In children under 10, high BP is usually secondary to an underlying disease or condition. Primary hypertension increasingly recognised in older, obese children.
Do repeated measurements, ideally automated home BP monitoring, before diagnosing hypertension. Check manually as well as with automated device. Beware “white coat effect”, even if not clearly anxious.
Use appropriate cuff size – cuff should cover at least 75% of the upper arm from the acromion to the olecranon (should be sufficient space at the antecubital fossa to apply stethoscope!) . An inappropriately small cuff will overestimate BP.
Gram negative diplococci, causing meningitis and septicaemia. Sometimes bone/joint infection. Neisseria (not meningitidis) responsible for ophthalmia neonatorum.
Main serogroups:
A – responsible for epidemics of meningitis across “Meningitis belt” of Sub-Saharan Africa, until Men A monovalent vaccine introduced in 2010 (still epidemics, but due to other serotypes). Hajj also triggers outbreaks.
B – 4 component vaccine introduced in 2015 to deal with B being the most common cause of invasive meningococcal disease since introduction of MenC vaccine. Based on vaccine developed for New Zealand epidemic.
C – used to be most common cause of invasive meningococcal disease in UK until vaccine introduced. So successful that early dose was dropped from routine schedule, although later resurgence in older children and young people, so teenage booster and university catch up programme introduced.
Clinically, notorious for rapidly evolving, often fatal septicaemia with non blanching rash and limb ischaemia. Curiously, meningococcal meningitis, on the other hand, is the most benign of the various causes of bacterial meningitis. Can be mixed picture, ranging from a few petechial spots only with an otherwise typical meningitis presentation, or else meningococcal septicaemia with neck stiffness, where presence of meningitis is actually a good prognostic sign.
Exquisitely sensitive to antibiotics. Meningitis epidemics in Africa treated with single IM dose ceftriaxone!!! Nasal carriage is the reason for spread, so prophylaxis for close contacts important.
Where to start!? Leaches, blood letting, pretty much everything doctors did in the pre-modern period…
Thalidomide and birth defects, of course. But unforeseen.
X-rays for pregnancy monitoring. Took years before people paid attention to the alarms. X-rays were also used for tinea capitis – not just brain tumours, strokes and ischaemic heart disease about 30% higher too.
Ribavirin (via SPAG machines) for RSV. Not harmful, just useless and expensive.
Iron supplements for preterm babies – increased sepsis.
Evidence that having a peanut allergy has worse quality of life for a family than having diabetes… Mostly due to fear of unexpected severe reaction, and restrictions on social activities particularly eating out, parties and holidays.
Allergic patients can feel embarrassed or even ridiculed for declaring their allergy. Allergy is often mocked in the media (Cobra Kai, the Box Trolls, Peter Rabbit), asthma in particular.
School and nursery are a particular area of concern, whether the right foods will be served, whether teachers or other children might bring allergens into school (food is sometimes used in classes, for example making bird seed balls), whether reactions will be managed appropriately, school trips. Children have died in school (Nasar Ahmed, Mohammed Ismaeel Ashraf).
APPEAL study 2022 – UK & Ireland, peanut allergy – 87% of parents/care-givers (not clear if mums or dads) felt moderately or severely restricted eating out, choosing where to eat (82%), special occasions (76%) and when buying food from a shop (71%). 52% of survey participants reported being bullied because of their allergy. But variable – some feel allergy has minimal impact on their health-related quality of life.
Mums tend to be more concerned by limitations in the child’s own social life, dads seem to care more about limitations in the whole family’s social life. [Stensgaard, Clin Exp Allergy 2017]. Mums are the ones most studied. There probably are significant differences between mums and dads. In some studies, parents overrate their child’s quality of life, but in others (particularly with teenagers) parents can be seen as over anxious. Teenagers tend to take on the perspective of the parent of the same sex.
