Allergy & Immunology

Question 1

Define allergen, allergic reaction, hypersensitivity reaction

Answer 1

Allergen: non-parasitic antigen that can elicit a type I hypersensitivity reaction

Allergic reaction: exaggerated reaction to allergen in normally functioning immune system (comes under broader term of hypersensitivity reaction, which includes auto-immunity)

Hypersensitivity reaction: 4 types widely recognised (type V more debatable)

Question 2

Type I hypersensitivity?

Answer 2

Immediate onset (15-30 mins from exposure).

Excessive IgE production following sensitisation to allergen. IgE-associated mast cells & basophils degranulate > histamine / tryptase / PG release. Up to 20% will have late phase response (symptoms recur in first 30 hours without repeat exposure - pathogenesis unknown, ?secondary to inflammatory changes initiated by initial response).

Asthma, atopic conditions, allergic rhinoconjunctivitis, anaphylaxis

Drug, food, insect venom allergies

Question 3

Type II hypersensitivity reaction?

Answer 3

Delayed onset (minutes to hours)

IgG-mediated cell destruction, complement system also involved. Antigens usually endogenous but may result from exogenous antigens attaching to cell membrane (haptens).

Goodpasture syndrome
Drug-induced haemolytic anaemia

Question 4

Type III hypersensitivity reaction?

Answer 4

Delayed onset (3-10 hours)

Soluble immune complexes (mostly IgG but may be IgM), complement system also has important role. Antigens can be endogenous e.g. SLE or exogenous e.g. chronic bacterial / parasitic infections.

Rheumatoid arthritis
Systemic lupus erythematosus

Question 5

Type IV hypersensitivity reaction?

Answer 5

Delayed (peaking at 48-72 hours)

Cell-mediated via T cells + macrophages

Contact dermatitis

Question 6

Type V hypersensitivity reaction?

Answer 6

Delayed

Endocrine-receptor mediated > impaired cell signalling, Grave’s disease

Myaesthenia gravis

Question 7

Discuss pathogenesis of atopy?

Management?

Answer 7

Atopic Triad: eczema, rhinitis, asthma.

Classically, develop in sequence alongside food allergy (the allergic march). Atopic individuals more likely to have genetic predisposition to Type I hypersensitivity reactions in response to common allergens. Circulating IgE levels are elevated + immunoassays may reveal a positive response of IgE to a specific allergen (in such tests, patient’s serum is exposed to specific antigen, if IgE binds the antigen, they are visualised by second antibody that binds the IgE).

Tx is symptomatic, dampening allergic response – tends to run in families although environmental exposure important in disease cause, prevalence increasing in industrialised areas: hygiene hypothesis > decreased human exposure to microbes > shift in immune response from cells involved in fighting infection to those involved in allergic pathways (increasing allergic disease in most high income countries).

Question 8

What is anaphylaxis?

Answer 8

Life-threatening emergency, rapid-onset clinical deterioration. May include

• Respiratory: laryngeal oedema > upper airway obstruction & stridor > bronchospasm > lower airway obstruction & wheeze
• GI: abdominal cramping, nausea, vomiting, diarrhoea
• CV: hypotension, tachycardia & shock
• Skin: urticaria + angioedema

Diagnosis based on history + presentation – tryptase levels (a proteinase contained in mast cells) can support diagnosis. It is measured as treatment begins + again within 1-4 hours.

Question 9

Management of anaphylaxis?

Answer 9

ABCDE, Remove allergen if possible

IM ADRENALINE + repeat at 5 MINS if NO RESPONSE
o <6 years: 150 mcg (0.15mL of a 1:1000)
o 6-12 years: 300mcg (0.30mL of a 1:1000)
o >12 years: 500mcg (0.5mL of a 1:1000)

Following resus + established case of anaphylaxis:

Chlorpheniramine: ameliorates histamine release by mast cells
• <6 months 250mcg/kg
• 6 months – years 2.5mg
• 6-12 years 5mg, >12 years 10mg

Hydrocortisone: suppresses immune response + may prevent late-phase reaction
<6 months 25mg
6 months – 6 years 50mg
6-12 years 100mg
>12 years 200mg

Long-term: allergen avoidance key in preventing future episodes, skin prick testing + immunoassay for IgE to specific allergens if doubt over the allergen. Prescribe Epipen (allergy clinic supervision) for some security in case of further anaphylaxis + appropriate training of the family / child / school. Allergen-specific immunotherapy involving gradual administration of increasing amount of allergen can modify immune response + induce protective change – can be used to prevent anaphylaxis to certain venoms / medications.

Question 10

Prognosis of anaphylaxis?

