=vasovagal syncope, but more specifically in response to stimulus.
Abortive measures, preventive measures, drugs discussed there and at POTS.
Cognitive behavioural therapy makes sense, if the trigger is a situation (eg attending hospital), rather than purely an actual physical stimulus.
See STARS for patient support.
NICE update 2021 a bit depressing:
Main thrust of update is that CFS/ME is a complex, chronic medical condition affecting multiple body systems and its pathophysiology is still being investigated. It affects everyone differently and its impact varies widely – for some people symptoms still allow them to carry out some activities, whereas for others they cause substantial incapacity. It is a fluctuating condition in which a person’s symptoms can change unpredictably in nature and severity over a day, week or longer.
Often it profoundly affects different aspects of the lives of both people with ME/CFS and their families/carers including social life, emotional wellbeing and education.
Another big theme is prejudice, disbelief and stigma experienced by patients.
US IOM expert panel have rejected the name “chronic fatigue syndrome”, as patients hate it! Myalgic encephalitis (ME) also rejected on basis of insufficient evidence that this is the pathological process. They suggest “Systemic exertion intolerance”, which is probably even more rubbish, in my opinion.
Diagnostic criteria: all of the following 3 [BMJ 2015; 350]
Substantial reduction/impairment in pre-illness levels of activity, that persists for more than six months [NICE 2007 says 3/12 for children], and accompanied by fatigue (often profound, new or definite onset, not the result of ongoing excessive exertion and not substantially alleviated by rest)
Worsening of symptoms after any type of exertion (including cognitive and emotional stress) – “post-exertional malaise“
Unrefreshing sleep, and/or sleep disturbance.
In addition, should have at least one of:
Orthostatic intolerance.
Doesn’t mention chronic pain?! NICE says reconsider diagnosis in absence of cognitive difficulties or chronic pain.
Evidence (reproducible) implicating certain infections as a trigger. Co-existing mood disorder in substantial proportion of patients, sometimes sleep-wake disorder – likely to perpetuate/exacerbate.
Brain imaging has identified alternations suggesting that it is a brain problem.
[NICE 2007]
NOT microbiology unless indicated: borrelia, HIV, Hepatitis viruses, EBV, CMV, toxoplasmosis
Cochrane review of graded exercise therapy – may benefit sleep, physical function, self-perceived general health, and no evidence that it worsens outcomes. Curiously, no evidence for loss of aerobic fitness! Perhaps graded exercise tackles a hyper-reactive CNS response to exercise-related physiological signals. Note that fear of physical activity becomes conditioned when it commonly exacerbates symptoms.
Warn that exercise programmes can make things worse rather than better. Exercise should only be done as part of supervised programme, with physiotherapist – don’t just tell them to go the gym more! Start below baseline activity level.
Relaxation techniques recommended by NICE.
CBT – should only be offered to manage symptoms, improve functioning and reduce distress. Again, not a “cure”. Analysis of both CBT and graded exercise suggests that benefit comes from reducing inactivity.
Sleep hygiene important. Include rest periods in plan but avoid day time naps, especially since sleep doesn’t usually help anyway!
Many people find exclusion diets useful, esp bowel symptoms, not recommended but involve dietician if attempted anyway.
Equipment to maintain independence can improve quality of life and should be part of overall management.
Beware boom-bust! Many patients over do it when they have a period of relative wellness. Flares and relapses are to be expected. Trigger? New medical problem? Adjust plan as necessary.
Pain and orthostatic intolerance are big issues for some people.
Severe CFS can increase risk of pressure ulcers, DVT, vitamin D deficiency and contractures.
Important to be honest at time of diagnosis. More optimistic in young people. Most adults improve, some are able to return to usual activities but others experience long term symptoms or relapse.
PACE trial aimed for less than full restoration of health as “recovery”, future trials should use clinically relevant improvement and patient self-perception.
[bmj 2015;350:h2087]
2010 Scottish Good Practice statement needs update.
2014 Report (adults and kids) finds that routine asthma care, management of previous and final attacks is generally poor, but particularly for children cf adults.
