What am I missing? The child with fever but no obvious cause

The fear that a significant illness wil go unreconised in a child is one that is always present for the clinician who sees acutely unwell children.  The stories that we hear of infections and other illnesses being "missed" fuels that anxiety.  The common sense side of us tells us that significant illness should manifest itself in an obvious way, but that doesn't stop us from asking the question, "What am I missing?" when we see a child with a febrile illness and no apparent cause?

Scenario

You have just seen Billy, a 1 year old child with a fever that started today.  They have no cough or runny nose.  They appear well and have a heart rate of 120.  Chest is clear, heart sounds are normal and abdomen is soft.  Tympanic membranes are not inflamed.  You may or may not have looked at their throat but if you did, there is nothing obvious to see.

What do you do?

The answer to this is to understand what the possible causes of fever are, know how to exclude them and have an idea of how likely they are.  The latter brings us onto an important question:

How likely is significant or dangerous infection in a child?

That depends on the child.

The most common risk factor that we encounter is the infant.  The likelihood of an unwell newborn having a significant infection is high.  This is further compounded by their non-specific symptoms and lack of physiological response in the first few weeks of life.  The risk of serious infection multiplied by the risk of underestimating the illness makes a baby under the age of 60 days a high risk patient.

After those first few weeks, the infant becomes less reliant on maternal antibodies and begins to produce a more vigorous response to infection, most of which are now viral.  As a result, the risk diminishes inversely.

Other risky patients are those with ongoing reasons to either have more significant infections or less obvious signs of serious illness.  These include children with neurodisability, immunodeficiency or chronic illness.

For the usually healthy child beyond early infancy, the very great probability is that an illness will be benign and that those infections that are dangerous will manifest themselves in some significant way.  This itself brings a challenge: complacency.  We become so used to good outcomes and fruitless investigations that we start to think that everything is an uncomplicated viral infection.
It usually is, but what if it isn't?  That brings us on to the next question:

What are the less common causes of fever in a child?

One way to think about the causes is within categories:

When there are so many possibilities, it is often best to consider the least common first.  Let's start with the non-infective.  These illnesses cause inflammation without active infection.  They are all very uncommon compared to other things on the list but that makes them easy to forget and therefore miss.

Kawasaki Disease - This is a vasculitis which can look like a prolonged viral illness.  The cause has not yet been identified but it is presumed to be a post-infective phenomenon.  If a child has had a fever for five or more days without a clear cause, we should check if the child fulfils the criteria for Kawasaki disease.  You can check the criteria in a book or use an online tool such as this one linked here.

Leukaemia - Haematological malignancy in children occasionally presents as an unexplained and prolonged pyrexia.  More often there are other symptoms and signs such as increasing lethargy, weight loss, pallor, bruising, bleeding and unexplained pains.

Systemic Onset Juvenile Idiopathic Arthritis (JIA) - this subtype of JIA is rare but is one possible cause of unexplained fever.  Often the fever is accompanied by a typical salmon pink rash and joint pains, even if there is no clinically obvious joint swelling yet.

These non-infective causes of fever should not be over-thought.  The presenting symptoms of childhood illness are often so non-specific that it can be all to easy to imagine zebras instead of horses.  The key to not missing these is to be aware of them as entities and to look for features of these in the child with unexplained fever, especially when that fever is prolonged.

Next, the sepsis question.  Every febrile child should be assessed for sepsis, whether a focus the fever is found or not.  That decision can be made easy for you in one of two ways.  Either the child is very well to the extent that sepsis can be ruled out, or the child is so unwell that sepsis is presumed.  Everything in between is a case of careful assessment, including risk factors and the trajectory of the illness.

So, if we have considered the very rare and the sepsis question, what we should be left with is a child who we think does not have sepsis and yet has a fever without an immediately obvious focus.  At this point we return to the list of possibilities.

The task in a child with fever and no clear focus is to rule these possibilities out, which is usually based on clinical assessment.  Start with the complications of upper respiratory tract infection (URTI) as these are the most common significant infections in children.

Mastoiditis - infection of the mastoid is usually a complication of otitis media infection there should be evidence of that.  Mastoiditis is excluded clinically if there is no erythema, swelling or significant tenderness of the mastoid process.