Answer 10

Prognosis: recurrence of severe anaphylactic reaction likely upon re-exposure to the antigen. Subsequent reactions can be of same severity, milder, or worse than the initial episode. Use of allergen-specific immunotherapy has transformed the prognosis for some allergens.

Question 11

What are food intolerances and hypersensitivities?

Answer 11

Immune system of young infants less able to discriminate food from pathogens therefore susceptible to food hypersensitivity.

Adverse food reactions refer to any adverse reaction following the ingestion of food or a food additive – broadly divided into 2 groups: intolerances + hypersensitivities.

Question 12

What is lactose intolerance?

How is it diagnosed?

Answer 12

Primary: most commonly due to lactase deficiency (lactose > hydrolysis > glucose + galactose). Until 5 years, most children have normal lactase levels, so primary uncommon (increased incidence with age + East Asian ethnicity).

Secondary lactose malabsorption: bacterial overgrowth following transient gastroenteritis and following mucosal injury e.g. coeliac disease, drugs, radiation, IBD.

Clinical manifestations:
• Lactose acting as osmotic laxative > diarrhoea & abdominal pain
• Lactose acting as growth substrate for intestinal bacteria: flatulence, bloating, abdominal distention

May be suspected following thorough history, supported by food diary & low faecal pH (<5) or presence of reducing substances in stool. Management: lactose restriction, maintaining calcium and vitamin D levels. Another option: lactase enzyme replacement.

Question 13

What is food intolerance?

Answer 13

Adverse physiological reactions

• Enzyme deficiency e.g. lactate deficiency, galactosaemia
• Psychological e.g. food phobia, direct effects of foods / additives e.g. monosodium glutamate additive

Delayed usually by at least a few hours (possibly longer). Rarely immediately life-threatening.

Bloating, abdominal pain, diarrhoea, skin rashes.

Large load usually required to trigger response

Question 14

What is food hypersensitivity?

Answer 14

Adverse immunological responses + allergies

o IgE mediated (type I): e.g. anaphylaxis, bronchospasm, urticarial

o IgE and cell mediated e.g. dermatitis, gastroenteritis, eosinophilic oesophagitis

• May be rapid onset (particularly IgE mediated)
• Can be immediately life-threatening
• Anaphylaxis, blood/mucus in stool, reflux, bloating, abdominal pain, diarrhoea, skin rashes, faltering growth
• Small amount can trigger severe reaction e.g. peanut allergy may be triggered when eating non-peanut based foods prepared by cooks who have handled peanut

Hypersensitivity: broadly describes immunological reaction which is reproduced on repeat exposure, can be classified as IgE mediated (type I) or non-IgE mediated reactions

IgE-mediated:
• peanut, soy, egg, fish, shellfish
• develop immediately
• classic type I hypersensitivity features

Non-IgE-mediated
• tend to present sub-acutely, may be chronic
• pathogenesis less clear but immune complex (type III) and cell-mediated (type IV) have been implicated
• Usually isolated GI symptoms e.g. nausea, vomiting, abdominal pain, diarrhoea

Diagnosis: careful history + exclusion of other causes, testing for IgE-mediated disease includes skin prick testing or specific IgE antibodies in blood. If doubt, or other tests not available, food challenge after period of eliminating allergen. If confirmed hypersensitivity, refer to dietician for advice on food exclusions.

Question 15

What is CMPI?

Answer 15

Cow’s Milk Protein Allergy

Ingestion of cow’s milk protein or maternal ingestion of cow’s milk protein (breastfed infants) > inflammatory responses in rectum & distal sigmoid colon.

IgE-mediated (onset <2 hours of exposure) or non-IgE-mediated (onset >2 hours of exposure). The term CMPA is usually used for immediate reactions and CMPI for mild-moderate delayed reactions.

Infants typically well but may report blood-tinged stool + occasionally change in frequency of stool, usually presenting at 2-8 weeks old. Regurg/vomiting/colic/cough possible.

Dermatological manifestations e.g. eczema, urticaria, are also common. IgE-mediated form may also present with cardiorespiratory compromise.

Treatment:
• Elimination of cow’s milk protein from diet (mother if breastfed)
• Use of protein hydrosylate formula (protein already broken down)
• In vast majority, can reintroduce cow’s milk at 9 months with no adverse effects

Majority resolve before age 5!

Question 16

What are immunodeficiencies?

Answer 16

Primary = inherited defect (often recessive – be vigilant for X-linked family history, early infant deaths, consanguineous FHx, infections apparent at ~6 months when protection from transplacental Ig diminishes).

Secondary (more common): may be related to systemic disease (SLE, malignancy), malnutrition, splenectomy, drugs, infection (e.g. HIV, EBV, measles).

