Haemophilia

General paediatrics, Haem/Oncology

The clinical severity of a patient’s hemophilia is gauged by the baseline clotting factor level, a value that remains fairly constant throughout that person’s life, and is pretty consistent through a family. Around 5% of normal is moderate.

Intramuscular injections should be avoided if at all possible. If they must be given, factor replacement therapy should precede the injection. Parenteral agents should be given intravenously or subcutaneously. Immunizations are administered subcutaneously.

Aspirin is contraindicated due to antiplatelet effect. Avoid NSAIDs if possible, and contraindicated if actively bleeding or being treated for a recent bleeding problem.

Indications for Factor Replacement Therapy

  1. Suspected bleeding into a joint or muscle.
  2. Any significant injury to the head, neck, mouth or eyes or evidence of bleeding in those areas.
  3. Any new or unusual headache, particularly one following trauma.
  4. Severe pain or swelling at any site.
  5. All open wounds requiring surgical closure, wound adhesive, or steri-strips.
  6. History of an accident or trauma that might result in internal bleeding.
  7. Necessity of a surgical or invasive procedure.
  8. Heavy or persistent bleeding from any site.
  9. Gastrointestinal bleeding.
  10. Acute fractures, dislocations and sprains.

Treatment

Hemophilia A

The treatment of choice for individuals with factor VIII deficiency is recombinant factor VIII. There are different brands, with different combinations of additives which may or may not be antigenic. Cryoprecipate and fresh frozen plasma are used only if factor cannot be obtained.

  • When bleeding is severe, or for a head injury, the appropriate dose of factor VIII is 50 units/kg. This should result in a factor VIII level of 80-100%. Half life is 8-10 hrs so repeat if necessary.
  • Mild Hemophilia A (factor VIII greater than 5%) with Non-Life/ Limb Threatening Bleeding may respond to desmopressin (some don’t) – 0.3mcg/kg IV over 30 minutes, else as nasal spray (Stimate, 1 spray in one nostril for individuals <50 kg and 1 spray in each nostril for individuals >50 kg). Otherwise, treatment dose is 15-25u/kg.

Hemophilia B

For individuals with Christmas disease (factor IX deficiency), recombinant factor IX is the treatment of choice. Fresh frozen plasma is only used if factor is unavailable.

  • When bleeding is severe, or head injury, the appropriate dose of factor IX is 100-120 units/kg. This should result in a factor IX level of 80-100%, but in Hemophilia B the response is variable so check the level and adjust as necessary.
  • Mild – 25-35u/kg, check level

Ideally let patients/parents reconstitute and administer their own factor. Families should have an emergency dose of factor concentrate or DDAVP in their home and to take it with them when they travel, esp if they do not live close to a hospital. Factor replacement should be offered within 1 hour of the patient’s arrival: it should be readily available, the patient should not be left waiting, and treatment should not be deferred pending x-rays or other results. The most experienced IV therapist or phlebotomist available should perform venipuncture – misses and tourniquets may cause painful hematomas which then limit further IV access – use the smallest needle possible unless volume replacement is needed..

Factor replacement must be administered intravenously by IV push over 1-2 minutes. Round the dose up to the closest full vial ie don’t throw away any left overs (excess factor does not create a hypercoaguable state but will prolong the therapeutic half-life of the product administered).

For individuals with inhibitors (antibodies to factor VIII or IX), treatment decisions may be more complicated. The care of inhibitor patients should be urgently discussed with the patient’s hematologist. If an individual with an inhibitor presents in a life- or limb-threatening scenario, the safest immediate action is to prescribe recombinant factor VIIa (rFVIIa, Novoseven) at a dose of 90 mcg/kg or activated prothrombin complex concentrates (FEIBA, Autoplex) at 75-100 units/kg (contraindicated in factor IX patients with a history of inhibitors and anaphylaxis). Hopefully the patient/family can provide information on response to second line therapeutic agents.

