Infection and immunity

What is the immediate management of sepsis?

Call for senior help early for experienced support. Give oxygen if the patient has evidence of shock or oxygen saturations are below 94% Obtain IV access (cannulation) Blood tests, including a FBC, U&E, CRP, clotting screen (INR), blood gas for lactate and acidosis Blood cultures, ideally before giving antibiotics Urine dipstick and laboratory testing for culture and sensitivities Antibiotics according to local guidelines. They should be given within 1 hour of presentation. IV fluids. 20ml/kg IV bolus of normal saline if the lactate is above 2 mmol/L or there is shock. This may be repeated. ·

What additional investigations may be performed?

Chest xray if pneumonia is suspected Abdominal and pelvic ultrasound if intra-abdominal infection is suspected Lumbar puncture if meningitis is suspected Meningococcal PCR blood test if meningococcal disease is suspected Serum cortisol if adrenal crisis is suspected

Which children should be tested for hep B?

Children of hepatitis B positive mums (screen at 12 months of age or any time after that) Migrants from endemic areas Close contacts of patients with hepatitis B

How is bacterial meningitis managed in the community and the hospital?

Community Children seen in the primary care setting with suspected meningitis AND a non blanching rash should receive an urgent stat injection (IM or IV) of benzylpenicillin prior to transfer to hospital, as time is so important. The dose will depending on their age. Giving antibiotics should not delay transfer to hospital. Where there is a true penicillin allergy, transfer should be the priority rather than finding alternative antibiotics. Hospital Ideally a blood culture and a lumbar puncture for cerebrospinal fluid (CSF) should be performed prior to starting antibiotics, however if the patient is acutely unwell antibiotics should not be delayed. Send blood tests for meningococcal PCR if meningococcal disease is suspected. This tests directly for the meningococcal DNA. It can give a result quicker than blood culture depending on local services, and will still be positive after the bacteria has been treated with antibiotics. There should be a low threshold for treating suspected bacterial meningitis, particularly in babies and younger children. Always follow the local guidelines regarding the choice of antibiotic. Typical antibiotics are: Under 3 months - cefotaxime plus amoxicillin (the amoxicillin is to cover listeriacontracted during pregnancy) Above 3 months - ceftriaxone Vancomycin should be added to these antibiotics if there is a risk of penicillin resistant pneumococcal infection, for example recent foreign travel or prolonged antibiotic exposure. Steroids are also used in bacterial meningitis to reduce the frequency and severity of hearing loss and neurological damage. Dexamethasone is given 4 times daily for 4 days to children over 3 months if the lumbar puncture is suggestive of bacterial meningitis. Bacteria meningitis and meningococcal infection are notifiable diseases, so public healthneed to be informed of all cases. In meningococcal septicaemia -Hypovolaemia · CVP and urinary catherisation should be done to assess fluid balance -Pulmonary oedema (from capillary leak) might need technical ventilation -myocardial dysfunction - inotropic support may be needed -DIC needs correcting with FFP and platelets

What are T cell disorders? Give examples

Conditions that cause abnormal or absent T cells will result in immunodeficiency. DiGeorge syndrome Purine nucleoside phosphorylase deficiency Wiskott-Aldrich Syndrome Ataxic Telangiectasia Acquired Immunodeficiency Syndrome Dunan syndrome

What is the ongoing management of sepsis? When can you stop antibiotics?

Continue antibiotics for 5 - 7 days if a bacterial infection is suspected or confirmed. Alter the antibiotic choice and duration once a source of infection is found and an organism is isolated. Bacterial culture and sensitivities can be very helpful in guiding antibiotics. A microbiologist can provide advice on the choice and duration of antibiotics. Consider stopping antibiotics where there is a low suspicion of bacterial infection, the patient is well and blood cultures and two CRP results are negative at 48 hours.

What are the signs of sepsis?

Don't underestimate observing the child from the end of the bed. Consider whether they look well or unwell. · Fever is the most common presenting symptoms of children Hard signs to look out for that can indicate sepsis are: Deranged physical observations: initially o Minimal tachycardia o Widened pulse pressure o Minimal tachypnoea o Minimally delayed capillary refill Prolonged capillary refill time (CRT) Later signs Fever or hypothermia, cool extremities Mental state changes Anuria Deranged behaviour Poor feeding Inconsolable or high pitched crying High pitched or weak cry Reduced consciousness Reduced body tone (floppy) Skin colour changes (cyanosis, mottled pale or ashen) Petechial or purpuric rash Shock involves circulatory collapse and hypoperfusion of organs.

How are allergies managed?

Establishing the correct allergen is essential Avoidance of that allergen Avoiding foods that trigger reactions Regular hoovering and changing sheets and pillows in patients that are allergic to house dust mites Staying in doors when the pollen count is high Prophylactic antihistamines are useful when contact is inevitable, for example hayfever and allergic rhinitis Patients at risk of anaphylactic reactions should be given an adrenalin auto-injector In certain cases, specialist centres may initiate a lengthy process of gradually exposing the patients to allergens over months, called immunotherapy, with the aim of reducing their reaction to certain foods or allergens. o Specific allergen immunotherapy can be used for treating allergic rhinitis and conjunctivitis, insect stings, anaphylaxis and asthma o During immunotherapy solutions of an allergen to which the patient is allergic are injected subcutaneously or administered sublingually on a regular basis for 3-5 years, with the aim of developing immune tolerance o It is highly effective in providing protection for many years o However, it must be carried out under specialist supervision due to the risk of inducing severe allergic reactions (anaphylaxis)

What investigations do you do for Kawasaki disease?

Full blood count can show anaemia, leukocytosis and thrombocytosis Liver function tests can show hypoalbuminemia and elevated liver enzymes Inflammatory markers (particularly ESR) are raised Urinalysis can show raised white blood cells without infection Echocardiogram can demonstrate coronary artery pathology

Can HIV positive mothers breastfeed?

HIV can be transmitted during breastfeeding, even if the mother's viral load is undetectable. Breastfeeding is never recommended for mothers with HIV, however if the mum is adamant and the viral load is undetectable, sometimes it is attempted with close monitoring by the HIV team.

What is the basic pathophysiology of HIV and how is it transmitted?

HIV is an RNA retrovirus. HIV-1 is most common type. HIV-2 is rare outside West Africa. The virus enters and destroys the CD4 T helper cells. An initial seroconversion flu like illness occurs within a few weeks of infection. The infection is then asymptomatic until it progresses and the patient becomes immunocompromised and beings developing AIDS defining illnesses and opportunistic infections, potentially years later. HIV can not be spread through normal day to day activities, including kissing. It is spread through: Unprotected anal, vaginal or oral sexual activity Mother to child at any stage of pregnancy, birth or breastfeeding. This is referred to as vertical transmission. Mucous membrane, blood or open wound exposure to infected blood or bodily fluids. This could be through sharing needles, needle-stick injuries or blood splashed in an eye.

At what 2 times at children to HIV positive parents tested?

HIV viral load test at 3 months. If this is negative, the child has not contracted HIV during birth and will not develop HIV unless they have further exposure. HIV antibody test at 24 months. This is to assess whether they have contracted HIV since their 3 month viral load, for example through breast feeding. If the 3 month test is negative and they are not breastfed, this should be negative. Note that the antibody test can be positive in infants who do not have HIV for up to 18 months of age. This is due to maternal antibodies that have crossed the placenta during pregnancy.

What are the complications of meningitis?

Hearing loss is a key complication - should have audiological assessment Seizures and epilepsy - due to local cerebral infarction Cognitive impairment and learning disability Memory loss Cerebral palsy, with focal neurological deficits such as limb weakness or spasticity o Local vasculitis: this may lead to cranial nerve palsies or other focal lesions o Subdural effusion: particularly associated with Haemophilus influenzae and pneumococcal meningitis, most resolve spontaneously, but may require prolonged antibiotic treatment o Hydrocephalus: may result from impaired resorption of CSF (communicating hydrocephalus) or blockage of the ventricular outlets by fibrin (non-communicating hydrocephalus), a ventricular shunt may be required o Cerebral abscess: the child's clinical condition deteriorates with the emergence of signs of a space occupying lesion, the temperature will continue to fluctuate, drainage of the abscess is required · DIC, thrombocytopenia · Septic arthritis · Pericarditis, bacterial endocarditis · Gangrene

What type of virus is hepatitis B and how is it transmitted?

Hepatitis B is a DNA virus. It is transmitted by direct contact with blood or bodily fluids. This may occur during sexual intercourse or sharing needles, for example amongst IV drug users or tattoos. It can also be passed through sharing contaminated household products such as toothbrushes or contact between minor cuts or abrasions. It can also be passed from mother to child during pregnancy and delivery.

How is hep C tested for?

Hepatitis C antibody is the screening test Hepatitis C RNA testing is used to confirm the diagnosis of hepatitis C, calculate viral load and identify the genotype

What type of virus is hep C? What is the disease course, complication and treatment??

