Following varicella vaccine introduction in Australia, coverage of greater than 80% at 2 years of age was achieved, with varicella hospitalizations reduced by almost 70%. 40% of hospitalized children were immunocompromised. Of hospitalized children age-eligible for varicella vaccine, 80% were unimmunized, including all cases (3) requiring intensive care. No deaths.
[Pediatric Infectious Disease Journal. , 17 December 2012]Category Archives: Immunology
Eczema
NICE (CG57, 2007) diagnostic criteria: itchy skin plus 3+ :
- visible flexural dermatitis (or visible dermatitis on the cheeks and/or extensor areas in children <18/12) – can look like dirt where darkened esp neck
- personal history of flexural dermatitis (or dermatitis on the cheeks and/or extensor areas in children <18/12)
- personal history of dry skin (xerosis) in the last 12 months
- personal history of asthma or allergic rhinitis (or history of atopic disease in a first-degree relative of children aged <4yr)
- onset of signs and symptoms under the age of 2 years (do not use this criterion in children under 4 years).
On examination, may also see lichenification (increased skin markings due to chronic rubbing), excoriations caused by scratching, and hyperlinear palms (look at thenar eminence).
Babies tend to get eczema on the face. Older infants get it on extensor surfaces. From walking age, antecubital and popliteal fossae. In children of Asian, black Caribbean and black African ethnic groups, extensor surfaces tend to be affected rather than flexures, and discoid or follicular patterns may be more common.
Severe (NICE criteria): widespread areas of dry skin, incessant itching, redness (with or without excoriation, extensive skin thickening, bleeding, oozing, cracking and alteration of pigmentation).
Cf Moderate: frequent itching, redness (with or without excoriation and localised skin thickening)
Risk factors
Eczema (or atopic dermatitis, same thing) associated with parental allergies (OR 1.94), parent-reported infection after birth (OR 1.45), parent-reported jaundice (OR 1.27). Being a migrant (OR 0.63) and keeping a dog (OR 0.78) are protective. Prenatal probiotics did not reduce risk (Lactobacillus rhamnosus GG, LGG). Respiratory viral infections in pregnancy associated with wheezing illness in infants (mothers with asthma) and eczema. [Australia, Ped All Imm 2014:25:151]. Febrile and gynae infections in pregnancy associated with eczema in child (Italy, Ped All Imm 2014:25:159]. Children of Japanese mothers with higher anxiety scores during pregnancy were more likely to be affected by eczema!
Immunology
Many roads lead to Rome! Can be seen as combination of impaired innate and distorted adaptive immunity, interacting in framework of cutaneous immune system with suboptimal barrier function. Epidermal barrier can be genetically disturbed, but gene expression (eg of filaggrin) is also influenced by microenvironment eg Th2 cells. Some genetic structural abnormalities can be seen to induce nonspecific inflammatory reaction (eg SPINK5 defects). And almost certainly, epigenetic regulation will affect gene expression in both keratinocytes and immune cells.
Facilitated antigen presentation mediated by IgE bound to high affinity IgE receptor FcEpsilonRI, on dendritic cells, is an important part of it. Vitamin D plays a key roll, stimulates Toll like receptors, increasing pro-inflammatory cytokines but studies equivocal whether low (or indeed high) levels increase risk.
Eczema can exist without IgE against aeroallergens and food allergens, so is primarily a non IgE mediated disease, although both IgE and non-IgE hypersensitivity can co-exist, particularly in babies.
Still not understood how eczema and Staph aureus interact. Colonization appears to amplify local inflammatory reaction, but also increases IgE against a large spectrum of other things (possibly including self proteins). It is as if there is something specifically different about how immune cells handle Staph. Toll like receptors esp TLR-2 recognize Staph aureus cell wall. Overgrowth of staph during flares is associated (preceded?) by loss of diversity of skin microbiome.
Unmasking of the HSV entry receptor Nectin-1 in adherence junctions, among other things, contribute to eczema herpeticum. See Flares, below.
