Category Archives: Immunology

Testing for antibiotic allergy

March 30, 2016Allergy, General paediatricsTherapyadmin

Henoch Schonlein Purpura

November 25, 2015Common, Dermatology, General paediatrics, Immunology, OPD, Renal, Rheumatologyadmin

or HSP. Usually preschool but any age! Boys more than girls. Vasculitis, leucocytoclastic with IgA predominance. EULAR criteria 2010.

Features:

Urticarial rash becoming purpuric but still raised (pathognomic), predominantly on lower limbs, especially extensor surfaces incl buttocks, but sometimes trunk, rarely face (infant). Accompanying soft tissue swelling, as seen in photo in feet.
Arthralgia (not migratory, cf acute rheumatic fever)
Abdo pain, diffuse, colicky, often severe – possible intussusception, melaena
Proteinuria (30+ mmol/mg albumin:creatinine ratio), 2+ red cells on dip or 5+ on microscopy (or casts) indicating glomerulonephritis, usually asymptomatic cf streptococcal, but a few develop diffuse proliferative lesions with irreversible renal damage.
Scrotal rash/bruising common, rarely torsion
Rarely encephalitis, seizures, pulmonary haemorrhage

Pathology

Leukocytoclastic vasculitis with glomerular mesangial IgA deposits. Biopsy of patients with IgA nephropathy identical, and indeed both groups have defective IgA1 glycosylation, which may explain why they may aggregate and precipitate IgA in small vessel walls as well as in the glomerular mesangium.

Complications

Complications and relapse associated with age esp over 6yr. 50% relapse, usually within 6 weeks but can be up to a year later; 50% of those will relapse more than once. Treat with NSAIDs (unless renal involvement!) for joint pain, analgesics for abdo pain. Small study from Turkey found that Ranitidine reduced symptoms.

Steroids (prednisolone 1-2 mg/kg/day for 1-2 weeks) are suggested (grade 2 recommendation) within 3 days of onset of severe abdominal pain (defined as pain requiring hospital admission) or acute GI bleeding – after exclusion of intussusception, of course.

Steroids are also suggested for orchitis, after excluding torsion.

Reviewing 101 children with abdo involvement those who did not receive steroids had an average of 5 days of abdominal pain, whereas all those treated recovered within 24 to 48 hours of starting steroids (letter, J Pediatr Gastroenterol Nutr. 31(3):323-4, 2000).

Abdominal pain is a predictor of renal involvement, so maybe that’s the best reason for giving steroids… (Kidney Int 1998; 53:1755-9).

Renal disease

20 to 90% risk of renal disease, but generally mild (mostly just mild proteinuria and/or haematuria)! Normal urinalysis at day 7 has 97% negative predictive value for chronic renal disease [PLoS One 2012;7:e29512].

About 56% of those children with renal disease develop signs and symptoms of renal disease a week or more after presentation, although generally in first month. Can be up to 6 months later. Incidence of renal failure in HSP nephritis is just 2 to 5%. Risk factors are severe abdominal pain (OR=2.1), age >8yrs (OR=2.7), and relapsed HSP (OR=3).[Arch Dis Child. 2010 Nov;95(11):877-82. doi: 10.1136/adc.2009.182394]

A normal urinalysisNB Children who appear to recover may have significant renal disease many years later. (Lancet. 339:280282, 1992).

If more than 50% crescents on biopsy, then poor prognosis. Only 1% get that far.

Archimedes in 2012 found 3 RCTs of steroids, treatment courses 2-4 weeks, seemed to shorten duration of abdominal pain, with most obvious effect when used early.

Dudley trial of early steroids (day 7) failed to find any benefit at 12 months (n=352). Quite a high proportion of drop outs unfortunately, but prob not enough to influence results. Doesn’t answer question of what to do if severe disease at onset eg nephrotic range. [Arch Dis Child. 2013 Oct;98(10):756-63.]

