CARPA - Complement Activation-Related Pseudo-Allergy

This is a simplified explanation of CARPA – there are more resources available at the bottom of the page for further reading for those who are interested in knowing more.

What does this term mean?

The Complement System is the name of a group of proteins which circulate in the blood and tissue fluids. They are activated by the presence of molecular components they don’t recognise. This can be bacteria or viruses, but also damaged human cells and drug components they have never encountered before.

The proteins become sequentially activated in an enzyme cascade which can trigger an inflammatory immune response. This is what the term Activation-Related refers to.

Pseudo-Allergy means that the reaction is not a genuine IgE allergy but can present itself as one. A genuine allergy means that the body reacts in the same or similar way every time it is exposed to a specific allergen and can be detected by an IgE blood test. A pseudo-allergic reaction can be a single incident that would not be repeated on a subsequent exposure to the same allergen and would not show any sensitisation in an IgE blood test.

Why does the body react this way?

The body mounts an immune response against what it considers to be harmful biological and chemical agents.

There are 3 ways a reaction might take place and each is distinct in how the symptoms appear, how long after ingestion/injection they appear as well as dose dependence and cross-reactivity.

  • The drug binds to proteins already present and forms new antigens causing an allergic immune reaction.
  • The drug has off-target activity (e.g., if a drug was meant to target a bacterial infection, but instead caused an inflammatory response in the skin).
  • The drug stimulates or inhibits receptors or enzymes of inflammatory cells.

  • What things cause these reactions?

    Vaccines, various medications, occasionally food additives, preservatives, colouring and artificial flavours have all been noted to cause these types of pseudo-allergic reactions.

    What symptoms do they cause?

    Most commonly CARPA reactions involve the skin. Generalised reactions could cause urticaria (hives or welts), angioedema (swelling under the skin), non-allergic asthma and eczema flare ups.

    Localised reactions could cause abscesses (lumps containing pus), nodules (lumps under the skin) or granulomas (small lumps), this is more likely the case with intravenous drugs, vaccines and insect bites.

    Occasionally a pseudo-allergic reaction can be anaphylactic in nature which is what would cause a misdiagnosis of a true allergy.

    What is the importance of knowing whether a reaction is CARPA or a true allergy?

    Misidentifying a singular incident as an allergy can sometimes lead to treating subsequent illnesses with medicines that are not optimised for recovery due to a perceived allergy. The most cited example of this is penicillin allergy, it is thought that in the US that 10% of patients have a penicillin allergy recorded, but the true number of those with an actual allergy is much lower. A noted penicillin allergy can lead to alternative, but less effective, antibiotics being used and would rule out a whole group of medicines which are penicillin related for treatment.

    Multiple allergies are becoming more common and this often leads people to impose a strict restrictive diet on themselves. This can lead to a poor diet lacking in essential nutrients and frustration over a lack of eating options. Knowing which reactions are genuinely allergic reactions and which are a single incident of CARPA can bring more options back into a diet.

    This is why food diaries continue to be an important tool in diagnosis of your allergies – noting the times reactions took place and what medications were taken are a necessary starting point for a proper diagnosis.

    Click here for a free to download food diary with tips on how to complete or follow the link to the paperback Allergy Resources Food Diary.


    Opioid Allergy, Pseudo-allergy, or Adverse Effect?

    Articles and Journals

    Drug-Induced Anaphylaxis in Children, 2024

    Complement-mediated dialysis reaction during regular hemodialysis treatment: a case report, 2024

    Administration of the Second Dose of mRNA COVID-19 Vaccine to a Woman With Immediate Reaction to the First Dose, 2023

    Anaphylaxis to additives in vaccines, 2022

    Management of penicillin allergy in primary care: a qualitative study with patients and primary care physicians, 2021

    COVID-19 vaccine-associated anaphylaxis: A statement of the World Allergy Organization Anaphylaxis Committee, 2021

    Stress, pseudoallergens, autoimmunity, infection and inflammation in chronic spontaneous urticaria, 2019

    Dietary Habits in Patients with Chronic Spontaneous Urticaria: Evaluation of Food as Trigger of Symptoms Exacerbation, 2018

    Overview of Complement Activation and Regulation, 2013

    Complement activation-related pseudoallergy: A stress reaction in blood triggered by nanomedicines and biologicals, 2014

    Allergy, pseudo-allergy and non-allergy, 2011

    Incremental build-up food challenge – a new diagnostic approach to evaluate pseudoallergic reactions in chronic urticaria: a pilot study, 2009

    Effects of a pseudoallergen-free diet on chronic spontaneous urticaria: a prospective trial, 2009

    Diagnostic approach for suspected pseudoallergic reaction to food ingredients, 2008

    Let me know if you found any of these interesting or useful. If you spot an article or research that you think is interesting you can message me or tag me on Facebook or Twitter - links at the bottom of the page.

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