Atopy patch test (using intact protein allergens) can prove type IV reactions. Correlates with oral food challenge. Hyper IgE syndromes are important differential for AD, STAT3 mutations, skin (and other) abscesses, recurrent pneumonia (and pneumatocoele), connective tissue and skeletal abnormalities, mucocutaneous candidiasis. DOCK8 type Hyper IgE syndrome show sensitization predominantly against food allergens, which is a clue (STAT3 and AD show predominantly sensitization to aeroallergens).
Normal looking skin is not immunobiologically normal! Invisible inflammation, hence still needs treatment. Pimecrolimus and betamethasone both normalize expression of filaggrin, the later is perhaps a better anti-inflammatory but steroids reduce expression of enzymes for lipid and protein synthesis, so may impair skin barrier restoration.
Triggers
Stress, humidity, extremes of temperature can cause flares of atopic eczema. But what causes a flare in some can apparently help in others! Any factors causing flares should be avoided where possible.
UVB causes sunburn. UVA (longer wavelength) more relevant to photosensitivity reactions. Both cause long term skin damage. EU commission recommends UVA protection making up at least 1/3 of total suncream SPF. A few available on prescription for photodermatosis (incl vitiligo) but not for eczema per se. Lipscreen (Uvistat) available for chronic/rec HSV labialis. Sunsense is lotion.
Avoid wool in contact with skin. No evidence that bio detergent or fabric softener a major problem. Avoiding excessive product and not overloading machine (so disperses fully) prob more important.
Management
See eczema management.
Parental support
National eczema society, British Association of Dermatologists, Eczema Outreach Scotland.
Scombroid Poisoning
Differential diagnosis to allergy. Basically Histamine poisoning, rather than release of endogenous stores! Mild examples are not uncommon but severe cases rare. Clue is that several people who eat the same seafood meal fall ill with similar allergic symptoms!
Histamine and other amines are produced by bacteria from certain amino acids (can occur during production eg Swiss cheese or by spoilage). Particularly affects fish of the Scombridae family (viz tuna, mahi mahi, bluefish, sardines, mackerel, amberjack, and abalone) but can be any food containing the right amino acids and subject to the right bacterial enzymes.
Initial symptoms, not surprisingly, include tingling or burning sensations in the mouth, rash, itching. Headaches are frequently seen. May progress to nausea, vomiting and diarrhoea.
Depending on the distribution of the histamine in the food, not everyone at a meal may be affected. Cooking or freezing do not reduce the toxic effect. Contamination is not apparently detectable by the eye or nose.
Differential – see episodic autonomic symptoms.
Fish/shellfish allergy
Seafood as a term includes fish and shellfish. Shellfish usually refers both to crustaceans and molluscs, even though some molluscs don’t have shells (octopus/squid, for example), so not the best term.
But allergy to one does not imply allergy to the other! In fact, shellfish allergy is linked strongly to house dust mite allergy rather than fish, probably since they are all invetebrates with the same sort of Tropomysins. Co-sensitivity is relatively common (20-40% of fish allergic also allergic to shellfish) so must simply be atopic disposition!
Chordata (finned fish) subdivide roughly into bottom feeders, mackerel/tuna [perciformes] group, salmon/trout [salmoniformes] group and the rest (so called “bony fish”) but this doesn’t mean much in allergy terms. The best studied allergen Gad c1, found in cod, is a parvalbumin. These are found in muscle, esp slow twitch white flesh (cf dark muscled, fast fish eg tuna, swordfish). At least 50% of those with allergy to one type of fish will be allergic to another; there are no good predictors for this. Cod allergy typically means allergy to herring, plaice and mackerel but not great published evidence. Anaphylaxis UK and Allergy UK do not discuss cross reactivity at all (risk of cross contamination, of course). “White fish” is used as a grouping but doesn’t really have much biological meaning (and confusing because there is a N American white fleshed fish called whitefish…).
The rate of cross reactivity between different kinds of shellfish/molluscs is high since there is less variation in tropomysins.
Shellfish (crustaceans) are related to molluscs including abalone, clam, mussel, squid, octopus. Allergy to these is more common in countries where these are commonly eaten viz Spain, Japan – which is not surprising when you think about it, although typically surprising to the people who live there.
Sneaky places you find seafood:
- Soups eg bouillabaisse
- Pate
- Seafood “crab” sticks – usually fish, not crab!
