Part 2 of Medically Unexplained Symptoms this month. Also antibiotics in cystitis, too many investigations in community acquired pneumonia, carotenaemia and heart murmurs in unwell children. Do leave comments below:
NICE on Lyme disease this month – just in time for the weather to pick up and the tics to start biting. Also a reminder on the risk factors for SIDS, what to do in a terrorist attack, how to manage a child with a non-blanching rash and a discussion on the use of the antistreptolysin O titre. Do leave comments below:
MCV- Mean Corpuscular Volume. (with thanks to Dr Xanna Briscoe and Prof Irene Roberts)
A measure of the size of the red blood cells.
Raised MCV- macrocytosis– may occur with or without anaemia. Physiological macrocytosis in the absence of anaemia occurs in neonates, especially those with Down syndrome, and during pregnancy.
Macrocytic anaemia- may be secondary to nutritional deficiencies in B12 and Folate leading to ineffective or abnormal erythropoiesis. This is easily diagnosed using simple blood tests. Where deficiency is excluded bone marrow examination may be required to identify rare causes such as myelodysplasia or Fanconi anaemia.
There are several drugs that may lead to macrocytosis, some of which are commonly used in the paediatric population. These include several chemotherapeutic agents, antibiotics and antiviral medications. It is also seen in congenital heart disease, hypothyroidism and Down Syndrome.
Additional investigations- guided by the history. It is important to check a reticulocyte count if a macrocytic anaemia is discovered. Reticulocytes are immature erythrocytes- which are large, and indicate increased erythropoiesis. Chronic reticulocytosis may falsely elevate the MCV. The absence of a raised reticulocyte count in the presence of severe anaemia suggests an inability of the bone marrow to produce red cells, eg due to inherited or acquired red cell aplasia.
Kaferle, Joyce, and Cheryl E. Strzoda. “Evaluation of macrocytosis.” American family physician 79.3 (2009).
Microcytosis– small red blood cells. Typically seen in iron deficiency anaemia; in the paediatric population at different ages the cause differs. In younger children and toddlers lack of supplementation may lead to deficiency. This is a particular issue in those that drink large volumes of cows milk as a substitute for iron containing foods. The main differential diagnosis is beta- or alpha-thalassaemia trait. Measurement of serum ferritin is the most useful test to identify iron deficiency- this will be low in iron deficiency and normal in beta- or alpha-thalassaemia trait.
In adolescence the pubertal growth spurt, and menorrhagia may be a causative factor. Further investigation will aid in determining the causes of microcytic anaemia (see below).
W Owen Uprichard, James Uprichard. Investigating microcytic anaemia. BMJ 2013;346:f3154
As published in April 2017 Paediatric Pearls newsletter…..
|Increased MCV (macrocytosis)||Decreased MCV (microcytosis)|
|Vitamin B12 DeficiencyFolic Acid DeficiencyAlcohol Abuse
|Iron Deficiency AnemiaThalassemiaHemoglobinopathy
Anemia of Chronic Disease
Chronic Renal Failure
MCV is expressed in femtoliters = 10^-15 liters
MCV cutoffs vary by age and by lab reference
MCV Normal Range:
- Newborn: 95 to 121 fl
- Ages 6 months to 2 years: 70 to 86 fl
- Ages 12 to 18 years
- Boys: 78 – 98
- Girls: 78 – 102
- Age over 18 years: 78 to 98 fl
MCV Cutoffs for Microcytic Anemia:
- Age 1-2 years: <77 fl (CDC)
- Age 3-5 years: <79 fl (CDC)
- Age 6-11 years: <80 fl (CDC)
- Age 12-15 years: <82 fl (CDC)
- Age >15 years: <85 fl (CDC)
- Recommended adult microcytic MCV cutoff varies
Some sources advocate MCV <78 and others <82
So, you’ve got the FBC back and it shows microcytic anaemia. How can you work out which of the above factors is causative?
If you only asked for FBC and the child is more than 6 months old, try this:
|Anaemia of chronic disease||Thal trait (alpha OR beta)||Iron deficiency anaemia||Thal trait + IDA||Haemoglobinopathy|
|Hb||↓||N / ↓||↓ / ↓↓||↓ / ↓↓||↓ or ↑|
|MCV||N / ↓||↓ / ↓↓||↓ / ↓↓||↓ / ↓↓||↓ or ↑|
|MCH||N / ↓||↓ / ↓↓||↓ / ↓↓||↓ / ↓↓||↓ or ↑|
|RBC||↓||N/↑||N / ↓||N / ||↓ or ↑|
|RDW||N||N||↑||↑||↓ or ↑|
Therefore a child of 6 months or older with hypochromic, microcytic anaemia with an increased RDW has presumed iron deficiency. They could have thalassaemia trait as well….