Key feature is recurrent infection however child with intact immune system will have several respiratory and gastrointestinal infections every year. Suspicious features:
• Concurrent infections & multiple sites
• Persistent and/or recurrent infections resistant to Abx
• Atypical, opportunistic or unusual organisms e.g. PCP
• Faltering growth
• Recurrent severe infections in sterile sites e.g. pneumonia, meningitis

Question 17

Investigations for immunodeficiencies?

Answer 17

FBC (lymphopaenia normal in infection, but persistent is suspicious, anaemia + thrombocytopaenia in severe, chronic + recurrent infection – secondary to bone marrow suppression, thrombocytosis may occur in chronic inflammatory state, eosinophilia suggests allergy or parasitic infection

IgG IgM & IgA (maternal IgG confers protection until 6 months of age but following this, low levels can indicate humoral immune deficiencies), poor response to childhood vaccines (e.g. poor antibody production pneumococcus, diphtheria and tetanus, also indicates humoral immune deficiencies)

HIV testing (for any child with T cell deficiency)

Complement levels (any pt with recurrent infection or Neisseria meningitides), lymphocyte levels (low: indicates defect in cellular immunity – important in SCID as classification based on absence of presence of cytotoxic T cells, T helper cells, B cells and NK cells).

Question 18

What is CVID?

Answer 18

Common variable immunodeficiency

Group of conditions primarily due to failure of antibody production (hypogammaglobulinaemia).

Recurrent resp infections (esp. encapsulated bacteria e.g. Streptococcus pneumoniae) and faltering growth.

IV immunoglobulin is mainstay of treatment, but severe cases may need bone marrow transplant.

Question 19

What is CGD?

Answer 19

Chronic Granulomatous Disease

Primary immunodeficiency characterised by recurrent + severe bacterial & fungal infections, with granuloma formation due to defects in phagocyte NADPH oxidase. It is more common in males and in offspring of consanguineous parents. The majority of cases are diagnosed in the first 5 years – diagnosis of CGD is suggested by recurrent and persistent infections, and infections caused by catalase-producing organisms e.g. Staphylococcus aureus.

Question 20

Fever - green traffic light?

Answer 20

Normal colour

Normal response to social cues, smiles, awakens quickly, strong normal cry or not crying

Normal respiration

Normal cardiovascular parameters, well hydrated

Question 21

Fever - amber traffic light?

Answer 21

Pallor reported by carer

Abnormal response to social cues, no smile, wakes only with prolonged stimulation, reduced activity

Nasal flaring, tachypnoea (>50 if 6-12 months, >40 if >12 months), SaO₂ ≥95% RA, chest crackles

Tachycardia (>160 if <12 months or >150 if 1-2, >140 if 2-5), capillary refill ≥3s, dry mucous membranes, poor feeding / reduced urine output

OR:
Age 3-6 months
Temp ≥39
Fever ≥5 days
Rigors
Swelling of limb or joint
Non-weight bearing limb / not using extremity

Question 22

Fever - red traffic light?

Answer 22

Pale / mottled / ashen / blue
Unresponsive to social cues, appears ill to healthcare professional, asleep or if roused does not stay awake, weak / high-pitched / continuous cry / unresponsive
Grunting, tachypnoea >60 (any age), moderate or severe chest recession
Reduced skin turgor

OR
Age <3 months
Non-blanching rash
Bulging fontanelle
Neck stiffness
Status epilepticus
Focal neurological signs

Question 23

What is prolonged fever, recurrent fever, FUO/PUO, periodic fever

Answer 23

Prolonged fever: exceeds expectation for single episode of illness e.g. >3 weeks with infectious mononucleosis, >10 days in gastroenteritis

Recurrent fever: can be from a single illness or from multiple illnesses occurring at different intervals, usually lasting months or years – should trigger further investigations, particularly with no obvious infective aetiology (and if sign of recurrent infection, may be possible concern about immunodeficiency).

Fever / pyrexia of unknown origin (FUO or PUO): fever where a focus cannot be found, usually applies to a fever lasting >3 weeks, with no focus identified despite intensive initial investigations. FUO may last for over a year, particularly if it is due to inflammatory disorders, other causes include infection + neoplasm.

Periodic fever: predictable episodes lasting days-weeks, recur sporadically or at regular intervals – no infective cause & child is well between episodes. Familial Mediterranean fever (hereditary autoinflammatory) is the most common syndrome, but collectively they are rare

Question 24

Actions if <3 months with fever?

Answer 24

Full septic screen (FBC, U&Es, urine MC&S, CXR, LP)

Treat for presumed sepsis or meningitis until results (both can present with isolated fever or even no fever)

Question 25

HSV1 in children?

Answer 25

Primary infection typically causes oral infection (cold sores), affecting facial area around mouth, lips, tongue, gingiva, palate. Incubation period variable but ~8 days, prodromal period possible (tingling + soreness where lesions will appear), and occasionally fever.