How bad previous reactions have been, interestingly, does not in itself contribute significantly to quality of life – in some cases, not having ever had a reaction can make families more anxious, because they don’t know what to expect! In one study, having multiple allergies and having an adrenaline pen was associated with worse quality of life. [Protudger, Clin Transl Allergy 2016]
Parents can feel guilty if their child has a reaction, a failure of their duty to protect. Mums can feel guilty about having “caused” their child’s allergy, either through their own medical history or what they ate or didn’t eat in pregnancy (even there is no good evidence for this being a factor).
Better quality of life is seen in allergic families with greater self efficacy for food allergy management, and lower perceived likelihood of a severe reaction [Knibb, Pediatric Allergy & Immunology. 27(5):459-464, August 2016].
APPEAL-1 study
8 European countries, questionnaire study of adults and children with peanut allergy.
Only a minority remembered getting any training in future
emergencies or use of medication, after their initial reaction. There was a low
rate of satisfaction with AAI training!
43% reported bullying, and a third of these described it as
severe.
65% confident in ability to recognize a reaction, but only
45% confident about knowing when to use an AAI and 59% how. 62% say the carry AAI all the time.
25-30% said it was not easy (or rarely easy) to talk to
friends or family about their allergy, although most felt confident talking to
new people about their allergy. Friends and family were generally seen as “believing
there is too much concern over allergy” even though overall they were seen as
having a good awareness and understanding of allergy (cf other people, where
this was seen as the opposite).
Dutch respondents had lowest rates of uncertainty and stress
around activities, and for feeling anxious.
At same time, they had the highest rates of confidence around knowing
when and how to use AAI. France had
highest rate of being made to feel different in a negative way, and feelings of
isolation.
NB – likely to be the most affected families who
participated.
An acute inflammatory demyelinating polyradiculopathy, almost certainly autoimmune since antibodies to ganglioside are often found. Some cases are purely motor, others are mixed motor and sensory. About a quarter follow Campylobacter infection, where there is clear homology between bacterial epitopes and gangliosides. Strongly associated with HIV in the tropics.
Usually gradual onset over a few days but rarely can be over a few hours. Diarrhoeal illness a few weeks previously suggests campylobacter. Presents with pain, numbness, paraesthesiae, weakness. Weakness may initially be proximal or distal (distal alone suggests “withering” axonopathy eg toxin). Facial nerves often affected (see Miller Fisher syndrome, below).
Reflexes usually lost early but sometimes persist. Autonomic features may occur (vagal nerve involvement) eg urinary retention, sinus tachycardia, ileus. The degree of paralysis can be extreme – up to 20% require ventilation.
Gradually worsens, peaks at around 2 weeks (by definition, within 4 weeks). Then there is a variable plateau phase. 20% will have persisting disability; fatigue is common. Myelinopathy usually recovers quite rapidly; axonopathy takes months to years. Neuronopathy is where the dorsal root ganglion cell body itself is damaged, and may never recover. [Am Fam Physician 2020]
The diagnosis is often pretty obvious but investigations should be done to rule out other causes. If purely motor, differential includes hypokalaemia, polio, myasthenia gravis, botulism, acute myopathy.
MRI brain and spinal cord – low threshold! Consider if acute or rapidly progressive, predominantly sensory symptoms (including back pain), predominant sphincter disturbance at presentation, clear sensory or marked motor level. MRI may show enhancing nerves esp cranial nerves, but more usefully excludes:
a spinal lesion (eg prolapsed disc, haemorrhage or tumour)
para-sagittal cerebral lesion, which can present as acute painful flaccid paraparesis
Acute Transverse Myelitis
ADEM
Lumbar puncture – Elevated CSF protein has high PPV but not specific (and may be normal within seven days of onset). Pleocytosis eg >50 cells/mm3 suggests another diagnosis. In children, lumbar puncture is not always necessary to make a definite diagnosis, and should be reserved for cases where the diagnosis is in doubt. Oligoclonal bands present in CSF and plasma.
