Tuesday, 30 April 2019

Rashes in children: What is the diagnosis? - Probably a virus

A rash is a very common feature of a paediatric presentation and is often the primary reason for seeking medical advice.

I think that clinicians also sometimes feel a bit of anxiety about rashes.  What does the rash mean?  Should I be able to diagnose the illness based on the rash?

The rash can be diagnostic but often it is not.  Even when the rash gives a specific diagnosis, that diagnosis is usually a virus and treatment remains symptomatic and supportive.

These are some important questions to have answers to when assessing a child with a rash.
  • Is the child well? If not, how unwell are we talking about and for how long?
  • Is the child febrile?
  • How did the rash start?
  • How has the rash changed since it started?
  • Is the rash itchy?
When examining the child, it is important to avoid the temptation to focus excessively on the rash.  The child should have a systemic examination that will identify any cardio-respiratory, abdominal or neurological abnormality.

The rash itself is then in context of an assessment that has determined whether the child is significantly unwell or has any significant abnormal findings.  What this tells us is whether the rash is of importance because the child is quite unwell, or more of interest since the child is well.  In the well child with no significant abnormal findings, a diagnostic rash can still give useful information in terms of prognostication and the ability to give specific advice about what to do from a infection control point of view.

Let’s look at some specific rash related diagnoses that are accompanied by non-specific symptoms such as pyrexia-

Roseola Infantum
What does it look like?
This infection is most commonly seen between the ages of 6 months and 3 years.  The classical presentation is of a significant fever but a surprisingly well child with non-specific symptoms such as coryza and pharyngitis.  Essentially, the child has all the signs of a viral upper respiratory tract infection (URTI) but with an impressive fever.

A macular patchy erythematous rash often appears as the fever starts to resolve.  Typically the rash is more prominent on the trunk than limbs.
What causes it?
Human herpes virus 6

What specific advice is there for this diagnosis?
None.  Treatment is symptomatic.

What does it look like?
Chickenpox is a vesicular (small fluid filled lesions) rash which is usually found all over the body.  Children are usually either mildly febrile and unwell in the first few days, or not unwell at all.  The rash is often itchy.
What causes it?
Varicella zoster virus

What specific advice is there for this diagnosis? 
There is no specific treatment.  If the child seems unwell then paracetamol (acetaminophen) is the preferred treatment for systemic symptoms.  While there is some concern about using ibuprofen, the evidence strongly suggests that this concern is unfounded.  However, most children do not become significantly unwell with chickenpox and it is unusual for symptoms to require more than paracetamol.  If a child with chickenpox is very unwell, that is a clinical situation that mandates a careful assessment to consider the possibility of sepsis, usually in the form of invasive streptococcal infection.
Itching can be treated with antihistamines.  In the UK, it is usual practice to ask that the child is kept out of school or nursery until day 7 of the rash, at which point new lesions are not forming and the existing spots are crusting.

Hand, foot and mouth disease
What does it look like?
Vesicles on the face around the mouth, ulcers inside the mouth, vesicles on the hands and feet and perianal vesicles or ulceration.  (Somehow the perianal bit got left out when naming this childhood infection)  The child is usually systemically well but when the rash is appearing may be a little miserable and pyrexial.

What causes it?
Coxackie virus

What specific advice is there for this diagnosis?
Treatment is symptomatic.  This is a good opportunity to practice the philosophy of “treat the child, not the fever.  Many children with hand, foot and mouth disease are not febrile but may be in significant discomfort from the oral lesions.  The importance of analgesia to help the child be comfortable enough to drink should be emphasised.
The UK public health advice for hand, foot and mouth disease is that in itself, it does not mandate and absence from school or nursery.

Pityriasis rosea
What does it look like?
The classical pityriasis rosea rash starts with a herald patch in the form of a well localised erythematous area somewhere, usually on the trunk.  This may go unnoticed and if seen rarely causes alarm.  The generalised rash that follows is what usually leads to the seeking of a medical opinion.  This rash is an impressive patchy pink rash with the pattern of the patches following the lines of the dermatomes of the skin on the trunk, forming what is described as a “Christmas tree” distribution.

What causes it?
Human herpes virus

What specific advice is there for this diagnosis?
The child is usually well at the time of the Christmas tree-like rash appearing so no specific treatment is needed.  It should be explained that the rash may last for a few weeks.  There is no need for the child to be excluded from school or nursery.

