Measles

General paediatrics, Infectious disease

Notifiable.

Currently not an outbreak in Scotland but surging numbers in England (esp West Midlands and London) October 2023-January 2024, with worldwide outbreaks – Kazhakstan, Yemen, Ethiopia, Pakistan.

Extremely infectious – in a vulnerable population, you can expect 15-20 more cases per index case (R0 number). Incubation period is 7-21 days, typically 10-12 days. Infectious period is 4 days before to 4 days after onset of rash. Starts with a prodrome of cough, coryza, conjunctivitis and fever lasting 2-6 days (peaks at day 4-5). Then the rash appears: brick red, maculopapular, starts behind ears, spreads from face on to trunk and then everywhere including palms/soles. Discrete spots may then coalesce. With time the rash may darken (“stain”) and may desquamate. The child is typically irritable – compare other common childhood rashes.

Koplik’s spots are pathognomic but easily missed as they appear early in the illness, disappearing within a few days of the rash starting. They are grey or white spots on the buccal mucosa opposite the 2nd molars.

Case definition is:

  • a fever (temperature 38ºC or higher) and
  • generalised maculopapular rash lasting three days or longer and
  • either cough, coryza or conjunctivitis.

Diagnosis is by oral fluid test else throat swab (or urine) for PCR. Send blood for IgG/M too.

Complication

Significant effect on immune function.

Measles pneumonia most common cause of mortality.

Encephalitis well recognised. Roald Dahl’s daughter Olivia died of it in the 60s and he was a strong supporter of immunisation thereafter.

Management

  • Check vulnerable contacts. Risk window is 4 days prior to rash, to 4 days after onset of rash (peak infectivity before rash appears).
    • Immunosuppressed (biologics or chemo) Group A – may have had good immune response to vaccination earlier in life. Check Measles IgG if in doubt. Susceptibility depends on age, history of previous measles infection, vaccine status. See table 3 below.
    • Immunosuppressed Group B – known vulnerable else unlikely to have adequate antibody levels. Check Measles IgG and treat if negative or unable to check (some will just need IVIG regardless).
    • Pregnant women – even equivocal measles IgG considered protected (neutralisation assays show detectable antibody). Check if only one measles vaccine given or unvaccinated (allow 6 days for result). HNIG used.
    • Infants under 6 months get HNIG as little transplacental transfer of measles antibody, and wane. 6-8 months old with household contact considered high risk and should get HNIG, for other exposure can get MMR.
    • From 9 months onwards, MMR, ideally within 3 days. Beyond 3 days may still help protect against other potential exposures in outbreak.
    • immunosuppressed but also infants and pregnant women. There is not an explicit definition for close contact. Ideally vaccination should be offered within 3 days.
      • Pregnant vaccinated women should be fine, if in doubt do rapid antibody levels, give HNIG (Human Normal Immunoglobulin, NOT MMR) if necessary, repeat serology at 3/52.
      • Infants under 6/12 should get HNIG, unless mother has had natural measles (or born before 1970!). Else MMR, unless 6-8/12 old and a household contact or high risk.
    • IVIG/HNIG should be given within 72 hours of exposure (up to 6 days). Protects for 3 weeks, after which another dose required if further exposure. Dose for IM is 0.6mg/kg up to a maximum of 1,000mg
  • Respiratory protective equipment should be worn when caring for confirmed or suspected cases viz FFP3 respirator.

[HPA Guidance 2024]

Vaccination

Measles now endemic again in England and many European countries, with cases increasing year on year with only a slight reversal during lockdown. Before vaccines, pretty much inevitable part of childhood.

Andrew Wakefield in 1998 didn’t help – no immediate problem with his false paper (due to herd immunity), first death not until 2006, at which point rate 13x higher than pre-Wakefield. Vaccine hesitancy continues to be one of the biggest global health challenges of our time.

MMR clinical symptoms occur 7-14 days post-vaccination. Very rare after booster. Tends to be mild fever, rash and conjunctivitis.

Porto Outbreak

March-April 2018, 96 confirmed cases in a hospital in Porto, Portugal. Mostly vaccinated Health care workers!!!