Nerve conduction studies – may be normal in the first week! Demyelinating pattern. May be useful in children who present with atypical features, normal CSF protein after the first week following presentation or in categorising the subtype of GBS – for example, Acute motor axonal neuropathy (AMAN)
U&E (hypokalaemia)
Creatine kinase (myositis)
Acute and convalescent serum for viral and mycoplasma antibody titres (Mycoplasma pneumoniae, EBV, CMV, Borrelia burgdorferi).
Throat swab; stool microscopy, culture and sensitivities (Campylobacter jejuni)
Antiganglioside antibodies (for example, anti-GQ1b antibodies in Miller-Fisher syndrome)
Monitor respiratory ability with serial peak flows.
Consider also:
Heavy metals and toxins (lead, mercury, arsenic, organophosphates)
Urinary porphyrins
Botulinum toxin identification (stool, serum) (but eyes usually involved)
Diphtheria (but eyes usually involved)
Drug toxicology screen
trial of intravenous edrophonium (Tensilon) and/or oral pyridostigmine (minimum of five days) for myasthenia gravis if investigations have been normal or negative
Enteroviruses incl Poliomyelitis – fever, asymmetry of weakness, lack of sensory involvement, CSF findings and PCR from throat/stool
In endemic regions, tick bite paralysis closely resembles AIDP. Seasonal, affects young children predominantly. CSF protein is usually normal and the electrophysiological studies are consistent with a pre-synaptic defect at the neuromuscular junction rather than a peripheral neuropathy. The patient usually recovers rapidly after removal of the tick but full return of strength may take several weeks. Failure to detect the tick may result in the death of the patient.
The initial progressive phase lasts 10-30 days. If deterioration continues beyond four weeks, the diagnosis of GBS is pretty much excluded – suggests chronic inflammatory polyneuropathy (CIDP). In rapid, aggressive disease complete quadriplegia can develop in 2-5 days; apart from need for respiratory support, autonomic involvement can provoke life-threatening arrhythmias and hypertension. Aspiration pneumonia is another major risk.
Children should be admitted to PICU if they have:
flaccid tetraparesis
severe rapidly progressive course
reduced vital capacity at or below 20 ml/kg
bulbar palsy with symptoms
autonomic cardiovascular instability viz persistent hypertension or labile blood pressure, or arrhythmias.
Plasma exchange is gold standard. Surprisingly, steroids do not appear to have any benefit (cf CIDP), as they can sometimes make things worse or slow the recovery. Perhaps nerve damage at presentation is already programmed/complete? Or do they impair healing? IVIG 0.4g/kg for 5 days (started as soon as possible and ideally within first 2 weeks, although benefit may extend up to 4 weeks) is as effective as plasma exchange (in adults, Cochrane) and probably quicker as well as safer. The conventional dose of immunoglobulin is a total of 2 g/kg, over 3-5 days, whatever protocol that avoids waste best! In kids, 250 ml/kg plasma exchange or roughly a triple-volume exchange probably best.
For pain which is resistant to conventional analgesia, gabapentin and carbamazepine may be useful.
Mortality in childhood GBS is less than 5%. Deaths may be caused by ventilatory failure (rare now), cardiac arrhythmias, dysautonomia and pulmonary embolism. Full recovery within 3-12 months is experienced by 90-95% of children with GBS; that leaves 5-10% with permanent neuro deficits, but most of those tend to have only minor disability.
Subtypes
Miller-Fisher syndrome = ophthalmoplegia with ataxia & absent reflexes. GQ1b antibodies are highly sensitive and specific, found particularly in ocular motor nerves. Beware botulism and diphtheria, which also affect eyes!
Cullen’s and Grey Turner signs (umbilical and flank bruising respectively).
Amylase level not prognostic. False positive liver/renal impairment, GI inflammation. False negative in 10%, esp drug induced!
Lipase more specific, only done in Huddersfield?! Stays high for longer.
Low calcium, high glucose seen.