If you asked for other tests or are at liberty to repeat the blood test, here are some suggested extra investigations and their interpretation:
|Investigation||Iron deficiency anaemia||Thalassaemia trait||Sideroblastic anaemia||Chronic disease|
|Hb electropheresis||normal||Β thalassaemia- raised A2
α trait- normal
Part 2 of “Decoding the full blood count” with thanks to Dr Alexandra Briscoe, paediatric registrar at Whipps Cross University Hospital, and Professor Irene Roberts, professor of paediatric haematology at Oxford.
Haematocrit/packed cell volume
Haematocrit/ packed cell volume- the proportion of blood that is made up of cells (not plasma); it is measured as a percentage or fraction.
Low haematocrit is seen in anaemia, though it will not tell you the direct cause for the anaemia.
Raised haematocrit is seen in polycythaemia, in the newborn infant this is termed Neonatal Polycythaemia.
Defined as a venous haematocrit > 65%, occurring in 0.4-5% of healthy newborns. Symptoms are believed to be due to hyperviscosity. On examination children appear plethoric, and may have multi-systemic symptoms. These include- CNS features of irritability, cerebrovascular accidents and seizures. Apnoea and respiratory distress occur as a result of decreased pulmonary blood flow. In addition infants may demonstrate poor feeding, and may in rare cases develop necrotising enterocolitis (NEC.) Renal effects include renal vein thrombosis, oliguria, proteinuria and haematuria. Hypoglycaemia and thrombocytopenia (Vlug, 2013) are also seen commonly.
The development of polycythaemia occurs secondary to increased erythropoiesis as a consequence of chronic fetal hypoxia. IUGR and placental insufficiency- due to post-dates pregnancies, pre-eclampsia and maternal smoking, increase the incidence of polycythaemia. Infants of diabetic mothers, those with Beckwith –Weidemann, and congenital thyrotoxicosis are also at increased risk.
There has been much debate as to whether delayed cord clamping increases the incidence of polycythaemia. Current NICE guidelines recommend cord clamping between 1-5 minutes after delivery, provided there is no concern regarding the infant’s heart rate or need for resuscitation. In a Cochrane review of cord clamping practices and neonatal outcomes in 2013 McDonald et al found that delayed cord clamping was associated with increased risk of jaundice requiring phototherapy, however beneficial outcome in terms of iron stores- with a 50% reduction in iron deficiency at 3-6 months. They reported no difference in incidence of polycythaemia in 5 trials measuring this outcome.
Current management of symptomatic polycythaemia is a partial exchange transfusion.
Vlug RD, Lopriore E, Janssen M, et al. Thrombocytopenia in neonates with polycythemia: incidence, risk factors and clinical outcome. Expert Rev Hematol. 2015 Feb. 8 (1):123-9. [Medline].
ID: CD004074 McDonald, Susan J, Middleton, Philippa, Dowswell, Therese Morris, Peter S
Effect of timing of umbilical cord clamping of term infants on maternal and neonatal outcomes
Cochrane Database of Systematic Reviews 2013
What are normal haematocrit levels?
(taken from http://www.medicinenet.com/hematocrit/page2.htm)
The normal ranges for haematocrit depend on the age and, after adolescence, the sex of the individual. The normal ranges are:
- Newborns: 55% to 68%
- One (1) week of age: 47% to 65%
- One (1) month of age: 37% to 49%
- Three (3) months of age: 30% to 36%
- One (1) year of age: 29% to 41%
- Ten (10) years of age: 36% to 40%
- Adult males: 42% to 54%
- Adult women: 38% to 46%
These values may vary slightly among different laboratories.
Vitamin D deficiency in children with thanks to Dr Jini Haldar, paediatric registrar at Whipps Cross University Hospital.
Vitamin D is an essential nutrient needed for healthy bones, and to control the amount of calcium in our blood. There is recent evidence that it may prevent many other diseases. There are many different recommendations for the prevention, detection and treatment of Vitamin D deficiency in the UK. The one outlined below is what we tend to do at Whipps Cross Hospital.
