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Immunology and allergy

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Sullivan Nicolaides Pathology
Clinical Articles iconClinical Articles

Guide to Allergy Testing

Allergic disorders result from an inappropriate, usually IgE-mediated, immune response upon exposure to either environmental or food allergens. Common manifestations of allergy include rhinoconjunctivitis, asthma, eczema, acute urticaria and anaphylaxis. Disorders, such as chronic urticaria, hereditary angioedema and T-cell contact dermatitis (metal allergy), while clinically similar in some ways, are not IgE-mediated. Allergic disease manifests in different ways through life and the likely causative agents can also change with age (see Table 1).

Tests used in the diagnosis of IgE-mediated allergy

Total IgE Higher levels of total IgE are often found in patients with allergic conditions. However, normal total IgE does not exclude allergy. Total IgE is also elevated in other conditions including parasitic infections and allergic bronchopulmonary aspergillosis. It is used increasingly in determining anti-IgE therapy in moderate to severe asthmatics. Allergen-specific IgE Allergen-specific IgE can be detected for a large variety of allergens. The presence of a specific IgE to allergen can suggest allergic disease and is detected via a blood test (RAST or radioallergosorbent test) or skin prick test. RAST tests detect many of the different proteins within an individual allergen. Recombinant allergen testing Of the many proteins within a substance, only a few may cause allergic symptoms. Recombinant allergen testing looks for specific characterised protein within an allergen. Interpretation of RAST tests The presence of detectable specific IgE to an allergen does not confirm the patient is allergic to that substance. All results must be interpreted in conjunction with the clinical history of the patient. Low levels of detectable specific IgE can confirm the presence of allergy in the right clinical context. RAST testing aids in the assessment of, and identification of allergic sensitisation, but is not to be used alone as the deciding factor for inclusion or exclusion of allergy. As the level of specific IgE increases, the likelihood of clinical relevance also increases. As shown in Table 2, different allergens have different specific IgE level cutoffs at which serious allergy is >95% likely (positive predictive value or PPV). The range of values is vastly different between allergens and is affected by age and also by geographic region. Table 2 defines levels at which exposure, or a challenge, would be highly hazardous for a patient. Importantly, many patients could have serious reactions at much lower levels.   [table id=1 /]   [table id=2 /]

RAST tests

RAST tests are available for a range of allergens, however Medicare criteria limits rebates based on the number, type and frequency of tests. Medicare Australia limits rebates for RAST tests to a maximum of four specific allergens and/or mixes per pathology request and a maximum of four RAST test episodes per year. When ordering RAST tests, it is advisable to include allergens the patient feels are relevant and those likely for the clinical scenario. For common clinical scenarios we recommend the following: Childhood eczema Age <2 years: Milk, Egg, Wheat, Peanut Age >2 years: Milk, Egg, Peanut, Dust mite Additional allergens or an extended RAST combined allergy panel may be ordered. Asthma and allergic rhinoconjunctivitis Dust mite, Grass mix, Animal dander Additional allergens may be ordered or substituted if relevant (e.g. cat dander instead of animal dander). An extended RAST inhalant panel is also available. Default panel if no allergens are specified and no clinical notes are provided Age <5 years: Dust mite, Grass mix, Food Mix Age >5 years: Dust mite, Grass mix, Animal Mix Anaphylaxis Anaphylaxis is a severe life-threatening allergic reaction. It is recommended these patients require specialist assessment by a clinical immunologist or allergist. Initial testing should look for the causative allergen if possible. It is important to note that a negative RAST test does not exclude the allergen tested. RAST testing recommendations ­
  • Test individual likely causative allergen i.e. food, stinging insect. ­
  • Tryptase, if done within 2-6 hours of reaction, can support the occurrence of an allergic reaction. ­
  • Useful as an assessment of mastocytosis (condition with increased numbers of mast cells)

