DTaP (Diphtheria, Tetanus and Pertussis) (2, 3, 4 and 40-60 months)
Diphtheria is a toxoid vaccine, as is the tetanus component
Pertussis vaccine is made from highly purified selected (antigenic) components of the Bordatella pertussis organism
The vaccine is produced by treating with formaldehyde, to fix, and an adjuvant (e.g. aluminium phosphate or aluminium hydroxide) to increase its antigenicity
NB This vaccination does not prevent the transmission of the organisms concerned
There is a very small increased risk of febrile seizure after the DTaP BUT NO INCREASED RISK OF EPILEPSY
If a patient has a full blown seizure after the first/second vaccination, it is a reasonable contraindication for further DTaP vaccinations
IPV (inactivated polio vaccine) (3, 4 and 40-60 months)
Also called the Salk vaccine
Contains inactivated strains of polioviruses 1-3.
The inactivated vaccine carries no risk of causing vaccine associated paralytic polio (of which there is a tiny risk using the oral polio vaccine)
However, it doesn’t effectively induce immune sensitisation in the gut, and so is less effective at protecting against wild-type polio which can be introduced in the GI tract
NB The OPV is more effective and more widely used in outbreaks/epidemics of polio (this includes vaccination of contacts of polio). However, the OPV should not be given to immunodeficient patients at risk of the disease.
NB This vaccine does not prevent transmission of the virus
Hib (Haemophilus influenzae type B) (2, 3, 4 and 12-13 months)
Composed of capsular polysaccharide from cultured H Influenzae type B bacteria, conjugated to protein.
The efficacy is around 94-100% and the vaccine also reduces nasopharyngeal carriage and therefore confers herd immunity.
Pneumococcal Conjugate Vaccine (PCV) (2, 4 and 12-13 months)
Composed of purified capsular polysaccharide from 13 types of pneumococcus conjugated to an antigenic protein combined again with adjuvant
NB This is not the same as the adult pneumococcal vaccine, which contains polysaccharide from 23 strains, but does not have them bound to protein (and thus, in young children <2, it does not induce an immune response)
Occasionally children may feel a bit unwell for a day or two after the vaccination. This should settle and advice is for antipyretics, fluids and rest as required
Rotavirus vaccine (2 and 3 months)
Attenuated live vaccine against rotavirus
Small risk of intussusception (look out for unwell, tummy ache, vomiting, and abnormal ‘redcurrent jelly’ stools:- emergency)
More commonly children feel a bit unwell, and occasionally diarrhoea
Meningitis C vaccine (3, 12-13 months and 12-18 years)
Comes as part of the Hib/MenC conjugate vaccination- inactivated vaccine
Very effective (95%)
Can cause fever and vomiting in a minority (again, supportive care until this resolves)
Very rarely, the MenC vaccine can be associated with fainting, seizures and numbness/hypotonia
Mumps, Measles and Rubella vaccine (12-13 months and 40-60 months)
Attenuated live vaccine containing all three viruses. It does not contain any thiomersal or other preservatives.
Very effective against rubella (95%); effective in measles (~90%) and mumps (80-90%)
It is not uncommon for the child to feel unwell, mild fever, vomiting/diarrhoea a week or so after the vaccination (local reaction is also common as with other vaccinations)
It is rare to cause anything else (occasionally febrile seizures)
Although there is a technical risk of meningitis given the vaccine is live, this has only been shown to occur in several cases traced to one strain in Finland- never in UK)
NB Whilst the MMR contains traces of egg, it has not been shown to be significant to cause reactions in children who are allergic (i.e. safe)
A note about MMR and autism. After much research, no significant evidence has been produced that supports a link between MMR and autism. It is ultimately the parents’ decision as to whether their child receives a vaccination. As a doctor, you may present them with the information they need to make an informed decision, and you should respect their wishes.
HPV (12-13 years in girls)
Contain virus-like particles for HPV virus strains
Note that the vaccine offered in the UK contains VLPs for HPV types 16 and 18, which cause over 70% of all cervical cancers
There is also a quadrivalent vaccine which covers types 6 and 11 also
There is no risk of catching warts/cancer from the vaccine, and side effects (other than local reactions) are rare.