Hepatitis C is an RNA virus. It is spread by blood and bodily fluids. No vaccine is available. It is now curable in adults, using direct acting antiviral medications. These treatments are not yet available for children. In adults: 1 in 4 fight off the virus and make a full recovery 3 in 4 develop chronic hepatitis C Complications: Liver cirrhosis and associated complications of cirrhosis Hepatocellular carcinoma

What is done to prevent vertical transmission?

Hepatitis C is passed from infected mothers to their babies about 5 - 15% of the time. Hepatitis C antivirals are not recommended in pregnancy and there are no additional measures that are known to reduce the risk of transmission. Babies and children tend not to have any symptoms or pathology associated with hepatitis C infection. It is very unlikely that children will pass on hepatitis C to others as they do not engage in sexual activity or IV drug use. Parents should be educated about hepatitis C and the modes of transmission.

How is encephalitis managed?

Intravenous antiviral medications are used to treat the suspected or confirmed underlying cause: Aciclovir treats herpes simplex virus (HSV) and varicella zoster virus (VZV) Ganciclovir treat cytomegalovirus (CMV) Repeat lumbar puncture is usually performed to ensure successful treatment prior to stopping antivirals Aciclovir is usually started empirically in suspected encephalitis until results are available. Other viral causes have no effective treatment and management is supportive. Followup, support and rehabilitation is required after encephalitis, with help managing the complications.

What is the normal number of infections for a child to have in a year? When should you investigate further (what features)?

It is normal for a healthy child to have 4 - 8 respiratory infections per year. When starting nursery or school and during winter months children are likely to pick up recurrent infections. Children with these features should be referred to a specialist for further assessment. Chronic diarrhoea since infancy Failure to thrive Appearing unusually well with quite a severe infection, for example afebrile with a large pneumonia Significantly more infections than expected, particularly bacterial lower respiratory tract infections Unusual or persistent infections such as cytomegalovirus, candida and pneumocystis jiroveci

What are possible complications of encephalitis?

Lasting fatigue and prolonged recovery Change in personality or mood Changes to memory and cognition Learning disability Headaches Chronic pain Movement disorders Sensory disturbance Seizures Hormonal imbalance

Explain the skin sensitisation theory of allergy

Leading theory on origin of allergies two main contributors to a child developing an allergy to a food: There is a break in the infant's skin (from eczema or a skin infection) that allows allergens, such as peanut proteins, from the environment to cross the skin and react with the immune system. The child does not have contact with that allergen from the gastrointestinal tract, and there is an absence of GI exposure to the allergen. The theory is that allergens entering through the skin are recognised by the immune system as being foreign and harmful proteins. The immune system reacts by becoming sensitised to that allergen, so that when it next encounters that allergen again it will launch a full immune response (an allergic reaction). When a baby is weaned at around 6 months, if they are regularly eating foods that contain that allergen, their GI tract is regularly being exposed to that protein. The GI tract will recognise that allergen as a food and not a foreign or harmful protein, and inform the immune system that it is a safe thing to be exposed to. The theory is that regular exposure to an allergen through food and preventing exposure to that allergen through the skin barrier can help prevent food allergies developing.

How is encephalitis diagnosed? CIs to LP?

Lumbar puncture, sending cerebrospinal fluid for viral PCRtesting CT scan if a lumbar puncture is contraindicated MRI scan after the lumbar puncture to visualise the brain in detail EEG recording can be helpful in mild or ambiguous symptoms but is not always routinely required Swabs of other areas can help establish the causative organism, such as throat and vesicle swabs HIV testing is recommended in all patients with encephalitis Contraindications to a lumbar puncture include a GCS below 9, haemodynamically unstable, active seizures or post-ictal.

When are vaccinations given for meningitis?

Meningitis B vaccine - 8 weeks, 16 weeks and 1 year. 6 in 1 vaccine that includes Hib - 8, 12 and 16 weeks old. Pneumococcal -Babies born on or after 1 January 2020- 12 weeks and 1 year of age. before this date - at 8 and 16 weeks and a booster at 1 year. Babies are offered a combined Hib/Men C vaccine at 1 year of age. MMR - 1 year of age. They'll then have a second dose when they're 3 years and 4 months old. ACWY - Young teenagers, sixth formers and "fresher" students going to university for the first time are advised to have the vaccination.

Define meningitis, meningococcal septicaemia and meningococcal meningitis

Meningitis is defined as inflammation of the meninges. Neisseria meningitidis is a gram negative diplococcus bacteria. They are circular bacteria (cocci) that occur in pairs (diplo-). It is commonly known as meningococcus. Meningococcal septicaemia refers to the meningococcus bacterial infection in the bloodstream. the cause of the classic "non-blanching rash" Meningococcal meningitis is when the bacteria is infecting the meninges and the cerebrospinal fluid around the brain and spinal cord.

What might the features be of different diagnoses that can cause sepsis?

Meningococcal disease - non-blanching rash Bacterial meningitis - neck stiffness Herpes simplex encephalitis = focal neurological signs, focal seziures Pneumonia - crackles in chest UTI - abdo pain, urinary freq/dysuria Septic arthritis - swelling of limb or join, non-weight bearing Kawasaki disease - fever for more than 5 days

How is transmission prevented during birth?

Mode of delivery will be determined by the mother viral load: Normal vaginal delivery is recommended for women with a viral load < 50 copies / ml Caesarean sections are considered in patients with > 50 copies copies / ml and in all women with > 400 copies / ml IV zidovudine should be given during the caesarean if the viral load is unknown or there are > 10000 copies / ml Prophylaxis treatment may be given to the baby depending on the mothers viral load: Low risk babies, where mums viral load is < 50 copies per ml, should be given zidovudine for 4 weeks High risk babies, where mums viral load is > 50 copies / ml, should be given zidovudine, lamivudine and nevirapine for 4 weeks

What is SCID caused by?

More than 50% of cases are caused by a mutations in the common gamma chain on the X chromosome that codes for interleukin receptors on T and B cells. This has X-linked recessive inheritance. There are many other gene mutations that can lead to SCID including: JAC3 gene mutations Mutations leading to adenosine deaminase deficiency

What is chronic hep B? What is the risk of this?

Most children fully recover from the infection within 2 months, however a portion go on to become chronic hepatitis B carriers. In these patients the virus DNA has integrated into their own DNA and they continue to produce the viral proteins. The risk of developing chronic hepatitis Bafter exposure is: 90% for neonates 30% for children under 5 Under 10% for adolescents

What are the features of hep B?

Most children with chronic hepatitis B are asymptomatic, with normal growth and development and normal liver function tests. Less than 5% will develop liver cirrhosis and less than 0.05% will develop hepatocellular carcinoma before adulthood. These risks increase once they enter adulthood.

How is patch testing done?

Patch testing is the most helpful in determining an allergic contact dermatitis in response to a specific allergen. It is not helpful for food allergies. This could be for latex, perfumes, cosmetics or plants. A patch containing the allergen is placed on the patient's skin. The patch can either contain a specific allergen, or a grid of lots of allergens as a screening tool. After 2 - 3 days the skin reaction to the patch is assessed.

How does mumps present? Complications?

Patients experience an initial period of flu-like symptoms known as the prodrome. These occur a few days before the parotid swelling: Fever Muscle aches Lethargy Reduced appetite Headache Dry mouth Parotid gland swelling, either unilateral or bilateral, with associated pain is the key feature that should make you consider mumps. It can also present with symptoms of the complications, such as: Abdominal pain (pancreatitis) Testicular pain and swelling (orchitis) Confusion, neck stiffness and headache (meningitis or encephalitis) Complications Pancreatitis Orchitis Meningitis Sensorineural hearing loss

How is hep B managed?

Prevention - Vaccination involves injecting the hepatitis B surface antigen. The vaccine requires 3 doses at different intervals. Vaccination to hepatitis B is now included as part of the UK routine vaccination schedule as part of the 6 in 1 vaccine. Most children with chronic hepatitis B are asymptomatic and do not require treatment. They require regular specialist follow up to assess monitor their serum ALT, HbeAg, HBV DNA, physical examination and liver ultrasound. Where there is evidence of hepatitis or cirrhosis, treatment with antiviral medications may be considered.

Define sepsis and septicaemia

Septicaemia - is when bacteria enter the bloodstream, which triggers sepsis Sepsis - is an overwhelming and life-threatening response to infection, the host response includes the release of inflammatory cytokines and activation of endothelial cells, that can lead to tissue damage, organ failure, shock and death

What are the short and long term complications of HIV?

Short term complications · Opportunistic infections: TB, PCP, Toxoplasmosis, MAC, VZV, HSV, CMV, Candida · Blood problems: thrombocytopenia, anaemia, neutropenia · Diet: need high energy, high protein Long Term complications · Compliance · Failure to thrive · Risk of transmission · HIV encephalopathy · Neuropathy and myelopathy · Cancers: Kaposi's sarcoma, Non-Hodgkin's lymphoma

What post exposure prophylaxis is needed?

