopnoea, syncope, fatigue, vomiting, diarrhoea, abdominal pain, myalgias, poor feeding; history of travel to endemic areas may suggest a specific infectious aetiology; history of autoimmune disease or exposure to possible toxic substances or drug

                        Exam

                        tachypnoea, hypotension, rales, elevated neck veins, S3 gallop, S3 and S4 summation gallop, pericardial friction rub, murmur, peripheral hypoperfusion, sinus tachycardia, atrial and ventricular arrhythmias, hepatomegaly, altered sensorium

                        1st investigation
                        • ECG:

                          most commonly displays sinus tachycardia or non-specific ST-segment and T-wave abnormalities; low voltages; axis deviation

                        • echocardiography:

                          global and regional left ventricular motion abnormalities and dilatation, valvular regurgitation, reduced ejection/shortening fraction, ventricular hypertrophy, heart block

                        • cardiac enzymes:

                          elevated

                          More
                        Other investigations
                        • endomyocardial biopsy (EMB):

                          histopathological findings of myocardial cellular infiltrates ± myocardial necrosis

                          More

                        Herpes simplex virus (HSV) infection

                        History

                        neonates: maternal fever at time of delivery, presentation within the first month of life, 3 manifestations (disseminated disease, CNS involvement, skin/eyes/mucous membrane involvement), most neonates have skin manifestations such as grouped vesicles, lethargy, and poor feeding with disseminated disease or CNS involvement; older children: may have encephalitis with alteration in mental status, personality changes, and seizures (commonly focal)

                        Exam

                        neonates: fever or temperature instability with hypothermia, vesicles on skin/eyes/mouth, respiratory distress and jaundice with disseminated disease, neurological signs with CNS involvement; older children: focal neurological findings with encephalitis

                        1st investigation
                        • viral culture:

                          virus detected

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                        • HSV PCR:

                          positive

                          More
                        Other investigations
                        • glycoprotein G-based type-specific serology (gG1 and gG2):

                          positive antibody to HSV-1 or HSV-2

                          More

                        Human immunodeficiency virus (HIV) infection

                        History

                        perinatal acquisition: primary acute infection generally asymptomatic; adolescents: primary acute infection presents with fever, fatigue, and malaise

                        Exam

                        primary acute infection in adolescents: fever, adenopathy, hepatosplenomegaly, rash

                        1st investigation
                        • serum HIV rapid test:

                          positive

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                        • serum HIV ELISA:

                          positive

                          More
                        Other investigations
                        • serum Western blot:

                          positive

                          More
                        • serum HIV-1 DNA PCR assay:

                          positive

                          More

                        Toxoplasmosis

                        History

                        malaise, rash, confusion, arthralgias, immunocompromised patient, exposure to cat faeces

                        Exam

                        altered mental state, seizures, focal neurological deficits, cervical or supraclavicular lymphadenopathy (especially bilateral, symmetrical, non-tender)

                        1st investigation
                        • serological testing:

                          positive IgG and IgM antibodies

                          More
                        Other investigations

                          Rocky Mountain spotted fever

                          History

                          headache, confusion, malaise, nausea, vomiting, myalgia, abdominal pain, diarrhoea, history of a tick bite

                          Exam

                          rash (commonly petechial and involving palms and soles, but may be maculopapular only), conjunctivitis, altered mental status, lymphadenopathy, peripheral oedema, hepatomegaly

                          1st investigation
                          • serology:

                            positive for detection of rickettsial antibodies

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                          Other investigations
                          • skin biopsy:

                            rickettsiae found via immunostaining of tissue specimens

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                          Sarcoidosis

                          History

                          cough, fatigue, arthralgias, wheezing, photophobia, red eye, blurred vision, weight loss, headache​

                          Exam

                          weight loss, lymphadenopathy, erythema nodosum, uveitis​

                          1st investigation
                          • CXR:

                            hilar lymphadenopathy

                          Other investigations
                          • skin or lymph node biopsy:

                            non-caseating epithelioid granuloma

                          Hodgkin's lymphoma

                          History

                          night sweats, poor appetite, weight loss, dyspnoea, cough, generalised pruritus

                          Exam

                          lymphadenopathy, hepatomegaly, splenomegaly

                          1st investigation
                          • FBC with differential:

                            abnormally low or high WBC count, anaemia, thrombocytopenia

                          • CXR:

                            mediastinal mass

                          • excisional lymph node biopsy or core biopsy:

                            Hodgkin's cells within an appropriate background cellular milieu

                          Other investigations

                            Thyroid storm

                            History

                            weight loss, tremors, palpitations, diarrhoea, diaphoresis, fatigue, nausea, vomiting

                            Exam

                            tachycardia, history of dropping weight percentiles suggestive of thyrotoxicosis, tremors, goitre, thyroid bruit, agitation, hyper-reflexia, stupor, hepatomegaly