Non-randomized prospective clinical trial of 223 kids showed that steroids were effective in reducing the severity of abdominal and joint pain and in treating renal disease – steroids did not prevent the development of nephritis [Archives of disease in childhood. 2010;95:877–82, doi: 10.1136/adc.2009.182394 ]. Previous systematic review suggested that steroid treatment at diagnosis did not reduce the median time to resolution of abdominal pain but did significantly reduce the mean resolution time, and increased the odds of resolution within 24 hours.

There is no proven benefit of corticosteroids in the treatment of established HSP nephritis (2009 Zaffanello systematic review, evidence is poor), but used anyway.

The major risks of corticosteroid treatment in children with HSP are masking an acute abdomen or intussuception, and GI bleeding.

Follow up

UK Kidney association guideline 2022 – for uncomplicated presentation, do frequent dipstick checks, for example weekly for first 4-6 weeks then monthly. BP check at presentation and then if evidence of nephritis. No need for parents to check at home otherwise. 6 months minimum (audit criteria, rather than recommendation).

If hypertensive or urinalysis pos, then do proper urine protein:creatinine ratio, U&Es, MC&S. Isolated haematuria is benign. As soon as urinalysis becomes normal, child can have routine follow up.

Scottish guideline was that persisting proteinuria of + or more needs more frequent follow up eg 2 weekly, 2 monthly then 3 monthly with the second line investigations.

Refer urgently for confirmed hypertension, or nephrotic range proteinuria (P:CR over 200mg/mmol).

Refer for biopsy if persisting severe proteinuria (UP: UC >250 mg/mmol for up to 4
weeks), persisting moderate proteinuria (UP: UC 100–250 mg/mmol for 3 months),
AKI stage 1 or greater (creatinine >1.5 × previous baseline or >1.5 × upper limit of normal for age). Treatment depends on histology and severity of clinical features.

ACE inhibitor is suggested (grade 2 recommendation) for persisting mild/moderate proteinuria.

A systematic review found no risk of long-term renal impairment in children with Henoch-Schonlein purpura with normal or minimal urinary findings without nephritic or nephrotic syndrome or renal failure (Arch Dis Child 2005;90:916-20). If urine analysis is normal at presentation, then test for 6 months after the last symptoms. If there is renal disease at presentation, then the risk for progression seems to be more associated with rising proteinuria during follow-up rather than presentation features. (Am J Kidney Dis 2006;47:993-1003)

Vasculitis

November 10, 2015General paediatrics, Immunologyadmin

Inflammation of blood vessels, clinical manifestation depends on which part of the body (often widespread) and what size vessel affected.

Classic presentations are:

rash esp purpuric, pernio (swelling of subcutaneous tissue),
ischaemia eg infarction (brain, gut, digits),
nephritis,
asthma.

The Chapel Hill system provides definitions for 10 different forms of adult vasculitis but is of debatable utility. EULAR consensus criteria look pretty good [Annals of the Rheumatic Diseases. 65(7):936-41, 2006. PMID 16322081].

Differential: hyperlipidaemia esp severe familial, coagulopathy, fibromuscular dysplasia (familial).

Primary vasculitis

Classified by size of vessel affected (although a degree of overlap often exists):

Large vessel ie aorta- Takayasu. May be preceding inflammatory-type illness. ?headache/dizziness, ?inflamm eg Raynauds, episcleritis etc. Claudication, absent pulses, subclavian bruit.
Medium vessel – Kawasaki disease, Wegener’s (C-ANCA pos, nasal/oral lesions, pulmonary lesions, GN, granulomata), Polyarteritis Nodosa (PAN: livedo, neuropathy, aneurysms), Churg Strauss (ANCA pos, asthma, eosiniophilia, neuropathy)
Small vessel vasculitis – Henoch Schonlein Purpura (HSP) is the classic one, but also cryoglobulinaemia (?hyperviscosity, assoc with malignancy and chronic viral infection)

Secondary vasculitis

eg SLE, mixed CT, infective esp streptococcus.

Investigations

Characterized by one or more anti-neutrophil cytoplasm auto-antibodies. These are screened for by immunofluorescence (IF) that can reveal specific patterns of staining, viz pANCA (peripheral staining), cANCA (cytosol staining). cANCA is predominantly due to Peroxidase 3 antibodies, and is seen in Granulomatosis with polyangiitis (previously Wegener’s granulomatosis, so should be Wanca?!), pANCA is mainly due to Myeloperoxidase antibodies and bacterial permeability increasing factor (BPI), and is seen in 50% of microscopic polyangiitis.

