Code Ready
Log inSign up free

Level 2 of 6Must-remember

Fever with rash and meningococcal disease

Assess, manage and stay safe — enough on its own

The card — assess, manage, caution

Assessment— look, ask, measure

  • Treat the syndrome as the emergency it is: a non-blanching rash with fever is meningococcal disease until proved otherwise, even though fewer than 10% of children — and in some clinical settings fewer than 1% of patients — presenting this way are found to have meningococcal disease, most having a viral infection; treat presumptively and immediately, then let culture, molecular testing and the clinical course sort the cohort out.
  • Undress the patient completely and examine the whole skin in good light — including buttocks, perineum, palms, soles, conjunctivae and palate — testing every lesion for blanching with a clear glass and palpating it, because haemorrhagic red papules that do not blanch indicate palpable purpura characteristic of necrotising vasculitis, whereas red papules that blanch can be a manifestation of many different diseases.
  • Describe the morphology precisely, because the differential turns on it: a macule is flat with changed colour and blanches; non-palpable purpura is flat bleeding into the skin — under 3 mm in diameter the lesions are petechiae, over 3 mm ecchymoses; palpable purpura is raised, due to inflammation of the vessel wall with subsequent haemorrhage; an eschar (*tâche noire*) is a necrotic lesion covered with a black crust; purpura by definition does not blanch.
  • Mark the margin of the rash with a skin pen and record the time: its rate of evolution carries more information than any single snapshot, and a rash extending beyond that line within the hour indicates fulminant disease.
  • Do not be reassured by an absent or blanching rash: a non-blanching petechial or purpuric rash develops in more than 80% of cases but is often absent early, is usually initially blanching (macules, maculopapules or urticaria) and indistinguishable from more common viral rashes, becoming petechial or frankly purpuric over the following hours, and some patients, including those with overwhelming sepsis, may have no rash at all.
  • Ask about the early septicaemic symptoms, which are non-specific and influenza-like: fever, headache and myalgia with vomiting and abdominal pain — and specifically about limb pain, pallor (including a mottled appearance and cyanosis), and cold hands and feet, which may be prominent and frequently precede the rash, so an adolescent with fever and severe leg pain may be in the first hours of septicaemia with clean skin.
  • Look for shock: tachycardia, poor peripheral perfusion, tachypnoea and oliguria, with decreased cerebral perfusion leading to confusion, agitation or a decreased level of consciousness; measure capillary refill (over 3 seconds is a red flag), peripheral temperature and the skin-to-core temperature gap, heart rate, blood pressure, conscious level and urine output.
  • In a child, never accept a normal blood pressure as reassurance: hypotension is a late sign in children, who more commonly present with compensated shock — tachycardia, poor peripheral perfusion and a normal blood pressure; capillary refill, peripheral temperature, mottling, heart rate, conscious level and urine output carry the information.
  • Look separately for raised intracranial pressure, because it pulls management the opposite way: reduced consciousness, relative bradycardia and hypertension, focal neurological signs, abnormal posturing, unequal, dilated or poorly reactive pupils, impaired corneal responses, seizures and a bulging fontanelle — most deaths from meningococcal meningitis alone are associated with raised intracranial pressure.
