C3 is the major complement component. Associated with bacterial infections esp gram neg eg Meningococcus, Enterobacter, Haemophilus, E coli. Gram pos infections also seen. Some increase in autoimmune eg SLE but this is more well recognized with C1q, C2 and C4 def.
Secondary C3 def seen with nephritis (complement activation products in kidney), but also with hereditary factor I and H deficiency (cofactors in C3 product cleavage).
Age of child and type of bugs found important. SCID and severe DiGeorge can present in first few months of life (failure to thrive, chronic diarrhoea, recurrent viral infections, thrush). Antibody defects tend to present in later childhood; neutrophil problems in between (which goes to show how good your innate immunity is).
On average, a young infant will get 5-6 resp infections per year; if day care + older sibs that goes up to 12/yr.
ESID diagnostic protocol is not particularly simple but does help by starting with clinical presentations. [Clin Exp Immun 2006; 145:204]
Consanguinity.
Scars, nails, creases.
Always test for HIV!
IgG will be maternal in first 6 months of life. IgM reaches adult levels in toddlerhood. IgG in young childhood. IgA only in adolescence – often low in young children, deficiency only diagnosed after age 4. Immunoglobulin levels can be high in HIV, Digeorge, CGD.
IgG subsets are controversial – not great evidence that they are responsible for increased infections. High IgM can indicate a problem with class switching eg Hyper IgM syndrome.
Lymphocyte counts:
| Total Lymph count (5th centile) | Age |
| 2.9 | 2-3/12 |
| 3.6 | 4-8/12 |
| 2.18 | 12-23/12 |
| 2.4 | 2-5yr |
| 2 | 7+yr |
| (Comans, JPed 1997;130:388) | |
Functional abs – pneumo often worse response esp polysacch.
Subsets – EDTA, fresh, room temp (else CD4 drops – “fridge AIDS”). CD3 are T cells, which then subdivide into CD4 and CD8 T-helper cells. CD19 and 21 are B cells, CD56 are NK cells. CD4 numbers should exceed CD8 – reversed ratio seen in HIV. A specific NK problem has been described with increased susceptibility to herpesviruses and papillomaviruses. Abnormal NK numbers also seen in Chediak-Higashi, CD40 ligand and NEMO (?). Low CD4 seen in steroids, sepsis, Digeorge, CVID, Ataxia telangiectasia, Coeliac.
If subsets normal, look at proliferation studies (signalling problem rather than maturation problem).
A total hemolytic complement (CH50 or CH100) screening assay looks for defects in the complement pathway. AH50 or AH100 tests the alternative pathway. [C3/C4 are not enough!]
[Peds 11.127.810]
Data Protection Principles:
Data protection act 1998 governs access to medical records. Other acts address rights to data not relating to individuals (Freedom of information 2000), or access to records for deceased individuals or for insurance or employment reasons. It is the duty of the Data Controller (ie whoever decides how data is used) to recognize that a request in written form (incl an email) is a valid request ie no specific form required, data protection act does not need to be cited.
Doctors are still permitted to informally allow access to notes eg for purposes of confirming list of medication.
Applies only to living individuals and excludes anonymized data.
Patients have right to know whether data about them is held, but no need for them to be informed each time it is used. If factual content is disputed, patient has right to have details amended but should be done so that it is clear change has been made in light of new information. If doctor believes existing record is accurate statement of clinical opinion, they may offer patient opportunity to add statement of their own opinion.
If record requested, must be supplied in a permanent format unless disproportionate effort involved, and in a format acceptable to the patient.
Under statutory instrument 2000 no 413 (Disclosure if information that may harm somenone’s health) data controller can restrict access to record but otherwise there is no restriction on the type or age of record (eg electronic or paper). GMC advises that potentially causing upset is not sufficient grounds to withhold access.
Access must be given within 40 days of request and any applicable fee.
Use of records must be according to the principles of processing fairly and lawfully, obtaining only for specific purposes, adequate, relevant and not excessive; and held only for as long as necessary. Where use of records is being considered for more indirect purposes, eg audit, then must be done carefully, by named data controller.