These patterns and antibodies are also associated with rheumatoid arthritis, CF, IBD, drug induced vasculitis, Churg Strauss syndrome, autoimmune liver disease etc.

But in children these are not very sensitive and in any case no evidence that distinction influences treatment or prognosis. The type of ANCA seems to be related to the population rather than the disease! Probably has direct toxic effect.

Imaging is the second modality of investigation, esp MR angiography.

Untreated, these diseases have 90% 2 yr mortality…

Hereditary angioedema

October 19, 2015General paediatrics, Immunologyadmin

=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).

Clinical

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!

Diagnosis

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.

Acute attacks

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!?

“Wait and see” is only an option for attacks not involving the face, neck, or abdomen and intestine.
Attenuated androgens no longer available – stanozolol (up to 16 mg/day) or danazol (up to 1 g/day) given early (may shorten its duration).
Tranexamic acid weak – needs to be taken immediately – most don’t bother now
Upper airway esp voice alteration and dysphagia – give C1 INH promptly. How easily can family find veins?? Else family bring to emergency department! Dose depends on weight and seriousness of reaction. In a life-threatening situation we recommend 1000–1500 U. In other situations 500–1000 U is often sufficient. Administering C1 INH concentrate shortens the duration of attacks by about a third and also halves the time to the beginning of the relief of symptoms.
For acute attacks of abdominal oedema, pain relief should be given at an appropriate level. Non-steroidal anti-inflammatory drugs are useful.
If the attack is severe, C1 INH concentrate should be infused at the same dose as above. Early intervention prevents avoidable pain and reduces disruption to the patient’s life. The patient should be observed closely until symptoms start to improve. The median time to the beginning of the relief of symptoms after concentrate infusion is 0.5–1.5 h, with complete resolution of symptoms after 24 hr. If symptoms persist at a high intensity 2 h after infusion, additional C1 INH concentrate should be given and alternative diagnoses should be considered.
No benefit from steroids or antihistamines! Adrenaline has only a transient and modest effect.
Home therapy is recommended for children with frequent and debilitating attacks, under the condition of medically supervised training.
Recombinant C1-INH concentrate (Ruconest) similar.
Subcut bradykinin B2 receptor antagonist Icatibant safe, effective and convenient (subcut) for acute attacks. Less rapid onset but then you can do it yourself. Similar price. Theoretical risk of thrombosis

Short-term prophylaxis

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.

Long-term prophylaxis

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:

Experts strongly advocated taking body weight into account in treatment in pediatrics. Discomfort emerged as to whether appropriate dosing is possible for patients between 12 and 18 years of age with fixed doses established in adults.
For attenuated androgens, sufficient data are lacking on the long-term safety over decades of use Should there be a reason for its use in isolated cases, the initial dose (see above) should only be administered for a short period (e.g., for short-term prophylaxis prior to elective procedures).
Tranexamic acid (less effective than attenuated androgens) is recommended for long-term prophylaxis in patients for whom pdC1-INH is not available or in whom attenuated androgens are deemed unacceptable. Side effects are nausea, vomiting, diarrhoea, muscle cramps. Thrombosis is theoretical risk, not seen in practice, in US restricted as evidence in animals of tumours, regular eye examination and LFTs recommended in BNF.

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]

Prednisolone allergy

August 24, 2015Allergy, General paediatrics, Immunologyadmin

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]

Oral allergy syndrome

August 19, 2015Allergy, General paediatrics, Immunologyadmin

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 –

primary IgE peanut or tree nut allergy who have only had oral symptoms so far (but are are risk of severe reactions, due to sensitisation to storage proteins, typically found in seed/kernel)
benign PFS, where allergic to Bet v 1, its homologues (eg Ara h 8, Cor a 1 – see peanut allergy) or other PR-10 or Profilin. These proteins are usually in the pulp of the fruit. Soya (Gly m 4) is an exception where soya milk can cause severe reactions.
PFS with potential for systemic reactions where allergic to LTP (typically found in the peel)