Extended RAST panels

Extended RAST panels have been developed to represent the common allergens encountered clinically in practice. They are particularly relevant in our geographic region and replace the skin prick test panel which is no longer available. Additional allergens may also be requested. All results must be interpreted in conjunction with the patient’s clinical history. Extended RAST Food Panel ­
  • Covers common food-related allergens
  • Almond; Hazelnut; Sesame seed; Banana; Mango; Shrimp (prawn); Cashew; Milk (cow); Soybean; Codfish; Peanut; Walnut; Egg white; Rice; Wheat
Extended RAST Nut Allergy Panel ­
  • Broad collection of commonly consumed nuts, including peanuts ­
  • Individual nut testing with appropriate clinical history is preferred ­
  • Recommend to discuss results with a clinical immunologist or allergist
  • Almond; Macadamia; Pine nut; Brazil; Peanut; Sesame seed; Cashew; Peanut (Ara-h2); Walnut; Hazelnut; Pecan
Extended RAST Combined Allergy Panel ­
  • Combination of common food and environmental allergens ­
  • Replaces the skin prick test panel (no longer available)
  • Almond; Dust mite; Mould mix; Cashew nut; Egg white; Peanut; Cat dander; Grass mix; Shrimp (prawn); Codfish; Hazelnut; Soy; Dog dander; Milk (cow); Wheat
  • * Preferable for children (<12 years) due to low serum volume
Extended RAST Inhalant Panel ­
  • Covers common environmental allergens ­
  • Useful for asthma and allergic rhinitis
  • Acacia (wattle); Blomia tropicalis; Dust mite; Alternaria alternate; Cat dander; Eucalyptus; Aspergillus fumigatus; Cladosporium; Horse dander; Bahia grass; Common ragweed; Johnson grass; Bermuda grass; Dog dander; Perennial rye grass

Recombinant allergens

Omega-5 gliadin ­
  • A component of wheat ­
  • Associated with anaphylaxis ­
  • Often in the context of eating wheat and physical activity within 1-2 hours
Alpha-gal (mammalian meat allergy) ­
  • Associated with anaphylaxis; often delayed following consumption of meat (beef, lamb, pork) ­
  • Related to tick bites
Peanut Allergy Risk Assessment ­
  • Peanuts like all food is made up of many different proteins ­
  • Ara-h2 is associated with anaphylaxis to peanut ­
  • Can assist with risk assessment and should be done in conjunction with a clinical immunologist or allergist ­
  • A negative Ara-h2 in peanut positive patient does not imply there is no risk to anaphylaxis
  • Results of RAST tests can also be of use in monitoring ongoing allergy in patients in conjunction with their treating clinician

How to order allergy tests

RAST tests - standard panels Medicare Australia limits rebates for RAST tests to a maximum of four specific allergens and/or mixes per pathology request and a maximum of four RAST test episodes per year. Extended RAST tests (Medicare rebate + $120* per panel)
  • Extended RAST Food
  • Extended RAST Nut
  • Extended RAST Combined
  • Extended RAST Inhalant
Please note, extended RAST panels are not bulk billed. Recombinant allergen tests (Medicare rebate + $60* each)
  • Alpha-gal
  • Omega-5 gliadin
  • Peanut (Ara-h2)
  • Peanut Allergy Risk Assessment
  General Practice Pathology is a regular column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs. The authors provide this editorial free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.
Expert/s: Sullivan Nicolaides Pathology
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Dr Linda Calabresi
Clinical Articles iconClinical Articles