Atypical presentations – mac-pap rash only, low fever.

Chances of an “escape variant” not covered by vaccine almost zero.

Hyper IgM syndrome

General paediatrics, Immunology

A group of primary immunodeficiencies characterised by inability to class switch, so high IgM but low IgA and G, leading to susceptibility to infection but also autoimmune problems.

Misnomer because high IgM is a clue but not always found!

Various inheritance patterns but mostly X-linked so variable penetrance/severity. Most affect CD40 ligand production.

Usually presents in infancy – skin, lung, sinus, eye infections. Particularly prone to Pneumocystic pneumonia, histoplasmosis, cryptosporidium.

  • Bronchiectasis seen
  • Histoplasmosis leads to fever, cough, lymphadenopathy
  • Chronic cryptosporidium diarrhoea, progressing to cholangitis and cirrhosis
  • Failure to thrive
  • Warty or chronic papular rash
  • Osteomyelitis a particular problem for type 4 where there is less susceptibility to infection otherwise and presentation can be later in life.

Autoimmunity

  • Neutropenia
  • Thrombocytopenia
  • Thyroid disease
  • Kidney disease
  • Inflammatory bowel disease

Malignancy

Increased rate of various malignancies seen.

Paediatric multi inflammatory syndrome associated with COVID19 (PIMS-TS)

Infectious disease

Condition seen in context of SARS-Cov2 infection, with similarities to Kawasaki syndrome.

Neutrophilia (most), lymphopenia, single or multiorgan dysfunction.  Possibly Kawasaki criteria. Exclude other infectious cause including shock syndromes and myocarditis (but don’t delay seeking advice).

Abnormal fibrinogen, d-dimer, ferritin, hypoalbuminaemia. Other features eg coagulopathy variable.

PCR for SARS-Cov2 often negative, but antibody positive.

WHO refer to PIMS-TS as Multisystem Inflammatory Syndrome in Children (MIS-C), case definition is similar but requires at least 3 days of fever and either evidence of COVID-19 on PCR or serology or a likely contact with COVID-19.

In England, PICU admission related to age 15-17yrs, female, black/Asian. Length of PICU stay generally short, some require ECMO, majority survive. [Ward, MedRxIv 2021]



Asthma and allergy stereotypes

Common, General paediatrics, Respiratory

Le Chiffre in Casino Royale may use a custom metal inhaler, but the implication is clear – he is not as masculine as James Bond.

“Mikey from “The Goonies,” who is portrayed as vulnerable and nervous and is seen taking puffs from his inhaler whenever a situation is particularly scary. Stevie from “Malcolm in the Middle” who suffers from severe asthma can barely make it through a sentence without gasping for breath and wheezing uncontrollably.

“Though he is also proclaimed a genius, it is this perceived weakness that becomes his defining characteristic.

“The stereotype even translates to cartoons, with Carl Wheezer from “Jimmy Neutron: Boy Genius” and Millhouse from “The Simpsons” represented as weak and timid individuals who are used as comic relief whenever they are upset and need a puff from an inhaler to control their symptoms triggered by anxiety.” [American lung association blog]

In the film Hitch, the lovable accountant Alfred uses his inhaler when he is scared to take action.  Until he is inspired to greater manliness, and he throws it away and mounts the steps to kiss his girl in passion, no longer shackled by his psychological, rather than medical, condition. [https://mbtimetraveler.com/tag/asthma-portrayal-in-television-and-movies/]

Even JK Rowling is guilty – see her TV show “The casual vacancy”.

Stephen King’s It has a hypochondriac asthmatic character Eddie Kaspbrak – although at least there is a genuinely terrifying scene where he has an asthma attack and his inhaler has run out – but even this has been triggered by bullying, enforcing the “nerd” stereotype.

Wheezy in Toy Story 2 is also a rather pathetic character.

Positive role models lacking. David Beckham and Harry Styles are some of the few.