The Department of Health and the Chief Medical Officers recommend a dose of 7-8.5 micrograms (approx. 300 units) for all children from six months to five years of age. This is the dose that the NHS ‘Healthy Start’ vitamin drops provide. The British Paediatric and Adolescent Bone Group’s recommendation is that exclusively breastfed infants receive Vitamin D supplements from soon after birth. Adverse effects of Vitamin D overdose are rare but care should be taken with multivitamin preparations as Vitamin A toxicity is a concern. Multivitamin preparations often contain a surprisingly low dose of Vitamin D.
Indications for measurement of vitamin D
1. Symptoms and signs of rickets/osteomalacia
- Progressive bowing deformity of legs
- Waddling gait
- Abnormal knock knee deformity (intermalleolar distance > 5 cm)
- Swelling of wrists and costochondral junctions (rachitic rosary)
- Prolonged bone pain (>3 months duration)
2. Symptoms and signs of muscle weakness
- Cardiomyopathy in an infant
- Delayed walking
- Difficulty climbing stairs
3. Abnormal bone profile or x-rays
- Low plasma calcium or phosphate
- Raised alkaline phosphatase
- Osteopenia or changes of rickets on x-ray
- Pathological fractures
4. Disorders impacting on vitamin D metabolism
- Chronic renal failure
- Chronic liver disease
- Malabsorption syndromes, for example, cystic fibrosis, Crohn’s disease, coeliac disease
- Older anticonvulsants, for example, phenobarbitone, phenytoin, carbamazepine
5. Children with bone disease in whom correcting vitamin D deficiency prior to specific treatment would be indicated:
- Osteogenesis imperfecta
- Idiopathic juvenile osteoporosis
- Osteoporosis secondary to glucocorticoids, inflammatory disorders, immobility
Symptoms and signs in children of vitamin D deficiency
1. Infants: Seizures, tetany and cardiomyopathy
2. Children: Aches and pains: myopathy causing delayed walking; rickets with bowed legs, knock knees, poor growth and muscle weakness
3. Adolescents: Aches and pains, muscle weakness, bone changes of rickets or osteomalacia
Risk factors for reduced vitamin D levels include:
- Dark/pigmented skin colour e.g. black, Asian populations
- Routine use of sun protection factor 15 and above as this blocks 99% of vitamin D synthesis
- Reduced skin exposure e.g. for cultural reasons (clothing)
- Latitude (In the UK, there is no radiation of appropriate wavelength between October and March)
- Chronic ill health with prolonged hospital admissions e.g. oncology patients
- Children and adolescents with disabilities which limit the time they spend outside
- Institutionalised individuals
- Photosensitive skin conditions
- Reduced vitamin D intake
- Maternal vitamin D deficiency
- Infants that are exclusively breast fed
- Dietary habits – low intake of foods containing vitamin D
- Abnormal vitamin D metabolism, abnormal gut function, malabsorption or short bowel syndrome
- Chronic liver or renal disease
Management depends on the patient’s characteristics:
A. No risk factors
No investigations, lifestyle advice* and consider prevention of risk factors
B. Risk Factors Only
1. Children under the age of 5 years: Lifestyle advice* and vitamin D supplementation.
Purchase OTC or via Healthy Start
Under 1 year: 200 units vitamin D once daily
1 – 4 years: 400 units vitamin D once daily
2. Children 5 years and over – offer lifestyle advice*
C. Risk Factors AND Symptoms, Signs
- Renal function, Calcium, Phosphate, Magnesium (infants), alkaline phosphatase,
- 25-OH Vitamin D levels, Urea and electrolytes, parathyroid hormone
Children can be managed in Primary Care as long as:
- No significant renal impairment
- Normal calcium (If <2.1 mmol/l in infants, refer as there is a risk of seizures)
If further assessment is required consider referral to specialist. **
Patient’s family is likely to have similar risk of Vitamin D deficiency – consider investigation ant treatment if necessary.
*Life style advice
Exposure of face, arms and legs for 5-10 mins (15-25 mins if dark pigmented skin) would provide good source of Vitamin D. In the UK April to September between 11am and 3pm will provide the best source of UVB. Application of sunscreen will reduce the Vitamin D synthesis by >95%. Advise to avoid sunscreen for the first 20-30 minutes of sunlight exposure. Persons wearing traditional black clothing can be advised to have sunlight exposure of face, arms and legs in the privacy of their garden.
Vitamin D can be obtained from dietary sources (salmon, mackerel, tuna, egg yolk), fortified foods (cow, soy or rice milk) and supplements. There are no plant sources that provide a significant amount of Vitamin D naturally.