Almost half did not seek medical help before death. 10% deaths within 1 month of discharge from hospital for asthma. Many being treated for mild/mod asthma, but review suggested prob poorly controlled severe asthma. Widespread over reliance on reliever inhalers and underuse of preventers. Overall 39% had used more than 12 blue inhalers in the year before death. 80% of deaths did not get 12 preventer inhalers in the previous year. Nearly half had not had an asthma review in previous year.
Poor follow up of previous severe attacks (but only about 20% had been in A&E in the previous year).
Delays in primary and secondary care in about a 1/3 of final attacks.
In 93% children and young people, one or more avoidable factors relating to patients, their families and their environment: eg exposed to smoke or smoked, allergy,
Poor recognition of risk of adverse outcome from asthma.
Any patient prescribed more than 12 relievers in a year should have urgent review. Follow up should be made after every ED attendance for asthma. Every hospital discharge should have hospital outpatient follow up.
Should have personal asthma action plan (PAAP).
Better education on when to use asthma medication, recognise poor control, how/when to seek emergency advice.
Triple A online test!
See GP within 48hrs of discharge.
Associations with depression and anxiety. Obesity mentioned.
=C1 esterase inhibitor deficiency. Acquired angioedema seen, esp ACE inhibitor associated acquired AE, more common in blacks and transplant patients.
Sense of smell is impaired in HAE, correlates with complement levels!
Angioedema is bradykinin mediated, hence why different from urticaria and not responsive to antihistamines, steroids etc.
Prothrombin fragment F1 and 2 plus D-dimer levels have diagnostic value in acute attacks.
Consensus algorithm in 2010 (more recent American viewpoints).
Recurrent circumscribed, non-pruritic, non-pitting oedema. Not usually painful unless a pressure area. Can affect virtually anywhere but typically extremities. Upper respiratory tract involvement eg tongue, pharynx and larynx accounts for the reported 15–33% mortality. Abdominal pain with vomiting are dominant symptoms in approximately 25% (intestinal wall and mesenteric oedema).
Urticaria is not a feature of C1 INH deficiency. However, prodromal “serpiginous” erythema has been reported in up to 25% of patients which may be mistaken for urticaria or even cellulitis.
Classically, oedema develops gradually over several hours, continues to progress slowly for 12–36 hr, and then subsides after 2–5 days. Sudden onset abdo pain without visible oedema can occur, with or without diarrhoea.
Attacks can be once a year in some, weekly in others. Triggers are trauma including dental work, surgery; infection; emotional stress; drugs eg OCP, ACE inhibitors (which can cause oedema without HAE, of course). Can present under 1yr of age. Laryngeal attacks tend to come later in life (rarely under age 3). Gets worse with puberty.
Good dental hygiene important in prevention!
Testing under age 1 unreliable so always repeat. Baseline C4 is low in 98% of cases so good screening test – if normal during attack then review diagnosis! No need for CH50.
Low C1 inhibitor suggests type 1 HAE. Acquired is possible in people over 40 without family history, C1q low in these cases.
If normal C1 inhibitor but strong clinical suspicion, do C1 inhibitor functional assay to look for type 2 HAE. If still normal, repeat testing during attack.
Type 3 HAE has normal C1 inhibitor and function – mainly women. Due to Factor XII gene mutations and others.
Genetic testing (SERPING1) may be useful where these tests not conclusive.
Human pdC1-INH (Berniert, Cinryze else Conestat-alpha which comes from transgenic rabbits) is recommended for all attacks (for adults and children). Not licensed for acquired? Beware rabbit allergy!?
Children don’t need prophylaxis as much as adults, but is recommended for surgery in the head and neck area. pdC1-INH is recommended, if not available, use danazol. Tranexamic acid can also be used.
Give C1-INH up to 24hrs before procedure (with/without further dose post-procedure), or else 48hr steroids/TA before and after.
The only treatment option for long-term prophylaxis in children is pdC1-INH. Question is not just frequency of attacks but severity (laryngeal vs hand, for example).
Attenuated androgens worked but not available. Side effects not great, include weight gain, virilization, muslce cramps, jaundice. In children, stunts growth.
C1 inhibitor has short half life so needed every 2-3 days. Subcut works for prophylaxis! Costs £140K per year.
Berotralstat – oral kallikrein inhibitor – some GI upset, long QT. NICE/SMC approved. £10 000 per month so similar.