[Medical and Scientific Advisory Council (MASAC) of the US National Hemophilia Foundation 2003]

Haematuria

Common, General paediatrics, OPD, Renal

In a study of 342 kids with asymptomatic microscopic haematuria, no cause was found in the large majority of patients. The most common cause discovered was hypercalciuria (16% of patients) followed by post–streptococcal glomerulonephritis (1%). No evidence for value of early detection of hypercalciuria (may be at long-term risk for nephrolithiasis and bone demineralization).  The children with asymptomatic post–streptococcal glomerulonephritis all improved spontaneously and without complication.  None had evidence of urinary tract infection! Clinically insignificant abnormalities in the upper urinary tracts of 5 children and grade 3 reflux in 1  [Arch Pediatr Adolesc Med. 2005;159(4):353-355. doi:10.1001/archpedi.159.4.353]

Asympt recurrent can be monitored for 5yr!

Beware:

  • frank blood,
  • protein,
  • hypertension,
  • other features (joints, rash, wt loss)

Haematuria defined as persistent dipstick positive on at least 3 occasions for at least 3 months. Else as >2rbc per HPF (not same as flow cytometry). Then consider:

  • Red cells or not?
    • myoglobinuria = haemolysis
    • beetroot!
    • Porphyrins, other unusual pigments
  • Proteinuria or not?

If spot urine abnormal, repeat on early morning urine and then proceed to 12-14hr collection. Urine calcium/creatinine has age specific normals, high at birth (up to 1.5 in toddlers) falling to adult max of 0.7 at age 7. High levels especially significant in the presence of a normal plasma calcium

Investigations – only do bloods if macroscopic or nephritis suspected:

  • Do urine culture and microscopy.
  • Do PCR if proteinuria.
  • If macroscopic, do FBC, U&Es, LFTs, Coag.
  • Renal USS
  • Screen family members with urinalysis
  • Spot urine calcium/creatinine
  • If acute nephritis, do C3/4, ASOT, immunoglobulins, ANCA, anti GBM as below.
  • If stones suspected, do 2 sets of spot urine Ca/creat, Oxalate/creat, Urate, amino & organic acids, pH, KUB.

Differential is:

  • Tumour – bladder (colour changes during voiding, dysuria with sterile culture) or kidney
  • IgA nephropathy – persistent, progressive in 30%, diagnosis on biopsy
  • Alports – usually X dominant, deafness in minority, cataracts in 10%
  • Sickle cell – 1% macroscopic, 16% microscopic. Papillary necrosis, usually painless, episodic. May progress to sickle nephropathy.
  • Venous thrombosis – esp neonates, nephrotics.
  • Vascular – AVM, Nutcracker syndrome (compression of the left renal vein between the abdominal aorta and SMA)
  • Nail-patella syndrome (BM disorder, like Alports)
  • Polycystic Kidney Disease

Biopsy if persistent high grade microscopic, or microscopic with proteinuria (>150 mg/24 hr)/hypertension/impaired renal function, or 2 episodes of gross haematuria. Cystoscopy for bladder problem.

Health anxiety

General paediatrics, Medical, Patients, Psychology

DSM-5 has “illness anxiety disorder”, defined as preoccupation with the idea that you’re seriously ill, based on normal body sensations (such as a noisy stomach) or minor symptoms (such as a minor rash), to the degree that it gets in the way of normal life. Other features are persistence of such ideas over 6 months, finding little or no reassurance from negative test results or a doctor’s reassurance, repeatedly checking body, avoiding people, places or activities for fear of health risks.

In other words, hypochondriasis. Which gets its name from the idea that such feelings came from liver/spleen/gall bladder (“melancholy” – black bile).  William Cullen, in Edinburgh in the 1790s, appeared to take a particular interest in this.

For the sake of diagnosis, this disorder requires the absence of symptoms, which excludes the large group of people who have similar preoccupation and fears about non-specific or unexplained signs and symptoms.

Health anxiety is therefore a broader concept, and can include anyone who is more desperate for relief from worry, than for relief from actual symptoms.

Cyberchondria = combination of increased pathologisation of society, and ability to browse the internet.  Because provides the opportunity to find very serious, extremely unlikely explanation for problems.

Diagnosis of health anxiety is well accepted by patients if explained respectfully!