Slapped Cheek Syndrome (Fifth Disease)
What does it look like?
Most of the features are non-specific: Fever, coryza, sore throat.  The name comes from the typical bright red rash which appears (usually) on both cheeks.  The redness is both more impressive and more consistent than the flushed cheeks seen in febrile children.  This is often followed by a more non-specific, patchy, popular, blanching erythematous rash on the rest of the body.

What causes it?

What specific advice is there for this diagnosis?
For the purposes of managing the child, treatment is symptomatic.  Most cases of slapped cheek resolve without complications.

A rare but significant complication of parvovirus is an aplastic crisis secondary to the effect of the virus on the bone marrow.   A history of recent parvovirus infection followed shortly afterwards by significant or atypical illness or pallor should prompt the testing of a full blood count.

Parvovirus infection in pregnancy carries a risk of miscarriage or hydrops fetalis (due to the same aplastic crisis).  Parvovirus is not treatable and most pregnant women are immune.  In most places, the advice for pregnant women who come in contact with parvovirus is to seek medical assessment if they subsequently become ill, especially if they develop a rash of any kind.  If serology confirms parvovirus infection then the pregnant woman should be referred to the fetomaternal team.  Through the marvels of modern medicine, it is now possible to transfuse a baby in utero and potentially keep them well long enough to reach a gestation where it delivery is an option.

What does it look like?
Typically the child is febrile, coryzal and coughing for a couple of days before the rash appears.  The rash itself is an erthematous maculopapular rash which usually starts on the head before spreading to the rest of the body.
Kopliks spots are diagnostic but rarely seen as they don't hang around for long.  These are small white spots that appear on the inside of the cheeks, opposite the molars.
Measles should be suspected when a child has significant non-purulent conjunctivitis or is particularly miserable despite analgesia.  Unlike uncomplicated viral illnesses, the child is usually quite unwell several days into the illness when the rash appears. (Consider a differential diagnosis of Kawasaki Disease in the child who has had fever for five days as many of the features overlap.  Unlike Measles, early specific treatment for Kawasaki Disease is essential)

What causes it?
Measles virus

What specific advice is there for this diagnosis?
Measles infection requires specific infection control measures and in the UK is a notifiable disease.  There is no specific treatment for Measles and at presentation, the key decision is about how unwell the patient is.  If well enough to be managed at home, it is very important to avoid unnecessary admission to hospital as this might lead to infection of those most at risk.  However if the child is showing signs of significant infection (mainly encephalitis) then admission is probably necessary.  If referring to secondary care it is essential that the accepting team are aware that Measles is suspected so that the child can be kept away from others from the moment of arrival to hospital.

Viral Urticaria
What does it look like?
It looks like an allergic reaction or nettle sting.  The itchy, raised red and white rash can be seen in any part of the body and can be quite alarming.  Typically this rash appears as the illness is getting better.  Lesions appear and disappear several times a day.  If the onset of the rash is accompanied by other symptoms appearing (such as wheeze, oral swelling or vomiting) then acute IgE mediated allergy should be suspected.  Viral urticarial should not be accompanied by the appearance of these symptoms.

What causes it?
One of many possible viruses

What specific advice is there for this diagnosis?
It should be explained that the rash is caused by the virus and the child’s immune system.  The rash doesn’t tell us anything specific about the infection and doesn’t mean anything bad about the illness or the child.   While anthistamines may reduce the itching, they do not seem to make the rash go away any faster.  The rash will usually resolve spontaneously over the space of several days.

It is notable that children who develop viral urticaria are sometimes taking antibiotics when the rash appears.  This can cause concern regarding possible drug allergy.  The evidence suggests that a large number of children developing rashes while taking antibiotics are simply manifesting a viral rash (including urticaria).  This association is contributing to the overdiagnosis of antibiotic allergy.  Many specialists are now advising that a label of antibiotic allergy is not given to a child if they have an acute illness that could be viral, the only symptom is a rash and it is the first time the child has had a rash while taking antibiotics.

Non-specific Viral Rash
What does it look like?
These rashes can appear during the acute infection or recovery phase of the illness.  Typically the rash is a diffuse, patchy erythema.  It may be macular or papular.  In the majority of cases, all of the rash blanches.  Occasionally, a few petechiae can be found.  In a population vaccinated against most strains of meningococcus, a small number of petechiae is most likely to be part of a viral rash.  Indeed, finding one or two petechiae is within normal for a well child at any point. (1)
What causes it?
Any virus that is on the rash B-team could be responsible.  If it's not a diagnostic rash, you can't make a specific diagnosis.