Significant exposure to a patient with meningococcal infections such as meningitis or septicaemia puts people at risk of contracting the illness. This risk is highest for people that have had close prolonged contact within the 7 days prior to the onset of the illness. The risk decreases 7 days after exposure. Therefore, if no symptoms have developed 7 days after exposure they are unlikely to develop the illness. Post exposure prophylaxis is guided by public health. The usual antibiotic choice for this is asingle dose of ciprofloxacin. It should be given as soon as possible and ideally within 24 hours of the initial diagnosis.

Explain to a parent why they shouldn't be sacred of the MMR vaccine

Since the study in 1998, the MMR vaccine, as well as other vaccines, have been extensively investigated with much more rigorous scientific research and statistical power, such as a meta-analysis with over one million patients. All subsequent scientific literature has disproved any link between the MMR and autism.

What are the viral markers for hep B?

Surface antigen (HBsAg) - active infection E antigen (HBeAg) - marker of viral replication and implies high infectivity Core antibodies (HBcAb) - implies past or current infection Surface antibody (HBsAb) - implies vaccination or past or current infection Hepatitis B virus DNA (HBV DNA) - this is a direct count of the viral load When screening for hepatitis B, test HBcAb (for previous infection) and HBsAg (for active infection). If these are positive do further testing for HBeAg and viral load (HBV DNA). HBsAb demonstrates an immune response to HBsAg. The HBsAg is given in the vaccine, so having a positive HBsAb may simply indicate they have been vaccinated and created an immune response to the vaccine. The HBsAb may also be present in response to an infection. The other viral markers are necessary to distinguish between previous vaccination and infection. HBcAb can help distinguish between acute, chronic and past infection. We can measure IgM and IgG versions of the HBcAb. IgM implies an active infection and will give a high titre with an acute infection and a low titre with a chronic infection. IgG indicates a past infection where the HBsAg is negative. HBeAg is important. Where the HBeAg is present it implies the patient is in an acute phase of the infection where the virus is actively replicating. The level of HBeAg correlates with their infectivity. If the HBeAg is higher, they are highly infectious to others. When they HBeAg is negative but the HBeAb is positive, this implies they have been through a phase where the virus was replicating but the virus has now stopped replicating and they are less infectious.

How is HIV tested for?

Testing can be done by any doctor, nurse or other trained person. Informed consent should be documented before testing. It is good practice to involve both parents and child when getting consent for testing. Results should be given in person, by a suitably knowledgable clinician. Positive results may be due to maternal antibodies in children aged under 18 months. This does not necessarily mean they are HIV positive. Discuss results with an infectious disease specialist before informing parents that the child has HIV. Two options exist for testing: HIV antibody screen: this tests whether the immune system has created antibodies due to exposure to the HIV virus. This is the standard screening test, but it can give false positive in babies of HIV positive mums, due to maternal antibodies that cross the placenta. It can take up to 3 months for antibodies to develop after exposure to the virus. HIV viral load: this tests directly for viruses in the blood. This will never be falsely positive, but may come back as "undetectable" in patients on antiretroviral therapy.

Explain the HPV vaccine to parents

The HPV vaccine is ideally given to girls and boys before they become sexually active. The intention is to prevent them contracting and spreading HPV once they become sexually active. The current NHS vaccine is Gardasil, which protects against strains 6, 11, 16 and 18: Strains 6 and 11 cause genital warts Strains 16 and 18 cause cervical cancer

Outline the vaccination schedule

The UK vaccination schedule is constantly changing. It is also slightly different depending on when the child was born. Always look up the latest schedule when giving vaccines. 8 weeks: 6 in 1 vaccine (diphtheria, tetanus, pertussis, polio, haemophilus influenzae type B (Hib) and hepatitis B) Meningococcal type B Rotavirus (oral vaccine) 12 weeks: 6 in 1 vaccine (again) Pneumococcal (13 different serotypes) Rotavirus (again) 16 weeks: 6 in 1 vaccine (again) Meningococcal type B (again) 1 year: 2 in 1 (haemophilus influenza type B and meningococcal type C) Pneumococcal (again) MMR vaccine (measles, mumps and rubella) Meningococcal type B (again) Yearly from age 2 - 8: Influenza vaccine (nasal vaccine) 3 years 4 months: 4 in 1 (diphtheria, tetanus, pertussis and polio) MMR vaccine (again) 12 - 13 years: Human papillomavirus (HPV) vaccine (2 doses given 6 to 24 months apart) 14 years: 3 in 1 (tetanus, diphtheria and polio) Meningococcal groups A, C, W and Y

What investigations would you do?

The choice of investigations will be guided by a full history and examination. Full blood count: low neutrophils suggest a phagocytic disorder and low lymphocytes suggest a T cell disorder Immunoglobulins: abnormalities suggest a B cell disorders Complement proteins: abnormalities suggest a complement disorder Antibody responses to vaccines, specifically pneumococcal and haemophilus vaccines HIV test if clinically relevant Chest xray for scarring from previous chest infections Sweat test for cystic fibrosis CT chest for bronchiectasis

How is mumps diagnosed and managed?

The diagnosis can be confirmed using PCR testing on a saliva swab. The blood or saliva can also be tested for antibodies to the mumps virus. Mumps is a notifiable disease, meaning you need to notify public healthof any suspected and confirmed cases. Management is supportive, with rest, fluids and analgesia. Mumps is a self limiting condition. Management of complications is also mostly supportive.

Can a hep B positive mum breastfeed?

The hepatitis B virus can be found in the breast milk of mothers with hepatitis B. Babies of these mothers have already been exposed to the virus during pregnancy and birth. They should also receive the hepatitis B vaccine and hepatitis B immunoglobulin infusion. Therefore, the general advice is that it is safe for hepatitis B positive mother to breastfeed provided their babies are properly vaccinated.

What is the incidence and epidemiology of meningitis/meningococcal septicaemia? What are the most common causes?

The most common causes of bacterial meningitis in children and adults are Neisseria meningitidis (meningococcus) and Streptococcus pneumoniae (pneumococcus). In neonates the most common cause is group B strep (GBS). GBS is usually contracted during birth from GBS bacteria that live harmlessly in the mother's vagina. · 60% of CNS infections are viral · Over 80% of patients with bacterial meningitis in the UK are <16 with 5-10% mortality · Over 10% of survivors are left with long-term neurological impairment · Only meningitis is present in 30-50% of cases of invasive meningococcal disease, whereas 7-10% of cases only have features of septicaemia and 40% have both · It occurs more commonly in males, peak incidence is 6-24 months, with most cases being <4 years · Infants <6 months are generally protected by maternal antibodies · As many as 30% of teenagers and 10% of adults carry meningococci in their respiratory tract at any given time · The clinical difference between septicaemia and meningitis is important because patients who present with shock are treated differently than patients who present primarily with increased ICP · The prevalence is thought to be relatively rare for complement deficiency, but up to 30% of people with recurrent meningococcaemia have it · Mumps meningitis is now rare in the UK due to the MMR vaccine

What are the causes of viral meningitis? How is it investigated and managed?

The most common causes of viral meningitis are herpes simplex virus (HSV), enterovirus andvaricella zoster virus (VZV). A sample of the CSF from the lumbar puncture should be sent for viral PCR testing. Viral meningitis tends to be milder than bacterial and often only requires supportive treatment. Aciclovir can be used to treat suspected or confirmed HSV or VZV infection.

How is Kawasaki disease managed?

There are two first line medical treatments given to patients with Kawasaki disease: High dose aspirin to reduce the risk of thrombosis IV immunoglobulins to reduce the risk of coronary artery aneurysms, given in first 10 days Aspirin o Continued at a low antiplatelet dose until echocardiography at 6 weeks reveals the presence or absence of aneurysms Patients will need close follow up with echocardiograms to monitor for evidence of coronary artery aneurysms. TOM TIP: Kawasaki disease is one of the few scenarios where aspirin is used in children. Aspirin is usually avoided due to the risk of Reye's syndrome. This is a unique fact that examiners like to test. · When the platelet count is very high, antiplatelet aggregation agents may also be used to reduce the risk of coronary thrombosis · Children with giant coronary artery aneurysms may require long-term warfarin therapy and close follow-up · Children suspected of having the disease but who do not have all the clinical features should still be considered for treatment · Sometimes, fever recurs despite treatment and these children are given a second dose of IVIG · Persistent inflammation and fever may require treatment with infliximab, steroids or ciclosporin

What questions should you ask in an allergy history?

Timing after exposure to the allergen Previous and subsequent exposure and reaction to the allergen Symptoms of rash, swelling, breathing difficulty, wheeze and cough Previous personal and family history of atopic conditions and allergies

How is the risk of transmitting hep B reduced at birth?