Lanadelumab – subcut monoclonal kallikrein inhibitor. 2-4 weekly. Similar cost.
At the current pediatric consensus meeting for German-speaking countries, several concerns were raised about these international consensus recommendations:
Autoimmune HAE can be treated with C1-INH but some are resistant due to rapid catabolism so icatibant seems a good option. HAE with normal C1-INH function do not respond to antihistamines or steroids but do respond to C1-INH, tranexamic acid, danazol.
[ Eur J Pediatr (2012) 171:1339–1348]
[Bowen et al. Allergy, Asthma & Clinical Immunology 2010, 6:24]
Gilbert’s syndrome is an hereditary, chronic/episodic, mild unconjugated hyperbilirubinemia. Due to impaired hepatic bilirubin clearance (glucuronyltransferase deficiency). Otherwise liver function is normal.
It does not cause chronic liver disease. Non pruritic. Jaundice may be provoked by fasting, surgery, dehydration, alcohol ingestion, infectious illnesses, heavy physical exertion, and lack of sleep. Symptoms eg tiredness are due to exacerbating condition, not high bilirubin!
Common, 2–10% of the general population, many undiagnosed. At least 30% of people with Gilbert’s syndrome never develop symptoms.
Gilbert’s syndrome can be diagnosed when the person has:
Differential is Crigler Najjar type 2 – can cause persistent jaundice in childhood (cf type 1 = severe jaundice in first few days of life).
No treatment is required.
Some drugs should be used with caution in people with Gilbert’s syndrome:
[NICE clinical knowledge summary]
Parent/family information at https://childliverdisease.org/liver-information/childhood-liver-conditions/gilberts-syndrome/
Or Cot death? Or SIDS (Sudden infant death syndrome)?
It is well recognised that some babies go to sleep apparently healthy, and then don’t wake up in the morning. Even after a full post mortem (PM) investigation, no cause is found. This unexplained phenomenon however has some very well recognised features eg age 2-6 months, prematurity, maternal smoking, poor socio-economic conditions, prone sleeping.
SUDI was originally defined by CESDI (Confidential Enquiry into Stillbirths and Deaths in Infancy) as death between 7 and 365 days where unexpected and unexplained at autopsy, during an acute illness that was not recognised as life-threatening, due to an acute illness of less than 24 h duration in a previously healthy infant (or death after this if life had only been prolonged by intensive medical care); definition also includes deaths from a pre-existing occult condition, and deaths from any form of accident, trauma or poisoning.
I find SUDI most useful for describing the initial situation one may find oneself in, particularly from the point of view of bereavement, need for medical and police investigation. Interestingly, many of the same risk factors pertain to both deaths unexplained (ie SIDS, or strict SUDI) and to accidental deaths (with the exception of prone sleeping).
SIDS is the ICD recognized term, so is what is generally put on a death certificate. However pathologists vary in their use of the terminology, some will use “Unascertained” to mean SIDS, others will use SIDS but reserve Unascertained for cases where there are additional factors that somehow cast doubt on the diagnosis.
Similarly, overlying (smothering) as a cause of SUDI is often inferred from the history, but may be specified on the death certificate to differentiate from SIDS.
PM finds a cause in about a 1/3 of cases) eg
See also Prevention, and Sudden unexpected postnatal collapse.
Clinical picture, whereby kidneys leak protein, leading to hypoalbuminaemia. This results in oedema, particularly noticeable around the eyes, but also peripherally and as ascites. Mechanism is thought to be loss of negative charge on basement membrane. Usually idiopathic, mostly Minimal change glomerulonephritis. Otherwise can be focal segmental gomerulosclerosis (10-20%), secondary (eg HSP, SLE).
Mostly boys, 2 to 1 ratio. 5% go on to Chronic Renal Failure. Hypertension unusual so consider non minimal change glomerulonephritis if hypertensive at presentation. Classic features are:
Check FBC, U&Es, creat, albumin, LFTs, varicella IgG (to check status before starting steroids), cholesterol, HBV/HCV, C3/4. Urinalysis, urine culture, protein:creatinine ratio. Urine sodium <10mmol/l indicates hypovolaemia.