**Criteria for referral
- Criteria for management in primary care not met
- Deficiency established with absence of known risk factors
- Atypical biochemistry (persistent hypophosphatemia, elevated creatinine)
- Failure to reduce alkaline phosphatase levels within 3 months
- Family history (parent, siblings) with severe rickets
- Infants under one month with calcium <2.1mmmol/l at diagnosis as risk of seizure. (Check vitamin D level of mothers in this group immediately and treat, particularly if breast feeding.)
- If compliance issues are anticipated or encountered during treatment.
- Satisfactory levels of vitamin D not achieved after initial treatment.
Vitamin D levels, effects on health and management of deficiency
|< 25 nmol/l (10micrograms/l)||Deficient. Associated with rickets, osteomalacia||Treat with high dose vitamin D
Lifestyle advice AND vitamin D (ideally cholecalciferol)
• 0 – 6 months: 3,000 units daily
• 6 months – 12 yrs: 6,000 units daily
• 12 – 18 yrs: 10,000 units daily
|vitamin D 25 – 50 nmol/l (10 – 20micrograms/l||Insufficient and associated with disease risk||Over the counter (OTC) Vitamin D supplementation (and maintenance therapy following treatment for deficiency) should be sufficient.
• Lifestyle advice and vitamin D supplementation
< 6 months: 200 – 400 units daily (200 units may be inadequate for breastfed babies)
Over 6 months – 18 years: 400 – 800 units daily
|50 – 75 nmol/l (20 – 30micrograms/l)||Adequate||Healthy Lifestyle advice|
|> 75 nmol/l (30 micrograms/l)||Optimal Healthy||None|
Course length is 8 – 12 weeks followed by maintenance therapy.
Checking of levels again
As Vitamin D has a relatively long half-life levels will take approximately 6 months to reach a steady state after a loading dose or on maintenance therapy. Check serum calcium levels at 3 months and 6 months, and 25 – OHD repeat at 6 months. Review the need for maintenance treatment. NB: the Barts Health management protocol uses lower treatment doses for a minimum of 3 months and then there is no need for repeat blood tests in the majority of cases of children satisfying the criteria for management in primary care.
Serum 25 OHD after 3 months treatment Action
|>80nmol/ml||Recommend OTC prophylaxis and lifestyle advice||as required|
|50 – 80 nmol/mL||Continue with current treatment dose||reassess in 3 months|
|< 50 nmol/mL||Increase dose or, in case of non-adherence/concern refer to secondary care.|
It is essential to check the child has a sufficient dietary calcium intake and that a maintenance vitamin D dose follows the treatment dose and is continued long term.
Some recommend a clinical review a month after treatment starts, asking to see all vitamin and drug bottles. A blood test can be repeated then, if it is not clear that sufficient vitamin has been taken.
Current advice for children who have had symptomatic Vitamin D deficiency is that they continue a maintenance prevention dose at least until they stop growing. Dosing regimens vary and clinical evidence is weak in this area. The RCPCH has called for research to be conducted. The RCPCH advice on vitamin D is at http://www.rcpch.ac.uk/system/files/protected/page/vitdguidancedraftspreads%20FINAL%20for%20website.pdf
Article by Dr Hajera Sheikh, paediatric registrar
Assessment in Secondary Care
• Lifestyle Assessment
• Menstrual History
• Obstructive Sleep Apnoea: Snoring, difficulty breathing during sleep, morning headaches or fatigue
• Symptoms of co-morbidity including psychological
• Drug use (particularly glucocorticoids and atypical antipsychotics)
• Family history, particularly diabetes <40 yrs, early heart disease <60 yrs
• Height, weight, BMI
• Obesity pattern: generalised, central (greater risk of adverse cardiovascular outcomes), buffalo hump and neck (may be suggestive of Cushing syndrome)
• Blood pressure
• Pubertal assessment
• Acanthosis nigricans (indicative of insulin resistance, first seen round neck and axillae)
• Signs of endocrinopathy
• Dysmorphisms: (Look out for early onset obesity, learning difficulties, deafness, epilepsy, retinitis, dysmorphic features, hypogonadism)
• Thyroid function
• Fasting lipids (total and HDL cholesterol), triglycerides
• Liver function, including ALT
• Fasting glucose and insulin not usually done first line
Refer to Paediatric Obesity/Endocrinology or other specialist service if further investigation is required
• Genetic studies
• Thyroid studies: T3, thyroid antibodies, calcium, phosphate