BSACI peanut and tree nut allergy guidance is to go with typical history and only test if:

Atypical/severe reactions
reactions to processed rather than raw plants (including roast nuts)
Soya products other than soya milk
Tree nuts other than hazelnut, almond, walnut
Legumes other than peanut

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:

Pru p 3 for LTP allergy– if reacts to cooked food or other atypical features (even if not peach specifically!)
Gly m 4 if soya milk negative (PR-10 but can be severe reactions). Gly m 5/6/8 if atypical
For hazelnut and almond, best to do prick to prick, for raw AND roast; if positive, do Cor a 1 (PR-10, so PFS) with 9 and 14 (which would suggest primary)
Ara h 2 if any standard tests for peanut positive (should be negative in PFS) – if negative, Ara h 1/3/6
Jug r 1 if walnut tests positive, Ber e 1 for brazil nut.

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:

severe seasonal asthma
Acid suppression therapy!
Jackfruit!

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]

Macrolide allergy

July 17, 2015Allergydrugsadmin

The majority of cases reported are non immediate reactions eg maculopapular rash, urticaria. The incidence of anaphylactic reactions is extremely low.

Less than 15% of those suspected of having macrolide allergy are finally confirmed as allergic, mainly by direct provocation testing.

Cross-reactivity between the different macrolides is variable and little information is available.

Current Opinion in Allergy and Clinical Immunology 14(4), August 2014, p 278–285. DOI: 10.1097/ACI.0000000000000069

Penicillin allergy

July 17, 2015Allergydrugsadmin

Children with pneumonia with a label of penicillin allergy were found to have:

higher risk of hospitalization (RR 1.15)
acute respiratory failure (RR 1.27)
and need for intensive care (RR 1.46; 95% CI, 1.15-1.84)
increased cutaneous drug reactions (RR 2.43)

[US Journal of Allergy & Clinical Immunology in Practice. 11(6):1899-1906.e2, 2023 Jun.]

Cephalosporins

Atanaskovic-Markovic et al found that cross-reactivity between cephalosporins and penicillins varied between 0.3 and 23.9%, being higher among penicillins and between first-generation and second-generation cephalosporins.

However, it has recently been shown that all penicillin allergic children can tolerate cefuroxime, presumably as it has a different side chain.

Cross-reactivity appears to be higher in immediate reactions, and when penicillins and cephalosporins are identical or similar in the R1 side chain, as happens with the first and second-generation cephalosporins.

Currently BNFc says to avoid cefalosporins if history of immediate penicillin hypersensitivity, but if use of cefalosporin is “essential” then can be used (but not cefalexin!).

Canadian study did oral challenges for non-blistering rashes – safe – but mostly cefprozil allergy (and linked to food allergies).

De-labelling

In hypothetical case of de-labelled patient, 47% of anaesthetists would not prescribe penicillin to patient anyway (n=5000)!

Primary care don’t always remove label even after de-labelling! (patient held records would help…)

Needs culture change in primary care and paeds of documenting reactions!

Make sure note is added to patient record when de-labelled. Electronic labels don’t necessarily help – not always possible to remove an allergy label from drug prescription system, depending on the system, may only allow subsequent note to be added. Free text systems do not encourage accurate description!

Alabama trial from NIHR to report on RCT of de-labelling in primary care; SPACE study in secondary care (nurse/pharmacist delivered).

See Testing for antibiotic allergy.

Nasal flu vaccine

May 26, 2015General paediatrics, Immunology, Infectious diseaseimmunisationadmin

Live attenuated influenza vaccine (LAIV). Now available in quadrivalent form, Fluenz Tetra in Europe, Flumist in US. Transmission to another person has only ever been documented once, and it was asymptomatic!

The extra B hopefully makes it better than 2014/15 where poor coverage. Live attenuated is more effective and has less systemic effects than injected vaccines.

Current annual programme in Scotland is for all 2-5yr olds to be offered vaccine by public health, whereas all primary and secondary school children will be offered vaccine at school.

Cut off for 2yr olds is age 2 on 1st September.