Reasonable steps should be taken to ensure that “subject access requests” are genuine and to verify identities, particulary if request seems unusual,or disproportionate (eg whole of case record rather than just certain dates). Eg Solicitor letters, is signed mandate included and recent?
Not appropriate to hand over notes and let someone else do the sifting – data controller must take appropriate measures to prevent unauthorised or unlawful processing (eg alterations) or accidental loss.
Patient has right to have data explained to them in understandable terms eg jargon, undecipherable text. If unable to contact the original author, data controller must make an effort to provide explanation, which is no different from what they would do in their own day to day work.
You can ask why data is being requested, eg as part of verification of whether an agent is acting within the scope of their authority, but no legal duty for this info to be provided.
See also Confidentiality
NICE CG250 updated September 2025 to recommend 3 day antibiotic course for non-severe pneumonia in children without complications or underlying disease aged 3 months to 11yrs. Extend to 5 days if necessary. If penicillin allergic, offers 3 days clarithromycin (or 5 days Doxycycline for 12+). (Guideline includes adults so harder to use than BTS…)
NICE recommends co-amoxiclav first line for severe disease (based on oxygen requirement, clinical signs, poor feeding/intake etc).
SIGN/BTS pneumonia guideline last revised 2011 – microbiology bit more subtle now: yes, anything between 1/3 and 2/3 are viral, particularly under 2 years, and probably a third are mixed, but you still get pneumococcus and mycoplasma in infants.
Strep pneumoniae (Pneumococcus) is the most common bacterial cause of pneumonia in childhood.
Pneumococcus causes about one-third of radiologically confirmed pneumonia in children aged <2 years.
PCV7 has dramatically decreased IPD due to vaccine serotypes in the UK, but a steady increase in vaccine serotype replacement is evident in the UK.
Group A streptococci and S aureus disease are more likely than pneumococcal to progress to ICU or empyema.
Overall, viruses account for 30-67% of CAP (community acquired pneumonia) cases in childhood and are more frequently identified in children aged <1 year than in those aged >2 years.
1/3 of cases of CAP (8-40%) represent a mixed infection.
Mycoplasma is not unusual in children aged 1-5 years.
Age is a good predictor of the likely pathogens:
Wheeze used to be seen as excluding pneumonia, but now only comment is that it can be one of the clinical features of pneumonia, none of which is very specific. Bacterial pneumonia should be considered in children when there is:
Wheeze and chest pain can be symptoms of pneumonia. But none of the symptoms of pneumonia are very specific for pneumonia.
In children over 3yrs, history of difficulty breathing is an additional valuable symptom.
Consider bacterial pneumonia if recurrent/persistent fever >38.5 together with recession and tachypnoea.
CXR not useful in mild cases, certainly not necessary if admission not being considered. I would consider if hypoxia was disproportionate to degree of breathlessness (suggests collapse), suspicion of effusion (stony dullness on percussion) or pneumothorax.
CXR is not useful in establishing viral vs bacterial vs atypical aetiology!
Repeat CXR in convalescence is only required for persisting symptoms, lobar collapse or round pneumonia.
CRP etc not useful in establishing viral vs bacterial vs atypical aetiology!
Microbiological investigation not necessary routinely, but important if complications or ICU needed.
Under 2yrs, mild lower resp tract symptoms are not usually due to pneumonia (esp if pneumococcal immunized) so do not need to be given antibiotics – but review if symptoms persist.
No longer age related antibiotic cut offs.
Amoxicillin is first choice, macrolide is an alternative (as is co-amox). Macrolide should be added if poor response or if severe (D level recommendations though).
In influenza pneumonia (higher rate of staph), co-amoxiclav is recommended [D]. Similarly for measles.
Oral antibiotics equivalent to IV (if tolerated) even in severe disease (PIVOT trial, Nottingham). But IV for complicated or signs of septicaemia. Recommended IV antibiotics include amoxicillin, co-amoxiclav, cefuroxime, cefotaxime, ceftriaxone. Rationalize as able, change to oral when clear evidence of improvement.