• Cushing syndrome investigations
• Oral glucose test
• PCOS studies (LH, FSH, adrenal androgens, Sex Hormone Binding Globulin, prolactin, pelvic ultrasound)
• Sleep Study
Dysmorphic and monogenic syndromes associated with obesity:
Main clinical obesity associated syndromes:
• Autosomal dominant
Biemond syndrome (some cases)
• Autosomal recessive
Biemond Syndrome(some cases)
• X-linked inheritance
• Single gene lesions affecting leptin metaboilsm
Congenital leptin deficiency
Leptin receptor mutation
Prohormone convertase 1 mutation
Melanocortin 4 mutation
Clinical features suggesting obesity may be secondary to another condition or syndrome
• Severe unremitting obesity
• Disorders of the eyes
Retinal problems, especially retinitis pigmentosa
Narrow palpebral fissures
Abnormally positioned palpebral fissures
Severe squint (eg Prader-Willi)
• Skeletal abnormalities
• Sensorineural deafness (eg Alstrom syndrome: sensorineural deafness, diabetes mellitus, retinal dystrophy, obesity)
• Microcephaly and/or abnormally shaped skull
• Mental retardation
• Renal abnormalities
• Cardiac abnormalities
Neglect and emotional abuse is the safeguarding topic this month. ED advice on the management of minor head injuries, a report from BPSU in hypocalcaemic fits secondary to vitamin D deficiency, the new UK immunisation poster and a bit on crying babies. Hope you find it all helpful. Comments welcome below
Allergy – notes from a recent allergy update course with thanks to Dr Su Li, paediatric consultant @ Whipps Cross.
www.allergyuk.org – good factsheets on rhinitis, oral allergy syndrome etc.
www.itchysneezywheezy.co.uk is a collaborative project for patients, their parents and health professionals on all aspects of atopic illness.
RCPCH allergy care pathways for health professionals (eczema, anaphylaxis, urticaria, mastocytosis, food, drug and venom allergies etc. etc.)
www.bsaci.org (stores patient management guidelines and has recently been accredited by NICE – milk, nut and penicillin allergy guidelines all currently in progress)
How to make a diagnosis:
1. Allergy focussed clinical history
2. Allergy tests – tests look at sensitisation not clinical allergy, defines probability of allergy
Skin prick tests
Provocation tests / food challenge
IgE ranges :
|< 0.35||Grade 0|
|0.35 – 0.7||Grade 1|
|0.7 – 3.5||Grade 2|
|3.5 – 17.5||Grade 3|
|17.5 – 50||Grade 4|
|50 – 100||Grade 5|
|> 100||Grade 6|
Test equivalence :
|Skin prick||< 3 mm||3-7 mm||>7 mm|
|IgE||< 0.35||0.35 – 50||> 50|
Probability of allergy :
|< 3 mm||3-7 mm||> 7 mm|
|High clinical suspicion||Possible allergy||Probably allergy||Allergic|
|50:50||Possible allergy||Possible allergy||Probably allergy|
|Low clinical suspicion||Not allergic||Possible allergy||Possible allergy|
If ‘possible allergy’ consider food challenge.
- Your risk of anaphylaxis to peanut is 1% per year if you have a nut allergy.
- If you have had anaphylactic reaction, your risk increases to 5% per year, therefore always prescribe Adrenaline Autoinjector (EpiPen).
- The degree of positivity of a test does not change the risk of anaphylaxis.
- Your risk of having a peanut allergy is 8 times more if you have a sibling with a nut allergy – consider screening siblings.
- Common allergens associated with eczema are egg, peanut and cows milk.
- If you are allergic to egg, consider testing for the peanut and milk as they often co-exist
- Egg exclusion diets can improve eczema symptoms however there is an increased risk of anaphylaxis if you come into contact with egg whilst on an
- Consider a food challenge after 1 year as egg allergies often resolve.
Cows Milk Protein Intolerance:
- This is a non IgE mediated disease, allergy testing will be negative.
- Typical symptoms tend to be eczema or GI upset including reflux, vomiting, ‘colic’, constipation, loose stools, blood and mucous in stools.
- Management includes a 2-4 week trial of extensively hydrolysed formula (Nutramigen / Peptijunior) or amino acid formula (Nutramigen AA / Neocate).
- If breastfeeding, mothers need to go onto an exclusion diet (including soya).
- Do not use over the counter partially hydrolysed formula milks, these still contain cows milk protein.
- Refer to a dietician if on an exclusion diet.
- Consider diagnosis of FPIES (food protein intolerance enteropathy syndrome).
- Cows milk protein intolerance usually resolves around 14 months of age.
- At this age, introduce soya milk first. If well tolerated, introduce cows milk.