The vaccine is very effective (99% at preventing lesions)
Initially, there was some controversy over the age at which girls were being offered this vaccine (some parents felt that, because this was essentially a sexually transmitted disease, this was too young).
It is important to reassure parents that girls should be vaccinated before sexual activity- and that the option of later vaccination is possible should this be requested.
Counselling parents about vaccinations
In general, most parents will be happy for their child to receive vaccinations and will have questions about what to expect after (and any potential side effects)
If a parent has specific concerns:
Listen to the concern in full; it is a good idea to wait to the end of this and explain the vaccination in full afterwards, paying attention to the concerns, before answering any questions at the end (avoids repeating/confusing)
It is a good idea to explain that vaccines are continually being monitored for safety; do explain the local and common side effect with all vaccines
Early response (type I immediate): Smooth muscle contraction/spasm in response to allergen (IgE mediated- mast cell degranulation and histamine release)
Occurs in all patients
Late response (type IV delayed): recruitment of eosinophils, neutrophils, Th2 lymphocytes and macrophages which release lipid mediators and cytokines e.g PGE2, IL-4/5; to cause bronchoconstriction, vascular congestion, mucosal oedema, mucus production and reduce mucociliary transport.
Eosinophil granules such as major basic protein and cationic protein (MBP and ECP, respectively) affect smooth muscle tone by increasing intracellular calcium concentrations and inhibiting muscarinic (inhibitory) receptors, and thus increasing resting tone and hypersensitivity
Hyperreactivity is thought to be as a result of hypertrophy of smooth muscle secondary to the inflammatory process (airway remodelling)
NB Hypersensitivity is a ‘quicker’ reaction; hyperreactivity is a ‘bigger’ reaction. Hyperresponsiveness is a mixture of both, as seen in asthma.
Presentation and Diagnosis
(According to SIGN/BTS guidelines)
Episodic respiratory symptoms (one or more of)
Wheeze (make sure to clarify what the patient/parent means by wheeze)
About things that will increase the likelihood of asthma:
Worse at night/early morning
Occur in response to a trigger e.g. exercise, pets, cold etc
Occur in response to taking aspirin or beta blockers
Occur separately/independently from colds/coughs (isolated coughs/colds are unlikely to be asthma-related)
Cough is usually non-productive. A productive cough is unlikely to be asthmatic. A chronic cough without wheeze is unlikely to be asthmatic
Personal/family history of atopy
Are there any triggers, e.g. temperature, exercise, allergy etc
If they are at school, ask whether they have to miss school/PE.
Other things that increase the likelihood of asthma
Widespread wheeze on auscultation
Improvement (in symptoms or lung function) with treatment (in children)
Otherwise unexplained low FEV1 or PEF or peripheral blood eosinophilia
In patients with a ‘high probability of asthma’ (based on above history/examination)- investigations are usually not required (straight to first-line management)
In patients with a ‘low probability’, consider a more detailed investigation, a different diagnosis or referral to a specialist
In patients with an ‘intermediate probability’, offer spirometry first line
FEV1 (Forced expiratory volume in 1 sec) may be reduced in asthma but is hugely dependent on build, fitness etc and is often unreliable in diagnosing asthma (serial FEV1 values are equally unhelpful)
Instead FEV1/FVC ratio may be more useful (decreased in obstructive disease)
Similarly, residual volume/total lung capacity ratios may be more useful
Reversibility testing(testing FEV1 after treatment)
Bronchodilator reversibility testing: before undertaking bronchodilator testing, the patient should stop short-acting beta2 agonists for 6 hours, long-acting bronchodilators for 12 hours and theophyllines for 24 hours. Administer bronchodilator (at least 400 micrograms salbutamol) and repeat spirometry after 15 minutes.