Peritonsillar abscess - A collection of pus in the peritonsillar tissues is manifested by swelling which displaces the tonsil.  At the time of writing this, throat examination is not routinely performed due to the COVID-19 pandemic.  However, peritonsillar abscess is highly unlikely in a child who is willing to drink or eat.  If the child is refusing all oral intake, it may be necessary to use droplet PPE, including eye protection, to visually exclude peritonsillar abscess.

Lymph node abscess - Inflamed or enlarged lymph nodes are a common finding in children with URTI. Occasionally, the lymph node becomes bacterially infected.  When this happens, the lymph node is more enlarged and painful.  The overlying skin is often erythematous.  Another common feature is that the child becomes reluctant to turn their neck due to the pain from inflammation of the surrounding tissues.  These infected lymph nodes may respond to high dose oral antibiotics, however they may require incision and drainage.  Discussion with or referral to ENT is therefore advisable.

Osteomyelitis and septic arthritis - This is a good example of something that is rare but also often missed when it is a cause of unexplained fever.  Infection in a bone or joint can be visible or hidden.  If a parent has noticed a swollen, red or hot area or that the child has localising signs in a limb, that can lead to early diagnosis.  It is also the case that in a significant number of cases, the infection is not identified early on.  It is no surprise when a febrile child is miserable and moves less.  It is not common practice for clinicians to examine every bone and joint in a febrile child.  However, this is something that needs to be done if a child has an unexplained fever.  If limbs have not been examined for swelling, hot spots or erythema at first presentation, I would suggest that this should be done at the second assessment should fever persist and remains unexplained.

Urinary tract infection (UTI) - UTI is probably the most common cause of fever without a clinically obvious focus in children.  The younger the child, the less likely they are to present with specific symptoms.  Fever without obvious cause is an indication to screen the child for UTI.  Blind treatment with antibiotics is not recommended.  Urine should ideally be sent for culture so that treatment is based on the most robust result - a significant bacterial growth.

Meningitis and encephalitis - Central nervous system (CNS) infection is the most feared of the causes of fever without focus.  In the younger child, symptoms are less specific.  Infants may be irritable, jittery and not feeding well.  Vomiting and excessive sleeping are also common features but again, non-specific.  In an infant with an open fontanelle, this should be examined.  A bulging fontanelle (when not crying) is a red flag sign.  Older children may exhibit classical signs of neck stiffness, headache and photophobia.  Younger children are more likely to stand out because they just won't settle or have an abnormal tone or conscious level.  CNS infection is usually ruled out by the child demonstrating normal interaction or behaviour, often after adequate analgesia has been provided.

Appendicitis - In an older child, recognising appendicitis is done in a similar way to adult practice.  Appendicitis is rare in younger children but when it does occur, it can easily be missed.  Guarding tends to be a later sign in the pre-school child because their abdominal wall muscles are not very strong.  Children often cry or otherwise appear distress when their abdomen is examined, leaving the clinician uncertain.  Analgesia and reassessment is a good way of clinically ruling out appendicitis if the initial assessment is ambiguous.

Pneumonia and empyema - Lower respiratory tract infection (LRTI) is common in children.  Cough and fever are non-specific symptoms and are not grounds for diagnosing LRTI on their own.  Hearing crepitations on auscultation is also a common finding that should not be given too much weight.  Many LRTIs in children are viral and self-limiting.  Important discriminators are how unwell the child is, their work of breathing and more specific focal signs such as localised reduced air entry or a dull percussion note.

Tropical diseases - If a child has an unexplained fever and has recently returned from an area with e.g. malaria, they need to be referred to secondary care for investigation.

And finally...

So if Billy looks well and behaves in a way that effectively rules out sepsis and meningitis, his fever without clear focus means that we should look just a bit harder.  A urine sample should be taken to exclude UTI; blind treatment with antibiotics is not recommended without good evidence of UTI.

If there are reasons to suspect one of the less common (than uncomplicated viral infection) causes of fever, referral to secondary is likely to be the way forward.  If there is no evidence of a significant cause and what you are left with is a reasonably well child with an unexplained fever, the final question is, "should I refer this child or send them home with safety-netting advice?"