Most asymptomatic, children can present with fever, distress, reduced oral intake + dehydration.

Supportive treatment with topical anaesthesia + oral rehydration salts if dehydrated, rarely required admission for IV fluids

Question 26

HSV2 in children?

Answer 26

Other manifestations: meningoencephalitis, eczema herpeticum & eye infections, for which IV antiviral agents may be acquired.

HSV-2 can potentially cause congenital herpes infection following intrauterine exposure or vertical transmission during delivery, neonatal herpes infection can result in CNS infection (meningoencephalitis) + disseminated infection with significant risk of disability and death, even if treated (IV acyclovir).

Question 27

HHV6 in children?

Answer 27

Most common cause of roseola infantum

Incubation ~10 days

Child 6 months – 2 yrs

2-3 days of fever, when fever subsides, widespread rash emerges (often on day 6 therefore known as ‘sixth disease’)

Often causes parental anxiety as child appearing to be getting better before rash emerges, but condition is benign (no treatment required).

HHV-6 also implicated in encephalitis, hepatitis + febrile convulsions

Question 28

What is chickenpox?

Answer 28

VZV: acquired though contact with infected individuals, incubation 10-21 days.

Prodromal features usually 1-2 days before rash: fever, malaise, headache, abdo pain. Itchy rash: macules > papules > vesicles which crust over. Lesions can turn haemorrhagic.

• Infectious from 48 hours before onset of rash > all lesions crusted over

Diagnosis usually clinical but swabs for PCR if required.

Question 29

Management and complications of chickenpox?

Answer 29

Antivirals unnecessary in healthy children (usually self-limiting), however, indicated in asymptomatic neonates (if mother acquires chicken pox <7 days before or <4 days after delivery), adolescents + immunocompromised (often more severe)

VZ immunoglobulins are used in certain high risk groups.

If fever persists, consider complications:
o Bacterial infection: Staph aureus and Strep pyogenes infections
o Cerebellar ataxia
o Varicella encephalitis
o Pneumonitis
o Hepatitis
o Thrombocytopaenia
o Nephritis

Shingles: reactivation typically in adulthood: painful eruptions of vesicles in dermatomal distribution, antivirals e.g. aciclovir, valaciclovir, can shorten duration of pain and speed up resolution of lesions. Shingles vaccine now available and routinely offered to elderly adults.

Question 30

What is EBV?

Symptoms?

Diagnosis?

Answer 30

Transfer by oral secretions (‘kissing disease’), major cause of infectious mononucleosis (glandular fever), which can also be caused by CMV, toxoplasmosis + HIV. Long incubation period (4-8 weeks).

Prodrome includes headache + general malaise. Classic triad: fatigue, pharyngitis, lymphadenopathy.

Others: fever, hepatosplenomegaly, rash, jaundice). Fever is often high (39-40°C) + can last ~1 week, however, sometimes >2 weeks.

Diagnosis usually clinical, however, atypical lymphocytes + atypical serology can assist. Heterophile antibody tests e.g. Paul-Bunnell test or Monospot test, insensitive in children <2 years but can be useful in older children

Question 31

Signs of EBV? (exam findings)

Complications?

Answer 31

Fever, hepatosplenomegaly, rash, jaundice. Fever is often high (39-40°C) + can last ~1 week, however, sometimes >2 weeks.

Difficult to distinguish pharyngitis by EBV from Group A streptococci (both can present with pustular tonsils + palatal petechiae)

o Palpable nodes: anterior + posterior cervical, submandibular + epitrochlear
o Enlarged exudative tonsils

Very long period of infectivity (can shed for >1 year) + is an oncovirus therefore potential to cause Burkitt’s lymphoma, Hodgkin’s lymphoma & nasopharyngeal carcinoma if not controlled by immune system.

Classic: rash developing after amoxicillin exposure.

Splenic rupture: rare but potentially life-threatening so advised to avoid contact sports or strenuous activity until fully recovered

Question 32

Management of EBV?

Answer 32

Supportive treatment (EBV usually self-limiting), although some develop ongoing fatigue + fever.

Corticosteroids given if complications: impending airway obstruction, thrombocytopenia with haemorrhage, autoimmune haemolytic anaemia, Guillain-Barre, Reye’s syndrome, interstitial pneumonia, myocarditis, seizures with meningitis.

Question 33

What is influenza?

Answer 33

Seasonal viruses causing epidemics every winter in temperate climates (transmitted by respiratory droplets), divided into groups A, B & C.

Circulating strains include H1N1 (2009 pandemic), H3N2 & influenza B viruses.