Those with minimal change tend to be responsive to steroids and do not need a biopsy. But if atypical or unresponsive (allow 4 weeks) then biopsy indicated; or if:
Remission defined as 3 consecutive days neg or trace protein. Most remit within 1 month, refer if no response by then – allow 8/52 before labelling steroid resistant .
1/3 no relapse, 1/3 infrequent, 1/3 frequent. Nephrotic relapse defined as 3+ protein for 3 days, but also refer if 2+ for 7 days. Treat relapse with prednisolone 2mg/kg until proteinuria suppressed for 3 days, then taper over 4-8 weeks. In frequent relapsers (ie 2+ within first 6 months, or 4+ within any 12 month period), may become steroid dependent (ie relapses during weaning) so consider Levamisole (2.5mg/kg alternate days, SE reversible neutropenia), cyclophosphamide, ciclosporin etc.
As with any condition requiring high dose steroids, remember vaccinations, varicella, bones.
Children with steroid-resistant nephrotic syndrome who are homozygous or compound heterozygous for NPHS2 (podocin) mutations do not respond to standard steroid treatment and have a reduced risk for recurrence of nephrotic syndrome (with focal segmental glomerulosclerosis) after renal transplantation. Available through UK Genetic Testing Network for children with nephrotic syndrome that is resistant to treatment with steroids, presents in the first 3 months of life or has a histological picture of focal segmental glomerulosclerosis on renal biopsy.
Identified as a group by BPSU, led by Julie-Clare Becher in Edinburgh. As with SUDI, previously well appearing baby suddenly suffers cardiorespiratory failure, with death or severe neurological disability as a result.
Her 2011 report highlighted an association with prone position and breast feeding. One third of of cases had an underlying pathological or clinical condition but over half probably due to accidental suffocation, frequently unrecognised by parents themselves.
Some suggestion that cases are underreported, and that cases are increasing due to increased early skin-skin practices without adequate supervision. In a big survey from Sweden, most happen within first 2 hours of birth, often during first breast feeding attempt.
The process of referral to procurator fiscal, bereavement support, prolonged delay in post mortem report etc is common to SUDI, even if only a few of the underlying risk factors are shared.
A BAPM protocol is available, detailing elements of history eg family tree, drug/alcohol/smoking history, obstetric history; plus investigations eg Kleihauer, placental histology, skeletal survey, PHOX2B gene (congenital central hypoventilation syndrome), fibroblast culture from skin biopsy. In a death, most if not all should be done routinely by pathology.
In terms of prevention, standard SUDI precautions are emphasized – avoid prone position, co-bedding, head covering, beware sedating drugs etc. Education of parents regarding warning signs and upper airway control. Better non-obtrusive monitoring.
[Arch Dis Child Fetal Neonatal Ed 2012;97:F30−F34. doi:10.1136/F30 adc.2010.208736; Translational Stroke Research , Volume 4, Issue 2, pp 236-247]
Both type I and type IV allergic reactions associated with corticosteroids have been reported in the literature. Due to drug itself, the excipients making up the drug, or both?
Corticosteroids have been classified into 5 different categories based on their structural and chemical properties:
| Group | Agents |
| A | Hydrocortisone
Methylprednisolone Prednisolone |
| B | Budesonide
Triamcinolone |
| C | Betamethasone
Dexamethasone |
| D1 | Mometasone furoate
Fluticasone propionate |
Cross-reactivity outside of these groups has only really been seen with group D2, which includes only lesser known steroids eg hyrdocortisone 17 butyrate, and group A. Budesonide has also been described to exhibit some cross-reactivity with group D2, due to a stereoisomer, rather than its group conformation. There is also some cross-reactivity with sex hormones, although the clinical significance is unclear – there is a type of cyclical dermatitis which is thought to be related to endogenous progesterone sensitivity.
[Allergy. 2009 Jul;64(7):978-94. doi: 10.1111/j.1398-9995.2009.02038.x]
Used interchangeably with Pollen food syndrome, although PFS is probably a better name because it is more specific and more closely represents what is going on. Only described in 1942!