What specific advice is there for this diagnosis?
It's important to explain that the rash doesn't have any specific meaning. For example, a child with this rash does not need to be kept out of school, for infection control reasons at least. Safety-netting advice should mainly centre around the illness, not the rash.  The rash may well persist after the child's illness has resolved.

Many specific rashes start of as non-specific so if the rash changes significantly they may need to be reassessed.  In particular they should know how to assess for non-blanching rash.

Erythema Multiforme
What does it look like?
As the name (What, no Latin?) suggests, it is a rash with multiple forms.  The rash varies from place to place rather than being uniform in appearance.  The rash varies in appearance and texture.  The typical target lesions that also help make the diagnosis are circular and have a dark red centre.
What causes it?
The rash is in many ways very similar to urticaria in children.  It may be a drug reaction but is more commonly triggered by a virus.  That virus is not usually specifically identified.  Atypical bacterial infection, most commonly mycoplasma, may also trigger erythema multiforme.

What specific advice is there for this diagnosis?
Essentially the same applies to Erythema Multiforme as applies to viral urticaria and non-specific viral rashes.  If there is no obvious specific cause, safety-netting for the illness is most important.

Because Erythema Multiforme can rarely progress to Stevens-Johnson Syndrome, it is worth advising the family to seek reassessment if the child develops an inflamed mouth.

Henoch-Schonlein Purpura (HSP)
What does it look like?The typical HSP rash is a purpuric rash on the lower limbs, predominantly on the buttocks and extensor surfaces.  This is often fully apparent at presentation but sometimes the initial rash is not purpuric.  In some cases other symptoms precede the rash.
Typical symptoms of HSP include leg pains and abdominal pains, though in some cases HSP is asymptomatic.

What causes it?
The cause is unknown, however it is presumed that this vasculitic process is triggered by infection.  In that sense, it can be considered a viral rash.

What specific advice is there for this diagnosis?
Most cases of HSP are suitable for outpatient management and in many cases this is well within the remit of the General Practitioner.  A full explanation of the condition, possible complications and how to manage/ followup can be found here.

Bringing it all together
So there you have it - a reasonably comprehensive list of common rashes seen in childhood infections.  In most cases, the rash will not give a specific cause.  In every case, the clinical condition of the child is by far the more important part of the assessment.  After all, it's probably a virus and you probably can't treat that.

Edward Snelson
Rash decision maker

Disclaimer - it might not be.
  1. Downes AJ, Crossland DS, Mellon AF Prevalence and distribution of petechiae in well babies Archives of Disease in Childhood 2002;86:291-292.

Tuesday, 9 April 2019

What is the deal with fever?

Fever scares parents.  The internet is full of scaremongery about what fever can do to you.  For the uninformed parent, fever not only suggests the possibility of serious infection, it is the enemy.  It must be stopped before it harms the child.

Fever confuses clinicians.  For the clinician, fever indicates an infection (most of the time).  Can it tell me what kind of infection and where it is though?  Fever is sometimes associated with raised heart rate, cool peripheries and general malaise.  This picture can be very difficult to discern from sepsis.  Fever therefore presents a dilemma.  If the tachycardia and lethargy could be simply associated with a febrile moment, do I wait to see if the red flags resolve when the fever settles?  If that resolution happens (by far the most likely outcome), I have avoided unnecessary treatment and admission, both of which are at best unpleasant and inconvenient (at worst they both carry their own small risk of morbidity and mortality).  If it later turns out that the child was septic (unlikely but always possible), then the delay, intended to remove the confounder of fever, may have caused harm.
So if fever causes confusion and anxiety, it’s probably a good thing to be clear about a few things to do with fever.   Let’s work through some common questions.

Is fever helpful or necessary in fighting infections?

This is something that is frequently posed: that fever is a normal feature of an immunological process.   It is then suggested that we should not interfere with it.  I’m afraid that this argument holds little water.  Unless there is good evidence that the height of the fever correlates with better outcome (and unsurprisingly this is not the case) then we can’t attribute the death of the microbes to a thermal effect.  Yes, fever may be a part of a process but that doesn’t make it necessary or desirable.  Are fumes a normal outcome from an engine running?  Yes.  Would it be great if we could get the same performance from our engines with less or no fumes?  Yes.  Fever is a sign that the immune system is doing something but there is no good evidence that reducing fever is harmful to the body’s business of fighting the infection.