To reduce the risk of the baby contracting hepatitis B, at birth (within 24 hours) neonates with hepatitis B positive mothers should be given both: Hepatitis B vaccine Hepatitis B immunoglobulin infusion Infants are given an additional hepatitis B vaccine at 1 and 12 months of age. They will also receive the hepatitis B vaccine as part of the normal 6 in 1 vaccine given to all infants aged 8, 12 and 16 weeks. They are tested for the HBsAg at 1 year to see if they have contracted hepatitis B.

Give examples of toxin vaccines

Toxin vaccines contain a toxin that is normally produced by a pathogen. They cause immunity to the toxin and not the pathogen itself. Examples are the diphtheria and tetanus vaccines.

What is the Coombs and Gell classification of hypersensitivity reactions - type 1-4

Type 1: IgE antibodies to a specific allergen trigger mast cells and basophils to release histamines and other cytokines. This causes an immediate reaction. Typical food allergy reactions, where exposure to the allergen leads to an acute reaction, range from itching, facial swelling and urticaria to anaphylaxis. Type 2: IgG and IgM antibodies react to an allergen and activate the complement system, leading to direct damage to the local cells. Examples are haemolytic disease of the newbornand transfusion reactions. Type 3: Immune complexes accumulate and cause damage to local tissues. Examples are autoimmune conditions such as systemic lupus erythematosus (SLE), rheumatoid arthritisand Henoch-Schönlein purpura (HSP) Type 4: Cell mediated hypersensitivity reactions caused by T lymphocytes. T-cells are inappropriately activated, causing inflammation and damage to local tissues. Examples are organ transplant rejection and contact dermatitis. Non-IgE mediated · Usually a delayed onset of symptoms and more varied clinical course

What is Wiskott-Aldrich syndrome?(WAS) What are its features?

X-linked recessive condition with a mutation on the WAS gene. It causes abnormal functioning of T cells. Other features include: Thrombocytopenia Immunodeficiency Neutropenia Eczema Recurrent infections Chronic bloody diarrhoea

Give examples of inactivated vaccines

a killed version of the pathogen. They cannot cause an infection and are safe for immunocompromised patients, although they may not have an adequate response. Examples are: Polio Flu vaccine Hepatitis A Rabies

What is Omenn syndrome (cause)? What are the classic features?

a rare cause of SCID. It is the result of a mutation in the recombination-activating gene (RAG 1 or RAG 2) that codes for important proteins in T and B cells. It has autosomal recessive inheritance. The syndrome is caused by abnormally functioning and deregulated T cells that attack the tissues in the fetus or neonate. This leads the classic features of Omenn syndrome: A red, scaly, dry rash (erythroderma) Hair loss (alopecia) Diarrhoea Failure to thrive Lymphadenopathy Hepatosplenomegaly

Explain DiGeorge syndrome and the features

aka 22q11.2 deletion syndrome, results from a microdeletion in a portion of chromosome 22 that leads to a developmental defect in the third pharyngeal pouch and third branchial cleft. One of the consequences of this is incomplete development of the thymus gland. An underdeveloped thymus gland results in an inability to create functional T cells. CATCH-22 mnemonic: C - Congenital heart disease A - Abnormal facies (characteristic facial appearance) T - Thymus gland incompletely developed C - Cleft palate H - Hypoparathyroidism and resulting Hypocalcaemia 22nd chromosome affected

Who requires a lumbar puncture?

all children: Under 1 month presenting with fever 1 to 3 months with fever and are unwell Under 1 year with unexplained fever and other features of serious illness

What is X-linked agammaglobulinaemia?

also known as Bruton's agammaglobulinaemia. This is an X-linked recessive condition. Abnormal tyrosine kinase gene needed for B cell maturation. It results in abnormal B cell development and deficiency in all classes of immunoglobulins. It causes similar issues to common variable immunodeficiency.

What is Kawasaki disease? Who is it seen in and what is a key complications?

also known as mucocutaneous lymph node syndrome. It is a systemic, medium-sized vessel vasculitis. It affects young children, typically under 5 years, with peak at end of first year. There is no clear cause or trigger. It is more common in Asian children, particularly Japanese and Korean children, Afro-Caribbean ethnicity. It is also more common in boys. A key complication is coronary artery aneurysm. · Young infants tend to be more severely affected than older children, more likely to have 'incomplete' cases, in which not all the cardinal features are present · Although the specific cause is unknown, it is likely to be the result of immune hyperreactivity to a variety of triggers in a genetically susceptible host · A polymorphism in the ITPKC gene, a negative regulator of T-cell activation on chromosome 19 is strongly associated with susceptibility to the disease

What is ataxic telangiectasia? What are the features?

autosomal recessive condition affecting the gene coding for the ATM serine/threonine kinase protein on chromosome 11. This protein is important in several functions of DNA coding, meaning that a mutation in this gene leads to problems coding for many other genes. Defect in DNA repair. Low numbers of T-cells and immunoglobulins, causing immunodeficiency and recurrent infections. Ataxia: problems with coordination due to cerebellar impairment Telangiectasia, particularly in the sclera and damaged areas of skin Predisposition to cancers, particularly haematological cancers (lymphoma) Slow growth and delayed puberty Accelerated ageing Liver failure

What is Purine Nucleoside Phosphorylase Deficiency (PNP)?

autosomal recessive condition. PNPase is an enzyme that helps breakdown purines. Without this enzyme, a metabolite called dGTP builds up. This metabolite is exclusively toxic to T cells. Increased levels of dGTP causes low levels of T-lymphocytes. There are normal levels of B cells and immunoglobulins. Clinically, patients immunity to infection gradually gets worse. They become increasingly susceptible to infections, particularly viruses and live vaccines.

What is the pathology of meningococaemia? Transmission and virulence factors?

caused by Neisseria meningitides 13 serotypes · most significant of these are A, B and C · In the UK, most deaths used to be due to type C · Humans are the only known reservoir for N. meningitides, can transmit organisms by aerosol or nasopharyngeal secretions, meningococcal infection is preceded by nasopharyngeal colonisation · Meningococci then enter the blood stream and spread to specific sites, such as the meninges, joints or disseminate throughout the body · 5% of individuals become asymptomatic carriers · Meningococci have 3 importance virulence factors o The polysaccharide capsule o Lipo-oligosaccharide endotoxin: mediates invasion and is the protein that our body responds to o Immunoglobulin A1 protease: which cleaves membranes and helps the organism survive intracellularly · Much of the damaged caused by meningitis is as a result of the host response rather than the organism itself, the release of inflammatory mediators and activated leucocytes together with endothelial damage, leads to cerebral oedema, raised ICP and decreased cerebral blood flow

Explain common variable immunodeficiency. What is deficient? What does this lead to/associated with? How do you manage?

caused by a genetic mutation in the genes coding for components of B cells. The result is deficiency in IgG and IgA, with or without a deficiency in IgM. This leads to recurrent respiratory tract infections, typically leading to chronic lung disease over time. Patients are unable to develop immunity to infections or vaccinations. They are also prone to immune disorders such as rheumatoid arthritis, and cancers such as non-Hodgkins lymphoma. Management is with regular immunoglobulin infusions and treating infections and complications as they occur. Later onset

What are complement proteins most important for?

complement disorders affect the complement proteins that make up the complement system, which helps destroy pathogenic cells. Complement proteins are most important in dealing with encapsulated organisms, such as: Haemophilus influenza B Streptococcus pneumonia Neisseria meningitidis

Give examples of live attenuated vaccines

contain a weakened version of the pathogen. They are still capable of causing infection, particularly in immunocompromised patients. The following vaccines are live attenuated vaccines: Measles, mumps and rubella vaccine: contains all three weakened viruses BCG: contains a weakened version of tuberculosis Chickenpox: contains a weakened varicella-zoster virus Nasal influenza vaccine (not the injection) Rotavirus vaccine

How is SCID managed?

fatal unless successfully treated. Management should be in a specialist immunology centre. Management involves treating underlying infections, immunoglobulin therapy, minimising the risk of new infections with a sterile environment, avoiding live vaccines and performing haematopoietic stem cell transplantation.

Explain what an allergy is

hypersensitivity of the immune system to allergens. Allergens are proteins that the immune system recognises as foreign and potential harmful, leading to an allergic immune response. These proteins are types of antigen. Atopy is a term used to describe a predisposition to having hypersensitivity reactions to allergens. It refers to the tendency to develop conditions such as eczema, asthma, hayfever, allergic rhinitis and food allergies. These conditions are referred to as atopic conditions. Patients often have more than one atopic condition, and atopy frequently runs in families.

What are the common causes of encephalitis?

infective or non-infective causes. Non-infective causes are autoimmune, meaning antibodies are created that target brain tissue. The most common cause is infection with a virus. Bacterial and fungal encephalitis is also possible although much more rare in the UK. The most common viral cause is herpes simplex virus (HSV). In children the most common cause is herpes simple type 1 (HSV-1) from cold sores. In neonates it is herpes simplex type 2 (HSV-2) from genital warts, contracted during birth. Other viral causes include varicella zoster virus (VZV) associated with chickenpox, cytomegalovirus associated with immunodeficiency, Epstein-Barr virus associated with infectious mononucleosis, enterovirus, adenovirus and influenza virus. It is important to ask about vaccinations, as the polio, mumps, rubella and measles viruses can cause encephalitis as well.

