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.
Experimental studies have shown that faecal transplants or other attempts to modify bacterial commenals can prevent or treat food allergy.
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.
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.
Can be diagnosed even in newborns by hemoglobin electrophoresis.
Screening programmes exist in some countries, so that prophylactic oral penicillin can get started early, preventing sepsis.
Presents in infancy or early childhood. 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.
Sepsis (may precipitate crisis or complicate it)
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.
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.
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.
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:
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).
Splenic sequestration – Seen in infants and young children. Precipitated by fever or dehydration. Symptoms are:
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:
Warm bath, hydration, analgesia
Catheterize if unable to urinate
Sedation eg diazepam
Aspiration + irrigation – ideally within 4-6hrs of onset. Else shunt.
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.
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.
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)
Although anaemia is common in SCD, repeated transfusions lead to the possible complications of:
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.
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.
Pneumococcal prophylaxis is essential for all children. Polysaccharide vaccine should be offered with repeat doses as per Green book.
Hepatitis B immunization
Splenectomy for recurrent splenic sequestration.
Recurrent or stuttering priapism (etilefrine orally is another option here)
Chronic organ damage eg renal failure
Failure to thrive
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.
Stepwise approach, with early recognition of eczema flares. Use lots of emollient frequently, even if skin clear. Management can then be stepped up or down, according to the severity of symptoms, with the addition of the other treatments as listed below.
Mild atopic eczema
Moderate atopic eczema
Severe atopic eczema
Mild potency topical corticosteroids
Moderate potency topical corticosteroids
Potent topical corticosteroids
Topical calcineurin inhibitors
Topical calcineurin inhibitors
Mostly underused. Should always be used, even when the skin is clear (see immunology of eczema). 250-500g per week for most! 1FTU (finger tip unit) covers palm sized area. Apply in downwards motion, in direction of hair rather than rubbing (which might increase irritation). Allow to soak in as much as possible.
Should be easily available to use at nursery, pre-school or school.
Aqueous cream not recommended as “leave on” (ok as soap substitute) says NICE – higher risk of skin reactions. Not much evidence to say one better than another, so whichever suits family best, be it a combination of products or one product for all purposes! Only risk is is flammability, and slipping when washing!
Offer a choice of unperfumed emollients to use every day for moisturising, washing and bathing. Offer an alternative if a particular emollient causes irritation. Spray on emollients are also available, if skin is really sore. Ideally allow several minutes between different creams where practical. Pump dispensers preferred (and don’t share!) as bacterial contamination possible, which may make skin worse. Folliculitis another risk with emollients.
Quickest is steroid first, ideal is emollient first, steroid 20 mins later! But family preference.
Ointments are greasier, so messy, and leaves you looking shiny. Relatively free from additives so perhaps less likely to lead to irritation, but can occlude, leading to heat rash. Good for fissured skin. Cream applies better to moist, weeping areas. Lotion good for scalp (most soluble).
Stinging may just be under treated eczema, which will only improve with regular topical steroids. [BMJ 2019]
Combined antibacterial products available, good for flexures eg Dermol 500 lotion, Dermol 600 bath emollient, Fucidin H (hydrocortisone), Trimovate (clobetasone), Fucibet (betamethasone).
Baths should be short (max 20 minutes), not too hot, towel dry by patting not rubbing. Oats in muslin bag or sock can be squeezed under tap and as sponge. Use a bath additive eg Oilatum NOT bubble bath (beware how slippery the bath gets) and a soap substitute – or just apply your usual emollient before hand, rinse off, and re-apply. Cleans just as well as soap!
For scalp eczema, if inflamed then use your usual topical steroid, applied directly to scalp rather than hair. For scale, you can just use emollients and/or emollient wash products instead of shampoo, usually all you need for babies. Shampoo for older children should be unperfumed and ideally labelled as being suitable for eczema; washing the hair in bath water should be avoided. Coal tar shampoo eg Capasal available. Otherwise, apply emollient at night (use old pillowcase), wash out in morning [itchybaby.co.uk].
Note that Fucibet is potent steroid, don’t confuse with Fucidin H (mild)!
Use mild potency only for the face and neck, except for short-term (3–5 days) use of moderate potency for severe flares.
Use moderate or potent preparations for short periods only (7–14 days) for flares in vulnerable sites such as axillae and groin.
Do not use very potent preparations in children without specialist dermatological advice, or potent topical corticosteroids in children aged under 12 months .[ie you can/should prescribe everything else!]
Only apply topical corticosteroids to areas of active atopic eczema (or eczema that has been active within the past 48 hours), which may include areas of broken skin.
Exclude secondary bacterial or viral infection if a mild or moderately potent topical corticosteroid has not controlled the atopic eczema within 7–14 days.