                            1st investigation
                            • thyroid stimulating hormone:

                              suppressed

                            • T4:

                              markedly elevated

                            Other investigations

                              Serotonin syndrome

                              History

                              history of certain medications or medication combinations (e.g., selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, tricyclic antidepressants, etc.); rigors, sweating, twitching, agitation/delirium, headache, nausea, diarrhoea

                              Exam

                              tachycardia, hypertension, dilated pupils, tremor, hyper-reflexia, clonus, muscle rigidity, ocular or inducible clonus, agitation, diaphoresis, hyperactive bowel sounds, shock

                              1st investigation
                              • no initial test:

                                clinical diagnosis

                              Other investigations

                                Serum sickness/serum sickness-like reaction

                                History

                                history of exposure to serum (serum sickness) such as rabies vaccine, crotalid antivenom; onset 1-3 weeks after drug exposure such as penicillins, trimethoprim-sulfamethoxazole that recurs on rechallenge (serum sickness-like reaction); rash, joint pains, malaise, pruritus

                                Exam

                                polyarthritis, urticaria

                                1st investigation
                                • no initial test:

                                  clinical diagnosis

                                Other investigations

                                  Factitious fever

                                  History

                                  older child/adolescent; inconsistent history/symptoms, psychosocial history; socially isolated[123]

                                  Exam

                                  normal examination; indifferent affect

                                  1st investigation
                                  • no initial test:

                                    clinical diagnosis

                                  Other investigations

                                    Factitious disorder imposed on another (formerly Munchausen syndrome by proxy)

                                    History

                                    young child; inconsistent history/symptoms, psychosocial history, previous history of child abuse or concerns

                                    Exam

                                    may be normal; may have signs of physical abuse (bruises, retinal haemorrhages, fractures)

                                    1st investigation
                                    • no initial test:

                                      clinical diagnosis

                                    Other investigations

                                      Heat-related illness

                                      History

                                      exposure to hot weather, malaise, confusion, muscle cramps, thirst, poor urine output, seizures

                                      Exam

                                      tachycardia, tachypnoea, vomiting, diarrhoea, dehydration, altered mental status, hypotension; hot, dry skin (frequently but not always)

                                      1st investigation
                                      • FBC:

                                        haemoconcentration, thrombocytopenia

                                      • renal function test:

                                        renal failure

                                      • LFT:

                                        transaminitis

                                      • creatine kinase:

                                        elevated

                                      Other investigations

                                        Paediatric autonomic disorders

                                        History

                                        decreased or increased body temperature, headache, dizziness, syncope, feeding problems, vision problems, recurrent vomiting, hyperhidrosis or hypohidrosis, absent tears, diarrhoea, poor growth, delayed development, Ashkenazi Jewish parents, history of aspiration or vomiting, excessive or diminished sweating, emotional lability, self-mutilation

                                        Exam

                                        hypertension/postural hypotension, absent tears, abnormal reflexes, anisocoria, respiratory dysfunction

                                        1st investigation
                                        • no initial test:

                                          clinical diagnosis

                                        Other investigations
                                        • genetic testing:

                                          positive for known mutation

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                                        Dengue fever

                                        History

                                        residence in or travel from a dengue-endemic region within past 2 weeks; severe disease is more likely in those aged 1 to 5 years; myalgia, arthralgia, headache (constant frontal); severe retro-orbital pain on eye movement or pressure; symptoms more common in dengue haemorrhagic fever include lethargy, restlessness, pleuritic chest pain, dyspnoea

                                        Exam

                                        fever, skin flushing/rash on face, neck, and chest; exam findings more common in dengue haemorrhagic fever include petechiae, purpura, positive tourniquet test, epistaxis, gingival bleeding, haematemesis, melaena, venipuncture site bleeding, hepatomegaly, abdominal distension, cough; signs of circulatory collapse seen in dengue shock syndrome

                                        1st investigation
                                        • FBC:

                                          leukopenia, thrombocytopenia, elevated haematocrit

                                          More
                                        • LFTs:

                                          usually elevated, particularly alanine and aspartate aminotransferases

                                        • serum albumin:

                                          <35 g/L (<3.5 g/dL)

                                          More
                                        • serology:

                                          positive

                                          More
                                        • reverse transcription-polymerase chain reaction (RT-PCR):

                                          positive

                                          More
                                        • non-structural protein 1 (NS1) detection:

                                          positive

                                          More
                                        Other investigations
                                        • coagulation studies:

                                          variable

                                          More
                                        • CXR:

                                          blunting of the costophrenic angles in erect position (severe disease)

                                          More
                                        • abdominal ultrasound:

                                          may show ascites, abnormalities of liver/gallbladder (severe disease)

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