How is an LP done and what is measured?

involves inserting a needle into the lower back to collect a sample of cerebrospinal fluid (CSF). The spinal cord ends at the L1 - L2 vertebral level, so the needle is usually inserted into the L3 - L4 intervertebral space. Samples are sent for bacterial culture, viral PCR, cell count, protein and glucose. A blood glucose sample should be sent at the same time so that it can be compared to the CSF sample. The samples need to be sent immediately.

What is RAST testing?

measures the total and allergen specific IgE quantities in the patient's blood sample. In a patient with atopic conditions such as eczema and asthma, the results will often come back positive for everything you test.

What is selective Ig A def? Explain pathology. When might you come across this clinically?

most common low levels of IgA and normal levels of IgG and IgM. IgA is present in secretions of the mucous membranes, such as saliva, respiratory tract secretions, GI tract secretions, tears and sweat. IgA protects against opportunistic infections of these mucous membranes. Selective IgA deficiency is a mild immunodeficiency. Patients are often asymptomatic and never diagnosed. Patients have a tendency to recurrent mucous membrane infections, such as lower respiratory tract infections, and autoimmune conditions. The place you are likely to come across IgA deficiency is when testing for coeliac disease. The blood tests for coeliac disease are the IgA levels of anti-TTG and anti-EMA antibodies. When you test for these antibodies, it is important to also test for total immunoglobulin A levels. If the total IgA is low due to an IgA deficiency, the coeliac test will be negative, even when they have coeliac disease. In this circumstance, you can test for the IgG version of anti-TTG or anti-EMA antibodies or simply do an endoscopy with biopsies.

What investigations are done for allergies?

most reliable - clear and detailed history. There are three main ways to test for allergy: -Skin prick testing -RAST testing, which involves blood tests for total and specific immunoglobulin E (IgE) -Food challenge testing Skin prick testing and RAST testing assess sensitisation and not allergy. This is important, because it makes these tests notoriously unreliable and misleading. hey often come back showing that the patient is sensitised to many of the things you have tested for, and it becomes very challenging to explain to the child or their parents that the positive test results do not mean it is unsafe for the child to eat those foods. Foot challenge testing is the gold standard investigation for diagnosing allergy, however it requires a lot of time and resources and is only available in selected places.

Hoe might a neonate or infant present with meningitis?

non-specific signs and symptoms · The younger the child, the less likely they are to exhibit the classic symptoms of fever, headache and meningeal signs · Meningitis in the neonatal period is associated with maternal infection or pyrexia on delivery a child <3 months may have very non-specific symptoms o Hyperthermia or hypothermia o Change in sleeping or eating habits Poor feeding o Irritability o Lethargy o Vomiting o High pitched cry o Seizures · More specific signs include meningism and bulging fontanel · A child who is quiet at rest, but cries when moved or comforted may also have meningitis · After 3 months, the child may display symptoms more often associated with bacterial meningitis with fever, vomiting, irritability, lethargy or any change in behaviour · After 2-3 years, the child may complain of headache, stiff neck and photophobia

What are the two phases of an IgE mediated reaction?

o Early phase: occurring within minutes of exposure to the allergen, caused by release of histamine and other mediators from mast cells - urticaria, angioedema, sneezing and bronchospasm o Late phase: may also occur after 4-6 hours, this causes nasal congestion in the upper airway, cough and bronchospasm in the lower airway · The majority of severe life-threatening allergic reactions are IgE mediated · Involves IgE and mast cells, the IgE is derived from B-cells that are activated by exposed TH2 cells via the release of IL4 · The initial exposure leads to the recruitment of eosinophils · The IgE molecules bound to the Fc receptors on mast cells are cross-linked by specific antigens · This cross-linking leads to the release of preformed inflammatory mediators and the production and subsequent release of arachidonic acid derived inflammatory mediators · The mediators have the effect of inducing inflammation and leads to marked vasodilation, smooth muscle contraction, increased small vessel permeability and increased secretion of mucus

How does meningococcal septicaemia present?

o Fever o Rash: may initially be erythematous and maculopapular then may change to petechiae and purpura o Vomiting o Headache o Myalgia o Abdominal pain o Tachycardia/tachypnoea o Hypotension o Cool extremities o Initially normal conscious level

What are the main causative organisms in at risk groups eg immunocompromised. chronic respiratory illness?

o Immunodeficiency: predisposes to SIRS (systemic inflammatory response syndrome) from various usual and unusual pathogens but particularly Pneumococcus o Chronic respiratory illness: particularly at risk from Pseudomonas

What might you notice OE of allergy?

o Mouth breathing: children who habitually breathe with their mouth open may have an obstructed nasal airway from rhinitis, and there may also be a history of snoring or OSA o An allergic salute: from rubbing an itchy nose o Pale and swollen inferior nasal turbinates o Hyperinflated chest or Harrison sulci from chronic undertreated asthma o Atopic eczema affecting the limb flexures o Allergic conjunctivitis: may also be prominent creases (Dennie-Morgan folds) and blue-grey discoloration below the lower eyelids · Growth needs to be checked: especially in those with food allergy, where dietary restrictions or malabsorption can lead to nutritional compromise and in those treated with high-dose inhaled/nasal/topical corticosteroids

What are the other causes of meningitis? What groups do they affect?

o Neonates - 3 months: Group B strep, E.coli, Listeria o 1 month - 6 years: N. meningitis, Strep. Pneumoniae, H. influenza o >6 years: N. meningitis, Strep. pneumoniae

What is cerebral malaria?

o a rapidly developing encephalopathy which only occurs in 20-50% of people who develop malaria o It occurs when parasites adhere to the cerebral microvasculature causing blockage, this leads to a shortage of oxygen to this site and therefore numerous complications o Elevated ICP and seizures

Who receives the BCG vaccine?

offered from birth to babies who are at higher risk of tuberculosis. These are babies with relatives from countries of high TB prevalence or who live in urban areas with a high rate of TB. It may also be given to children arriving from areas of high TB prevalence or in close contact with people that have TB.

Give examples of subunit and conjugate vaccines

only contain parts of the organism used to stimulate an immune response. They also cannot cause infection and are safe for immunocompromised patients. Examples of subunit and conjugate vaccines are: Pneumococcus Meningococcus Hepatitis B Pertussis (whooping cough) Haemophilus influenza type B Human papillomavirus (HPV) Shingles (herpes-zoster virus)

What is mannose-binding lectin deficiency? What is the consequence?

relatively common in the general population. A deficiency leads to inhibition of the alternative pathway of the complement system. In otherwise healthy individuals, it seems to be relatively unimportant and does not seem to cause major immunodeficiency. In patients who are otherwise susceptible to infection (e.g. cystic fibrosis) this can lead to a more severe variant of their existing disease.

How is food challenge testing performed?

should be performed in a specialised unit with very close monitoring. The child is gradually given increasing quantities of an allergen to assess the reaction, starting with almost non-existent quantities diluted further in other foods, for example mixing a small amount of peanut into a bar of chocolate. Children are monitored very closely after each exposure. This can be very helpful in excluding allergies for reassurance.

What is severe combined immunodeficiency (SCID)?

the most severe condition causing immunodeficiency Children with SCID have almost no immunity to infections. It is a syndrome caused by a number of different genetic disorders that result in absent or dysfunctioning T and B cells.

What is the pathology of sepsis? 4 components

the result of a severe systemic inflammatory response The causative pathogens are recognised by macrophages, lymphocytes and mast cells. These cells release vast amounts of cytokines, such as interleukins and tumor necrosis factor, to alert the immune system to the invader. These cytokines activate other parts of the immune system. This immune activation leads to further release of chemicals such as nitrous oxide that causes vasodilation. The immune response causes inflammation throughout the body. Many of these cytokines cause the endothelial lining of blood vessels to become more permeable. This causes fluid to leak out of the blood into the extracellular space, leading to oedema and a reduction in intravascular volume. The oedema around blood vessels creates a space between the blood and the tissues, reducing the amount of oxygen that reaches the tissues. Activation of the coagulation system leads to deposition of fibrin throughout the circulation, further compromising organ and tissue perfusion. It also leads to consumption of platelets and clotting factors, as they are being used up to form the blood clots. This leads to thrombocytopenia, haemorrhages and an inability to form clots and stop bleeding. This is called disseminated intravascular coagulopathy (DIC). Blood lactate rises as a result of anaerobic respiration in the hypo-perfused tissues with an inadequate oxygen. A waste product of anaerobic respiration is lactate.