[BMJ 2016;353:i2250]

Mastocytosis

Dermatology, General paediatrics

Proliferation of mast cells.  Can be restricted to skin or be systemic, with infiltration of bone marrow, spleen, liver and lymph nodes.  Systemic involvement not always obvious in the skin! Messy though, since mast cell mediators might act systemically even if mast cells themselves not widespread.

Systemic mastocytosis can present with episodic symptoms of dyspnoea, collapse (hypotension), reflux, diarrhoea.  Rather non-specific, so easily missed.  May also have hepatosplenomegaly, lymphadenopathy, osteoporosis, bone abnormalities.

Skin lesions may be present but not always dramatic (might just look like freckles).  May be history of dermatographism, recurrent itching, flushing and/or urticaria.  Different skin patterns seen, but overlapping:

  • mastocytoma – slightly raised, can be slightly pigmented.  Physical irritation eg scratching causes flare and weal (Darier’s sign).  Can be present at birth, tend to be a good size eg 2-4cm nodule, may be blistering (in first 2 years of life only), else appear in first year of life.
  • Urticaria Pigmentosa – usually presents in first 2 years of life, freckles or larger nodules/papules/plaques.  Can be blistering.  Resolves if not improves at puberty.
  • Diffuse cutaneous mastocytosis (DCM) – no distinct lesions visible! Serious.
  • Telangiectasia macularis eruptiva perstans (TMEP) –  brownish small macules with telangiectasia, generally in adults.  Can be systemic.

So look at skin, try Darier’s sign (not v sensitive).  Feel for liver and spleen.  Check Tryptase level (rarely normal even in systemic – compare baseline to peak, rather than just absolute level). Consider bone marrow biopsy to look for mast cells. Consider bone scan to look for abnormalities.  PCR for the D816V mutation in KIT gene?

Management

Control triggers (very individual):

  • Stress (emotional/physical), sleep deprivation, pain
  • Physical stimuation eg heat/cold, exercise/sex, sunlight, skin/scalp friction or trauma (tickling!)
  • Bee/wasp stings
  • Drugs esp aspirin/NSAIDs, opiates
  • Alcohol

60% of kids resolve during puberty!

In later life there is a slightly higher risk of haematological disorders including cancer. There is also an increased risk of osteoporosis.

Stabilize mast cells:

  • Anti-histamines, including H2 blockers.  Titrate dose to effect.
  • Cromoglycate
  • PUVA offers some temporary relief

Emergency treatment: Adrenaline auto-injectors for –

  • systemic
  • previous systemic reactions
  • Extensive blistering lesions?

UK support group at www.ukmasto.org [Jess Hobart]

[Am Fam Physician. 1999 Jun 1;59(11):3047-3054.]

Colic = Cry-Fuss Behaviour

Common, General paediatrics, Nutrition, OPD

Cry-fuss behaviour (=colic etc), mean is just short of 2hrs per day for first 6 weeks, reduces to 72 minutes by 10-12 weeks.

“Colic” suggests that there is a bowel issue, usually suspected due to drawing legs up, passing wind – but these could be considered normal for crying and distress, of any cause.  Reflux (GORD) is often blamed, yet international consensus states there is no evidence to support an empiric trial of acid suppression as a diagnostic test in infants and young children, even though symptoms tend to be less specific [Vandenplas, J Pediatr Gastroenterol Nutr. 2009 Oct;49(4):498-547. doi: 10.1097/MPG.0b013e3181b7f563]!

Cause

Mums with an anxiety disorder prior to pregnancy are at higher risk of having a child with excessive crying at 2, 4 or 16 months postpartum compared with mothers without an anxiety disorder.  Risk increased further for mothers who developed an anxiety disorder during pregnancy.

So does maternal anxiety lead to “intrusive” parenting, in turn increasing infant crying ?[Arch Dis Child 2014;99:800–6]. Else fetal programming?  Genetics?

What’s the influence of fathers!?

Surprisingly, maternal depressive disorders, cf anxiety, experienced before or during pregnancy, did not predict maternal report of excessive infant crying.  Is the difference withdrawal, rather than intrusiveness?

