Diagnostic and treatment dilemmas in well children with petechial rash in the emergency department
Intended for healthcare professionals
Evidence and practice    

Diagnostic and treatment dilemmas in well children with petechial rash in the emergency department

Andriana Summers Doctor, Emergency Department, Airedale General Hospital, Airedale NHS Foundation Trust, Keighley, West Yorkshire, England

Why you should read this article:
  • To be aware of the differential diagnoses associated with petechial rash before initiating treatment for invasive meningococcal disease

  • To recognise the value of a tailored approach to the investigation, treatment and discharge of well children with petechial rash in the emergency department (ED)

  • To avoid over investigation and overtreatment of well children with petechial rash in the ED

This article presents a discussion based on a case study of an eight-month-old boy with petechial rash who presented at the emergency department (ED). Blood tests were obtained and intravenous antibiotics were administered. The patient was admitted to the children’s ward and was discharged the next day. It was suspected that the rash was caused by a non-specific viral illness.

Non-blanching rashes, such as petechial rash, in well children often lead to diagnostic and treatment dilemmas in the ED. Clinicians fear missing the diagnosis of invasive meningococcal disease, which results in blood tests, cannulation and early administration of antibiotics. Non-blanching rashes have many potential causes and extensive tests and antibiotic treatment may not always be necessary and have the potential to cause harm. A tailored approach to investigate, treat and discharge well children with petechial rash from the ED is advocated.

Emergency Nurse. doi: 10.7748/en.2022.e2138

Peer review

This article has been subject to external double-blind peer review and checked for plagiarism using automated software

Correspondence

andromishka@yahoo.co.uk

Conflict of interest

None declared

Summers A (2022) Diagnostic and treatment dilemmas in well children with petechial rash in the emergency department. Emergency Nurse. doi: 10.7748/en.2022.e2138

Published online: 31 August 2022

An eight-month-old boy was brought to the emergency department (ED) by his mother because of a 24-hour history of lethargy. A temperature at home had not been recorded. An episode of projectile vomiting after eating was reported. There was no preceding cough or coryzal symptoms. He had been taking oral fluids well and had wet nappies. On examination he was noted to be happy, smiling and alert. The vital signs were within the normal range for his age, he was well perfused and afebrile. Petechial rash was noted to his legs and arms that had not been present at initial assessment and had started to appear while waiting in the ED. There was no evidence of purpuric rash. Brudzinski’s and Kernig’s signs were negative.

Intravenous (IV) access was obtained. Full blood count, urea and electrolytes, C-reactive protein (CRP), meningococcal polymerase chain reaction and blood cultures were obtained. A dose of IV ceftriaxone 80mg/kg was given, and the patient was admitted to the children’s ward. He was discharged the next day after remaining clinically well and all laboratory tests were normal. It was suspected that the rash was caused by a non-specific viral illness.

Key points

  • Non-blanching petechial rash is the eruption of pinprick-sized lesions, caused by extravasation of blood from the capillaries into the surrounding tissues

  • Petechial rash is a common presentation in children attending emergency departments (EDs)

  • Most petechial rashes are typically seen in tonsillitis, upper respiratory tract infections and viral illnesses

  • The prevalence of invasive meningococcal disease (IMD) is low in the UK

  • Children with IMD or meningitis usually appear unwell

  • There is no single laboratory finding or fever parameter that is sensitive enough to diagnose IMD

  • A tailored approach, in accordance with newly developed pathways to investigate, treat and discharge well children with petechial rash from the ED, may be appropriate

Petechial rash

Petechial rash describes the eruption of petechiae, pinprick-sized lesions measuring less than 2mm in size, caused by extravasation of blood from the capillaries into the surrounding tissues, which does not blanch on application of pressure to the overlying skin. Pathophysiological causes of petechiae are trauma to the capillaries, low levels of circulating platelets or inflammation of the capillary walls (McGrath 2021). Petechial rash is not an uncommon finding in children who present to the ED, however, it causes significant anxiety in parents and clinicians who primarily associate petechial rash with invasive meningococcal disease (IMD) (Thomas et al 2016). Although there are many other causes of petechial rash (Table 1), children still undergo unnecessary tests or receive IV antibiotics prematurely (Barnetson et al 2016). This is because symptoms of IMD can vary among patients (Meningitis Research Foundation 2018). IMD occurs when Neisseria meningitidis (meningococcus), an often harmless bacterium that colonises the nasopharynx, evades the body’s defences and causes sepsis and life-threatening meningitis (Karlsson et al 2021).

Table 1.