How do you risk assess a child under 5 with a fever? What age group should be treated immediately at a certain fever?

traffic light system for the assessment of serious illness in these children. This categorises children as green (low risk), amber (intermediate risk) or red(high risk). Colour: normal colour versus cyanosis, mottled pale or ashen Activity: active, happy and responsive versus abnormal responses, drowsy or inconsolable cry Respiratory: normal breathing versus respiratory distress, tachypnoea or grunting Circulation and hydratio n: normal skin and moist membranes versus tachycardia, dry membranes or poor skin turgor Other: other concerning signs, such as fever > 5 days, non blanching rash, seizures or high temperatures < 6 months It is worth remembering that all infants under 3 months with a temperature of 38ºC or aboveneed to be treated urgently for sepsis, until proven otherwise. Where children are low risk and managed at home, parents need clear verbal and written safety-net advice about when and how to seek further medical attention.

What is mumps? How is it transmitted?

viral infection spread by respiratory droplets. The incubation period is 14 - 25 days. Mumps is usually a self limiting condition that lasts around 1 week. Management is supportive, and involves treating the complications if they occur. Taking a vaccination history is essential when considering a diagnosis of mumps. The MMR vaccine offers around 80% protection against mumps.

What is the consequence of complement deficiency? What is the most common type?

vulnerability to certain infective organisms, leading to recurrent infections with these organisms. Complement deficiencies make children particularly susceptible to infections of the respiratory tract, ears and throat. Complement deficiencies are also associated with immune complex disorders, such as systemic lupus erythematous, as an incomplete complement cascade leads to immune complexes building up and being deposited in tissues, leading to chronic inflammation. C2 deficiency is the most common complement deficiency. Vaccination against encapsulated organisms is very important in patients with complement deficiencies.

How will SCID present?

will present in the first few months of life with: Persistent severe diarrhoea Failure to thrive Opportunistic infections that are more frequent or severe than in healthy children, for example severe and later fatal chickenpox, Pneumocystis jiroveci pneumonia and cytomegalovirus Unwell after live vaccinations such as the BCG, MMR and nasal flu vaccine Omenn syndrome

How might HIV present?

· A proportion of HIV-infected infants progress rapidly to symptomatic disease and onset of AIDS in the 1st year of life · However, other infected children remain asymptomatic for months or years before progressing to clinical disease, some asymptomatic children will only be identified in adolescence at routine screening following diagnosis in another family member · Clinical presentation varies with the degree of immunosuppression o Mild: lymphadenopathy or parotitis o Moderate: recurrent bacterial infections, candidiasis, chronic diarrhoea and lymphocytic interstitial pneumonitis (LIP) o Severe: diagnoses include opportunistic infections (e.g. Pneumocystis jiroveci - PCP), severe FTT, encephalopathy, malignancy · The lymphocytic infiltration of the lungs may be caused by a response to the HIV infection itself, or it may be related to EBV infection · More than one clinical feature is often present, an usual constellation of symptoms, especially if infectious, should alert one to HIV infection

What are the common drug allergies?

· Allergy skin and blood tests can be used to support a diagnosis of drug allergy, but a drug challenge may be the only way to conclusively confirm or refute the diagnosis, this is contraindicated after a severe allergic reaction and an alternative drug should be sought · Examples o Antibiotics: penicillin and cephalosporins o Local anaesthetic: lidocaine o Analgesics: aspirin, NSAIDS o Opiates: codeine, morphine o Dextran (antiplatelet) o Radiocontrast media · There is a form called the yellow card that should be submitted with the details of the incident to the medicines and healthcare products regulatory agency

What is the difference between a food allergy and intolerance?

· Allergy: immune reaction to a protein · Intolerance: lack of enzyme to break down protein · In infants most common causes are milk, egg and peanut · In older children: peanut, tree nut, fish and shellfish

Outline a strategy for prevention and treatment of infection in immune suppressed children

· Antimicrobial prophylaxis o T-cell and neutrophil defects: give cotrimoxazole to prevent pneumocystis jiroveci infection, itraconazole or fluconazole to prevent other fungal infections o B-cell defects: give antibiotic prophylaxis (e.g. azithromycin) to prevent recurrent bacterial infections · Antibiotic treatment: prompt treatment of infections, appropriate choice of antibiotics and a generally longer courses with lower threshold for IV therapy · Screen for end organ disease e.g. CT scan in children with antibody deficiency to detect bronchiectasis · Immunoglobulin replacement therapy: for children with antibody deficiency and can be given IV so a central venous line may be used · Bone marrow transplantation: can be a matched sibling donor, matched unrelated donor or haploidentical transplant, used for SCID and chronic granulomatous disease Gene therapy: for certain forms of SCID but associated with a risk of leukaemia

How is EBV diagnosed?

· Atypical lymphocytes: numerous large T cells seen on blood film · A +ve Monospot test: the presence of heterophile antibodies, this test is often negative in young children with the disease · Seroconversion with production of IgM and IgG to EBV antigens

How are meningococcal sepsis and meningitis investigated?

· Bloods: FBC and differential count, glucose, coagulation screen, CRP, U&E and LFTs · Blood gas for acidosis · Culture: blood, throat swab, urine, stool · Rapid antigen test for meningitis organism in blood, CSF or urine · LP for CSF unless contraindicated Lumbar puncture o MS+C o Cell count: polymorphs, lymphocytes and RBCs o Gram stain o Protein, glucose o Viral PCR - rule out herpes simplex and enterovirus · Serum for comparison of convalescent titres · PCR for possible organisms in blood and CSF · Consider CT/MRI head and EEG

How can urticaria and angioedema be classified into acute and chronic?

· Chronic urticaria: >6 weeks is usually not allergic, it results from a local increase in the permeability of capillaries and venules, these changes are dependent on activation of skin mast cells o Acute: resolve within 6 weeks, allergy such as food or drug reactions or infection are common triggers o Chronic idiopathic: intermittent for at least 6 weeks o Physical urticarias: cold, delayed pressure, heat contact, solar, vibratory urticarial o Water (aquagenic) o Sweating (cholinergic) or exercise-induced o Aspirin and other NSAIDs o C1-esterase inhibitor deficiency - angioedema only

How might leucocyte function defects present?

· Delayed separation of umbilical cord, delayed wound healing, chronic skin ulcers and deep-seating infection · Leucocyte adhesion deficiency (LAD): deficiency of neutrophil surface adhesion molecules leads to inability of neutrophils to migrate to sites of infection/inflammation

How might infectious mononucelosis present? What other pathogenesises is it involved with?

· EBV is s also involved in the pathogenesis of Burkitt lymphoma, lymphoproliferative disease in immunocompromised hosts and nasopharyngeal carcinoma o Fever o Malaise o Tonsillopharyngitis: often severe, limiting oral ingestion of fluids/food, rarely breathing may be compromised o Lymphadenopathy: prominent cervical lymph nodes, often with diffuse adenopathy o Petechiae of the soft palate o Splenomegaly (50%) o Hepatomegaly (10%) o Abdo pain o A maculopapular rash (5%) o Jaundice o Retro-orbital headaches · Acute infectious mononucleosis presents with a history of 1-2 weeks of fatigue and malaise, however onset may be abrupt, the incubation period in adolescents is 30-50 days but is shorter in younger children · LUQ pain may be due to splenic enlargement and severe abdominal pain may indicate splenic rupture · Symptoms usually persist for 2-3 weeks but fatigue is often prolonged, infants and young children with primary infection are usually asymptomatic · Children younger than 4 years frequently have splenomegaly or hepatomegaly, rash and symptoms of an URTI · More than 90% of patients develop fever which is more severe in the afternoon, typically peaking at 38-39°C but may reach 40°C, fever resolves over 10-14 days · Pulse is normal and tachycardia is unusual · Symptoms may persist for 1-3 months, but ultimately will resolve, they are caused by the host immune response to the infection, rather than the virus itself

What is the epidemiology of HIV in the UK and worldwide?

· Globally, HIV infection affects over 2 million children · In the UK, in 2015, 23 children were newly diagnosed with HIV, 17 were born abroad and arrived in the UK at an older age, of the 860 children born in 2015 to women living with HIV, just one was known to have acquired the virus · The major route of HIV infection in children is mother-to-child transmission, which occurs during pregnancy, at delivery or through breastfeeding · The virus may also be transmitted to children by infected blood products, contaminated needles or through child sexual abuse

What are the complications of EBV?

· Hepatitis: 90% · Jaundice: 5% · Mild thrombocytopenia: 50% · Haemolytic anaemia: 0.5-3% · Upper airway obstruction due to tonsil hypertrophy · Splenic rupture · Neurological complications: coma, meningitis, encephalitis, cranial nerve palsies · Myocarditis and pericarditis · Reye syndrome: causes serious liver and brain damage, may lead to permanent brain injury or death · Chronic fatigue syndrome

How might B cell disorders present?

· In the first 2 years there are severe bacterial infections, especially of the ear, sinus', skin and pulmonary system, there is often diarrhoea and failure to thrive · Recurrent pneumonias can lead to bronchiectasis, recurrent ear infections to impaired hearing

What are the common causative organisms in neonates, infants, toddlers, pre-school and school children?