  • Know how infants and young children differ: classic signs of meningitis such as neck stiffness and photophobia are often absent, and they more usually present with fever and irritability and may have a bulging fontanelle, headache being rarely reported in early childhood; other danger signs are a high-pitched cry, refusal to feed, a floppy or inconsolable child, grunting or marked recession, and a carer's statement that the child is not behaving normally.
  • Send the bedside and laboratory tests that change management now: capillary glucose (hypoglycaemia is a common laboratory finding in severe meningococcal septicaemia and recurs), blood gas with lactate and base deficit, full blood count, coagulation screen, electrolytes with calcium, magnesium and phosphate, CRP, renal function, blood culture and whole-blood real-time PCR.Not available at your setup — Arterial blood gas, Coagulation (PT/INR), Serum electrolytes, Renal function (creatinine/urea), Blood culture.
  • Treat the paradoxical signs as markers of severe disease, not of mild illness: poor outcome is associated with absence of meningism, hypotension, young age, coma, a relatively low temperature (below 38°C), leucopenia and thrombocytopenia, to which the full prognostic list adds shock, purpura fulminans, disseminated intravascular coagulation, metabolic acidosis and a low ESR or CRP — so the quiet, cool patient without neck stiffness is the more worrying.
  • Score the Glasgow Meningococcal Septicaemia Prognostic Score (GMSPS), maximum 15: systolic blood pressure < 75 mmHg if under 4 years or < 85 mmHg if 4 years or older (3 points); skin-to-core temperature difference > 3°C (3); modified coma score < 8 or deterioration of at least 3 points in 1 hour (3); clinical deterioration in the hour before scoring (2); absence of meningism (2); extending purpuric rash or widespread ecchymoses (1); base deficit, capillary or arterial, > 8.0 mmol/L (1) — a score of 8 or more identifies severe disease with a high risk of death.Not available at your setup — Arterial blood gas.
  • Ask about the risk factors that change the whole assessment: terminal complement deficiency (C5–C9), properdin or factor D deficiency, or treatment with eculizumab, which increases risk up to 600-fold and may cause recurrent attacks; hyposplenism, hypogammaglobulinaemia and HIV; overcrowding, bars and nightclubs, kissing, tobacco smoking (odds ratio 4.1) and passive smoke exposure; and clusters in schools, colleges, universities, military training centres and refugee camps — the incubation period is 1–10 days, usually under 4.
  • Recognise the two chronic and late forms: chronic meningococcaemia, with repeated episodes of petechial rash with fever, joint pain, arthritis and splenomegaly, which may progress to acute septicaemia if untreated; and post-meningococcal reactive disease, an immune complex disorder developing about 4–10 days after onset with a maculopapular or vasculitic rash (2% of cases), arthritis (up to 8%), iritis (1%), pericarditis and/or polyserositis with fever, which resolves spontaneously.
  • Hold the main mimics in mind while you treat: viral petechial eruptions (enterovirus, influenza, EBV, CMV, parvovirus, measles) are by far the commonest cause; other bacterial sepsis with DIC is clinically indistinguishable; rickettsial disease (spotted fevers, scrub typhus, epidemic typhus), dengue, infective endocarditis, staphylococcal and streptococcal toxic shock, thrombotic thrombocytopenic purpura, haemolytic uraemic syndrome, Stevens–Johnson syndrome and toxic epidermal necrolysis, DRESS, leptospirosis, Henoch–Schönlein purpura, immune and drug-induced thrombocytopenia, small-vessel vasculitis, and mechanical petechiae or non-accidental injury.