Reflux

Consider 2 week trial of anti-secretory eg ranitidine (but NOT PPI – increase risk of infection esp respiratory and GI, associated with parietal cell hyperplasia, and possibly food allergy!).  But don’t assume improvement due to response!  Or investigate with pH monitoring.  Or stick to supporting parents!   Even if arching and refusing to feed, no evidence of effectiveness.

Infection

5% have UTI retrospectively, but in absence of other signs, investigations not routinely required.

Associations

Crying that lasts more than 3 h per day, for more than 3 days per week and for more than 3 weeks in a row—is associated with child abuse and maternal depression!  Higher scores on PND scale persists at 6/12 even if crying resolves…

6% of parents retrospectively admit physically abusive behaviours towards baby when crying.

Predicts shorter duration of breast feeding.

Persistent problems with cry-fuss behaviour at 5/12 associated with later behavioural problems (metanalysis, but confounded by psychosocial risk factors).

Management

Reassure the parents/carers that infantile colic is a common problem that should resolve by 6 months of age.

RCTs of behavioural sleep intervention under 3/12 did not decrease crying.  So encourage parent-infant reciprocity (ie responding to crying) until old enough to suit Gina Ford type regimented sleep regimes.

Encourage the parents to try relaxed cue based care, sleeping in the same room as the baby (not the same bed – beware SUDI) , offering physical contact esp skin to skin contact, and ensuring the baby gets lots of rich sensory experiences during the day.  This,  combined with average 10 hours of physical contact per 24hr (even if asleep), associated with 50% less crying and fussing. Only 37% of 3/12 babies sleep 8hrs straight at night.

Night waking is associated with co-sleeping and breast feeding, but breast feeding does not equate with less total sleep for parents over the whole 24hr period (quality, however, may be inferior).

Over sensitive babies may benefit from OT/Physio, but beware removing sensory stimulus as associated with neurodevelopmental problems.  Massage, wrapping may help, little evidence for chiropractic, craniosacral, nutritional.  Offer diverse sensory stimulation (through parents’ own social life and activities).

If symptoms are severe (subjective, of course) or persist after 4 months, consider an alternative underlying cause for symptoms.

NICE says seek specialist advice from a paediatrician if infant is not thriving, or symptoms are not starting to improve or are worsening after 4 months of age.

Caveat for GPs is “Seek specialist advice if Parents/carers feel unable to cope with the infant’s symptoms despite reassurance and advice in primary care.”

 

Feeding

Feed refusal is often linked, often impaired mutual regulation of feeding that result in entrenched patterns of difficult feeding esp breast feeding issues.

The following suggest a feeding problem –

  • 4 heavy disposable nappies per day minimum
  • 3-4 yellow curdy stools if breast fed minimum
  • Nipple/breast pain, attachment problems
  • falling asleep within 10 minutes, feeding longer than 30 minutes (active feeding ie not including dozing, interacting) regularly
  • clicking sound, gurgly sounds, absence of swallowing sounds
  • Increased resp effort

Expect 125g per week growth average in first 3 months.  Tongue tie only really relevant to breast feeding babies.

Babies who have infrequent large feeds are not necessarily abnormal, and cue based feeding rather than scheduled 3-4hrly feeds often works better.

So offer feed calmly, unless already full blown crying, in which case calm holding eg skin to skin until more settled.  Cochrane review concluded that pacifier use does not interfere with breast feeding in mothers who are motivated.

Some evidence for trial of hydrolysed formula. RCT of 107 breast fed babies with colic excluded dairy, soy, wheat, nuts, fish and shortened duration of crying, but only CMPI really substantiated.  Probiotic has helped in RCT but roles of feed management, lactose overload etc need to be elucidated first?

Functional lactose overload? – as feed progresses, fat level usually increases so transit time slows.  If insufficient fat, rapid transit leads to lactose fermentation in colon (lower cholecystokinin levels seen).

Parent Support

The self-help support group Cry-sis for families with excessively crying or sleepless children, has a website and runs a national telephone helpline (0845 122 8669).