Is fever harmful to the brain?

The simple answer is that no, fever itself is not harmful as long as it is due to a functional immune response.  That doesn’t mean that the infection couldn’t be harmful, but a fever is not harmful in itself as far as we know.
(There is such a thing as malignant pyrexia which has a high morbidity and mortality rate.  Malignant pyrexia is not a normal physiological response, fever during an infection is.)

Is fever always significant?

Not always.  Sometimes a raised temperature is not even a fever.  It can be environmental.  Babies in particular are prone to getting hot if overdressed or in a hot room.

If a raised temperature is due to infection, the issue of how determined we should be when we look for a focus is a complicated one.  Different circumstances will require different approaches.  The history and examination are important but so is the age of the child.  Babies have a much higher incidence of sepsis and serious bacterial infections.  The threshold for investigation is far lower in a three week old than a three year old.

Consider these two scenarios:

  • A three year old presents with the parent saying that they were really hot at home that morning.  They now have a normal temperature.  Examination is completely normal and the child looks well.  Heart rate and other parameters are all normal.
  • A three week old presents with the parent saying that they were really hot at home that morning.  They now have a normal temperature.  Examination is completely normal and the child looks well.  Heart rate and other parameters are all normal.

In the first scenario the pre-test probability of significant infection is low as long as there are no special circumstances (returning traveller etc.) but in the second they are far higher.

Does fever cause febrile convulsions?

Probably not.  A review article (1) previously reported that the available evidence showed that antipyretic use was not associated with a reduced rate of febrile convulsions.  This is entirely plausible as two events which repeatedly occur together do not have to be one causing the other.  It makes perfect sense that both the fever and the fit could be caused by biochemical changes brought about by either the infection or the body’s response to it.

There was a new paper (2) published in 2018 in which the authors claimed to have clearly demonstrated that antipyretics reduced the recurrence rate of febrile convulsion in children who had already had a fit.  The recurrence rate of fits during the same illness was so high in this study as to suggest that either the data was skewed or that the population was so different to normal as to make the results difficult to apply to practice.  Although this latest publication did challenge the accepted view that lack of fever control is not to be blamed for febrile convulsion, many have seen it as a blip rather than a reason to change their practice.  I remain open minded but still in the “fever does not directly cause the fit” camp.

Does the height of the fever indicate a more serious infection?

The answer to this is, “not really.”  A fever of 40C is slightly more likely to indicate a serious bacterial infection (SBI) than a temperature of 38C in an unwell child.  Despite this weak correlation, height of fever is an unreliable indicator of SBI.  Ultimately the decisions and diagnosis should be made based on other findings.  A child with a fever of 40C, a red throat, red ears and no signs of SBI probably has a viral URTI.  A child with a temperature of 38C with cough, grunting and focal reduced air entry and coarse crepitation in the chest is presumed to have pneumonia.  The number of the temperature itself is of little use in making those decisions.  Undoubtedly, a high fever might act as a speed bump to a clinician, making them look twice and think carefully.  That’s no bad thing.  However a higher temperature shouldn’t mandate a different diagnosis or course of action.
Should we be treating fever in children?

Fever, it seems, is neither harmful nor beneficial.  The medicines that we give to children should in theory be administered with the aim of reducing pain and general malaise.  In practice, children who are febrile usually display signs of feeling unwell.  This means that we end up giving them medication anyway.  The reason may be different but the end result is the same.

If a child is febrile but seems to feel entirely well and demonstrates no evidence of pain, it seems entirely reasonable to not treat the fever for the fever’s sake.  That scenario does happen but is reasonably uncommon.

We should probably de-emphasise the role of fever in the clinical assessment.  The presence of fever is an important piece of information in the acute assessment of a child but only to trigger a search for a focus.  Once it is known that the child has an infection, the focus should be on useful discriminators such as appearance, behaviour, duration and pattern of the illness.
Fever is an important feature of history and examination.  The significance and cause of the fever is the question which then occupies the clinician’s mind.  If the cause and effect of the symptoms are found to be benign, the fever becomes a detail, not a task.  We treat the child not the fever.