2021 trial in UK & Ireland – excluded under 6 months and under 6kg or severe underlying chronic condition. Excluded anybody already treated with beta lactam antibiotics for 48+ hrs or any other antibiotic for any duration.
Twice daily amoxicillin 35-50mg/kg/d for 3 days was equivalent to higher doses for 7 days. Longer course had 2 days less cough. [JAMA 2021]
Susan Lipsett et al from Boston suggest that most of these kids would probably have improved without antibiotics anyway – they discharged 80% of kids who fulfilled CAP-IT criteria but who had normal x-rays without antibiotics (!) and only 2% came back! [JAMA Open 2024]
Strongly against NG tubes in severely ill esp infants. Use smallest nostril if cannot be avoided
Use oxygen if sats <=92%
Monitor bloods daily if on IV fluids
Chest physio is NOT beneficial – at least, not routinely, potentially if focal collapse identified and slow to come out of oxygen.
If going home, advice on managing fever, preventing dehydration, identifying deterioration.
Follow up severe pneumonia, empyema and lung abscess until recovered completely and CXR near normal.
Essentially supportive. Oxygen, feeding, respiratory support if necessary. Beware secondary bacterial infection, lobar collapse, pneumothorax, concomitant UTI.
Not recommended by NICE. Cochrane 2010, patients treated with nebulized 3% saline had a significantly shorter mean length of hospital stay compared to those treated with nebulized 0.9% saline (MD -1.16 days, 95% CI -1.55 to -0.77, P < 0.00001). No significant adverse events related to 3% saline inhalation were reported. Not recommended for emergency departments as 2 doses didn’t seem to affect clinical scores.
But subsequent studies less impressive. SABRE trial randomized 317 infants to 3% hypertonic saline nebulised every 6 h from admission compared with nothing (ie, standard care). No difference between the two arms of the study in time to discharge [Legg and Cunningham, Arch Dis Child 2015;100:1104-1105].
But AAP guidelines recommend nebulized hypertonic saline for infants hospitalized with bronchiolitis, with the expectation of reducing bronchiolitis scores and length of stay when it is expected to last more than 72 hours. Some think potentially an advantage for hypertonic saline in reducing admission rates from the emergency department [DOI: 10.5863/1551-6776-21.1.7]
Franklin study of early high flow oxygen use – babies were randomized as soon as they needed oxygen. Not generally what happens, of course.
So it seems to me that if you have facility to do high flow, you will find that at least a quarter of your oxygen dependent bronchiolitis babies “need” it. I’m not sure this is a useful or meaningful study. Babies may be more comfortable on high flow, and you may prevent the odd ICU admission, which is definitely worth considering. [N Engl J Med 2018 Mar 22;378(12):1121-1131.]
A study to see if safe to discharge babies with less than normal saturations. RCT of 308 infants, no need to admit if sats >92% AND >50% feed requirements.
For those needing admission, start oxygen only if <90%, and only discharge once sats >90% continuously over 4hr period including sleep, and taking >75% feeds! Exclude babies with risk factors (<3/12, ex-prem, CLD etc– should have sats >92%)
Compared with standard pulse oximeter parameters (treat <94%), no difference in adverse events eg high dependency, readmission. Excluded prems, recent oxygen therapy, CF or other chronic lung disease, immune deficit. [Edinburgh, Steve Cunningham, Lancet 2015; 386: 1041–48]
Study in emergency departments (n=213) found that babies discharged with artificially raised saturations (+3%) actually were less likely to be readmitted than babies with true oxygen saturations, suggesting that it’s a poor predictor (probably true for other respiratory conditions, too).
One study found better outcomes with neb adrenaline and systemic steroids but subgroup analysis and not adequately powered.
First described in the literature in 1908! For egg. Noon and Freeman described grass immunotherapy in 1911. First double-blind trial was by William Frankland in 1954 for subcutaneous grass immunotherapy for seasonal asthma.