There’s also parent info including a video at http://www.nhs.uk/Conditions/Colic/Pages/Introduction.aspx

 

[https://cks.nice.org.uk/colic-infantile#!scenario]

[Clinical review BMJ 2011;343:d7772  doi: http://dx.doi.org/10.1136/bmj.d7772]

Capillary refill time (CRT)

Clinical, General paediatrics

In children over 7 days of age, the upper limit of normal CRT is approximately 2 s when measured on a finger, and 4 s when measured on the chest or foot, irrespective of whether the child is feverish or not. Longer pressing times and ambient temperature outside 20°C–25°C are associated with longer CRT.

Evidence suggests that the use of stopwatches reduces variability between observers.

Recommend following standardised CRT method: press on the finger for 5 s using moderate pressure at an ambient temperature of 20°C–25°C. A capillary refill time of 3 s or more should be considered abnormal.  Other timings apply to other sites.

[Systematic review – 21 studies on 1915 children.  Arch Dis Child doi:10.1136/archdischild-2014-307079]

Uncertainty

Generic

“Medicine inhabits an inexact territory with terrifying hazards, and the best way to avoid them is to demand honesty from everyone.  The first truth that we must accept is that human beings are not perfect…  We must lose the fear that we’ll be blamed if [our patients] find fault” (Margaret Mccartney, BMJ)

The discipline of medicine concerns the manipulation of knowledge under uncertainty (Siddharta Mukherjee).

Blood Culture

Clinical, General paediatrics, Infectious disease

Essential investigation in sepsis, particularly where unusual organisms or deep seated infection eg endocarditis.

The volume of the sample is important. Small volumes have higher false negative rate, and are slower to become positive – 6ml superior to 2ml [j Peds 1996].

Traditionally, thought to be most effective when done at time of pyrexia, but there is little evidence for this.  In a study of 1,436 adult patients with bacteremia and fungemia, the likelihood of documenting bloodstream infections was not significantly enhanced by collecting blood specimens for culture at the time that patients experienced temperature spikes. Nor was there any benefit for any subgroup eg patient age, gender, white blood cell count and specific cause of bacteremia. [J Clin Microbiol. 2008 Apr; 46(4): 1381–1385.  doi:  10.1128/JCM.02033-07]

Also traditionally, considered negative at 48 hours. Canadian study of 98 positive blood cultures in babies up to 90 days of age found 96% of true pathogenic cultures were positive at 24 hours, with 100% positive at 36 hours. Mean time to positivity was 14.4 hours in pathogenic bacteria and 23.2 hours in contaminants.  [DOI: 10.1093/jpids/piv078]

US study of 256 non-critically ill babies up to 60 days of age found median time to positive blood cultures of 16.6 hours for pathogens cf 25.1 for contaminants, for CSF cultures 14 hours for pathogens cf 40 for contaminants. 82% of pathogens positive within 24hrs for both blood and CSF [can’t see figures for 36/48hrs yet, full text embargoed?][Hosp Peds 2020]

Another US study of 392 cases (outside of PICU) found 96% of pathogens positive by 36hrs (95% CI 95-98), and 99% at 48hrs. But not clear how many of these would have been well enough to go home at 36 hours.  Estimated that observation >36hrs would identify 1 bacteraemic infant for 1250-2778 infants [Biondi, JAMAped2014]. Note that there were significant differences between organisms (E coli faster, staph slower), and between sites (sample volumes? time to inoculation?). No correlation with degree of fever, interestingly.

Current Western Australian guideline, FeBRILe3, appears to be safe.

Canadians have published a new position statement too.

In a tertiary neonatal unit, 72 hours was considered necessary. [ADC Fetal & Neonatal 2001]

Plagiocephaly

Clinical, Common, General paediatrics, OPD

Differential

The clinical criteria for a unilateral lambdoid synostosis consist of an ipsilateral occipital flattening, a depressed ipsilateral ear lobe (inferior movement) and a parallelogram-like shape in the posterior view. All three of these signs were present in the eight synostotic infants. Furthermore, all children had developed a compensatory contralateral parietooccipital bulging that led to a slanted tree top-like shape of the head at follow-up. Normal posterior view (ie ears level) and anterior movement of the ear excludes LS [but photo looks like ipsi anterior movement in LS – is it contralat in PP??? No mention of anterior bossing, not obvious in photo].