Differential diagnoses of petechial and purpuric rashes in children and associated clinical features

ConditionOnsetClinical features
Bacterial sepsis, including invasive meningococcal diseaseRapid
  • Child usually looks unwell

  • Non-specific features

  • Meningism (headache, photophobia, neck stiffness, seizures) is not always present

  • Purpura and signs of shock are more specific for the presence of the condition

Acute leukaemiaAcute or subacute
  • Child may be well

  • Widespread petechial rash may be present on limbs and trunk

  • Non-specific symptoms such as lethargy, pallor and fever

  • Limp or bone pain

  • Other findings such as hepatic or splenomegaly and lymphadenopathy

Non-accidental injuryVariable
  • Unexplained findings

  • Bruising to face, ears and trunk

  • Petechiae in the superior vena cava (SVC) may suggest strangulation

Idiopathic thrombocytopenic purpuraAcute
  • Child usually looks well

  • Purpura is extensive and affects mucous membranes

  • Recent viral illness or immunisation

  • May have underlying autoimmune condition

DrugsVariable
  • Purpura is less common

  • Thrombocytopenia is more common

Congenital disordersChronic
  • Family or personal history of bleeding

  • Unexplained bruising

  • Epistaxis

Raised SVC pressureAcute
  • Petechial rash above nipple line and around eyes and mouth

  • Associated with severe coughing or vomiting

VasculitisSubacute, chronic
  • Viral infections with coryzal symptoms

  • Henoch-Schönlein purpura, usually preceding viral illness, purpuric rash to buttocks, shins and posterior thighs

(Thomas et al 2016)

A non-blanching rash with lesions that are more than 2mm in size is referred to as ‘purpuric’ (Table 1). It is a much less common presentation and is associated with a more serious underlying cause (Thomas et al 2016). The presence of purpura in an ill child is more indicative of IMD and has a sensitivity of 83% (95% confidence interval [CI] 68-98) and a specificity of 88% (95% CI 84-93) for meningococcal disease (Wells et al 2001, Klinkhammer and Colletti 2008, Thomas et al 2016).

Non-accidental injury is also an important diagnosis to consider, particularly where there is a delay in presentation, the history is incompatible with the rash and there is a concern about the interaction between parent and child. Typically, however, the location, pattern and site of a rash associated with non-accidental injury are different from that outlined in the case study and, together with the clinical presentation, non-accidental injury was not suspected in this instance.

Invasive meningococcal disease

The overall incidence and prevalence of, and mortality from, IMD have decreased over the past 20 years. There were 530 cases (0.95/100,000 people) recorded in England in 2018-19 in comparison with 1,016 cases (1.93/100,000 people) in 2010-11 (Subbarao et al 2021). Sustained decline in IMD is a result of the successful implementation of the UK immunisation programme in 1999 (meningococcal C vaccine) and 2015 (meningococcal B vaccine) (Parikh et al 2016). However, there has been no change in the rate of serious complications associated with IMD (National Institute for Health and Care Excellence (NICE) 2020) and one in five survivors has long-term disabilities, such as loss of limb(s), deafness or brain damage (Centers for Disease Control and Prevention (CDC) 2022). Non-blanching petechial or purpuric rash is therefore regarded as an alarming sign.

It is estimated that 10% to 30% of patients with meningococcal sepsis do not have signs of meningitis (Johri et al 2005), with up to 15% mortality despite appropriate use of antibiotic treatment (Nadel 2016, CDC 2022). In the early stages of meningococcal sepsis or meningitis, suggested to be in the first 4-6 hours, signs and symptoms may be indistinguishable from other self-limiting illnesses and Thompson et al (2006) found that the ‘time-window for clinical diagnosis was narrow’. The classic features of purpuric rash, meningism and impaired consciousness develop much later, with median onset between 13 and 22 hours (Thompson et al 2006). Rash is present in most cases of meningococcal sepsis, although most children with petechial rash will not have meningococcal disease (Wells et al 2001).

Clinical assessment of children with suspected IMD follows the same structure as assessment of any child where sepsis is suspected. Assessment is stratified as low, moderate or high risk according to the child’s appearance and age-appropriate vital signs (NICE 2017) (Figure 1).

Figure 1.

Sepsis risk stratification tool: children aged under 5 years in hospital

en.2022.e2138_0001.jpg

Laboratory tests

The presence of a non-blanching rash often triggers requests for extensive laboratory work-up that may not always be appropriate or necessary. This was echoed in the retrospective study by Dumitrascu-Biris et al (2016) who identified 41 children (1%) with fever and petechial rash out of a total 7,327 paediatric presentations to the ED over a period of one year. Most were aged under five years and the most common clinical diagnoses were: viral respiratory illness (49%), upper respiratory tract infection (17%), pneumonia (7%), asthma exacerbation (7%) and gastroenteritis (7%). Meningococcal disease was found in one case (2%). The results also showed that CRP and erythrocyte sedimentation rate (ESR) had poor specificity in detecting serious illness.