Type A named by surface proteins: haemagglutinin (H) and neuraminidase (N). Birds are natural host: also carried by pigs, dogs, horses, seals, whales, humans.
• Short incubation (1-4 days)
• Children infectious just before symptoms start and can shed virus for 2 weeks after infection
• Prodrome: fever, myalgia, headache
• Variable symptoms
o Infants: fever, difficulty breathing and feeding (similar to sepsis)
o Preschool: fever, signs and symptoms of URTI, acute otitis media, croup or pneumonia
o Older children: fever, chills, headache, myalgia, malaise

Rare manifestations: myocarditis, encephalitis, encephalopathy

Gold standard: culture from nasopharynx (PCR, rapid antigen detection test and immunofluorescence assays faster & more sensitive)

Treatment mainly supportive
o Oseltamivir shortens duration, reduces complication rate + severity if given within 48 hours of symptom onset - weighed against side effects & resistance
o Inactivated + live-attenuated vaccines: good efficacy.

Complications: tend to occur in very young, elderly and immunocompromised include: pneumonia, secondary bacterial infection, myocarditis, death.

Question 34

What is parainfluenza?

Answer 34

Very common cause of respiratory tract infection in children, transmitted from person to person and cause syndromes ranging from mild coryzal symptoms to bronchiolitis, croup and pneumonia which may be severe.

Treatment is supportive.

Question 35

What is adenovirus?

Answer 35

7 subgroups A-G + many serotypes.
Wide variety of syndromes, predominantly affect children 6 months – 5 yrs. Transmitted by respiratory droplets and faecal oral route depending on serotype. No seasonality – can cause sporadic outbreaks.

Commonly, cause febrile respiratory tract infections e.g. tonsillitis, croup, bronchiolitis, pneumonia.

Certain serotypes associated with severe bronchiolitis: constellation of fever, conjunctivitis, pharyngitis and cervical lymphadenopathy is typical.

Can also cause gastroenteritis, acute haemorrhagic cystitis, pericarditis, myocarditis, aseptic meningitis, encephalitis and transverse myelitis.

In children undergoing haematopoetic stem cell and other transplantation – causes high mortality

Diagnosis: culture, PCR + direct antigen detection

Generally, self-limiting & supportive treatment, if immunocompromised or transplanted patient: antivirals e.g. cidofovir and/or immunoglobulins

Question 36

What is enterovirus?

Answer 36

Includes Coxsackie viruses + echoviruses as well as polioviruses. Over 100 serotypes responsible for many childhood infections.

Most asymptomatic, and common non-specific symptoms: fever, rash, malaise, irritability, vomiting, diarrhoea, signs of upper respiratory tract infection. Enteroviruses found throughout the world and infections tend to occur most often in summer + autumn (mostly in children).

Incubation normally 2-5 days, mainly faecal-oral route, after replicating in GI + respiratory systems, virus can then spread to other organs. Clinical syndromes include:

1. Aseptic meningitis: neonate or child with non-specific symptoms or more typical meningitis symptoms, CSF shows predominance of lymphocytes and may show slight rise in protein with slight decrease in glucose, and enterovirus can be detected by PCR. Treatment is symptomatic and prognosis is good.
2. Hand-Foot-and-Mouth Disease: usually by Coxsackievirus A16 & Enterovirus 71. Vesicular lesions typically on hands, feet & mouth. Oral lesions can ulcerate, causing pain and refusal of food/drink. Usually resolves in a week (self-limiting). Enterovirus 71 can cause brainstem encephalitis, and epidemics occur in SE Asia. Coxsackievirus is also responsible for viral myocarditis
3. Polio: poliovirus has devastating CNS effects, eradicated in most parts of world due to vaccination program (2015: endemic only in Afghanistan and Pakistan), majority of poliovirus infections are asymptomatic, but can cause a non-specific viral illness, viral meningitis and classical paralytic polio with asymmetric flaccid paralysis.

Enteroviruses can also cause myositis, myocarditis, peridcarditis, herpangina (vesicular lesions on soft palate), pleurodynia (combination of fever and pleuritic chest pain) + eye infections.

Question 37

What is parvovirus B19?

Answer 37

Common cause of childhood infection – variety of syndromes. Very small DNA virus transmitted via respiratory droplets + through blood transfusion. Incubation 4-20 days. Most asymptomatic or mild, but classically present as erythema infectiosum aka slapped cheek syndrome or ‘fifth disease’.

Prodrome generally very mild: fever, malaise, coryzal symptoms 2-3 weeks before onset of facial rash (infectious during prodrome, not during rash).

Erythema infectiosum rash: cheek erythema, sparing nose, periorbital + perioral regions. After a few days, secondary lacy rash may occur and spread to extremities.

Generally symptoms resolve after a few weeks, but rash can recur with stimuli e.g. heat, exercise, sunlight.