Should always be done with extreme caution, if at all, if asthma. Available for wasp/bee stings, grass and tree pollen. Lots of evidence for food allergies, especially in younger children eg peanut immunotherapy. House dust mite sublingual now approved by NICE for resistant allergic rhinitis.
Some evidence that immunotherapy for rhinitis also prevents asthma, which fits with “one airway” hypothesis.
Immunotherapy should be initiated and monitored in a specialist centre experienced in immunotherapy.
Text message reminders doubles adherence – even non-personalised.
Immunomodulation with omalizumab appears to improve success rates of immunotherapy. Treatment with dupilumab (anti-IL4/13) reduces specific IgE levels in people with atopic dermatitis (clinical effect unknown just now).
EAACI indications for rhinoconjunctivitis immunotherapy includes:
Bad asthma and poor compliance are contraindications. Bad asthma was an exclusion criterium for most of the studies, so no evidence of safety. Poor evidence for under 5yrs (for HDM).
Polysensitization common, US tend to to treat all, Europe tends to pick 1 or 2 most useful, at intervals. 17 fatalities to date with immunotherapy. 1 per million injections (risk with sublingual much less, even though used for higher risk patients). Large local reactions common but don’t predict further reactions. Risk of systemic reaction only increased if recurrent. Consider predosing with antihistamine, else reduce dose.
Sublingual immunotherapy (SLIT) in children aged 4 to 12 years with grass pollen-allergic rhinitis/rhinoconjunctivitis significantly reduced symptoms and medication use, well tolerated, and no serious treatment-related events were reported. [Journal of Allergy & Clinical Immunology. 130(4):886-93.e5, 2012 Oct.]
In metanalysis by Dhami S et al, overall standardized mean difference (SMD) of -0.53 (95% CI -0.63, -0.42) in symptoms scores, roughly equal numbers of SCIT and SLIT studies, roughly equivalent scores. When looking just at children, benefit seems less (SMD -0.25 (95% CI -0.46, -0.05)). Continuous treatment probably slightly better than pre/co-season treatment. Manufacturers suggest “disease modifying effect” of treatment beyond first year, which has theoretical rationale. Four studies of long term outcome, demonstrates continuing benefit if treatment continued beyond first year [Allergy 2017].
Grazax (grass) can be safely administered by general practitioners (£80 per month, licensed from 5yrs up): tablet needs to be kept under tongue for at least 1 minute, first dose should be monitored by doctor for 20 minutes. Don’t eat or drink for 5 minutes.
Give antihistamines for local effects. Oral blistering occurs! Isolated cases of eosinophilic oesophagitis but impossible to link of course.
Contains fish gelatine but no reported problems in those with fish allergy. Severe asthma contraindication (in children, defined as <80% predicted FEV1 on treatment).
Aim to start 4 months before season starts, although still some benefit if started 2-3 months before. If no benefit in first season, no point continuing (according to Grazax own SPC).
Symptom relief begins only in the second season of therapy? BNFc says continue only for 3 yrs. Not approved by SMC for Scotland, because no great evidence for benefit after first year – would need individual patient treatment request. Rosie says children wouldn’t tolerate daily doses for months and years.
Pollinex subcut, given into middle third of upperarm. 2 versions: Trees, and 13 grasses incl rye. 3 injections at 7-14 day intervals each year (£450 each), before season starts. Maintenance kit of 4 vials also available, presumably if additional benefit thought possible. Manufacturer recommends using for 3 successive years. Asthma and beta blocker treatment are relative contraindications. Age 6+, not in SMC at all. [Metanalysis, Chest 2008; 133:589, Journal of Allergy & Clinical Immunology. 115(4):676-84, 2005 Apr.]
Some evidence for short course – in multicentre study of adults (not UK) with grass mix SPT positive rhinitis, 8 subcutaneous injections of placebo or Lolium perenne (LPP) were administered in 4 visits (2 jabs each visit, 30 mins apart, different arms) over 3 weeks between January and April. Combined symptom and medication score (CSMS) measured over the peak pollen season was reduced 15.5% (P = .041) during the peak period and −17.9% (P = .029) over the entire pollen season. Also lower rhinoconjunctivitis QOL global score (P = .005) compared with placebo group.