· Meningococcal infection is most common organism causing septic shock, which may or may not be accompanied by meningitis · Pneumococcus is the commonest organism causing bacteraemia, but it is unusual for it to cause septic shock · Neonates o Group B streptococcus o Gram -ve organisms: E.coli, H. influenzae and Listeria monocytogenes o Acquired from the birth canal or ascended into amniotic fluid o Late-onset sepsis the source of infection is often the environment and is caused by S. epidermis, S. aureus, E.coli, Klebsiella, Pseudomonas, Enterobacter, Serratia and Candida · Infants o H. influenzae type B, Strep. Pneumoniae, N. meningitides and Salmonella · Children o The pathogens are similar to infancy, although the presence of encapsulated organisms generally becomes less common

What antibiotics are used for neonates and older infants and children?

· Neonates <72 hours old (Gram -ve septicaemia) o Benzylpenicillin + gentamycin + cefotaxime · Newborns >72 hours old and infants in the first 6-8 weeks (unless a clear aetiology is known) o Amoxicillin + gentamicin/cefotaxime/ceftriaxone · In older infants and children o Cefotaxime (or ceftriaxome) alone o Gentamycin + amoxicillin o If anaerobic suspected + metronidazole · Patients with indwelling lines are given vancomycin is MRSA is suspected · If hospital acquired o Piperacilin + tazobactam

What are the clinical features of malaria?

· Predominantly from Plasmodium falciparum malaria · Children are the worst affected, especially children aged 6 months to 5 years · Fever: often not cyclical · Diarrhoea and vomiting · Flu-like symptoms · Jaundice, anaemia and thrombocytopenia · Whilst typically the onset is 7-10 days after inoculation, infections can present many months later · Children are particularly susceptible to severe anaemia and the gravest form of the disease, cerebral malaria

What are the causes of immunodeficiency in children?

· Primary o Uncommon o An intrinsic defect in the immune system, most commonly they are due to mutation on genes associated with immunological functions o Most are autosomal recessive, with a few being autosomal dominant or x-linked · Secondary o More common o Caused by another disease or treatment o Intercurrent bacterial or viral infection o Malignancy o Malnutrition o HIV infection o Immunosuppressive therapy o Splenectomy o Nephrotic syndrome · Immunodeficiencies are characterised by infections that are said to be Serious, Persistent, Unusual and Recurrent (SPUR), the type of defect often relates to the infections seen in that disease

How might neutrophil defects present?

· Recurrent bacterial infections: abscesses (skin, lymph nodes, lung, liver, spleen, bone), poor wound healing, perianal disease and periodontal infections, invasive fungal infections such as aspergillosis · Diarrhoea and failure to thrive, granulomas from chronic inflammation · Chronic granulomatous disease: most are x-linked recessive, some autosomal recessive, defect in phagocytosis as fail to produce superoxide after ingestion of micro-organism

What is the DDX for meningitis?

· Sepsis · Febrile seizures · Measles · Mumps · HSP · ITP · Reye's syndrome

What is septic shock and how is it managed?

· Shock: when the circulation is inadequate to meet the demands of the tissue leading to insufficient perfusion Septic shock is diagnosed when sepsis has lead to cardiovascular dysfunction. The arterial blood pressure falls, resulting in organ hypo-perfusion. This leads to a rise in blood lactate as the organs begin anaerobic respiration. Septic shock should be treated aggressively with IV fluids to improve the blood pressure and tissue perfusion. If IV fluid boluses fail to improve the blood pressure and lactate level, children should be escalated to the high dependency or intensive care unit where medication called inotropes (such as noradrenalin) can be considered. Inotropes stimulate the cardiovascular system and improve blood pressure and tissue perfusion. · The child may need o Tracheal intubation and mechanical ventilation o Invasive monitoring of BP o Inotropic support o Correction of haematological, biochemical and metabolic derangements o Support for renal or liver failure

How do you manage a drug allergy?

· Stop the drug · Start a new drug if the existing condition needs urgent treatment · Consider altering the dose or temporarily stopping the drug treatment · Consider the effects of drug-drug interactions · Consider the possibility of withdrawal effects if withdrawn too fast · Provide treatment for the allergy include A-E and medication as necessary

How is EBV treated?

· Supportive · When the airway is severely compromised - corticosteroids may be considered · In 5% of infected individuals, group A streptococcus is grown from the tonsils, this may be treated with penicillin · Ampicillin or amoxicillin may cause a florid maculopapular rash in children infected with EBV and should be avoided

List features of shock

· The clinical features of shock are manfestations of compensatory physiological mechansims to maintain the circulation and the direct effects of poor perfusion of tissues and organs · Early (compensated) signs - · blood pressure is maintained by increased heart and respiratory rate, redistribution of blood from venous reserve volume and diversion of blood flow from non-essential tissues such as the skin in the peripheries, which become cold, to the vital organs like brain and heart o Tachypnoea o Tachycardia o Decreased skin turgor o Sunken eyes and fontanelle o Delayed capillary refill (>2s) o Mottled, pale, cold skin o Core-peripheral temperature gap (>4°C) o Decreased urinary output · In shock due to dehydration, there is usually >10% loss of body weight and a profound metabolic acidosis, which is compounded by failure to feed and drink while severely ill · Late (decompensated) signs - · In late or uncompensated shock, compensatory mechanisms fail, blood pressure falls and lactic acidosis increases, it is important to recognise early compensated shock, as this is reversible, in contrast to uncompensated shock, which may be irreversible o Acidotic (Kussmaul) breathing o Bradycardia o Confusion/depressed cerebral state o Blue peripheries o Anuria o Hypotension

What are the complications of Kawasaki disease?

· The coronary arteries are affected in about 1/3 of affected children within the first 6 weeks of the illness, this can lead to aneurysms which are best visualised on echocardiography · Subsequent narrowing of the vessels from scar formation can result in myocardial ischaemia and sudden death · Mortality is 1-2%

How is malaria diagnosed and treated?

· The infection is diagnosed by examination of a thick film, if species (falciparum, vivax, ovale or malariae) are confirmed on a thin film, repeated blood films may be necessary Treatment · Quinine is required in most cases of Plasmodium falciparum seen in the UK, because of the emergence of chloroquine-resistant strains worldwide · Prophylaxis reduces, but does not eliminate the risk of infection · Prevention of mosquito bites with repellents and bed nets is also important

How is typhoid treated?

· The recent increase in multi-drug resistant strains, particularly from the Indian subcontinent means that treatment with cotrimoxazole, chloramphenicol or ampicillin may be inadequate A 3rd generation cephalosporin or azithromycin is usually effective

How is Kawasaki disease diagnosed? Criteria?

· There is no diagnostic test, instead the diagnosis is made on clinical findings · NICE guidelines say a child has Kawasaki disease if they have a fever >38°C for >5 days along with at least 4 of the following key symptoms o Polymorphous rash o Conjunctival injection in both eyes o Extremities: swollen, red and peeling o Cervical lymphadenopathy o Mucous membranes: red, dry, cracked, peeling, swollen or bleeding, strawberry tongue

What are the features/pathology of meningococcal septicaemia?

· This syndrome results from the activation and continued stimulation of the immune system by proinflammatory cytokines caused by endotoxin · Sepsis is most commonly caused by meningococcus in children, so should be suspected even in the absence of the characteristic rash 4 elements o Capillary leak - causes hypovolaemia, there is initial vasoconstriction to compensate but eventually there is decreased venous return and decreased cardiac output o Coagulopathy - o A severe bleeding tendency in meningococcaemia and presents with severe thrombosis in the microvasculature of the skin. Often in a glove and stocking distribution, sometimes requiring amputation o Metabolic derangement - o Profound acidosis occurs with severe metabolic abnormalities Including hypokalaemia, hypocalcaemia, hypomagnesaemia and hypophosphataemia o Myocardial failure - Function remains impaired even after the circulating volume is restored and metabolic abnormalities corrected . A gallop rhythm is often audible with elevated CVP and hepatomegaly

What are the clinical features and complications of typhoid fever?

· Typhoid is contracted from contaminated drinking water or food · A child with worsening fever, headaches, cough, abdominal pain, anorexia, malaise and myalgia may be suffering from an infection with Salmonella typhi or paratyphi · Gastrointestinal symptoms may not appear until the 2nd week ® diarrhoea or constipation · Splenomegaly, bradycardia and rose-coloured spots on the trunk may be present Complications · Gastrointestinal perforation · Myocarditis · Hepatitis · Nephritis

What is Duncan syndrome?