Also infects red blood cell precursors, therefore if chronic haemolytic disorder e.g. sickle cell disease or hereditary spherocytosis: can cause transient aplastic crisis. In immunocompromised patient: may cause anaemia & red cell aplasia

Other presentations: polyarthropathy (more common in adults)

During pregnancy can cause miscarriage, intrauterine death and hydrops fetalis

Diagnosis: serology or PCR, no antiviral effectively treats, but immunoglobulins can be given to immunocompromised patients to clear parovirus B19 viraemia.

Question 38

What is measles?

Answer 38

Caused by RNA paramyxovirus (highly contagious). Incubation 8-12 days, known as the ‘9-day measles’. Unimmunised, high school and college students most at risk. 3 stages: incubation > prodrome > symptomatic illness.

Prodrome: Cough, Coryza, Conjunctivitis (bilateral), Koplik spots: pathognomonic (white/grey spots in buccal mucosa, opposite molars)

Simultaneous rash with fever, typically behind ears and spreading downwards from head to toe, may become confluent + may then desquamate. Rash disappears in same head > toe order. Infectious from 4 days before rash onset > 4 days afterwards

Question 39

Diagnosis and treatment of measles?

Answer 39

Clinical Dx although lab tests e.g. measles antibody titre + PCR, may be useful

Supportive Tx but vitamin A may reduce severity (WHO: for children in low income countries to reduce morbidity and mortality)

Globally deaths have reduced by 75% (2000  2013), vaccine coverage must be >95% to prevent disease

Immunocompromised children without protective antibody levels should receive passive immunisation with immunoglobulin after exposure to measles

Immunoglobulin also recommended for certain immunocompromised groups e.g. symptomatic HIV-infected children (even if previously vaccinated), as can be particularly severe and cause a viral giant cell pneumonia (can be fatal)

Question 40

Complications of measles?

Answer 40

Otitis media
Pneumonia
Encephalitis
- Rare, typically several days after illness onset, symptoms include headache, irritability, seizures: neurological sequelae can follow: mortality ~15%

Diarrhoea

Dehydration

Subacute sclerosing panencephalitis (SSPE)
- Very rare, occurs many years (often 7-10 years) after initial illness and present with progressive neurological disease leading to death. Cause not clear: probably due to combination of persistent viral replication within the CNS and host immune responses.

Question 41

What is mumps?

Answer 41

Highly contagious, transmitted in respiratory secretions (before symptoms), & continue to shed during parotitis. Usually due to inadequate immunisation. Incubation 14-24 days. Non-specific prodrome: fever, myalgia, earache, headache. Parotitis develops 24 hours later (due to infection & inflammation), present in majority of symptomatic cases. Often starts unilaterally, but bilateral swelling will commonly occur and may last >1 week. Possible to have very minor or no symptoms at all.

Diagnosis usually clinical, may see leucopaenia and ↑amylase. Specific tests e.g. IgM mumps antibody or isolation of mumps virus, may be required in certain cases e.g. outbreaks or atypical cases where diagnosis is not clear.

Treatment is symptomatic, studies of viral shedding indicate child should be isolated for 5 days after onset of parotitis. MMR vaccine: cases much less frequently seen.

Question 42

Complications of mumps?

Answer 42

Mumps orchitis: commonest complication in males, although unusual in young children as it tends to affect post-pubertal males – acute swelling, pain and erythema of the scrotum with high fever. May cause testicular atrophy and subsequent reduced fertility, though this is rare. Mumps can also cause ovarian inflammation in females (which can also reduce fertility).

Meningoencephalomyelitis: aseptic meningitis, which generally has good prognosis, as well as encephalitis which may occur without the classical sign of parotitis.

Sensorineural deafness, pancreatitis, myocarditis and arthritis are also potential complications.

Question 43

What is rubella?

Answer 43

‘3-day German measles’ – acute viral infection causing mild disease in childhood, but can cause severe foetal infection including death and congenital defects.

Incubation 14-21 days, prodrome is rare but may include low-grade fever. May present with mild fever + maculopapular rash (similar to measles rash), spreading from face > body.
Contagious 2 days before rash to 5-7 days after.

Other symptoms: coryzal, conjunctivitis, lymphadenopathy (classically suboccipital, postauricular and cervical) – distinguishes condition from measles

Forchheimer spots on soft palate: pathognomonic

Diagnosis may be clinical but confirmed by PCR of saliva or antibody testing of blood/saliva. Treatment usually supportive and prevention relies on MMR vaccination.

Complications: rarely seen but may include arthritis, thrombocytopaenia and encephalitis.