In children aged 12 months or over, potent topical corticosteroids should then be used for as short a time as possible and in any case for no longer than 14 days. They should not be used on the face or neck. If this treatment does not control the atopic eczema, the diagnosis should be reviewed and the child referred for specialist dermatological advice.
Consider pulse treatment of problem areas of atopic eczema with topical corticosteroids for two consecutive days per week to prevent flares, instead of treating flares as they arise, in children with frequent flares (two or three per month), once the eczema has been controlled. This strategy should be reviewed within 3 to 6 months to assess effectiveness.
Teach how to recognise flares: increased dryness, itching, redness, swelling and general irritability. Give clear instructions on how to manage flares according to the stepped-care plan
Treat flares as soon as signs and symptoms appear and continue for approximately 48 hours after symptoms subside.
Eczematous skin is predisposed to staph aureus infection, and this may result in acute flares. Topical steroid is not contra-indicated in infection, but consider a steroid-antibiotic combination e.g. Fucibet, tailing down to steroid only over a week as things improve. If severe, topical corticosteroids with oral flucloxacillin would be a good option.
Eczema herpeticum can spread rapidly, forming extensive sheets of monomorphic eroded or umbilicated vesicles. Risk factors include early onset, clinical severity, high total serum Ige. Clinically, lymphopenia and fever are hallmarks of disease. Treatment is with aciclovir 200mg 5x a day for 5 days. Parents of children with eczema who have cold sores should be warned not to kiss their children until the sore has healed.
IgE antibodies to Malassezia furfur (a fungus) are found more commonly in eczema patients. Use of antifungals is under investigation.
Bandages and Garments
Cotton gloves help hand eczema eg pompholyx, but also reduce scratching. Nail care similarly important. Tubular bandages (Comfi-easy) keep cream in place, less scratch (but too hot?). Protects clothes too. Garments available, tubular or silk, which are looser, look less medical.
Wet wrap technique is 2 layers: wet 1st layer and wring out, 2nd layer dry. Should only be recommended by experts as higher absorption of steroids.
Ichthammol bandages soothing but messy – pleat, don’t wrap round. Or Zinc.
Duoderm hydrocolloid wound dressing good for putting on top of steroid in poorly healing areas (1-2/7) eg discoid.
Haelan topical steroid tape – for cracks, sticky, can be cut into shape eg T for wrapping around finger. Apply for 12 hrs. See youtube videos.
Cavilon spray or foam applicator is a no-sting barrier film esp hands. Lasts up to 72 hours.
Other treatment options
Tacrolimus 0.03% ointment (Protopic) has been licensed for use in children with moderate to severe atopic dermatitis unresponsive to conventional therapies. Application is twice a day at first for up to 3 weeks, reducing to once daily after three weeks until the atopic dermatitis is clear. More effective than mild topical steroid but not more than potent. No skin atrophy was observed when patients used it daily for up to 2 years. Should only be prescribed by doctors with adequate experience of treating with immunomodulatory agents; consider for patients vulnerable to steroid side effects. For unresponsive patients, referral to a dermatologist for wet-wrap bandaging, a short course of cyclosporin or ultra-violet treatment, in-patient care.
Pimecrolimus has been tested only in mild to moderate disease and has not been compared to mild topical steroids. It is not as effective as potent steroids. Tacrolimus and pimecrolimus have not been compared with each other. Tacrolimus and pimecrolimus are approximately 10 times more expensive than topical steroid preparations. (Arch 2004; 89)
Acupuncture reduces itch in placebo controlled cross over study vs cetirizine – flare size less too!
Infection with T solium can be asymptomatic, or lead to subcutaneous lumps, or enter the central nervous system.
In tissues, can cause muscle pseudohypertrophy, can enter the eye, can cause conduction defects.
In the brain, acute encephalitis, pseudotumour with raised intracranial pressure, dementia/psychosis, chronic meningitis and neuropathies, spinal cord compression.
Finding T solium in the stool has low sensitivity/specificity. CSF may show eosinophils but may be normal. Imaging shows rings or blobs, can look like TB. Can be calcified, doesn’t necessarily mean dead!
Treat with albendazole or praziquantel. Immune reactions to treatment can be severe (raised ICP).
So nematodes (round worms), cestodes (tapeworms), trematodes (flukes). Do not multiply in human hosts cf parasitic protozoa. Multiply through reinfection though! Most have life cycle in other hosts.
Mostly intestinal tapeworms, not that important, but Taenia solium eggs cause cysticercosis.
Hydatid cysts (larval stage of Echinococcus granulosus) are life threatening. Adult stage found only in dogs.
Complex life cycles involving snails. Cysts are ingested, with exception of schistosomiasis, where larvae (cercariae) penetrate skin. Migration within the body is a feature, where they end up causes problems even if it’s a dead end for the organism.