Children with asthma, not surprisingly, are highly sceptical of such portrayals. Non asthmatic children obviously don’t appraise movie scenes for their meanings but they do judge the social context of the drama [https://pubmed.ncbi.nlm.nih.gov/22574393/]

Few if any other medical conditions seem to get the same treatment…

Vitamin B12

General paediatrics, Nutrition

Sources are animal products including meat, fish, dairy and egg.

For vegans, yeast products (eg Marmite) or fortified breakfast cereal are the only places you get it.

High levels often seen in teenagers. Appears benign, although high levels reported with lymphoma and hypereosinophilic syndrome, plus liver disease.

Irritable Bowel Syndrome

Common, Gastro, General paediatrics

Rome IV classification gives definition as:

Recurrent abdominal pain, at least once per week for at least 3 months, associated with at least 2 of:

  • Associated with defecation
  • Change in bowel frequency
  • Change in stool form/appearance

Bloating has been removed from diagnostic criteria as it has no predictive value, being common across all kinds of GI issues.

Subtypes then based on stool form on symptomatic days – predominantly constipation, predominantly diarrhoea, mixed constipation/diarrhoea.

Normal physical examination supports diagnosis. Tests should include FBC to exclude iron deficiency anaemia, CRP for IBD, TTG antibody for coeliac disease.

Management

Trial of lactose, fructose and wheat free diet if suspected link to consumption of these foods (non coeliac gluten sensitivity occurs).

Low FODMAP diet is challenging but can help – should be supervised by dietician.

Reassurance – making diagnosis helps justify not investigating fruitlessly.

[J Clin Med 2017]

Proteinuria

General paediatrics, Renal

Dipstick testing is highly sensitive and picks up tiny amounts of protein (and blood) that isn’t necessarily of any concern.

A significant proportion of well people will have one or 2 pluses of protein on dip testing at any one time. More common with intercurrent illness.

Can happen with urine infection. Can happen with exercise.

Large amounts of protein loss can indicate nephrotic syndrome. PCR (or ACR) would typically be above 200.

Rarely PCR can be extremely high, but turns out not to be albumin but Tam Horsfall protein – can be ignored!

Grape allergy

Allergy, General paediatrics

Commonly associated with apple, peach, cherry allergy (rosaceae).

You can be allergic to some grape varieties but ok with others. Some may be allergic to grape but not wine, whereas others might not tolerate grape, wine or raisins/sultanas/currants.

Apart from wine, there’s also white wine vinegar, and vine leaves (stuffed in Greek and middle eastern cuisine!

Some people complain of bloating with grapes, this is usually fructose intolerance rather than allergy.

Reactions to wine (symptoms such as flush, rhinitis, asthma, and migraine) are not rare, but can be caused by different things:

  • type 1 immediate allergy to grape
  • type 1 immediate allergy to moulds (“the noble rot” for example is a mould that gives Tokay and Sauternes their character)
  • intolerance reactions to histamine and sulphite.

LTP sensitization seen, associated with anaphylaxis.

Microbiome

Allergy, Gastro, General paediatrics, Immunology

Substantial evidence that alterations in the gut microbiome early in life “imprint” gut mucosal immunity, which is probably important for development of food allergy.

Maternal factors, timing and how solids introduced all likely to be important.

Similarly, the “exposome” is the term for external factors influencing epithelial barrier immune balance – damage, inflammation, colonization, dysbiosis, translocation etc.

Great data from studies of Hutterite vs Amish populations in the US (same origin in Austria) – Amish are more traditional farmers, low technology use, v low atopy rates. See more on the farm effect on allergy here.

Transplacental factors discussed by Patrick Holt (Perth, WA) in 2009 (“soothing signals”).

MV130 is heat inactivated cocktail of bacteria – in RCT (n=120, under 3yrs) 6 months SLIT reduces episodes of recurrent wheeze by 40% in children, also lower duration and symptom scores. [Antonio Nieto, Madrid]

COVID 19 has shown how innate immunity isn’t actually fixed, and can be trained (“trained immunity”) esp BCG, LPS.

Experimental studies have shown that faecal transplants or other attempts to modify bacterial commensals can prevent or treat food allergy as well as asthma.

