Amaurosis Fugax

Transient and painless loss of vision in one eye.


  • Common clinical symptom of transient retinal ischaemia.
  • It can have a number of aetiologies but most commonly are cardiovascular.


  • Embolic
    • Carotid bifurcation thromboembolism
    • Cardiac emboli (e.g. mural, valvular)
    • Drug abuse-related vascular emboli
  • Haemodynamic
    • Atherosclerosis
    • Inflammatory arteritides
    • Hypoperfusion (e.g. cardiac failure, systemic diseases affected blood viscosity)
  • Ocular
    • Central retinal vein/artery occlusion
    • Retinal haemorrhage


  • Rapid onset of unilateral visual loss (10-15 seconds)
    • ‘Window-curtain’ development i.e. like a curtain being pulled over their eye
    • Lasting seconds-minutes
    • Clears slowly in the reverse direction from lost
  • It is important to evaluate for signs of TIA/stroke as well, e.g. hemiplegia/weakness, because patients will often be at risk of these events too.


  • FBC, ESR/PV may be done; may also want to do clotting/INR; ?lipid profile
  • Fluorescein angiography may help identify ophthalmic pathology


  • If thromboembolic, consider low-dose aspirin +/- statin

Anterior Ischaemic Optic Neuropathy


  • Ischaemia of the optic nerve can have several causes with differing severity.  They can be classified by cause and location depending on the symptoms and presentation.
    • Non-arteritic AION (around 5/100,000)
    • Arteritic AION (rarer- almost always associated with Giant cell arteritis)
  • Anterior ION affects the anterior 1mm segment of the optic nerve head- the optic disc. 
    • (Posterior ION can be due to any condition that causes ischaemia to any portion of the optic nerve posterior to the optic disc (i.e. will not cause disc oedema

Aetiology/Risk factory

  • Arteritic AION is almost always secondary to Giant cell arteritis (see here)
  • NAAION rarely occurs in isolation.  Risk factors include
    • Cardiovascular risk factors (hypertension, hyperlipidaemic, diabetes etc).  It is thought that inadequate perfusion of the optic disc is the main cause of ischaemia.  This could be made worse by
      • Small optic disc (increased vascular congestions
      • Dysregulation of blood flow to the optic disc (normally autoregulated but possibly altered by CVS risk factors)
        • Nocturnal hypotension- not uncommon in CVS patients- may worsen this
    • It is hypothesised that NAAION may not be caused (solely) by arterial factors, but by venous congestion, which would fit more with the symptoms and pathology (i.e. no haemorrhages etc)
    • Sleep apnoea syndrome has been linked with NAAION (? nocturnal increases in BP and subsequent optic disc vascular dysregulation)
    • Medications e.g. interferon alpha (? immune complex deposition in capillaries of the optic disc) NB No proven link


  • Acute (hours-days), painless unilateral visual loss
    • Blurring/clouding (rarely complete- if so consider alternative diagnosis)
    • Often central/inferiorly
    • Often on wakening
  • Rarely accompanying pain but headache/periocular pain may be present in 10% (consider also optic neuritis)
  • On examination
    • Most patients don’t have complete visual loss and on acuity examination, most will be between 20/64 and 20/200.
    • Colour loss can be present- often proportionate to visual acuity loss.
    • Pupils should be equal and round.  A relative afferent pupillary defect will be present (as long as other eye is normal)
    • Optic disc oedema is always present.  Often hyperaemic in NAAION and pallid in AAION; segmental (inferiorly more common)
    • Peripapillary splinter haemorrhages are common (cf uncommon in optic neuritis)
      • IndianJOphthalmol_2011_59_2_123_77024_f7
    • Retinal arterioles may show narrowings in the peripapillary region too


  • FBC, CRP and ESR/PV can be done to exclude/include GCA as a potential cause (this is very important as GCA can cause acute blindness- URGENT)
  • Otherwise NAAION is a clinical diagnosis


  • If GCA is found, treat with steroids
  • If NAAION is the diagnosis, unfortunately there is no treatment
    • Most patients’ vision will stabilise within several months, some will recover (20-40%, younger patients more likely), most will remain constant, others will deteriorate further

Childhood Immunisations


About the vaccines

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


Clinical diagnosis characterised by acute and reversible obstruction of the airways caused by inflammation, most commonly secondary to an abnormal hypersensitivity of the bronchioles.


  • Most common respiratory disease and chronic disease of childhood: around 1 in 11 (1.1 million) children in the UK are receiving treatment (thought that 1 in 12 adults are being treated)
  • Acute attacks can be life-threatening
  • Note that many patients ‘grow-out’ their asthma symptoms and are not receiving active treatment but rather have a past history of the condition.