Vaccinating the Immunosuppressed – Who, What and When

Vaccination in immunosuppressed adult patients has many facets and can be challenging for GPs who don’t deal with these cases regularly. But there are a few key considerations that can help guide clinicians, says Associate Professor Michael Woodward, Melbourne-based geriatrician, writer, researcher and passionate advocate for health promotion. Firstly, not all immunosuppression is equal. It is important to ascertain the degree of immunosuppression, as some people may be being unnecessarily denied vaccines because they are taking medication that can suppress the immune system but only at higher doses or in different formulations. “For instance, someone who is on inhaled corticosteroids for their asthma or on low dose (less than 20mg) prednisolone daily for just a few weeks is not significantly immunosuppressed and can be vaccinated in the same way as other people,” said Professor Woodward in an interview following his presentation at Healthed’s recent Annual Women's and Children’s Health Update in Perth. However, those on higher doses of steroids or on steroids more long-term, as well as those people who have conditions associated with immunosuppression such as haematological malignancy do need special consideration when it comes to vaccination. Most importantly, live vaccines are not to be given to this group. This includes the new herpes zoster vaccine (Zostavax), which absolutely contraindicated in severely immunocompromised patients. The consequences of inadvertently administering this vaccine to an immunosuppressed patient hit the headlines some months ago, highlighting the importance of this guideline. The other question often asked is whether patients who are known to be immunosuppressed, and therefore at greater risk of significant infections actually need more or stronger doses of the vaccines they are able to have. In some cases that is a very real and worthwhile consideration if you want to achieve the objective of immunoprotection, Professor Woodward said. For example, you might consider giving an immunosuppressed patient the pneumococcal vaccine (Prevenar 13) as opposed to the polysaccharide pneumococcal vaccine (Pneumovax 23). “The conjugate vaccine is generally slightly more likely to produce an immune response [than the polysaccharide vaccine],” he said. The other scenario where GPs might need to be considering vaccination in association with immunosuppression, is in patients who are scheduled for an elective splenectomy. The lack of a spleen is known to be associated with a reduction of the body’s ability to respond to a vaccine, so it is currently recommended that people who are about to undergo a splenectomy have the influenza, pneumococcal and the newer zoster vaccine. In addition, they should be vaccinated against H. influenza B and receive the two meningococcal vaccines currently available. All these are detailed as part of the pre-splenectomy recommendations on the spleen.org.au website, with the exception of the zoster vaccine, as the guidelines have yet to be updated. However, Professor Woodward says most health professionals in this area are advocating the inclusion of the zoster vaccine. Some of these vaccinations may also be given shortly after the removal of the spleen in cases where the splenectomy has been urgent, but this is generally not the remit of the GP. In general, the question of vaccination in the immunosuppressed patient can be complicated. It is a highly specialised area and Professor Woodward suggested, if in doubt GPs might want to seek input from a specialist in this area such as an immunologist or a rheumatologist.

Expert/s: Dr Linda Calabresi
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Dr Linda Calabresi
Clinical Articles iconClinical Articles

Avoid AF, Eat Nuts

Eating nuts at least three times a week reduces the risk of developing atrial fibrillation, Swedish researchers report. For the first time it has been shown that nut consumption has a linear, dose-response association with atrial fibrillation. The findings of this long-term, prospective study of over 60,000 adults, showed people who ate nuts three or more times a week were 18% less likely to develop AF than their non-nut-consuming counterparts. The study, published in the BMJ journal, Heart also found those adults with a moderate consumption of nuts (defined as up to 1-2 times a week) had a reduced risk of heart failure, but this benefit disappeared if the intake was greater than this. The study authors said it was already known that nut consumption was beneficial to heart health. “Meta-analyses of prospective studies have shown that nut consumption is inversely associated with death from cardiovascular disease, total coronary heart disease and total stroke,” they wrote. However, what was not known was exactly which cardiac conditions nut consumption affected and which outcomes it influenced. So back in 1997, they got this large cohort of men and women to complete a Food Frequency Questionnaire and then followed them up for the next 17 years utilising data from the much-admired Swedish National Patient and Death registers. In addition to nuts’ protective effect against atrial fibrillation and, to some degree heart failure, the study findings also seemed to suggest that eating nuts reduced the risk of non-fatal myocardial infarction and abdominal aortic aneurysm but this association did not hold true once confounders were taken into account. There was no link found between nut consumption and any other cardiovascular condition namely aortic valve stenosis, ischaemic stroke or intracerebral haemorrhage. Researchers suggested that nuts were effective through their anti-inflammatory and antioxidant effect, their ability to improve endothelial function and reduce LDL-cholesterol levels. They also said that the overall consumption of nuts among this study population was very low, maybe too low to have a meaningful effect on cholesterol levels. By far the majority of participants either didn’t report eating nuts at all or ate them only one to three times a month. But this may represent an opportunity for intervention. “Since only a small percentage of this population had moderate (about 5%) or high (<2%) nut consumption, even a small increase in nut consumption may have large potential to lead to a reduction in incidence of atrial fibrillation and heart failure in this population,” the study authors concluded. Ref: doi:10.1136/heartjnl-2017-312819

Expert/s: Dr Linda Calabresi
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Dr Linda Calabresi
Clinical Articles iconClinical Articles