CRP and ESR are acute phase reactants, which are not usually found in the serum of a healthy person and are therefore useful markers for illness severity, in infectious and non-infectious conditions (Fatima et al 2017). Their main role is to supplement clinical assessment and guide antibiotic treatment strategies where infection is clinically suspected (Markanday 2015, Nehring and Goyal 2022). CRP and ESR are measured in a different way and are noted to rise in the blood at different times and have different biochemical values (Table 2). A CRP level of more than 50mg/L is a severe elevation and associated with acute bacterial infections (Nehring and Goyal 2022), which is why it can be a useful adjunct to the diagnosis of IMD.

Table 2.

Common features of erythrocyte sedimentation rate and C-reactive protein

Acute phase reactantCommon features
Erythrocyte sedimentation rate
  • Measures blood viscosity (the distance that a vertical column of anticoagulated blood has fallen in 1 hour)

  • Rises within 24-48 hours of onset of inflammation

  • >100mm/hour – high specificity for infection, malignancy, arteritis

  • Levels fall slowly with treatment for infection

C-reactive protein
  • Protein produced by the liver

  • Rises after 12-24 hours

  • Peaks within 2-3 days

  • Normal range <1mg/L

  • >10mg/L marked elevation

  • >50mg/L severe elevation

  • Levels fall rapidly with treatment for infection

(Markanday 2015, Nehring and Goyal 2022)

A prospective study by Wells et al (2001) involved 218 children who presented at an English ED with petechial or purpuric rash of whom 111 had no fever. Meningococcal disease was found in 24 (11%) patients and most appeared ill at presentation (19/24) with a CRP level of more than 6mg/L.

A nine-year retrospective study by Kuppermann et al (1999) identified 381 children with meningococcal sepsis of whom 45 (12%) were unsuspected. The results showed that most of the unsuspected cases were younger (8.9 versus 14.2 months) and that temperature, white blood cell count and neutrophil count could not be reliably used to assess risk. The researchers concluded that routine blood tests would be of little use in situations where the probability of IMD was low, however, they did recommend screening patients with fever and petechial rash, known meningococcal disease contact or during meningococcal outbreaks.

The selective evaluation of children presenting with petechial rash and fever was proposed more than three decades ago in a study by Nguyen et al (1984). Of 129 children admitted to hospital with fever, petechial rash and who were well in appearance, 26 (20%) were found to have bacterial infection on blood culture, of whom 13 (10%) had N. meningitidis and eight (6%) had Haemophilus influenzae type B. There was no single laboratory finding or fever parameter that was sensitive enough to diagnose IMD, although it was evident that total white blood cell count, neutrophil count and ESR were normal in the study population without IMD.

The clinical manifestations of central nervous system infections in children can be challenging to diagnose, non-specific and devastating if not treated correctly (McDonald et al 2020). There is increasing use and availability of rapid molecular diagnostic tests for the detection of infectious organisms in cerebrospinal fluid (CSF) taken from a lumbar puncture (Feagins et al 2020). Lumbar puncture is regarded as the ‘gold standard’ for the diagnosis of bacterial meningitis and must be performed as soon as possible, and ideally before the administration of antibiotics (Griffiths et al 2018). Performing a lumbar puncture in young children is challenging and it is often difficult to obtain enough CSF for multiple tests. In the ED, antibiotics are frequently given before a lumbar puncture when IMD is suspected, which decreases the sensitivity of the lumbar puncture by 20% (Griffiths et al 2018).

Obtaining blood cultures as part of the laboratory work-up for IMD and before treatment with antibiotics is of fundamental importance (Tran et al 2020). Blood cultures are positive in 50-80% of bacterial meningitis cases (Brouwer et al 2012), however, negative blood cultures do not suggest lower bacterial load or less severe disease (Guiducci et al 2019).

Clinical practice guidelines

NICE (2020) recommends that any non-blanching rash in children should be treated as an emergency, while also keeping in mind that a purpuric rash may be absent in the early phase of the illness and may initially be blanching or macular (Marzouk et al 1991).

Current guidelines rely on retrospective data before the introduction of meningococcal B and meningococcal C vaccines in 2015 and 1999 respectively, when the prevalence of meningococcal infection in children with fever and non-blanching rash was up to 20% (Waterfield 2021). The Petechiae in Children (PiC) study (Waterfield et al 2021) has challenged the current NICE approach of aggressive testing and treating all cases with suspected IMD. In 1,329 immunised children who presented with fever and non-blanching rash, the study demonstrated the prevalence of meningococcal disease to be 1% (19/1,329). The low prevalence of IMD would suggest that most petechial rashes are caused by other, less serious pathologies, typically seen in tonsillitis, upper respiratory tract infections and viral illnesses (Hicks et al 2014).