Dhami metanalysis immunotherapy for asthma in kids – symptoms improved, less medication, esp HDM, grass, cat/dog. Not just severe asthma! But no prolonged benefit.
1 study of adults with poor control, HDM. Reduces time to first exacerbation.
Mite allergy prevention study n=111 HDM treatment effective. 2002 PAT study reduced asthma at 10yr follow up after grass/pollen treatment.
[Gillian Vance, Newcastle]
House dust mite immunotherapy with SLIT (3 doses per week) shown to have some benefit in RCT from Brazil (66 children and adults) using SCORAD eczema severity questionnaire. Placebo group showed 35% improvement over 18 months, SLIT group showed 55%. No difference in Dermatology Life Quality index, pruritus score or any of the various other measures used!
Array CGH (Comparative Genomic Hybridisation) tests for microdeletions, better than G-banded chromosome analysis and telomere MLPA but takes 3 months to do! So MLPA or FISH for urgent DNA test, else QF-PCR for trisomy screening (but store DNA too).
For competitive swimmers, note FINA doping control rules (based on the World Anti-Doping Agency regulations). Most asthma medications are on the Prohibited List including inhaled steroids and inhaled Beta2 agonists.
Therefore, elite athletes with asthma must apply for special permission to use these medications, known as the “Therapeutic Use Exemption” (TUE) program. If competing at FINA events, then you apply directly to the FINA Doping Control Review Board to have their applications considered. Lower level athletes should apply to their national anti-doping body.
Historically, people with epilepsy were “considered to have unique powers, even hailed as geniuses, regarded as having a sacred disease and leading sacred lives”. But then demonisation, persecution, social rejection. “Epileptic personality” described by psychiatry in 20th century. [Sacred lives, Ian Bone]
Self control is central to our self image and the manner in which we and society believe we should behave. Epilepsy jeopardises this. Patients often conceal. Guilt, loss of confidence and low mood common after seizures.
Definition: At least 2 unprovoked (or reflex) seizures, occurring more than 24hrs apart; else one unprovoked (or reflex) seizure and probability of further seizures similar to that seen in those who have had 2 unprovoked seizures (ie at least 60%); or recognized epilepsy syndrome. Also part of the definition is that epilepsy is considered “resolved” if age dependent syndrome and past applicable age, or else those who have been seizure free for 10 years and off medication for 5 years. (ILAE 2014)
Note that “seizure” does not have any real medical meaning! Transient signs/symptoms due to excessive or synchronous neuronal activity in brain (ILAE 2017) – but implies you can tell whether caused by abnormal brain activity, which can be hard!
First assessment:
Despite increasing sophistication, interpreting EEG remains an inexact science! Irregular background activity overlaps with detectable abnormality. Plus, only really picks up activity at surface of brain, and can miss simple partial seizures (but not tonic-clonic generalised). Review in 2000 did not find much evidence base. Requires dialogue between referrer and neurophysiologist. Diagnosis remains principally clinical – eg more than 1 tonic-clonic seizure, or multiple absences! Incidence of epileptiform activity in asymptomatic individuals appears to be about 1%, of which a few percent will develop epilepsy over the subsequent years. Abnormal activity is certainly more likely if structural abnormality, but still many will be and remain asymptomatic.<
50% of children with epilepsy have normal EEGs – so not a particularly useful test! Not only that, but in studies, at least 20% of “epileptics” were ultimately given a non-epileptic diagnosis! So request EEG with caution; should be used for confirming clinical opinion, or to guide treatment, not where symptoms are vague. Hence a firm diagnosis of epilepsy and then decisions about treatment may take some time; difficult for families to understand, but it is quite safe to be cautious esp considering the implications of a mistaken diagnosis.