Mechanisms include restoration of gut immune regulatory checkpoints (eg retinoic orphan receptor gamma T+ regulatory T cells), the epithelial barrier, and healthy immunoglobulin A responses to gut commensals.

[Rima Rachid, JACI 2021]

Sickle cell disease

General paediatrics, Genetics, Haem/Oncology

Autosomal recessive genetic disorder caused by a single nucleotide mutation of the haemoglobin ß-unit, from glutamic acid to valine. The resulting mutant haemoglobin S (HbS) is prone to distortion in cooler or hypoxic conditions, turning into a sickle shape. This damages the erythrocyte causing haemolysis.

The gene is more common among Africans and is occasionally seen in races from the Middle East and South Asia. Its existence is due to protection from malaria seen in sickle cell trait (the heterozygote form), due to shortened red cell lifespan.

You can of course get combinations of sickle cell with other genetic haemoglobin disorders.

Triggers for sickling include cold environment, acidosis, hypoxia and hyperviscosity eg dehydration. Blood flow in capillaries is impaired by the damaged red cells, which leads to a vicious cycle of increased tissue acidosis and hypoxia. Infarction may occur.

Diagnosis

Can be diagnosed even in newborns. Sickle test followed by haemoglobin electrophoresis.

Screening programmes exist in some countries, so that prophylactic oral penicillin can get started early, preventing sepsis.

Clinical

Presents in infancy or early childhood, often with episodes of painful, swollen hands or feet (hand-foot syndrome). The neonate with its high proportion of Haemoglobin F does not get symptoms until there is enough abnormal haemoglobin A produced for red cells to start to sickle.

Acute Crisis

  • Pain
  • Chest syndrome
  • Aplastic crisis
  • Gut crisis
  • Stroke
  • Priapism
  • Sepsis (may precipitate crisis or complicate it)

Pain

Pain can be widespread, but particularly involves bones, the spine, the chest.

Acute Chest syndrome

Can mimic pneumonia, with unilateral or bilateral signs of consolidation, pleuritic pain, and hypoxia. Pain is in chest wall, thoracic spine and upper abdomen. Leads to hypoventilation, causing vicious cycle of atelectasis and subsequently worse sickling. High mortality, so low threshold of suspicion.

  • Hypoxia should be managed aggressively, with respiratory support if necessary.
  • Antibiotics in infection contributing.
  • Avoid diuretics – signs may suggest pulmonary oedema, but likely to exacerbate hyperviscosity.

Aplastic Crisis

Usually secondary to Erythrovirus B19 (formerly known as parvovirus B19) infection, which can trigger transient bone marrow arrest. So sudden drop in haemoglobin with an absence of reticulocytes. Classic “slapped cheek” appearance may never become apparent. Can affect multiple members of a family simultaneously. Differential is spleen sequestration.

Abdominal crisis

Manifest as anorexia, abdominal pain, distension. Usually not diarrhoea or vomiting. Usually not rebound. Bowel sounds usually quiet.

  • Girdle or Mesenteric syndrome – ileus with vomiting. Associated with liver enlargement and bilateral basal consolidation.
  • Differential includes appendicitis, biliary colic or cholecystitis, ischaemic colitis.

Stroke

Typically affects middle cerebral artery territory but may affect any region of the brain; may be transient or permanent. Seizures may occur. Predictive factors are:

  • Previous TIA/stroke
  • Chest syndrome
  • Hypertension
  • Family history of SCD related stroke
  • Low HbF and/or low total haemoglobin
  • Doppler velocities >200cm/sec in children

Differential is meningitis, subarachnoid haemorrhage (associated with multiple intracranial aneurysms).