Both options are valid and the choice should be made in the best interest of the child.  In secondary care, the assessment of the child should be clinical in the majority of cases.  As such, referral may simply add a further clinical history and examination.  If a second opinion or physical period of observation is felt to in the child's interest, that is fine.  If not, it may be best to keep the child away from hospital and the risks associated with a secondary healthcare setting/

Before a final decision is made, risk should be considered.  For the majority of healthy children presenting to Primary Care (including the Emergency Department) with no specific risk factors, the likelihood of any febrile illness being a serious bacterial illness is very low.  That makes it perfectly reasonable for a child who has had a careful clinical assessment to be managed conservatively and with good safety-netting advice.

There are children who have a significantly higher risk.  As mentioned above, the most commonly encountered risk factor is the baby.  If your patient is a baby, especially if not yet started on their primary vaccinations, fever without focus warrants a referral to paediatrics.

Fever in a child who does not have an immediately obvious focus is a clinical conundrum for all of us.  Many children can be managed with a thorough history and examination.  If there are significant risk factors or specific findings then appropriate referral is likely to be the next step.

Edward Snelson
99% Type 1 decision maker
@sailordoctor

Disclaimer: If it's the clinician who has no focus, there's nothing I can do for you.

The Right Sort of Confidence - (Easter Egg: Acute abdominal pain in children)

I feel pretty confident that my car has the right amount of oil in the engine and air in the tires.  Why?  because that has been the case every time I check these things.  So why bother checking?

Paediatrics is a dangerous speciality because the usual outcome of any child presenting for assessment is that everything is fine.  Fever?  It's probably an uncomplicated viral infection.  Rash?  Virus.  Lump in the neck?  Virus.  You get the idea.

As a result, any one of us can become so used to the benign outcome that we don't expect the dangerous problems or the unusual causes of childhood symptoms.  This is called availability bias.  The last 50 children with this presenting complaint had a virus and got better, so this patient is likely to be the same.

Of course the statement about the likelihood is true, however people don't bring their children to us just for a probability estimate.  We are there to assess whether there is a significant problem that requires intervention.  To get there, we need to know what to look for.

Abdominal pain in children is a good example.  Children often get abdominal pains.  One of the most common presentations is abdominal pain during a febrile illness.  Most likely cause?  Virus.  I suspect that the significant pathology that is most often considered in this situation is appendicitis.  Appendicitis is relatively rare in younger children but paradoxically more difficult to diagnose, so while the chances of a 3 year old having appendicitis is very low, so are the chances that a 3 year old with appendicitis will get this diagnosed easily.

Appendicitis is at least on our minds and so we're probably not going to miss it through failure to look.  There are plenty of causes of abdominal pain that are easily missed for various reasons.  Lower lobe pneumonia, for example, is easily missed because it isn't in the abdomen.  Testicular torsion is easily missed if it isn't looked for.  You'd think that if a child or young person had a problem with their genitalia they might mention that.  They often don't.  If you don't look for torsion, you won't find it.

Here's a brief overview of some of the easily missed causes of abdominal pain in children:

Here is a more extensive list of possible causes of abdominal pain in children. (1)

Going through these, starting at one o'clock:

Mesenteric Adenitis - Yes, children with viral upper respiratory tract infection can get acute abdominal pains and can even have localised abdominal tenderness.  Children with more significant causes of pain can also have URTI, so if there are red flag signs or symptoms you should still take these seriously.
Non-IgE food allergy - This can cause acute abdominal pain but paradoxically is a diagnosis best not made acutely.  History, a food diary and follow-up are the way forward when food allergy becomes a possibility.
Gastroenteritis - When vomiting precedes abdominal pain then this makes gastroenteritis more likely.  Similarly, diarrhoea is a strong indicator of viral enteritis.  However, there is no such thing as always, so careful abdominal examination is key and signs that suggest a surgical cause should still lead to referral.
Gynaecological - The main thing to say about this is that it is a common pitfall to forget to even consider this possibility in children.  How often do you think ectopic pregnancy is considered in the differential of a 13 year old with acute abdominal pain?  It should always be remembered as a possiblity.  Do a pregnancy test.
Constipation - This is possibly the most common cause of afebrile acute abdominal pain in children.  There are two main pitfalls.  The first is to miss the diagnosis because the child or parent doesn't think the child is constipated.  The second is to think that because the presentation is acute, the problem just needs a brief period of treatment.  If they are constipated enough to present with acute pain, the problem is chronic and should be treated as such as per NICE guidelines.
Urinary Tract Infection - Abdominal pain +/- vomiting without diarrhoea is a common way for children to present with UTI.  There is no absolute rule on when and when not to test a urine but it is fair to say that significant diarrhoea usually precludes it for a couple of reasons.  In all other cases of acute abdominal pain, it is usually a good idea even if interpreting the result is not completely straightforward.
Colic - Truly a diagnosis of exclusion, but this can be a good history and examination. What to do with colic is covered here.
Appendicitis - Uncommon but not so rare that you won't see a case every now and then. Picking them out from the crowd can be difficult.  Good simple analgesia and reassessment after an hour is often a helpful discriminator for the grey cases if you can do that.
Testicular torsion - Inguinal and genital examination is part of the examination of a male presenting with abdominal pain.  Do it, even if the last 100 times were normal.
Intussusception - Rare but deadly.  Episodes of pallor and signs of being significantly unwell are reasons to suspect intussusception.  Bloody and mucousy (recurrent jelly-like) stools make it easier to diagnose but may be a late sign.
Diabetic Ketoacidosis - It is very easy to see how first presentations are initially diagnosed as viral illnesses.  If you've got a child who's a bit more lethargic or subdued than your typical gastroenteritis case, or if there is a report of polyuria, test a glucose.

In most cases, significant causes will be excluded by a thorough history and examination.  Often a urine test is a good idea and sometimes a second opinion will be necessary.  Abdominal X-ray is almost never useful in making a decision about referral.

Paradoxically,  the wrong sort of confidence comes from repeated experience of nothing bad happening.  The right sort of confidence comes from knowing that bad things will happen and knowing that we're ready for that eventuality.  This often happens once you've experienced the sharp end of an unexpected diagnosis.  If that has happened, congratulations!  You're now an expert.

Edward Snelson
Experienced if not Expert
@sailordoctor

Disclaimer - Experience doesn't always lead to expertise but it's a fairly important element. Bad experience is a good wad to develop great expertise but only if you have all the right elements in place to ensure that you learn without becoming a second victim.  I would like to see more work in that area, especially at the Primary/ Secondary Care interface.

Reference

1. The Essential Clinical Handbook of Common Paediatric Cases, Edward Snelson

A Paediatric Guide to Anatomy (Things You Should Know about Constipation and Urinary Tract Infection in Children)

Last week, Norfolk and Norwich University Hospitals announced the opening of the UK's first Senior Emergency Department.  A Senior Emergency Department is much like a Paediatric Emergency Department, except that this one will meet the needs of patients over the age of 80, instead of those under the age of 16.  The concept is the same - there is a specific patient group with a different set of needs and who present in different ways to the rest of the adult population.

Children have been able to access paediatric emergency departments for a long time now.  Children benefit from a child-friendly waiting area, an assessment that recognises the way that children are different from adults and treatment by clinicians who are specifically trained in child health.  Perhaps that makes it all sound very exclusive and mysterious.  What are these differences of which you speak?  Well, none of them are a great secret, but as is often the case, having something explained often helps it to be understood better, even if you already knew it.

So, here's something that you probably already knew, but was a fact that you hadn't necessarily known what to do with: Children have a considerable lack of body awareness. 

A child's approach to anatomy and physiology is fairly simple:  I eat, I wee and I poo.  I pick things up if I want them.  If I want to do any of those things in a different location then I move.  If the world isn't the way I want it to be, I make noises.

One of my top tips when teaching paediatric clinical examination is that children don't have a chest before they go to school.  To them, the space between mouth and stomach is presumably some sort of giant food processing area.  Functions like breathing and circulation only truly become a reality when a child is much older.  For that reason I never tell a young child that I am going to listen to their chest.  It only confuses them if you say that.  I tell them I am going to listen to their tummy and tell them what I can hear.  Usually, the answer is sausages.