- Worcestershire sauce (anchovy)
- Pizza (anchovy)
- Caesar salad (anchovy)
Reactions to seafood may not be allergic:
- Anisakis is fish parasite, worldwide distribution, with a range of different allergens. Larvae can cause immediate allergic response, but infection can also produce inflammatory symptoms of varying kinds, depending on where in the digestive tract the larvae are deposited.
- Scombroid toxicity esp associated with salmon, tuna, mackerel. Besides flushing, vomiting and wheezing, there can be severe headache and dizziness. Onset is minutes to hours.
- Ciguatoxin poisoning associated with reef fish eg sea bass, snapper. Onset is slower – 30 minutes to hours, besides cramps, D+V there can be myalgia and paraesthesiae.
- Shellfish (mostly bivalves) can be the source of a range of toxins with effects as diverse as paraesthesia, myalgia, ataxia, even seizures. Mostly D+V though.
Cod IgE >20 gives 95% PPV, other cut offs lacking. IgE>8 (>5 for salmon) predicts objective symptoms and non tolerance (cf partial tolerance).
Given importance of omega 3, unnecessary restriction should be avoided – Canning fish reduces immunogenicity, challenge? Interestingly, many fish allergens seem to get MORE allergenic with heating, not less – Gad c 1 is known to become airborne in steam without denaturing! Various cases of fatal anaphylaxis simply to inhaling vapour of frying fish (aerosolised proteins, NOT smell, that causes reaction).
[JACI 2017 letter – small numbers though]Food additives and allergy
Sorbic acid used as preservative. Very low level of toxicity, as rapidly metabolized (a fatty acid). A few reports of contact dermatitis and pseudo-allergy only.
Similarly with Tartrazine, MSG, Benzoate – in most children, there is very limited evidence for any role of food additives in causing non-allergic food hypersensitivity. Reactions may be more common in children with chronic urticaria and angioedema. While other symptoms including migraine, gastrointestinal disturbances and arthralgia have been attributed to food additives, there are no reproducible and consistent data from DBPC studies to support this.
Natural additives eg Annatto can also cause problems in some patients!
Sulphites (sulfites, eg sodium metabisulfite) and natural salicylates may cause skin (usually contact dermatitis, but can be angioedema), GI, respiratory problems (even anaphylaxis) but these are best termed adverse reactions as they have a pharmacological basis. Patch and IgE test available, however. Very common in our food – in fresh foods to control browning, soft drinks, dried foods (as preservative), wine and beer. Yet very rare in childhood and therefore hard to spot. Also seen in in anaesthetic solutions, antibiotics, adrenaline (!!!), cosmetics. Sulphites can have effects when used topically, orally or parenterally – mostly seen in those with asthma. Can be acute or chronic. Given the problem with using adrenaline, may need to be treated with steroids, antihistamines, bronchodilators instead! [Clinical & Experimental Allergy. 39(11):1643-51, 2009 PMID 19775253]
Salicylates are a large group of assorted foods and other things that can cause problems including anaphylaxis. Natural salicylates are generally acetylated so no need to automatically avoid them if intolerance to aspirin/NSAIDs.
[PJ Turner, J Paeds Child health 2010]
Pregnancy and nut allergy
No increased risk of peanut allergy with antenatal intake or intake during breast feeding, or with infant intake (Fox, J Allergy Clin Immunol. 2009 Feb;123(2):417-23). But did find dose response with household intake, esp peanut butter – so avoid!?
10 000 mums in US, not high risk, Eating Peanuts/Tree Nuts ≥5 times vs <1 time per month in their peripregnancy diet reduced risk of allergy by 2/3: odds ratio = 0.31; 95% CI, 0.13-0.75; Ptrend = .004). [Lindsay Frazier JAMA Pediatr. 2014;168(2):156-162. doi:10.1001/jamapediatrics.2013.4139]
60 000 mums in Danish National Birth Cohort, those eating peanuts and treenuts at least once weekly had kids with less asthma (OR 0.66), tree nuts also appeared to protect against rhinitis.