Management— do this, in order

  • Give an intravenous third-generation cephalosporin within minutes of suspecting the diagnosis, and suspect it on the rash alone: investigation must never delay antibiotic administration. Take cultures before the first dose only where venous access is quickly obtained; otherwise the antibiotic goes first, and whole-blood PCR preserves much of the yield.Doctor / Nurse
  • Ceftriaxone is first line: adult 2 g IV 12-hourly (maximum 4 g/day); paediatric 75–100 mg/kg per day (maximum 4 g/day) in one or two divided IV doses — in practice 50 mg/kg IV 12-hourly, maximum 2 g per dose.Doctor / Nurse
  • Cefotaxime is the alternative: adult 2 g IV 6-hourly; paediatric 200 mg/kg per day (maximum 8 g/day) in four divided IV doses, that is 50 mg/kg IV 6-hourly.Doctor / Nurse
  • Under 1 month of age avoid ceftriaxone (bilirubin displacement; precipitation with calcium-containing fluids) and give cefotaxime 50 mg/kg IV 6–8-hourly plus ampicillin 50 mg/kg IV 6-hourly.Doctor / Nurse
  • Add vancomycin if pneumococcal meningitis cannot be excluded: adult 15–20 mg/kg IV 8–12-hourly with level monitoring; paediatric 40–60 mg/kg per day in two to four divided IV doses; add doxycycline 100 mg orally or IV 12-hourly (paediatric 2.2 mg/kg per dose 12-hourly, maximum 100 mg, avoid in pregnancy) if rickettsial infection is plausible.Doctor / Nurse
  • Where no cephalosporin is available give benzylpenicillin 2.4 g IV (paediatric 50 mg/kg IV, maximum 2.4 g), and in severe beta-lactam allergy chloramphenicol 1 g IV 6-hourly (paediatric 25 mg/kg IV 6-hourly) — a delayed correct drug is worse than an immediate imperfect one; in resource-poor settings a single dose of ceftriaxone or an oily suspension of chloramphenicol has been used successfully.Doctor / Nurse
  • Open the airway and give oxygen: airway patency may be compromised if the conscious level is depressed as a result of shock (impaired cerebral perfusion) or raised intracranial pressure, and in meningococcaemia pulmonary oedema and pulmonary oligaemia (presenting as hypoxia) require oxygen therapy or elective endotracheal intubation.Doctor / NurseNot available at your setup — Endotracheal intubation kit.
  • Resuscitate the circulation with titrated boluses: an initial balanced crystalloid bolus of 500 mL over about 15 minutes in an adult, working towards 30 mL/kg within the first hour if perfusion is not restored, and 10–20 mL/kg in a child, reassessing heart rate, capillary refill, peripheral temperature, conscious level, chest sounds and urine output after each bolus.Doctor / Nurse
  • Examine the chest after every bolus — new crackles, falling saturations or rising work of breathing indicate that capillary leak has reached the lung — and track cumulative volume in mL/kg explicitly.
  • If shock persists after volume resuscitation at 40 mL/kg the risk of pulmonary oedema is high, and elective intubation is recommended to improve oxygenation and decrease the work of breathing; add vasoactive support when perfusion remains inadequate despite volume, with noradrenaline as first-choice vasopressor and an inotrope where myocardial depression predominates.Doctor / NurseNot available at your setup — Endotracheal intubation kit, Infusion pump.
  • Where raised intracranial pressure predominates, do the opposite: correct coexistent shock and give neurointensive care to maintain cerebral perfusion — this patient must not be flooded and must not be tapped; head elevation, airway protection, normocapnia and control of seizures are the priorities.Doctor / Nurse
  • For suspected bacterial meningitis give adjunctive dexamethasone 0.15 mg/kg IV (adult 10 mg) 6-hourly for 4 days, with or just before the first antibiotic dose; for meningococcal septicaemia therapeutic doses of glucocorticoids are not recommended, the exception being replacement doses for refractory shock with impaired adrenal responsiveness — conventionally hydrocortisone 50 mg IV 6-hourly in an adult, or 1–2 mg/kg IV 6-hourly in a child.Doctor / Nurse
  • Anticipate and correct the metabolic derangements — hypoglycaemia, acidosis, hypokalaemia, hypocalcaemia, hypomagnesaemia, hypophosphataemia, anaemia and coagulopathy: treat hypoglycaemia with 10% dextrose 2 mL/kg IV in a child, or 50–100 mL of 50% dextrose in an adult, and recheck hourly since it recurs; treat acidosis by restoring perfusion rather than with bicarbonate; correct calcium and magnesium actively because hypocalcaemia contributes to myocardial depression.Doctor / NurseNot available at your setup — Serum electrolytes.
  • Support the coagulopathy: fresh frozen plasma 15 mL/kg for prolonged clotting times with bleeding, platelets for active bleeding or a count below 50 × 10⁹/L, and cryoprecipitate for hypofibrinogenaemia; heparin is also indicated for the treatment of purpura fulminans, but this decision belongs after resuscitation and remains contentious where there is thrombocytopenia or active bleeding.Doctor / NurseNot available at your setup — Blood & blood products, Coagulation (PT/INR).
  • Keep ischaemic skin and limbs warm and elevated and document the demarcation margin: amputations are necessary in 1–2% of survivors, but unless there is local infection amputation should usually be delayed to allow the demarcation between viable and non-viable tissue to become apparent — compartment syndrome is the exception requiring urgent decompression.
  • Notify on clinical suspicion and apply droplet precautions, which may be discontinued after 24 hours of effective therapy.
  • Give secondary chemoprophylaxis to close contacts — household members, those who slept in the same room in the 7 days before onset, intimate and kissing contacts, and those whose mouth or nose was directly exposed to respiratory droplets during unprotected airway management, but not casual contacts: ciprofloxacin 500 mg orally as a single dose (adults and children over 12 years), rifampicin 600 mg orally 12-hourly for 2 days (child 1 month to 12 years 10 mg/kg, maximum 600 mg; infant under 1 month 5 mg/kg), or ceftriaxone 250 mg intramuscularly as a single dose (child under 15 years 125 mg), preferred in pregnancy.Doctor / Nurse
  • Warn rifampicin recipients of orange discoloration of body fluids, staining of soft contact lenses and reduced efficacy of the combined oral contraceptive; the index patient needs no further carriage eradication after ceftriaxone or cefotaxime.