Diagnosis mostly clinical. USS usually sensitive, else CT – more for complications (focal or diffuse enlargement, heterogeneous enhancement, irregular or shaggy outline, oedema of surrounding fat).
AXR may show sentinel loop, free gas (loss of psoas shadow). CXR for effusion.
Causes
I GET SMASHED
idiopathic (25% in children)
gall stones
ethanol
trauma
steroids – and other drugs, esp anti-epileptics, immunosuppressants eg azathioprine, cancer drugs.
mumps (even without parotitis), malignancy
autoimmune
scorpion sting!
But misses IBD, sepsis, Mycoplasma (early or late), genetic causes!
Management
Prognosis good in children. Scoring systems in adults eg Modified Glasgow-Imrie not applicable, various paediatric versions, of debatable value.
Fluid resuscitation then 1.5-2x maintenance requirements (not much evidence – don’t be afraid of positive balance! Keep urine output at 1ml/kg/hr), analgesia, early enteral nutrition if possible (to avoid bacterial translocation) else parenteral.
Antibiotics only for suspected sepsis.
Surgery eg necrosectomy.
1/3 acute recurrent (defined as recurrence after full recovery). Often anatomical problems. Chronic associated with genetic disorders, metabolic, autoimmune.
ERCP for anatomical causes. Pancreatic enzymes. Non opiate pain management eg tricyclics.
Raised CRP, ESR, ferritin (esp over 1000 – also haemophagocytic syndromes, haemochromatosis, liver disorders, malignancy)
Poor response to IVIG (cf Kawasakis)
Leucocytosis (neutrophilia, can be leukaemoid)
Thrombocytosis
Arthritis
Hepatosplenomegaly
Generalised lymphadenopathy
Pericarditis
Can be systemically very unwell and potentially life threatening complications may occur early in the disease course (eg pericarditis, macrophage activation syndrome or HLH, sepsis). See the Big Sick film from Netflix. Start high dose corticosteroids after careful exclusion of other diagnoses, especially infection, Kawasaki disease, and malignancy – difficult when arthritis is absent! But maybe you have to look harder…
Systemic features may predate the arthritis by several weeks and occasionally longer. Typically involves small joints of the hands and wrists, ankles, hips, knees, and cervical spine – about 30% ultimately develop severe polyarthritis.
There are no pathognomic tests or agreed diagnostic criteria for SOJIA! Classic features:
quotidian (=daily) evening spiking temperature, that returns to or falls below baseline by the morning.
Rash is faint, salmon pink maculopapular, most obvious during pyrexia. Usually not on the face so easily missed – typically on the trunk, inner thigh and axillae, especially on areas of trauma or pressure (Koebner phenomenon).
Treat with IV methylprednisolone pulses (30mg/kg over 4 hours, max 1g, once daily for 3 days) and ibuprofen (seems better than piroxicam for SOJIA!). Oral prednisolone may then be used while methotrexate is introduced.
Seven subtypes – only diagnose when symptoms for at least 3 months:
Oligo (persistent or extended) – Arthritis affecting up to four joints during the first six months of disease. If subsequently more than four joints are affected the term extended oligoarthritis is used, otherwise the term persistent oligoarthritis is used. This is the most common pattern (50% of all JIA) and usually involves large joints of the lower limbs, especially knees. These children have the best prognosis but are at high risk of asymptomatic uveitis (30%, and risk highest in monoarthritis!) and therefore must be screened regularly. In aggressive disease, can develop within 3 months of presentation. Girls mostly ankles, knees or wrists, 50% will be ANA positive and particularly associated with chronic (even subclinical) uveitis. Boys tend to get sacroiliitis and are HLA B27 positive, which is associated with acute uveitis…
Polyarthritis (rheumatoid factor -ve) – 5+ joints affected during first 6 months. Tends not to be hips! 17% of all JIA. Severity is very variable.