Sequestration syndromes

  • Splenic sequestration – Seen in infants and young children. Precipitated by fever or dehydration. Symptoms are:
    • Abdominal pain/distension
    • Rapidly expanding spleen (may or may not be painful)
    • Shock, pallor due to drop in haemoglobin (but high reticulocytes cf aplastic crisis)
  • Management is by fluid resuscitation with blood (type specific/O negative if necessary).
  • Hepatic sequestration: similar to splenic, although less shock, and possibly jaundice along with enlarging liver.
  • Priapism: =sustained painful erection. Potentially leads to peripheral gangrene, else cavernosal fibrosis and hence impotence. A urological emergency. Management:
    1. Warm bath, hydration, analgesia
    2. Catheterize if unable to urinate
    3. Sedation eg diazepam
    4. Aspiration + irrigation – ideally within 4-6hrs of onset. Else shunt.
    5. Top-up transfusion may be considered if unstable with other sickle related problems (aiming for Hb 10-12g/dl).
  • Sepsis. Children are relatively immunocompromised due to functional hyposplenism from recurrent spleen infarction. This increases susceptibility to capsulated organisms eg pneumococcus, salmonella, haemophilus.
    • Yersinia is a particular risk in children on desferrioxamine. Causes diarrhoea.

Management

  • Analgesia, aiming to get rapid symptom control with IV bolus doses of opiates eg morphine, diamorphine ideally within 30 minutes of admission, followed by infusion or regular oral doses. Paracetamol and non-steroidal anti-inflammatories may be synnergistic.
  • Oxygen, esp for acute chest syndrome. Debatable if effective for other problems.
  • Hydration, even hyperhydration eg 150% normal daily requirements, IV if necessary. Impairment of renal concentrating power may contribute to dehydration.
  • Warm environment
  • Identification and treatment of infection. Give treatment doses of penicillin (else erythromycin) even if no specific agent identified.
    • Treat with IV antibiotics if severe symptoms/signs
    • Add macrolide eg clarithromycin if chest symptoms
    • Treat empirically for Yersinia with ciprofloxacin if diarrhoea on desferrioxamine.
  • Folic acid (should be on already)

Transfusion

Although anaemia is common in SCD, repeated transfusions lead to the possible complications of:

  • Allo-immunization
  • Iron overload

Hence top up transfusion is only used for acute symptomatic anaemia eg cardiac failure, severe sequestration or pre-operatively. Do not transfuse above Hb 11g/dl. Regular transfusions have a prophylactic role – see on-going treatment below.

Hyperhaemolysis is a life threatening complication of red cell transfusion in sickle cell disease. Can be acute (within 7 days of transfusion) or delayed. Affects not just transfused but autologous cells so Hb can drop below previous level. Fever, haemogobinuria as usual; negative DAT, reticulocytopenia seen (cf parvo). Cover subsequent transfusion with IVIG and steroids; use erythropoietin to maintain. For elective surgery, prophylactic postop CPAP has been used without transfusion. Risk factors poorly defined.

Exchange transfusion

Undertaken to rapidly reduce the percentage of sickle cells in the circulation where life-threatening eg severe chest syndrome, stroke, multi-organ failure. The aim is to reduce %HbS to <20%. Complications are common eg fluid overload, transfusion reaction.

Other Treatments

  1. Pneumococcal prophylaxis is essential for all children. Polysaccharide vaccine should be offered with repeat doses as per Green book.
  2. Folic acid
  3. Hepatitis B immunization
  4. Splenectomy for recurrent splenic sequestration.

On-going treatment

Consider for:

  • Recurrent or stuttering priapism (etilefrine orally is another option here)
  • Stroke/TIA
  • Chronic organ damage eg renal failure
  • Failure to thrive
  • Intractable crises

Options:

  • Regular transfusions. The aim is to keep %HbS <25%. Compared with exchange transfusion, regular transfusions are just as good at reducing complications, are less challenging in terms of vascular access, involve less donor exposure, but cause more iron accumulation.
  • Hydroxyurea. Reduces frequency of crises and transfusion requirements, improves growth. Trials ongoing. Long term risks need to be clarified (toxicity, mutagenicity, teratogenicity).
  • Bone marrow transplant

Iron overload and chelation therapy

Iron overload can be monitored by means of Ferritin levels. Chelation therapy should commence at ferritin levels of 1000mcg/l, with desferrioxamine (desferal) the chelator of choice. Treatment should include vitamin C. Ophthalmological, audiological and cardiological review is necessary.