Tailored clinical practice guidelines were found to outperform NICE guidelines, resulting in higher specificity, lower investigation rate, lower antibiotic use and lower cost per patient (Davis 2021, Snelson and Waterfield 2021). The outcomes for morbidity and mortality were not examined, however. Whether the findings are widely transferable remains to be seen. Caution must be exercised if applied to settings with higher disease prevalence and lower rates of vaccine uptake. Borensztajn and Oostenbrink (2021) also raised concerns that individual clinicians’ decisions were associated with a higher number of missed IMD cases in comparison with those following the clinical practice guidelines.

After the PiC study was published, the British Society for Antimicrobial Chemotherapy (BSAC) (2021) devised a new national guideline for the assessment and management of children with fever and non-blanching rash. The BSAC guidance has been validated and recommended for adoption in the UK as the national standard of care for children presenting with fever and non-blanching rash (Waterfield 2021).

Reliability of Kernig’s and Brudzinski’s signs

Kernig’s and Brudzinski’s signs may be used to elicit the presence of meningeal irritation. Kernig’s sign occurs when extension of the knee on a flexed hip at 90 degrees causes pain and restriction beyond 135 degrees. Brudzinski’s sign occurs when the patient’s hips and knees flex on passive flexion of the neck while in a supine position. The reason for this is thought to be related to inflammation of the meninges that surround the brain and the spinal cord. With application of these signs, movement of the spinal cord or nerves against the inflamed meninges causes pain and resistance with movement (Tracy and Waterfield 2020).

Several studies have examined the reliability of Kernig’s and Brudzinski’s signs in the diagnosis of meningitis. Most conclude that both signs have 80-90% specificity (95% CI 68-96%) and much lower sensitivity of 26-66% (95% CI 36-65%) (Oostenbrink et al 2001, Curtis et al 2010, Amarilyo et al 2011, Bilavsky et al 2013). This suggests that both signs cannot be used reliably to exclude the diagnosis of meningitis and therefore were of limited value in the context of the case study. When present, however, the likelihood of meningitis is high and these remain important clinical signs that can be easily performed at the bedside.

Antibiotic treatment in well children with petechial rash

In the UK it is estimated that 41% of hospitalised children will receive a minimum of one antimicrobial agent (Gharbi et al 2016). Antimicrobial resistance in children is an increasing threat to the future management of common childhood infections (Wells and Piddock 2017). A recent report by the CDC identified emerging cases of penicillin-resistant and ciprofloxacin-resistant N. meningitidis in the US (McNamara et al 2020), with six serogroups (A, B, C, W, X, Y) causing most IMD globally (World Health Organization 2021). Empirical treatment with cefotaxime or ceftriaxone is common, which can later be changed to penicillin or ampicillin once N. meningitidis is confirmed as the causative pathogen (American Academy of Pediatrics 2018). Close contacts of patients with meningococcal disease are also at increased risk of the disease and are recommended to receive antibiotic prophylaxis with ciprofloxacin or ceftriaxone as soon as a suspected IMD case is identified (McNamara et al 2020). Emerging resistance to these antibiotics, however, is alarming and may pose a significant threat to future prophylaxis and treatment.

Paediatric pathways are now under review for children presenting to hospital with common community-acquired infections, among which are management of petechial/purpuric rashes (Horner et al 2021). The pathway shows that if a child with petechial rash is clinically well and there are no ‘red flags’ present, then a tailored approach to investigation, treatment and discharge from the ED may be appropriate. Petechial rash that is spreading is considered a ‘red flag’. Laboratory tests and administration of IV antibiotics were deemed appropriate in the case presented (BSAC 2021). Diagnostic uncertainty, however, will occasionally exist where the child appears well and the petechial rash is not spreading. Recommendations such as ‘if doubt remains, treat with antibiotics and admit to hospital’ (NICE 2010) do little to deter clinicians from requesting blood tests or giving antibiotics too soon. While NICE guidelines are safe, they involve greater use of tests and antibiotics in comparison with tailored clinical guidelines and compound the issue of antibiotic overuse and the risk of long-term resistance (Waterfield et al 2021).

Conclusion

The presence of petechial rash, even in a visibly well child in the ED, would still cause anxiety in parents and clinicians because of the fear of missing the diagnosis of IMD. In this case, the child was managed safely according to NICE guidelines, although it is clear that the administration of an IV antibiotic was possibly too soon and unnecessary. Emerging research advocates adopting tailored clinical guidelines in the future to investigate, treat and discharge well children with petechial rash from the ED. This approach aims to reduce potential harm from painful tests and antibiotic overuse, which risks long-term resistance and treatment failure.

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