For infants between 6 months and 2, previous hospital admission for lower respiratory tract infection (which would include all our bronchiolitis babies!) is a clinical risk indicator, along with asthma, chronic heart/kidney/neuroresp disease, or indeed anything else where you thing getting flu is likely to exacerbate the underlying condition.

If you miss your school appointment, up to the family to request another via NHS Lanarkshire vaccine helpline 01698 687456.

Although GPs aren’t much involved anymore in vaccine programme, they should still offer it if a family prefers it, or if a family are keen to get it earlier than they might otherwise as part of the schools programme.

Most kids will be offered nasal live flu vaccine (Fluenz Tetra). Contraindications to nasal flu vaccine are:

under 2yrs of age,
wheezing or extra bronchodilator within the previous 72 hours,
severe immunodeficiency (esp cellular) or immunosuppression eg leukaemia/lymphoma, high dose oral steroids
aspirin use (eg Kawasaki) – theoretical risk of Reyes [reported with wild type influenza and aspirin]

Kids on high dose inhaled steroids no longer require consultant approval to get nasal vaccine.

Kids previously in PICU for asthma, or who require regular oral steroids for asthma, require consultant approval to get nasal vaccine. Otherwise they should get injectable.

If you can’t have nasal, then should get injectable (inactivated) vaccine. Can be given from age 6 months.

A second dose is needed after 4 weeks minimum if you are in a clinical risk group, and under 9yrs, and this is the first time you are getting flu vaccine. This applies whether you get nasal or injectable flu vaccine.

For egg allergy, advice, as before, is that children with egg allergy – including those with previous anaphylaxis to egg – can be safely vaccinated with nasal vaccine in any setting (including primary care and schools). The only exception is for children who have required admission to intensive care for previous severe anaphylaxis to egg, who should be offered nasal flu vaccine in hospital [lack of data, not definite risk!].

If a kid with egg allergy has a contraindication to nasal flu vaccine (eg immunosuppressed) and needs injectable vaccine, then it should be either an egg free (cell based) injectable vaccine (the one from Seqirus is licensed from age 2) or low egg content (“split virion inactivated vaccine”), viz less than 0.12mcg/ml (equivalent to 0.06 µg for 0.5 ml dose).

NSAID hypersensitivity

May 21, 2015Allergy, General paediatrics, Immunologydrugsadmin

Ibuprofen etc are a common cause of reactions, but mostly non immune mediated, via COX -1 inhibition. Previously called pseudo-allergy or intolerance, best called hypersensitivity, then subdivided into allergic or non-allergic. Often occurs in patients with underlying problem eg asthma, chronic urticaria, rhinosinusitis – exacerbates underlying condition. Hypersensitivity can be to a single drug, or cross-reactive, ie to unrelated drugs from different families (salicylates ie aspirin, propionic derivatives eg ibuprofen, acetic acid derivatives eg diclofenac, etc). Cross reactivity suggests a non-immune mechanism. Without history to support single drug (or family) hypersensitivity, you would have to advise the patient to avoid all NSAIDs.

Testing

Skin testing with culprit drug is appropriate if you have an acute urticarial or angioedema reaction in a single drug/family.
Oral challenge is appropriate to confirm all types of hypersensitivity, esp in equivocal histories. At the same time, challenge with aspirin to check cross-reactivity, and with next best alternative NSAID. Start 1/10 dose, increase every 2 hours.
For nasal/bronchial symptoms, inhaled lysine aspirin is safer and faster, but only 77-90% sensitive cf 90% for oral. Intranasal is equivalent if inhaled/oral not possible.
If patient is on long term steroids, or else has been well controlled for a long time, sensitivity seems less!
Consider proceeding to challenge with COX2 (coxib) if challenge positive.

Aspirin desensitization works for NSAID exacerbated respiratory disease, and NSAID induced (cross reactive) skin disease, controversial for chronic urticaria and no data for single drug skin disease or anaphylaxis. But needs maintenance dosing so only really useful for chronic conditions eg needing antiplatelet therapy.

Allergy 2013:68;1219

Scottishpaeds

General paediatrics with a Scottish flavour