Risk Factors

  • Personal or family history of atopy (hayfever, asthma, eczema)
  • Inner city environment and socio-economic deprivation
  • Prematurity, low birth weight, viral infections in early childhood (particularly rhinovirus)
  • Maternal smoking, smoking environment or smoking personally


Consists of a triad of features:

  1. Airway Inflammation
    1. Inflammation is a feature consistent in all forms of asthma
    2. section2f2-3
      Inhaled antigens are recognised by IgE antibodies which activate mast cells and recruit T-helper (type 2) cells in the airway, which then produce inflammatory mediators such as histamine and leukotrienes) and cytokines (including IL-4 and IL-5). These cytokines cause the differentiation and production of eosinophils.
      Eosinophils migrate to the airway via binding of integrins to vascular cell-adhesion molecule (VCAM) and intercellular adhesion molecule (ICAM). These produce more inflammatory mediators.

      It is possible that the inflammation also causes the over-production of IgE and further hyperresponsiveness of the airways in allergic/atopic cases

  2. Airflow Obstruction/Bronchoconstriction & Airway Oedema
    1. Early response (type I immediate): Smooth muscle contraction/spasm in response to allergen (IgE mediated- mast cell degranulation and histamine release)
      1. Occurs in all patients
    2. 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.
  3. Bronchial Hyperresponsiveness
    1. 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
    2. Hyperreactivity is thought to be as a result of hypertrophy of smooth muscle secondary to the inflammatory process (airway remodelling)
      1. 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)
    • Cough
    • Difficulty breathing
    • Chest tightness
  • Particularly ask:
    • About things that will increase the likelihood of asthma:
      • Frequent/Recurrent attacks
      • 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
  • Features that decrease the likelihood of asthma
    • Prominent dizziness, light headedness, peripheral tingling
    • Chronic productive cough in the absence of wheeze or breathlessness
    • Repeated normal chest examination during exacerbation
    • Voice disturbance
    • Symptoms with colds/URTIs only
    • Significant smoking history (>20 pack years)
    • Cardiac disease
    • Normal PEF or spirometry when symptomatic

On Examination

  • Widespread wheeze is the key feature of asthma patients.
    • Other signs may include increased work of breathing (intercostal recession, cyanosis, increased respiratory rate etc)
  • Stridor, focal signs, failure to thrive, productive cough etc- are NOT signs of asthma and thus should be assessed appropriatedly

Differential Diagnosis

Cystic Fibrosis; Bronchopulmonary dysplasia; Ciliary dyskinesia; Aspiration (consider if vomiting/swallowing difficulty)/inhaled foreign body; Panic attacks; Tracheo/laryngeal disorders; immunocomprimisation; chest infection 


  • 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


  • Non-pharmacological
    • Allergen avoidance is not practical and lacking in evidence
    • Smoking cessation (parent and patient)
  • Pharmacological
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    • 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)
        • Platinum salts
        • Soldering flux resin
        • Glutaraldehyde
        • Flour
        • Epoxy resins
        • Proteolytic enzymes

For Notes on Acute Asthma attacks see here

Leukotriene receptor antagonists e.g. Montelukast

  • have both anti-inflammatory and bronchodilatory properties
  • should be used when patients are poorly controlled on high-dose inhaled corticosteroids and a long acting beta-2 agonist
  • Particularly useful in Aspirin-induced asthma
  • Associated with the development of Churg-Strauss syndrome

Birth Marks

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.

Pigmented Birthmarks

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)

DCF 1.0

  • 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
  • DO NOT CONFUSE WITH BRUISING (and vice versa)

Vascular Birthmarks

Stork Bite/Salmon Patch/Angel Kisses (Naevus Simplex)


  • 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
    • Propanolol may also be used (as can steroids)
    • BUT most regress completely within a few years.


Primary immunodeficiencies are genetic/congenital abnormalities of the immune system whilst secondary immunodeficiencies are acquired.


  • There are many primary immunodeficiency disorders- most are inherited genetic disorders and are very rare (symptomatic cases: 1/10000).  Most present in childhood and most present in males (X-linked).