An increase of >400ml in FEV1 from baseline is suggestive of asthma
More commonly, a similar test can be done with steroid inhalers but over 2 weeks
NB If spirometry shows no evidence of obstruction/asthma, consider other tests e.g. allergy (skin prick) tests, tests for bronchial hyperresponsivity (using methacholine, exercise or mannitol)
Peak flow measurements may only be useful in demonstrating some obstruction but are otherwise not particularly reliable and so should be interpreted with caution
Allergen avoidance is not practical and lacking in evidence
Smoking cessation (parent and patient)
NB Patients should start at step 2 if
they have had exacerbations in the last two years
using SABA 3 times a week or more
Symptomatic 3 or more times a week
waking one night a week
If there is a suggestion of occupational (or exposure) asthma (e.g. better during weekends/holidays) poorly responding to step 1-3, consider referral to specialist early (rather than later) for peak flow diary
Causes of occupational asthma include
Isocyanates (most common e.g. spray painting, foam moulding using adhesives)
Coloured marks on the skin that are present from birth or develop shortly after birth.
Can generally be classified as either pigmented, vascular or other.
Congenital Melanocytic Naevus
Common (1-3%), caused by over-proliferated melanocytes.
Usually appear initially as flat, pigmented lesions at birth and may may raise and grow hair as it ages, although many remain flat patches which grow with the child. Can be small (<1.5cm), medium (<20cm), large (<40cm) or giant (>40cm)
There is a small risk of melanomatous development, particularly with larger and/or nodular/irregular lesions
The decision to excise the lesion may be taken in small lesions but may not be possible in large/giant lesions
Giant lesions may require recurrent shaving of the superficial layers and/or curettage
Excision may be done for cosmetic reasons, concern over cancer, changes, a difficult area to monitor e.g scalp, sole etc
Otherwise, reassurance is all that is required.
Cafe au lait Spot
Common (solitary macules can be found in up to 15% of the population).
Usually oval, light brown (milky-coffee) colour patches (>0.5cm)
If one is noticed, others should be looked for. >6 cafe au lait marks (as well as other signs e.g. axillary freckling and macules) requires referral for the possible diagnosis of neurofibromatosis type 1.
Mongolian Spot (Dermal melanocytosis)
Blue-gray patch of skin usually affecting the lumbar region/buttocks, usually a few centimetres but can be larger
Thought to be due to failure of migration of melanocytes and entrapment within the dermis.
Far more common in Asian/Eastern population (up to 90%)
Most will disappear by age 3-5, but dark/large lesions may persist indefinitely
Common (33% of newborns)- flat, ‘salmon-coloured’ lesions usually over the eyes, scalp and neck, and can be bilateral and symmetrical- caused by telangiectasias within the dermis.
Blanch when pressed
40% resolve in the neonatal period and most resolve by 18 months
Port-wine stain (Naevus Flammeus)
Less common than salmon-patches (~0.3% of newborns).
Usually large, flat patch of purple/dark red skin; well defined border; usually unilateral and commonly on the face (rarely does it occur on both sides of the body)
These don’t resolve spontaneous- usually become darker with age.
Though to be due to abnormal dilation of papillary dermal capillaries/venules (possibly due to deficiency in perivascular peripheral innervation)
Laser treatment can be used to try and lighten some naevi, although response is variable. Laser treatment is only really used in infants with large, disfiguring naevi as the treatment itself can be scarring.
Strawberry naevus (Haemangioma)
Benign lesion of proliferating vascular endothelial cells- very common (3-5% of babies, particularly premature, twin, white, female)
Can present at birth or up to a month post-natally, most occur on the head/neck
Most cause no symptoms or problems, but some may require removal depending on the site
Characterised by failure of B cell differentiation into plasma cells and defective interaction between T- and B-cells
Causing reduced levels of immunoglobulin (IgG and IgA > IgM > IgE)
Up to half of patients also have associated T-cell dysfunction
Selective IgA Deficiency
Most common (1/300-700) but often asymptomatic/undiagnosed (incidence based on blood samples)
IgA is found mainly in mucosal membranes and is thought to prevent bacteria from attaching to mucosal surfaces
Patients are at increased risk of allergies and autoimmune disease (atopy is common)
Patients commonly present with recurrent URTIs, including sinusitis, as well as GI infections
Although IgA < 5mg/dl; IgG can be normal and patients can often respond normally to vaccinations. However, patients can respond abnormally (e.g. anaphylaxis) to blood/blood product transfusions due to the presence of IgA
Caused by mutation/absence of Bruton’s tyrosine kinase (Btk) gene- important in cell signalling pathways involved in B-cell maturation (rare: 1/350000-400000)
Failure of maturation and absence (/minimal levels) of all immunoglobulin (IgG, IgA and IgM)
Often present in the first year of life with recurrent otitis media; pneumonia; and sinusitis BUT 20% of children can present later (3-5 years)
Disorders of Innate (+/- Humoral) Immunity
Usually more severe than isolated Ig/B-cell disorders, presenting earlier in life with failure to thrive and severe infections
Another syndrome which can manifest from several, usually genetic, disorders- characterised by recurrent, severe and opportunistic infections, failure to thrive and chronic diarrhoea presenting in the young infant (usually a few months after birth).