1200 US mums (not high risk) Higher maternal peanut intake (each additional z score) during the first trimester was associated with 47% reduced odds of peanut allergic reaction (odds ratio [OR], 0.53; 95% CI, 0.30-0.94).[J Allergy Clin Imm Volume 133, Issue 5, May 2014, Pages 1373–1382. DOI: 10.1016/j.jaci.2013.11.040]
Erythema multiforme
Consists of well-circumscribed target-like lesions most commonly on the extremities. In about half of cases the cause is never found. Causes include:
- Herpes simplex virus
- Mycoplasma pneumoniae
- EBV
- Orf
- Hepatitis B
- Lupus erythematosus
- Drugs such as salicylates, penicillin, barbiturates.
Note how some causes are the same as erythema nodosum. Blistering can occur. EM can be thought of as on a clinical spectrum with Toxic Epidermal Necrolysis and Stevens Johnson syndrome at the extreme end, although the underlying pathology appears to be different.
There is no clear evidence that steroids help in erythema multiforme. Treatment is symptomatic support.
Stevens Johnson Syndrome and Toxic Epidermal Necrolysis
Closely related. Characteristically severe, diffuse mucocutaneous eruption with atypical flat target lesions, irregular, possibly purpuric, blistering, even haemorrhagic! Painful, like sunburn. Different pathology from Erythema multiforme! Evolve over 1-2 weeks, subside over further 2-3 weeks.
Other manifestations are fever (prodromal illness can manifest as URTI). Mucosal lesions (stomatitis, conjunctivitis/blepharitis, or genital inflammation) accompanied by at least 1 other visceral organ, such as hepatic, renal, trach/bronchial or gastrointestinal involvement. Urethral involvement can cause retention of urine. Chest and abdominal signs pretty common!
Urgent ophthalmology – uveitis can lead to blindness.
Toxic epidermal necrolysis = body surface area detachment >30%. SJS typically less than 10% detachment. Monitor using body maps.
Some genetic risk factors – eg S Asians.
Drug induced may not appear until up to 28/7 from start of treatment. Penicillin, other antibiotics, NSAIDs, anti epileptics are the usual causes. Consider any medicine (including oral contraceptive) in previous 2 months!? HSV, Coxsackie, influenza, EBV, Adenovirus, Enterovirus, strep A, mycoplasma, chlamydia.
Subepidermal bullae seen on biopsy (if done – no need usually). Do 2, just adjacent to blister. Direct immunofluorescence to exclude an immunobullous disorder. If staphylococcal scalded skin syndrome suspected, shave biopsy of blister roof for frozen section sufficient.
Beware BP cuffs, adhesive ECG leads and dressings. Wrist tags can cause trauma. Use soft silicone tapes, tubular bandages, adhesive remover. Chlorhexidine or even betnesol Mouthwash, topical anaesthetics. Burns unit? Decompress blisters but leave dead skin in place. 50:50 WSP and/or emollient sprays. Irrigation, non adherent dressings. Wet dressings for genitals. Avoid giving NSAIDs, codeine, given that they are associated with SJS!
Consider betnovate for erythematous, non detached areas once infection excluded.
Complications include Hyper/hypopigmentation, Onycholysis, depapillation of tongue. Adhesions, entropion, trichiasis. Not scarring unless secondary infection. GI strictures, blindness (as complication of uveitis) can occur.
Usually treated with steroids but controversial since some retrospective studies showed harm. IVIg given in addition has been disappointing, although has been associated with nephrotoxicity in adults. Seems to be T-cell mediated: CD8, CD56.
(PIDJ 2004)
Beer allergy
Well described, mostly due to a non-specific lipid transport protein (LTP) so likely to find various co-sensitivities. Some will be wheat, barley, maize, rice, yeast etc positive but history likely to be suggestive. Consider hops, metabisulphites. Malting, filtration etc probably affects allergenicity. Presence of alcohol may enhance absorption? In the case below, maize LTP eventually identified but patient could eat polenta and popcorn!
But individual beers vary in their allergenicity, and skin prick testing can reveal types that are safe! Hoegaarden in this report – Allergy 2012:67;1186
Vaccines
Green book page at Gov.uk has latest updates on immunization advice for UK. See:
- UK vaccine schedule
- Non-specific effects of childhood vaccines