Polyarthritis (RF +ve) – 7% of all JIA. Symmetrical polyarthritis, nodules, and Rheumatoid factor IgM +ve at least twice, 3 months apart. Typically adolescent girls of 10yrs+. Prognosis is guarded as early joint damage often occurs.
Systemic onset – SOJIA, 11% of all JIA. Can occur at any age, often pre-school but rarely in infancy. Males and females affected equally.
Enthesitis related arthritis – inflammation of tendon insertions eg sternum, around knee (at 2,6 and 10 o’clock positions), tibial tubercle, achilles/plantar, tibialis anterior, flexor digitorum insertion in foot. Often dactylitis. Asymmetric, distal lower limbs large joints commonly affected, high risk of developing ankylosing spondylitis in early adulthood – spine rarely affected early on. BASMI score consists of 5 measurements of spinal mobility. The group also includes arthritis or enthesitis with at least two of:
tenderness of the sacroiliac joint and/ or inflammatory spinal pain
HLA B27 positive (10% of normal population)
family history in a first or second degree relative of HLA B27 related disease (ie arthritis, IBD, Reiter’s, uveitis)
anterior uveitis (usually symptomatic with redness, pain and blurred vision)
arthritis after 8 years of age in a boy (esp large lower limb joints).
Psoriatic arthritis – esp umbilicus, behind ear, scalp. The arthritis is usually asymmetrical, mixed large/small joints. Often NOT psoriasis, at least initially, but includes children with arthritis and at least two of:
dactylitis (fat, sore fingers!)
pitting or onycholysis of nails
psoriasis in a first degree relative
Other arthritis – This group is for children with idiopathic arthritis that does not fit the other groups (or into more than one! eg Crohns & UC associated arthritis, features overlap). Downs syndrome children can get a resistant polyarthritis.
Presentation
Clinically, history of pain, swelling, stiffness. Pain is usually not severe, and often avoided completely by adapting movement; can occur at night, and occurs in the joint line. Degree of pain does NOT predict severity of synovitis. Swelling may be due to effusion or bony overgrowth. Stiffness not so severe as to cause gelling ie sitting still leads to freezing (cf myasthenia gravis, hypermobility). Bony overgrowth, discrepant leg length (longer with inflammation! Leads to postural scoliosis), wasting show chronicity.
Differentials:
Benign hypermobility – typically get pain related to exertion, short lasting although may occur at night.
SLE (high ESR with normal CRP, low WCC/platelets, autoantibodies) or dermatomyositis (stiffness, rather than true arthritis – proximal muscle weakness, high CK)
Investigations:
Mono JIA usually CRP <7 – else beware infection
Micro of joint fluid nonspecific
XR – to exclude tumour etc. Lucency in metaphysis may be marrow infiltration in leukaemia, Brodie’s abscess or Langerhans’ histiocytosis. Moth eaten appearance and onion skin periosteal reaction suggests tumour or infection.
RF v non specific, like autoantibodies, only significant in discriminating teenage girls with adult type Rheumatoid Arthritis.
US is good but operator dependent. MRI probably better, predicts extension in mono, 4-11/12 before clinical signs.
Treatment
NSAIDs and intra-articular steroids work quickly. Ibuprofen can be given at high dose (10mg/kg qds), else Diclofenac 3-5mg/kg in 3-4 divided doses, max 150mg. Piroxicam is once daily, which is convenient but it probably has more GI/cutaneous side effects. No longer considered appropriate for acute pain.
Routine NSAIDs are probably pointless; if you need regular anti-inflammatories, you should probably be on a disease modifying agent eg methotrexate.