Question 44

rewtrg

Answer 44

HIV: RNA virus (Retroviridae family): undergoes reverse transcription into proviral DNA & integrated within host genome. HIV infects lymphocytes, macrophages, monocytes & dendritic cells – causing majority of immune cells to die. Over time, triggers chronic immune activation and subsequent immunodeficiency state. Incubation 2-4 weeks, although can be longer. Most children acquire through vertical transmission (antenatally, perinatally or postnatally). Other modes of transmission: blood transfusion, sexual practice.

Newborn: can be rapid presentation, first few months with PCP, lymphadenopathy, hepatosplenomegaly, encephalopathy, faltering growth, chronic diarrhoea, oral thrush, disseminated TB infection, lymphoid interstitial pneumonitis.

Category A (Mild)	Category B (Moderate)	Category C (severe)
Lymphadenopathy
Parotitis
Hepatospelnomegaly
Dermatitis
Otitis media
Sinusitis	Lymphoid interstitial pneumonitis
Chronic thrush
Chronic diarrhoea
Persistent fever
Hepatitis, nephropathy
Recurrent HSV
Cardiomegaly	Candidiasis
Cryptococcosis
Cryptosporidiosis
Encephalopathy
Malignancy
PCP
Cerebral toxoplasmosis

Acquired Immunodeficiency Synrome (AIDs) occurs when patient susceptible to wide range of infections & malignancies.

Diagnosis: identifying HIV antibodies, followed by HIV viral load and CD4 count. Mothers routinely screened in UK, PMTCT – preventing mother-to-child transmission, by improving ART therapy among pregnant women.

Treatment: commence ART with at least 3 drugs from at least 2 classes (e.g. protease inhibitor, non-nucleotide reverse transcriptase inhibitor, nucleoside reverse transcriptase inhibitor) to maximise likelihood of successful treatment. With highly active ART (HAART), prevention of opportunistic infection with co-trimoxazole, immunisation and better nutrition, children expected to reach adult life but with slightly shorter life expectancy.

MDT required for diagnosis, disclosure to child / adolescent and maintaining adherence to ART / sexual health education.

Question 45

How to treat CMPI / CMPA?

Answer 45

If the symptoms are severe (e.g. failure to thrive) refer to a paediatrician.

Management if formula-fed:

• extensive hydrolysed formula (eHF) first-line replacement formula for infants with mild-moderate symptoms
• amino acid-based formula (AAF) in infants with severe CMPA or if no response to eHF; around 10% of infants are also intolerant to soya milk

Management if breast-fed

• continue breastfeeding
• eliminate cow’s milk protein from maternal diet
• use eHF milk when breastfeeding stops, until 12 months of age and at least for 6 months

CMPI usually resolves by 1-2 years of age. A challenge is often performed in the hospital setting as anaphylaxis can occur.

Question 46

wwdd

Answer 46

Bacterial Infections

Staphylococcus aureus: main staphylococcal species responsible for disease

• Skin & soft tissue infections e.g. cellulitis, orbital cellulitis, abscesses, impetigo.
• Invasive disease: osteomyelitis, septic arthritis, pneumonia, septicaemia, endocarditis

Organism can cause disease directly, but also capable of producing toxins which act as superantigens  massive T-cell activation & cytokine release  toxic shock syndrome, food poisoning & toxic epidermal necrolysis.

Treatment dependent on site & severity: beta-lactam antibiotics e.g. flucloxacillin are main treatment for methicillin-sensitive Staphylococcus aureus infections. Macrolides e.g. erythromycin, can be used if penicillin allergic. Glycopeptides e.g. vancomycin, are effective against methicillin-resistant Staphylococcus aureus (MRSA).

Healthcare-associated MRSA is multi-ressitant form, more common in hospital or healthcare institution, community-associated MRSA (CA-MRSA) tends to be found in young healthy people who may be colonised rather than actively infected & not usually multi-drug resistant.
Streptococcal infections: many types causing wide range of infections, like staphylococcus can cause skin and soft tissue infections, but can also cause serious invasive diseases e.g. meningitis, toxic shock syndrome, septicaemia. Treatment depends on disease, but will often be a penicillin. Pneumococcal vaccines effective in reducing morbidity & mortality from pneumococcal infections and are being rolled out to developing countries with the help of an international organisation (GAVI).