Besides helping me to know what to say to children, my knowledge of their lack of body awareness is crucial when it comes to understanding visceral presentations in children.  The important thing to understand is that children seem mostly unable to recognise the significance of visceral symptoms.  In other words, the feelings in their bowel and bladder either make no sense to them, or they are unable to articulate these feelings.  For whatever reason, young children have a tendency to leave bowel and bladder symptoms unreported, and so the presentation of problems such as urinary tract infection (UTI) and constipation are always delayed.

Take this case history example:
A two year old child presents with a 12 hour history of dysuria and frequency of urine.  They have no fever or abdominal pain.

Well, that's all very well, but that's just not how it goes.  Let's try something more realistic:
A two year old presents with a three day history of fever.  The child first presented two days ago and was diagnosed as having viral gastroenteritis.  The child is vomiting intermittently.  There is no blood or bile in the vomit.  The child does not have diarrhoea.
Today the parents have noticed that their child is more unsettled and they think that the child has abdominal pain, although the child has not specifically said that their tummy hurts.

Why is it important to recognise this peculiarity of children?

The first reason is that we need to be aware that UTI is a diagnosis that we have to actively  seek in children.  UTI in younger children does not have specific (urinary) symptoms.  Instead, all of the features are those also found in the more common viral infections such as gastroenteritis or URTI.

This does not mean that all unwell children should have a urine tested.  Routine testing would be great if it were painless for the family and the clinician.  Neither of these things are true.  Getting an uncontaminated sample (a 'clean catch') is hard work much of the time.  Interpreting the results and making sense of conflicting information is a challenge once a sample is obtained.  For that reason I would not routinely ask for a urine sample in a child who has an obvious otitis media for example.

The things that make UTI more likely in children include:

• previous UTI
• abdominal pain/ tenderness
• vomiting without diarrhoea
• a report of odd smelling urine
• absence of signs or symptoms of URTI
• new urinary symptoms (enuresis, dysuria)

The second reason is that we need to be aware that both UTI and constipation are likely to be well established by the time they are diagnosed.   This means that in children, we have to take each of these diagnoses a little more seriously.

Although most children with UTI are well at presentation, they probably have an infection that is a little more than what would be considered cystitis.  They may not have a proper pyelonephritis yet, but they are likely to have a more established infection than a young adult would have.  It is for this reason that we need to make sure that we do pick up a diagnosis of UTI as early as possible.  Every day left untreated increases the risk of renal scarring.

With constipation, the significance of the way it presents is more to do with the length of treatment needed to resolve the problem than the urgency to start treatment (as with UTI in children).  By the time that the child and parent are aware of the problem, constipation is usually very well established.  The child's bowel has been full of stool for weeks or months.  The bowel is stretched, weak and insensitive.  Prune juice and porridge are simply not going to do the job of resolving the constipation by the time that a child gets as far as their first medical assessment.

At this point, a short course of treatment for constipation simply will not suffice to truly resolve the problem.  Macrogol laxatives (the treatment recommended by the UK's NICE guideline) will do a great job, in almost every case, of clearing out the bowel.  This is not the same as treating the underlying condition.  We need to continue treatment until the bowel has a chance to do its thing again.

The effective treatment of idiopathic constipation in children requires two things.  Firstly, it requires adequate doses the right laxative (I avoid lactulose) for as long as it takes to allow the return of strength, shape and sensation to the bowel.  The consensus on this is that this will take about six months of maintenance therapy to achieve.

The second thing needed is some sort of modification to lifestyle that will help to avoid the return to constipation once treatment is stopped.  Changing diet, fluid intake and toileting habits may make all the difference, once the treatment has given the child their normal bowel back.

So I would suggest that we never think in terms of 'just a UTI' or 'a little bit of constipation' in children.  The delay in presentation, coupled with the extra time it may take us to actually get to the diagnosis means that neither of these terms apply.

I suspect that this could all be applied to the elderly with a little modification, but I'm not about to start GPseniorsTips.blogspot.com.  I'll just leave that thought with my innovative colleagues at the Norfolk and Norwich University Hospitals.

Edward Snelson
Part-time Vicerologist
@sailordoctor

Disclaimer - While I know deep down that it would be a terrible idea, part of me wants to combine a Paediatric Emergency Department with a Senior Emergency Department.  I can imagine how the two patient groups would be quite good for each other.  And that folks, is why I should never be allowed to have ideas.