Other signs include rashes, hepatopathy, chest infections (interstitial pneumonia (cf lobar pneumonia), fungal infections
Fairly rare at 1/75-100,000. Almost half of cases are x-linked (far more common in males) and others are autosomal recessive (with Jak3 and ADA deficiency)
Most commonly caused by a defect in the γ-chain of the interleukin receptors (X-linked)
Can encompass a range of white cell abnormalities
Most cause a T-cell defect- usually completely absent. Many also affect B-cell and NK cell production. A severe lymphopenia is seen on FBC.
Patients often do not mount any immune response to vaccinations and so can get symptoms with certain vaccinations
Patients will require IVIg and should be considered for an emergency bone marrow transplant
Without treatment, infections will usually kill the patient before they are 2 years old.
X-linked recessive condition characterised by
Recurrent bacterial infections of the sinuses/lungs
Eczema (resembles atopic dermatitis)
Bleeding tendency due to thrombocytopenia and platelet dysfunction. This can be of the form of bloody diarrhoea, purpuric rash or excessive bruising.
NB These patients are also at risk of autoimmune conditions e.g. autoimmune haemolytic anaemia, vasculitides (inc glomerulonephritis); IBD etc as well as non-Hodgkins lymphoma
Typically presents in infants/toddlers
Caused by a defect of the WAS-protein gene, normal function of which is required for normal antibody, T-cell and platelet function
As a result, patients often have low IgG (often normal B-cells- IgM may be affected but this may be a sign of CVID or other syndrome- IgA and IgE may be elevated); low T cell count (particularly CD8+) and low/small platelets
Management should involve vaccinations and active management of any infections; may involve transfusions and/or stem cell transplant
Most patients survive well into their 20s/30s if treated conservatively. Stem cell transplant can almost cure this condition and lengthen life span to normal.
Disorders of Phagocytic immunity
Chronic Granulomatous Disease
CGD is a group of genetic syndromes in which phagocytes are unable to kill bacteria/fungi that have been ingested.
Usually caused by a defective gene encoding NADPH oxidase enzyme responsible for oxygen radical formation
Most commonly X-linked or autosomal recessive
Usually presents <2 with recurrent bacterial/fungal infections e.g. fungal pneumonia, skin abscesses/infections, lymphadenitis, diarrhoea
commonly with Aspergillus fumigatus; Candida albicans and Candida glabrata
Granulomas of the skin and GI tract can also be seen
Investigations include a phagocytic oxidase activity (Nitroblue tetrazolium- NBT- microscopy stain) test and genetic test
Management is usually prophylactic antibiotics and antifungals
Co-trimoxazole (Trimethoprim + Sulfamethoxazole- 5mg/kg/day based on trimethoprim) is often used because is reduces bacterial infection without increasing the risk of fungal infections
Itraconazole is also used
Interferon gamma may also be used to enhance immune function
Prednisolone may be used in moderate-severe granulomatous disease, particularly if causing GI symptoms
Acute infections should be managed as per case
Disorders of the Complement System
Variety of complement deficiencies- each with specific features. Patients may be at risk of immune complex deposition disorders e.g. SLE, as well as recurrent bacterial infection
When to suspect immunodeficiency
≥8 ear infections in a year
≥2 serious sinus infections in one year
≥2 episodes of pneumonia in one year
≥2 deep-seated or unusually located infections
Recurrent deep skin or organ abscesses
Need for IV antibiotics to clear infections
Infections with unusual or opportunistic organisms