If EEG is negative, then proceed to a sleep EEG (where child is woken by parents at 3am, kept awake then brought to department and allowed to fall asleep during monitoring). This has 80% sensitivity. Failing that, Medilog or Video with continous monitoring. This is good for distinguishing non-epileptic tonic-clonic seizures, but does not rule out co-existing epilepsy.
Good for:
Beware – an EEG finding of partial epilepsy may not have a surgical lesion! Must be used in conjunction with MRI. A generalized epilepsy may have multiple foci, so if you are unlucky to capture just one you will be misled. Similarly, if secondary generalization occurs rapidly, its partial nature may be missed.
Not usually useful to do after multiple seizures, unless type or frequency changes significantly, in which case a new syndrome/prognosis may have developed.</p>
<p><em>”The brain is subject to maturation; there are multiple protecting and triggering factors, often unpredictable. Seizures may be rare and easy to treat for months and years, but may become more frequent and difficult to control later on. But in many children a precise syndromic diagnosis can be made, and a good final prognosis can be expected in most cases.”</em></p>
All children with recurrent seizures should have an ECG with calculated QTc. Children under 2 with epilepsy or with recurrent focal seizures (other than CECTS) should have an elective MRI brain scan. In most other cases the course is predictable. A normal MRI does not rule out a small dysplastic lesion, equally the finding of a lesion does not mean that it is the cause of the epilepsy. However, at least you can exclude a tumour or malformation.</p>
Focal/partial often have acquired or congenital lesions, often specific precipitating factors eg sleep, startle!</p>
<p>Consider:</p>
Should not be started after first tonic-clonic generalized seizure. Try not to start before EEG done as may mask features.
When to start? Complex – consider:
The risk of accidents due to a seizure is marginal, probably because seizures mainly occur during times of reduced activity (eg somnolence, sleep, meals) rather than during intense physical or mental activity. Risk assessment should be done and documented including bathing, showering, swimming. NICE only specifically mentions with reference to epilepsy and learning disability. SIGN states that normal activities should be encouraged, but supervision requirements should be individualized taking into account type of activity and seizure activity.
“There is an old and unjustified prejudice that brain damage may result from seizures: this does not happen in the great majority, and usually only occurs in unpreventable and very special situations.” (cf severe migraine, frequent syncope).
For generalized, lamotrigine or levetiracetam. Not Valproate for girls (risk of congenital malformations) or boys (evidence of effect on fertility) unless nothing else works
Others:
For partial, use carbamazepine (CBZ) or lamotrigine. Else:
If 6 months therapy with 2 different but appropriate drugs does not control (at adequate doses), then refer to tertiary centre for re-think on diagnosis.
Routine drug level monitoring is not required.
Consider withdrawing treatment when seizure free for 2+ years. But treatment may also be aimed at reducing cognitive effects, not just seizures: evidence for this comes from surgically treated epilepsies where rapid cognitive-behavioural improvement can be seen; and the fact that behavioural problems are more common in the months leading up to the first fit before diagnosis. For example:
More efficient use of known drugs (doses, slow release preparations), side effects of drugs, and new therapeutic options (treatment of acute seizures with nasal or buccal midazolam (EPISTAT) by parents at home, or in schools) can make a big difference to families.
Temporal lobe epilepsies, most often due to mesial temporal sclerosis (and often refractory to medical therapy) can be treated surgically with excellent prognosis. An increasing number of intractable focal epilepsies can now be treated surgically.
Archives of Disease in Childhood 2005;90:5-10, T Deonna
SIGN guideline 81
Refer to tertiary if –
SPEN network has pathways for first seizure, new diagnosis, continuing seizures.
See also Living with Epilepsy
Dame Fiona Caldicott’s review of original 1997
information governance recommendations – response to perceived
reluctance to share info appropriately.
Appropriate sharing should be the rule, not the exception. Given need for informed consent, concludes that patients should be better informed as to how their
information is used. Needs system for recording consent applicable
across all NHS and care systems. Sharing info with a private
organisation or local authority should be equally straightforward, if
data protection principles are applied.