  • Can be classified as disorders of immune systems:
    • B-cell and Immunoglobulin system- Mainly antibody deficiencies which account for the majority (50%) of cases
      • e.g. Common variable immunodeficiency, Selective IgA deficiency, Bruton’s/X-linked agammaglobulinaemia; Transient hypogammaglobulinaemia of the newborn; IgG deficiency
    • T-cell and cell-mediated immune system- accounts for 30% of cases
      • NB Many of these disorders span both T- and B-cells e.g. Severe combined immunodeficiency; DiGeorge syndrome; Wiskott-Aldrich syndrome; Ataxia-telangiectasia; X-linked hyper-IgM
    • Phagocytic (Polymorphic/mononuclear) system (including macrophage dysfunction)
      • e.g. Chronic granulomatous disease
    • Complement system (mainly complement deficiencies)
  • NB Many disorders span more than one system e.g. Severe combined immunodeficiency (T- and B-cells); DiGeorge syndrome; Wiskott-Aldrich syndrome; Ataxia-telangiectasia; X-linked hyper-IgM


Disorders of Humoral Immunity

  • Often present >6 months of age (loss of maternal antibodies), but can present late (into adulthood- see below)
  • Classically present with infections of encapsulated bacteria (tend to fight of viral and fungal infections with an intact innate immune system)
    • Chronic sinusitis / Recurrent acute sinusitis; other recurrent infections e.g. Strep pneumoniae pneumonia; unusual infections e.g. mycobacterial/fungal infections
  1. Common Variable Immunodeficiency
    • Not that common (1/75000); technically group of different disorders (a ‘heterogeneous syndrome’) with variable presentation and outcome
      • e.g. can present in infancy or into adulthood; can present in males and females (although females tend to have a better phenotype)
      • CVID is a diagnosis of exclusion (i.e. other causes of Ig deficiency should be ruled out)
    • Commonly associated with autoimmunity and family history
      • e.g. idiopathic thrombocytopenic purpura; haemolytic anaemia; thyroid disease; vitiligo; diabetes (insulin-dependent); rheumatoid arthritis; SLE; psoriasis; uveitis; IBD (mainly UC)
    • 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
  2. 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
  • Bruton’s/X-linked Agammaglobulinaemia
    • 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)
      • X-linked (male)
      • 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
  1. DiGeorge Syndrome
  2. Severe Combined Immunodeficiency 
    • 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.
  3. Wiskott-Aldrich Syndrome
    • 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

  1. 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

  • Warning History
    • ≥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
    • Family History
  • Warning Signs
    • Poor growth/Failure to thrive
    • Absent lymph nodes/tonsils
    • Skin lesions: telangiectasias, petechiae, dermatomyositis, lupus-like rash
    • Ataxia
    • Oral thrush (>1 year old)
    • Oral ulcers
  • If a patient has any one or more of the bold warning signs, and an immunodeficiency is suspected, IgG/IgM/IgA and a FBC can be measured to screen for a primary immunodeficiency


  • Most require high dose and IV antibiotics for treatment of acute infections.  Many will require prophylactic antibiotics too
  • Where appropriate, vaccines should be given
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    • Patients with T-cell deficiencies should receive cytomegalovirus-negative irradiated blood products
  • IVIg should be used to replace immunoglobulin
  • Stem cell/bone marrow transplants can be curative for cellular immunodeficiency

DiGeorge Syndrome


  • Genetic congenital syndrome caused by a deletion/mutation of the 22q11.2 gene
    • Autosomal dominant (high penetrance but variable expression); but de novo mutations are most common cause (90%)
    • Occurs in around 1/3000


  • Causes several midline problems caused by faulty migration of neural crest cells to the region of the 3rd and 4th pharyngeal pouches during development in utero.
    • Major cause of cardiac defects (e.g. Fallot’s tetralogy; Interrupted aortic arch; Truncus arteriosus and ventricular septal defects)
    • Can cause abnormal appearance
      • short philtrum of the upper lip, hypertelorism (increased distance between the eyes), mandibular hypoplasia, low-set and notched ears, hooded eyelids; long face and malar flatness
      • about half of patients also have short stature and/or microcephaly
      • occasionally patients can have a cleft palate which can cause problems with feeding in infancy
    • Patients can also have learning disabilities
    • Patients can also have airway abnormalities e.g. tracheoesophageal fistula, short trachea, laryngomalacia etc; and parathyroid hypoplasia
      • the latter can cause hypocalcaemia early in infancy due to lack of PTH (one of the diagnostic criteria)
  • Also causes defect in T-cell production and consequent immunodeficiency
    • Thought to be caused by thymic hypoplasia
    • Mainly defects in T cell production
      • Many patients will be born with low T cell (CD3+ T-lymphocyte) counts but will go on to regain some T cell numbers over the first few months of life and will rarely have features of immunodeficiency
      • In severe cases (total aplasia of the thymus- rare) patients will never produce adequate T cell numbers and will usually be severely affected by immunodeficiency

Investigations and Management

  • FISH is the main investigation to confirm diagnosis
  • Other investigations e.g. echocardiogram, FBC etc can assess the features
  • Similarly, patients should be managed as indicated by the features