Reflux Meds in Infants Doubles Risk of Allergy

Infants receiving acid suppressive medications are more than twice as likely to develop food allergies later in life, US researchers say. Findings from a large retrospective study, analysing data from almost 800,000 children, showed that being prescribed either an H2 receptor antagonist or a proton pump inhibitor in the first six months more than doubled the risk of developing a food allergy (hazard ratios of 2.18 and 2.59 respectively) when they got older. Similarly, the use of these medications was also found to associated with an increased risk of other allergies as well, including medication allergy (HR 1.70 and 1.84), anaphylaxis (HR 1.50 and 1.45) and, to a lesser extent, allergic rhinitis and asthma. As part of the same study, the researchers also looked at antibiotics in the first six months and, perhaps unsurprisingly found a link between this type of medication and developing an allergic condition. In the case of antibiotics, children were more likely to develop allergic respiratory conditions such as asthma and allergic rhinitis than food allergies. The findings have biological plausibility, the researchers said in JAMA. Acid suppressive medications inhibit the breakdown of ingested protein which, in turn facilitates IgE antibody production increasing the sensitivity to ingested antigens. The medications also, by definition, interfere with histamine which researchers now believe has a greater role in modulating immune system functioning than previously thought. The association between increased allergy and antibiotics, on the other hand supports findings from previous studies, and is thought to be related to the effect of the antibiotics on the gut bacteria or microbiome. It is one of a number of reasons why there has been growing pressure on clinicians to try to avoid prescribing antibiotics to infants. “While there has been increasing recognition of the potential risks of antibiotic use during infancy, H2 [receptor antagonists] and PPIs are considered to be generally safe and are commonly prescribed for children younger than a year,” the study authors say. Among the almost 800,000 children included in the study, 7.6% had been prescribed a H2 receptor antagonist in infancy and 1.7% had had a PPI. The researchers did concede that a limitation of this study could be ‘the potential bias from reverse causality’. Namely an infant’s symptoms of a food allergy could have originally been misdiagnosed as gastro-oesophageal reflux necessitating acid suppression, or early symptoms of asthma could have mistakenly been thought to be an indicator of a bacterial respiratory infection. However, the authors say, this is unlikely to be the whole story. Such scenarios cannot explain the increased rates of anaphylaxis or urticaria or medication allergy. And many food allergies don’t develop until well after the first six months so it would be unlikely that allergy would have caused the symptoms experienced by an infant. All in all, best practice, according to these researchers is to minimise the use of acid suppressive medications and antibiotics in children, particularly in children less than six months old. “This study provides further impetus that antibiotics and anti-suppressive medications should be used during infancy only in situations of clear clinical benefit,” they concluded.

Expert/s: Dr Linda Calabresi
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Dr Linda Calabresi
Clinical Articles iconClinical Articles

New hope for kids with severe food allergies

One of the new class of biologics may have a pivotal role in desensitising children with severe food allergies, US researchers say. That was the conclusion after their placebo-controlled study showed that a preliminary short course of the monoclonal antibody, omalizumab (Xolair) improved the safety and efficacy of oral immunotherapy in children with multiple severe Ig-E mediated food allergies. Admittedly the study was small, involving only 48 children aged 4-15 years, and only looked at children with Ig-E mediated allergies to multiple foods but the implications, the study authors say are important. These patients are a highly atopic population who are at risk of near-fatal or fatal food allergic reactions to multiple foods. There is plenty of evidence that oral immunotherapy is effective for single food desensitisation. However there has been little proof that immunotherapy works in children with allergies to multiple foods, and these are the ones more likely to accidentally ingest a food that may trigger anaphylaxis. Children with multiple food allergies are also far more likely to be unable to tolerate the oral immunotherapy. So in this phase 2 trial, those children in the treatment group were given omalizumab for eight weeks before commencing oral immunotherapy against a range of allergens including peanuts, cows milk and several different tree nuts. Outcomes were assessed by a food challenge at week 36 that looked at the ability to tolerate 2g of the trigger food. At the 36 week mark, 83% of children could now tolerate the allergenic food in the omalizumab-primed group compared with only 33% in the placebo group.  It also appeared that omalizumab was well-tolerated with no serious or severe adverse events occurring in those who received it. The impact of these findings on the lives of affected children should not be underestimated, the researchers suggest in The Lancet Gastroenterology and Hepatology. “[The] ability to increase an individual’s threshold of food ingestion to a serving of protein [for example] is important for their nutrition and overall quality of life,” they wrote. The study had its limitations, namely it remains unknown if the desensitisation was sustained but the finding that the anti-IgE cover made the oral immunotherapy more tolerable and therefore more effective is a major though incremental advance in the management of this increasingly prevalent condition. Ref: Lancet Gastroenterology and Hepatology. Published Online Dec 11, 2017 http://dx.doi.org/10.1016/52468-1253(17)30392-8

Expert/s: Dr Linda Calabresi

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