• Streptococcus pneumoniae: mild infections e.g. otitis media, pharyngitis, conjunctivitis & sinusitis but can also serious invasive disease e.g. pneumonia, meningitis, sepsis. Commonly carried as commensal organism (nasopharynx healthy child), spread to those at risk by respiratory droplets. Encapsulated organism therefore young infants & those with hyposplenism (e.g. sickle cell disease) are at high risk.
• Group A β-haemolytic streptococcus (i.e. Streptococcus Pyogenes): most commonly causes pharyngitis (diagnosed through throat swab) but can also cause severe invasive disease e.g. necrotising fasciitis, toxic shock syndrome & bacteraemia. It also causes puerperal sepsis, scarlet fever and longer term effects post-infection e.g. rheumatic fever, post-streptococcal glomerulonephritis and paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAs).

o Scarlet Fever: starts non-specific: sore throat, fever (usually >38.3), headache, fatigue, nausea & vomiting. Blanching rash develops on abdomen & chest 12-48 hours later, then spreads to neck/limbs/extremities. Characteristically red, generalised, punctate with rough, sandpaper-like texture. Particularly florid in skin folds of neck, axillae, groin, elbows, knees (Pastia’s lines). Skin may peel / desquamate (particularly at the tips of the digits) after the rash evolves. Examination may show: strawberry tongue (initially white covering, red papillae, white disappears  beefy red), cervical lymphadenopathy, flushed face with circumoral pallor, pharyngitis and red macules over hard & soft palate (Forchheimer spots). At risk patients: immunocompromised, co-morbidities e.g. diabetes mellitus, co-existing chickenpox or breaks in the skin.
o Management: admission & urgent assessment if valvular heart disease, significantly immunocompromised or suspected severe complication. If scarlet fever suspected and patient well: penicillin V TDS for first 10 days. Amoxicillin if poor compliance or cannot swallow tablets. Azithromycin if penicillin allergy. Paracetamol or ibuprofen, rest and fluids, notify PHE, symptoms should usually resolve within a week and Abx prevent complications, exclusion until 24 hours after starting Abx, return if worsen or not improved in 7 days. Avoid high risk individuals.

• Group B Streptococcus (GBS): common commensal in genital tract but can result in neonatal sepsis: women known to be GBS positive can have intrapartum Abx
• Viridians Streptococci: commensal organisms colonise oral, upper respiratory, GI & female reproductive tracts, but can cause endocarditis, bacteraemia and meningitis. Treatment depends on disease & organism isolated but generally with a penicillin.

Meningococcal infections: Neisseria meningitidis = gram negative diplococcus, can cause severe infections e.g. meningitis, meningococcal septicaemia. Main serogroups are A, B, C, W & Y. Meningococcus in nasopharynx of ~10% healthy people, transmitted between people and can spread to bloodstream & meninges. Infection most common in < 3 years. May present with classical signs of meningitis or septicaemia with characteristic non-blanching purpuric rash (meningitis can occur + or - septicaemia so rash may not be present). Highest mortality for meningococcal septicaemia, meningococcal meningitis alone has better prognosis.
• Diagnosis by blood culture, or CSF if meningitis is suspected.
• Blood may also be sent for meningococcal PCR
• Treatment: empirically if septicaemia or meningitis are suspected, without waiting for results  broad spectrum third generation cephalosporin (e.g. IV ceftriaxone). ICU may be required
• Notify PHE & contact tracing performed
• Vaccinations for serogroups A, B, C, W & Y incorporated into childhood schedule.

Lyme Disease: caused by Borrelia burgdorferi & acquired by tick bites – spread the infection by feeding on infected animals e.g. deer. May history of camping or walking in forest though actual bite may not have been noticed. Typical lesion: erythema migrans (target lesion) around bite with fatigue, lymphadenopathy, myalgia, headache, fever. Neurological features e.g. meningitis, facial palsy, cerebellar ataxia can occur 2-10 weeks after bite. Arthritis (usually affecting knee) can occur from 1 month to one year after the tick bite.
• Diagnosis confirmed via antibody testing
• Treatment started on suspicion of disease without waiting (antibodies may not be positive until 6 weeks after bite)
• Usually amoxicillin (or doxycycline if >12 years) for 2-3 weeks

Typhoid: caused by Salmonella typhi & form of enteric fever: initial abdominal pain & bloody diarrhoea + constitutional symptoms e.g. fatigue, dizziness. Fever classically rises throughout day and drops by the following morning. Spread generally by consumption of faecal-contaminated food or water. Salmonella paratyphi causes similar disease, usually less severe: paratyphoid. Diagnosis is by culturing organism from faeces, blood or urine.
• Treatment with quinolone e.g. ciprofloxacin for many years however increasing resistance seen, third generation cephalosporins such as ceftriaxone now first line
• Prevention: sanitation, clean water, vaccines

E. Coli: gram-negative motile bacilli that can cause UTIs, enteric infections and disseminated infections (e.g. meningitis, sepsis, pneumonia). Enterohaemorrhagic E. coli (EHEC), usually serotype 0157, is associated with haemolytic uraemic syndrome (HUS).
• Diagnosis: microscopy & culture
• UTIs usually treated with trimethoprim or amoxicillin, but severe infections will require IV Abx tailored to the susceptibility pattern
• If diarrhoea caused by E. coli 0157, Abx avoided as they may increase risk of HUS by increasing the amount of toxin release