German study – all LS cases obvious clinically. Where positional plagiocephaly was doubted, USS demonstrated patent sutures.

[Arch Dis Child 2015;100:152-157 doi:10.1136/archdischild-2014-305944]

Monitoring

Measure the oblique diameter left (ODL) and oblique diameter right (ODR) lines are drawn from points located 40° either side of the antero-posterior (AP) line. 40° is typically where deformation most notable.  Express as difference (the Oblique diameter difference (ODD) = ODL−ODR) or else ratio between the ODL and the ODR (oblique diameter difference index, or ODDI).

[European Journal of Pediatrics March 2006, Volume 165, Issue 3, pp 149-157]

Treatment

Dutch RCT of 6 months of helmet therapy (n=84 infants aged 5 to 6 months with moderate to severe skull deformation, exclusions were prems, muscular torticollis, craniosynostosis, or dysmorphic features). Full recovery was achieved in 10 of 39 (26%) participants in the helmet therapy group and 9 of 40 (23%) participants in the natural course group (odds ratio 1.2, 95% confidence interval 0.4 to 3.3, P=0.74). All parents reported one or more side effects.

[van Wijk RM BMJ 2014; 348 (); g2741]

Some evidence for bedding pillows (but SUDI risk?) and stretching exercises.

Haemangiomata

Clinical, Common, Dermatology, General paediatrics

2018 classification (ISVVA.org) – rather functional and lacking in poetry!

Basically benign tumours, involving blood vessels.  Seen in 12% of all infants  – more common in girls, whites, premature infants, twins and are babies born to mothers of higher maternal age!  Mostly seen in head and neck region, including the face, but can be anywhere.

Tumours distinguished from malformations.

Infantile Haemangioma

Cutaneous/mucosal haemangiomata usually develop after birth, appearing in the first 8 weeks of life.  They then develop and grow for 6-12 months, often resembling a strawberry.  Most then start to reduce and fade gradually, although it can take up to 9 years.   Often there will be complete disappearance with no cosmetic defect, but there may well be scarring, telangiectasia, or loose fibro-fatty tissue.

Can be further differentiated by depth (superficial tend to be raised and bright red, deep are generally darker red or even purple/blue, they can also be mixed) and extent/pattern (focal or segmental).

Typically they are in the skin and soft tissues, but can sometimes affect the liver or airways.  Associated with GLUT-1 positive staining on biopsy.

Congenital Haemangioma

Much less common. Present at birth and do not progress, although they may grow proportionally with child.  Oval or round, plaques or exophytic.  Some rapidly involute during the first year of life but otherwise they are permanent.

Vascular malformations

Grow slowly compared with vascular tumours.  Usually present at birth but perhaps inconspicuous until child grows.  Can involve arteries, veins, lymphatics in various combinations.

Capillary malformations most common – dilated capillaries, classic port wine stain (naevus flammeus).  Darken over time, do not regress.  Can be associated with bone or soft tissue overgrowth. Multiple can be associated with underlying AVM!

Nevus simplex is the classic “stork bite” at the nape, eyelid or forehead at birth. Lighter, regress.

Venous malformation more ill defined, bluish, easily compressible.  Multifocal tend to be autosomal dominant.  Some syndromes eg Blue rubber bleb naevus syndrome (widespread, including palms/soles).

Lympoedema and cystic hygroma are the lymphatic versions.

Others

  • Pyogenic granuloma – reaction to trauma, well demarcated, raised or even pedunculate
  • Telangiectasia eg Hereditary haemorrhagic telangiectasia (HHT)
  • Angiokeratoma – characteristic of tubersclerosis
  • PHACE syndrome (post fossa malformations, haemangiomata, arterial anomalies, cardiovascular defects, eye anomalies – but also midline defects)
  • Tufted angioma and Kaposiform haemangioendothelioma – similar histologically, but latter bruised, purpuric appearance, infiltrate into muscle/adipose tissue and associated with Kasabach-Merritt syndrome (consumptive coagulopathy).
[Seminar intervent radiol 2017][Ped dermatology 2016]