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.
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)
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.
Usually just a marker of atopy, so common with asthma, hay fever, eczema. Mild generally accepted as 0.5–1.5×109/L, moderate 1.5–5, and severe >5. Persistent would be over 2 weeks.
But beware rare things eg HyperIgE syndrome. Any evidence of organ impairment? Also seen with malignancy, PFAPA, Familial Mediterranean Fever. With the rheumatological conditions, eosinophilia is often severe (>5) but with malignancy, usually mild…
Described in 2015, revolutionary in that allergy is to an oligosaccharide (ie a sugar, not a protein), specifically galactose-alpha-1,3-galactose.
Accounts for anaphylaxis to cetuximab, a cancer drug, but even more bizarrely, allergy to red meat (beef and pork). The latter appears to follow sensitization through a tick bite, so is really only an issue in endemic areas eg parts of United States and Europe, Australia.
Anaphylaxis to red meat can be immediate or delayed, with or without exercise induction!
In a small series of beef allergic patients reported in 2003 (strong family history), skin prick and labial contact tests only positive in minority. All positive on IgE. In another series, most beef allergic were also gelatine allergic. Risk from gelatine is mostly from intravenous products, but big dose of jelly sweets as risk??? Interestingly, a proportion of “idiopathic” anaphylaxis turned out SPT positive for gelatine.
Bovine specific albumin (Bos d6) is another possible allergen for beef allergy – a minor cow’s milk allergen, so you would probably react to both – heat labile.
In Asia allergy described to galacto-oligosaccharides in
milk formula, also a carbohydrate!
Thought to be T cell independent!
IgE test available. Levels appear to fall over time unless continued tick exposure.
Emerging? Changes in land use (less sheep, more deer)? About 50 cases in Scotland (2025) – certainly not all rural so prob recreational exposure. Youngest 4yrs (Argyll). Mostly strongly co-factor modified; cf America (big steaks?)
Maize is also known as corn in English, but in America “corn” refers to wheat, so potential for confusion! Commonly used in Mexican cooking.
Allergy to maize is extremely rare. It is not one of the 14 allergens that has to be highlighted under UK/European law on ingredient labels. Cross reactivity with wheat, rice and other cereals seen on lab tests but rarely clinically relevant. It does seem to fit more with Southern European fruit allergy syndromes, including sunflower seeds.
Foods:
Sweetcorn, corn on the cob
Popcorn
Cornflakes and other breakfast cereals
Corn flour (used as a thickener so can be low level in lots of different things)
Baking powder often contains corn flour
Custard
Tortilla chips, tacos, nachos
Most wraps are made of wheat but some are made with maize or a mixture of the 2
Some of the toddler snacks by Organix/Ellas Kitchen etc
Cornmeal, used to make polenta and grits
Potentially corn flour could appear in tablets/medicines.
There are some reports of severe allergic reactions to fructose syrup derived from maize/corn, which is used in lots of things (including beer and other drinks). This probably isn’t a problem for most people with maize/corn allergy though, so you should only avoid this if anaphylaxis or likely previous reactions to it.
Corn oil certainly poses no allergy risk, as processing removes any allergenic proteins.
The name for pure natural rubber. Found all over the place – foam (mattresses), condoms, balloons, seals, adhesives. In hospitals, BP cuffs, elastic bandages, catheters and ET tubes, pulse oximeters… Not so often in surgical gloves now. Can cause mild and severe (anaphylaxis) reactions, plus delayed (non type 1) allergy. Allergy first described in 1979, became epidemic in 1980s.
The rubber tree Hevea brasiliensis is not the same as “rubber plants” (Ficus) you get as pot plants, although you can be allergic to those too, of course.
About half of latex allergic patients also have fruit allergies, especially avocado, banana, kiwi, melon but also chestnut and tree nuts.
Certain high risk groups:
Spina bifida
Health care workers
Atopic or irritant dermatitis may also be caused by rubber chemicals rather then latex itself.
Diagnosis
Blood IgE test – as with other IgE tests, potential for false positives esp with grass/fruit allergy.
Skin prick test with standardised latex
Prick through suspected glove! Needs latex free environment, of course. Potential for reaction to powder, rather than latex…
Glove test – wet hand! Risk of anaphylaxis.
Risk of Anaphylaxis
As with other allergies, seems to vary between individuals. And previous reactions do not reliably predict future reactions.
With health care, difficult. First on surgical list. Label patient. Latex free environment, as far as possible. Reports of probable reactions from IV fluids and needle puncture of bungs in IV sets.
Evidence that having a peanut allergy has worse quality of life for a family than having diabetes… Mostly due to fear of unexpected severe reaction, and restrictions on social activities particularly eating out, parties and holidays.
Allergic patients can feel embarrassed or even ridiculed for declaring their allergy. Allergy is often mocked in the media (Cobra Kai, the Box Trolls, Peter Rabbit), asthma in particular.
School and nursery are a particular area of concern, whether the right foods will be served, whether teachers or other children might bring allergens into school (food is sometimes used in classes, for example making bird seed balls), whether reactions will be managed appropriately, school trips. Children have died in school (Nasar Ahmed, Mohammed Ismaeel Ashraf).
APPEAL study 2022 – UK & Ireland, peanut allergy – 87% of parents/care-givers (not clear if mums or dads) felt moderately or severely restricted eating out, choosing where to eat (82%), special occasions (76%) and when buying food from a shop (71%). 52% of survey participants reported being bullied because of their allergy. But variable – some feel allergy has minimal impact on their health-related quality of life.
Mums tend to be more concerned by limitations in the child’s own social life, dads seem to care more about limitations in the whole family’s social life. [Stensgaard, Clin Exp Allergy 2017]. Mums are the ones most studied. There probably are significant differences between mums and dads. In some studies, parents overrate their child’s quality of life, but in others (particularly with teenagers) parents can be seen as over anxious. Teenagers tend to take on the perspective of the parent of the same sex.
How bad previous reactions have been, interestingly, does not in itself contribute significantly to quality of life – in some cases, not having ever had a reaction can make families more anxious, because they don’t know what to expect! In one study, having multiple allergies and having an adrenaline pen was associated with worse quality of life. [Protudger, Clin Transl Allergy 2016]
Parents can feel guilty if their child has a reaction, a failure of their duty to protect. Mums can feel guilty about having “caused” their child’s allergy, either through their own medical history or what they ate or didn’t eat in pregnancy (even there is no good evidence for this being a factor).
Better quality of life is seen in allergic families with greater self efficacy for food allergy management, and lower perceived likelihood of a severe reaction [Knibb, Pediatric Allergy & Immunology. 27(5):459-464, August 2016].
APPEAL-1 study
8 European countries, questionnaire study of adults and children with peanut allergy.
Only a minority remembered getting any training in future
emergencies or use of medication, after their initial reaction. There was a low
rate of satisfaction with AAI training!
43% reported bullying, and a third of these described it as
severe.
65% confident in ability to recognize a reaction, but only
45% confident about knowing when to use an AAI and 59% how. 62% say the carry AAI all the time.
25-30% said it was not easy (or rarely easy) to talk to
friends or family about their allergy, although most felt confident talking to
new people about their allergy. Friends and family were generally seen as “believing
there is too much concern over allergy” even though overall they were seen as
having a good awareness and understanding of allergy (cf other people, where
this was seen as the opposite).
Dutch respondents had lowest rates of uncertainty and stress
around activities, and for feeling anxious.
At same time, they had the highest rates of confidence around knowing
when and how to use AAI. France had
highest rate of being made to feel different in a negative way, and feelings of
isolation.
NB – likely to be the most affected families who
participated.