· inability to make a normal response to EBV and child either succumbs to infection or develops secondary lymphoma

What is the classical presentation of meningitis

· may be brief and fulminant or gradual with several days of URTI followed by more severe symptoms petechial rash - in 50% patients, axillaure, flanks, wrists, ankles, non blanching. This only occurs with meningococcal septicaemia. Other causes of bacterial meningitis do not usually cause the non-blanching rash. This rash indicates the infection has caused disseminated intravascular coagulopathy (DIC) and subcutaneous haemorrhages. · Opisthotonus is arching of the back with increased ICP, there may also be positive Brudzinski and Kernig signs o Brudzinski: involves lying the patient flat on their back and gently using your hands to lift their head and neck off the bed and flex their chin to their chest. In a positive test this causes the patient to involuntarily flex their hips and knees. o Kernig: involves lying the patient on their back, flexing one hip and knee to 90 degrees and then slowly straightening the knee whilst keeping the hip flexed at 90 degrees. This creates a slight stretch in the meninges. Where there is meningitis it will produce spinal pain or resistance to movement. · Headache · Fever · Vomiting · Photophobia · Lethargy · Neck stiffness · Seizures

What is hyper IgM syndrome?

: B cells produce IgM but prevented from switching to IgG and IgA

What are the normal ranges of BP, pulse, RR in paediatrics?

<1 RR >60 HR > 160 High SBP 110 2-5 RR >50 HR >140 High SBP 110 5-12 RR >40 HR >120 High SBP 120 >12 RR >30 HR >100 High SBP >120

What are the features of Kawasaki disease?

A key feature that should make you consider Kawasaki disease is a persistent high fever(above 39ºC) for more than 5 days. Children will be unhappy and unwell. The key skin findings are a widespread erythematous maculopapular rash and desquamation (skin peeling) on the palms and soles. Other features include: Strawberry tongue (red tongue with large papillae) Cracked lips Cervical lymphadenopathy Bilateral conjunctivitis o Inflammation of their BCG vaccination site

How is skin prick testing carried out?

A patch of skin is selected, usually on the patients forearm. Strategic allergen solutions are selected, for example peanuts, house dust mite and pollen. A drop of each allergen solution is placed at marked points along the patch of skin, along with a water control and a histamine control. A fresh needle is used to make a tiny break in the skin at the site of each allergen. After 15 minutes, the size of the wheals to each allergen are assessed and compared to the controls.

What is acquired immunodeficiency syndrome?

AIDS is caused by infection with HIV, which reduces the numbers of CD4 T-cells.

What are the 3 phases of Kawasaki disease?

Acute phase: The child is most unwell with the fever, rash and lymphadenopathy. This lasts 1 - 2 weeks. o Conjunctival injection o Extremities: swollen, red and peeling o Mucous membranes: red, dry, cracked, peeling, swollen or bleeding, strawberry tongue Subacute phase: The acute symptoms settle, the desquamation and arthralgia occur and there is a risk of coronary artery aneurysms forming. This lasts 2 - 4 weeks. o Peeling skin o Abdominal pain, vomiting, diarrhoea, urine that contains puss o Lethargy, headache, joint pain and jaundice Convalescent stage: The remaining symptoms settle, the blood tests slowly return to normal and the coronary aneurysms may regress. This last 2 - 4 weeks. (notes say 4-6) o However the child may still lack energy and is easily worn out during this time

Why is it important to establish whether a food allergy is really present?

Allergies have huge impact - having to be really careful buying/ordering food etc It is not uncommon for symptoms and histories of "allergy" to actually be a somatisation disorder rather than a true allergy. It is important to establish whether symptoms are down to an allergy, or more psychological, because an allergy diagnosis can lead to restrictive or unhealthy eating and do more harm than good. Allergy testing can play a role in reassuring patients that they do not have a true allergy to certain foods.

How does encephalitis present?

Altered consciousness Altered cognition Unusual behaviour Acute onset of focal neurological symptoms Acute onset of focal seizures Fever

Following exposure, how is an allergic reaction treated?

Antihistamines (e.g. cetirizine) Steroids (e.g. oral prednisolone, topical hydrocortisone or IV hydrocortisone) Intramuscular adrenalin in anaphylaxis Antihistamines and steroids work by dampening the immune response to allergens. Close monitoring is essential after an allergic reaction to ensure it does not progress to anaphylaxis.

How is HIV treated?

Antiretroviral therapy (ART) to suppress the HIV infection Normal childhood vaccines, avoiding or delaying live vaccines if severely immunosuppressed. o With the exception of BCG which should not be given as it is a live vaccine that can cause disseminated disease o Additional vaccination against influenza, hepatitis A, B & VZV should be considered Prophylactic co-trimoxazole (Septrin) for children with low CD4 counts, to protect against pneumocystis jirovecii pneumonia (PCP) Treatment of opportunistic infections The aim of antiretroviral therapy (ART) is to achieve a normal CD4 count and undetectable viral load. As a general rule, when a patient has a normal CD4 and undetectable viral load on ART, treat their physical health problems (e.g. routine chest infections) as you would an HIV negative patient. When prescribing medications check for interactions with the HIV therapy. The paediatric HIV multidisciplinary team should be involved in: Regular follow up to monitor growth and development Dietician input for nutritional support when required Parental education about the condition Disclosing the diagnosis to the child is often delayed until they are mature enough Psychological support Specific sex education in relation to HIV when appropriate

What are the normal, bacterial and viral indicators in the LP?

Appearance Normal - clear Bac - clear vir - clear Protein normal 0.2-0.4 bac - >15 vir - mildly raised or normal Glucose normal 0.6-0.8 bacterial - <0.5 vir = 0.6-0.8 White cell count <5 normal bac - >1000 and neutrophils vir = >1000 and lymphocytes Cultre normal - negative bacteria- bacteria viral - negative It makes sense that bacteria swimming in the CSF will release proteins and use up the glucose. Viruses don't use glucose but may release a small amount of protein. The immune system releases neutrophils in response to bacteria and lymphocytes in response to viruses.

List conditions that are the result of a hypersensitivity reaction. When in life do they present

Asthma Atopic eczema Allergic rhinitis Hayfever Food allergies Animal allergies · The presence of eczema or food allergy in infancy is predictive of asthma and allergic rhinitis in later life · Eczema and food allergy usually develop in infancy · Allergic rhinitis, conjunctivitis and asthma occur most often in preschool and primary school years · Rhinitis and conjunctivitis often precede the development of asthma, in children with asthma, up to 80% have coexistent rhinitisWt is o Inhalant allergens e.g. house-duct mite, plant pollens, pet dander and moulds in asthma, rhinitis and conjunctivitis o Ingestant allergens e.g. nuts, seeds, legumes, cow's milk, egg, seafood and fruits in acute allergic reactions or eczema o Insect stings/bites, drugs and natural rubber latex · Proteins with an unstable tertiary structure may be rendered non-allergenic by heat degradation or other forms of processing e.g. some children are allergic to raw apples, but can tolerate eating cooked apples

What is the pathology of B cell disorders? Give 3 examples

B cells are responsible for producing antibodies Abnormal B cells lead to a deficiency in immunoglobulins (antibodies). Deficiency in immunoglobulins is called hypogammaglobulinemia. Clinically, this leads to a susceptibility to recurrent infections, particularly lower respiratory tract infections. Selective immunogolobulin A deficiency Common variable immunodeficiency X-linked agammaglobinlinaemia Hyper IgM syndrome

When should you test for HIV?

Babies to HIV positive parents When immunodeficiency is suspected, for example where there are unusual, severe or frequent infections Young people who are sexually active can be offered testing if there are concerns Risk factors such as needle stick injuries, sexual abuse or IV drug use

How is hep C in children managed?

Babies to hepatitis C positive mothers are tested at 18 months of age using the hepatitis C antibody test. Breastfeeding has not been found to spread hepatitis C, so mothers are free to breastfeed their babies. If nipples become cracked or bleed breastfeeding should temporarily stop whilst they heal. Children often clear the virus spontaneously. Chronic infection with hepatitis C does not usually cause issues in childhood. Infected children will require regular specialist follow up to monitor their liver function and hepatitis C viral load. Medical treatment may be considered in children over 3 years. Treatment in childhood involves pegylated interferon and ribavirin, which are less effective and well tolerated compared with the adult treatments. Treatment is typically delayed until adulthood unless the child is significantly affected, because children are usually asymptomatic and newly available treatment for adults is highly effective.

What is C1 esterase inhibitor deficiency (hereditary angioedema)? How is it treated?

Bradykinin is part of the inflammatory response. It is responsible for promoting blood vessel dilatation and increased vascular permeability, leading to angioedema. Part of the action of C1 esterase is to inhibit bradykinin. An absence of C1 esterase causes intermittent angioedemain response to minor triggers, such as viral infections or stress, or without any clear trigger at all. Angioedema often affects the lips or face but can occur anywhere on the body, including the respiratory and gastrointestinal tract. The swelling can last several few days before self resolving. Angioedema can occur in the larynx and compromise the patients airway. Patients can be treated with intravenous C-1 esterase inhibitor as prophylaxis before dental or surgical procedures or in response to acute attacks of angioedema. A key test for hereditary angioedema (C1 esterase inhibitor deficiency) is to check the levels of C4 (compliment 4). C4 levels will be low in the condition. The exam question describe a patient with episodes of unexplained lip swelling and ask what test to perform. The answer is C4 levels.