Pollen Food Syndrome (PFS) refers to fruit and/or nut allergy, associated with birch pollen allergy (ie hayfever). The food allergy part of the deal however is usually mild, eg itching/tingling/scratching/numbness, of lips/tongue/throat (sometimes ears) only, which distinguishes it from primary peanut or tree nut allergy. Peri-oral rash, nausea, abdo pain are sometimes reported. Mild angioedema of tongue and lips can occur, as can cough – you would be more nervous about assuming PFS in this situation, of course.
Peeling root vegetables is a trigger in those who have vegetable types of PFS! Another reason why PFS is a better name.
Extremely common – probably 40% of children with birch pollen related hay fever (and more than 70% of adults)! Getting more common too – climate change related hay fever season, and more allergenic pollen (thought to be related to ozone levels, hence cities can be worse)…
Due to cross reactions between birch pollen and similar proteins (most commonly PR-10 group – also oak, beech, alder) found in fruit, particularly those fruit with pips inside and a peel eg apple, pear, peach – this group of fruit is known as Rosaceae and includes nectarine, cherry, apricot, plum.
Other fruits involved include Kiwi, Mango, Melon, Tomato, Raspberry, Strawberry. Kiwi and banana still quite common primary allergies. Can be both, of course!
Peanut, Hazelnut and almond most common nuts involved in PFS in UK.
Sometimes vegetables (Carrot, Celery, Potato, Asparagus, Pepper). Poppy seed, herbs and spices (Aniseed, Camomile, Coriander, Cumin, Fennel, Parsley).
Profilin group (Bet v2) about 20% of PFS in UK, more common in Southern Europe. Birch and oak too, but also olive tree, London plane, grasses (Phl p12), ragweed. Watermelon profilin cross reacts with melon, kiwi, peach.
There are other similar allergy syndromes including celery-spice-mugwort syndrome and latex allergy.
You may find that you can eat the fruit if peeled, tinned, cooked or processed (eg jam). The ripeness, even the specific species, can matter too. Cold storage may increase the risk of reactions. Freezing doesn’t seem to make any difference.
Some affected individuals even put up with the itching because they prefer not to miss out on their favourite fruit!
Often emerges in later childhood or early adulthood, and only after hay fever develops. Seen in up to 25% of kids, but they don’t always recognise it themselves! Big variations geographically, obviously related to distribution of birch.
The main impetus for making the diagnosis is to select patients with a lower risk of anaphylaxis, even if nut allergic. However, not always possible, and certainly not 100% reliable. Thought that about 3% of PFS patients have systemic rather than just oral symptoms, and 1-2% will have anaphylaxis. Potential confusion too because people who have primary IgE mediated peanut or nut allergy may of course also report isolated oral symptoms if low dose exposure. In the original description of oral allergy syndrome, 50% progressed to systemic reactions!
So, important to differentiate –
BSACI peanut and tree nut allergy guidance is to go with typical history and only test if:
BSACI guideline says beware younger children (under 8) with kiwi, melon or banana allergy, even if otherwise typical history – PFS unlikely.
Testing could be Prick to prick tests (important to get skin and pulp!), or else consider:
Oral challenges only possibly needed if avoiding multiple foods.
Pollen subcut immunotherapy does not seem to help PFS, unfortunately. Insufficient evidence about pollen sublingual immunotherapy. Some work around oral immunotherapy with fresh food or with isolated proteins.
The risk of anaphylaxis in PFS is quoted as 10%, but this is perhaps misleading as it usually relates to very high doses such as smoothies, tofu, soya milk. Other possible risk factors include:
Adrenaline autoinjectors are rarely justified.
But there are reports of anaphylaxis to peanut despite being exclusively Ara h 8 sensitised and passing an oral challenge – but had big dose on empty stomach! [https://doi.org/10.1111/cea.12425]
Golden Delicious, Granny Smith and Cox’s the worst of the fruit, with the most Mal d 1 (Bet v 1 homologue).
BSACI does not mention whether prick to prick with frozen is effective, only that you can still react to frozen fruit/veg.
More severe reactions described with jackfruit! Beware smoothies, protein shakes, edamame beans!
Bean sprouts, mange tout and sugar snap mentioned specifically as usually only lightly cooked, or just raw.
[Isabel Skypala, BSACI PFS guidance, Clin Exp Allergy 2022]