Joint injections are given under general anaesthetic in young children or with entonox in older children. Lederspan (triamcinolone) 1mg/kg max 40mg used for big joint, 0.5mg/kg for wrist, TMJ. Knuckles will only take 0.1-0.2ml before they start to leak (which leads to subcut atrophy). Injecting multiple (eg >6) sites can result in Cushings for 3-6/12. Better to pulse methylpred? (Kennilog is another formulation, but seems to give more Cushings). Most patients tolerate injections well and have no loss of function immediately after; physio is usually started after 24hr. How often? Balance of steroid effects and uncontrolled joint disease…
Methotrexate Side effects: GI (nause, ulceration, diarrhoea), hepatotoxicity (reversible elevations of serum liver enzymes eg 3x upper limit normal common), Pulmonary (oedema, pleuritic pain, pulmonary fibrosis, interstitial pneumonitis), mood changes, Renal (haematuria, dysuria, renal failure) – plus usual chemo stuff ie bone marrow suppression.
BNFc
Methotrexate is the disease modifying drug of choice – early use helps to reduce joint damage and minimise the exposure to, and side effects of, corticosteroids. Well tolerated in most children but often causes nausea the day after administration (so usually given on Friday to avoid affecting school). Avoid alcohol, as potentiates risk of cirrhosis. Takes 6-8 weeks to become effective so cover interval with intravenous methylprednisolone. The theoretical risk of malignancy and infertility has not so far been borne out in long term outcome studies. Folic acid improves tolerability but not clear what regimen to use – BNF suggests 5mg once weekly or 1mg daily, theoretically it should not be given within 24 hours of the MTX [so once weekly sounds easier]. Methotrexate is given once a week at 10-25mg/m2 – can be oral but subcut route improves bioavailability at doses beyond 10mg/m2. Metojet has better shelf life (10 months). Regular blood tests to monitor inflammatory markers and side effects eg monthly for 6 months then 3 monthly thereafter. Not great for axial disease ie HLA B27.
Steroids are useful for treating acute flares. Methylprednisolone can be given once daily for 3/7 to control severe exacerbations, then once weekly thereafter (30mg/kg, max 1g). Don’t work well for axial disease though ie HLA B27 (although may be good for peripheral joints) – TNF blockade (ie etanercept or infliximab) effective.
Patients who are refractory to high dose parenteral methotrexate are considered for monoclonal antibodies such as Etanercept/infliximab (TNF antibody), autologous stem cell transplantation, or very high dose immunosuppression.
Etanercept (Embrel) used to be twice weekly subcut injection but most now do once weekly 0.8mg/kg. £10 000pa.
Infliximab is an infusion, given at 0, 2, 6 weeks then 8 weekly thereafter. Children usually start at 5mg/kg. If control not achieved, a higher dose could be used else the interval reduced. Patients should get a CXR and Mantoux before starting in view of the particular risk of mycobacterial disease.
IV immunoglobulin has been used eg 2 doses on consecutive days monthly. Very expensive.
Mycophenolate – related to azathioprine. Used for connective tissue disease. SE gastrointestinal, liver, bone marrow. 600mg/m2 BD
Calcium and vitamin D supplements are often given for bone health.
Patients on immunosuppressants should avoid live vaccines and beware of infection. If unwell enough to need antibiotics they should probably stop treatment temporarily. Varicella is a particular concern – if contact with chickenpox and non-immune, consider VZIG or oral aciclovir for prophylaxis, and early IV aciclovir treatment. See Greenbook.
Not clear when to wean… Many patients do well for a year or so before their condition begins to worsen, swapping to another agent often works, and swapping back is also a useful option.
Outcome
JIA is a not a benign disease and outcome is variable. At least a third of patients have ongoing active disease into adulthood and many have sequelae eg:
joint damage requiring joint replacement
short stature from chronic disease compounded by steroid toxicity
localised growth problems (micrognathia or leg length inequality)
visual loss from uveitis
osteoporosis: one off DEXA scan not predictive of # (maybe better if serial scans?) so clinical. Minimize steroids; optimize exercise, nutrition, growth/puberty, calc/vitD/bisphosph
Bisphosphonates seem to be effective for increasing bone mass in JIA. Flu-like symptoms with first IV dose can be treated with paracetamol and tend not to recur.