Caution— what harms

  • Never let investigation delay the antibiotic. Delayed recognition of meningococcal disease or its associated physiological derangements, together with inadequate emergency management, is associated with poor outcome.
  • Never perform a lumbar puncture to confirm what the rash has already told you: when meningococcal disease is diagnosed clinically by the petechial rash, immediate intravenous antibiotics should be given and blood cultures taken — lumbar puncture is unnecessary, and it should generally be avoided in meningococcal septicaemia, as positioning for the procedure may critically compromise the circulation in the context of hypovolaemic shock.
  • Do not treat a normal CT as clearance to tap: some authorities have recommended CT before lumbar puncture because of the risk of cerebral herniation, but a normal CT scan is not uncommon in the presence of raised intracranial pressure in meningococcal meningitis, and the decision should be made on clinical grounds; the contraindications are raised intracranial pressure, uncorrected shock, disordered coagulation, thrombocytopenia, respiratory insufficiency, local infection and ongoing convulsions.Not available at your setup — CT scan.
  • Never accept a normal blood pressure in a child as reassurance — hypotension is a late sign and compensated shock is the usual presentation.
  • Never read leucopenia, thrombocytopenia, a low CRP or ESR, absence of meningism or a temperature below 38°C as mild illness — they are markers of severe disease and poor outcome.
  • Do not be misled by a normal full blood count: values may be normal or low in rapidly progressive disease, and a lack of rise does not exclude the diagnosis; in the presence of fever and a petechial rash a raised CRP, procalcitonin or ESR is suggestive, but a normal or low value neither excludes it nor reassures.
  • Do not choose penicillin as the initial empirical agent where a cephalosporin is available: although unusual in most isolates, reduced meningococcal sensitivity to penicillin (minimum inhibitory concentration 0.12–1.0 µg/mL) has been reported, and the third-generation cephalosporin is chosen also to cover the various other (potentially penicillin-resistant) bacteria that may produce an indistinguishable clinical syndrome; penicillin becomes appropriate once resistance information is available.
  • Do not give therapeutic doses of glucocorticoids for meningococcal septicaemia — only replacement doses for refractory shock with impaired adrenal responsiveness, and that on limited evidence.
  • Do not run to a preset fluid volume: aggressive fluid resuscitation with unbuffered electrolyte solutions was found to increase mortality in febrile African children, and studies of lower volumes of buffered solutions are required; neither withhold fluid nor fill blindly — give measured boluses with reassessment after each, and accept earlier vasoactive and ventilatory support rather than continuing to fill.
  • Do not treat acidosis with bicarbonate — restore perfusion instead — and do not forget that hypoglycaemia recurs, so recheck it hourly.
  • Do not amputate early: unless there is local infection, amputation should be delayed to allow demarcation to become apparent; compartment syndrome is the exception requiring urgent decompression.
  • Do not chase immunomodulatory adjuncts: various other adjunctive therapies have been considered, but few have been subjected to clinical trials and none can currently be recommended — activated protein C benefited adults in sepsis trials, but trials in paediatric sepsis found no benefit and indicated a potential risk of bleeding complications.
  • Do not mistake post-meningococcal reactive disease for relapse: new fever, rash and arthritis at about 4–10 days is an immune complex disorder treated with non-steroidal anti-inflammatory agents until spontaneous resolution occurs, not with more antibiotic or unnecessarily prolonged therapy.
  • Do not spoil the microbiology: media containing sodium polyanethol sulfonate, which may inhibit meningococcal growth, should be avoided, and viability falls if transport to the laboratory is delayed; skin aspirate adds little compared with blood culture plus PCR, throat swab has limited diagnostic value since the organism is normal flora, urinary antigen testing is insensitive, serological testing has not been adequately studied, and CSF antigen testing by latex agglutination is insensitive and should be replaced by molecular diagnosis where possible.Not available at your setup — Blood culture.

Refer / escalate

Escalate immediately — and transfer to paediatric or adult intensive care — for shock persisting after 40 mL/kg of fluid (elective intubation is then recommended), a falling conscious level, signs of raised intracranial pressure, extending purpura or peripheral ischaemia, a GMSPS of 8 or more, or any need for vasoactive support, ventilation or renal replacement; call for help while giving the first dose of ceftriaxone, never after it.

PreviousNext

Read the full lesson free

Create a free account to unlock every page, the level exams, and progress tracking.

Sign up freeLog in