Background to why I created this blog post.

For many years, I’ve read numerous comments and posts where people mention hives (full medical term urticaria).  As far as I know, this is an issue that has never bothered me all of my life …… until recently.  I’ve never had any allergies other than certain cats and dogs (….I guess there might be a connection there).  I’m currently taking an anti-histamine tablet each day until the issue resolves.  My normal reaction to these changes is to research, so here is my research!

The response in patient groups to questions about hives (urticaria), or indeed anything ‘itchy‘, always includes feedback from people who automatically assume a NET connection and then mention histamine.  That is fine and not far from being factual about hives. However, these comments nearly always infer linkages to the release of histamine from NETs.  Like many situations, correlation isn’t always causation.

So, when you look at the incidence rate of 20 percent of people having a brush with hives at some time during their lives; and the most common causes of urticaria (see below), you quickly start to work out that this is a medical condition which many NET patients are likely to succumb to at some point in their lives.  Histamine is not just there to add to the symptoms of the various NET syndromes, it is a natural allergic and inflammatory reaction of your body’s reaction to a foreign protein.

Histamine is released from cells in response to an antibody called immunoglobulin E (IgE). This antibody may be secreted in response to an invading pathogen such as a virus, bacteria, or an allergenic substance such as pollen, i.e. it’s a natural response to inflammation. Histamine can also be released in response to injury caused by toxins.

Most hives situations are acute i.e. short term where the rash clears completely within six weeks but most cases within 24 to 48 hours – this is actually what I have been experiencing.  Add in the itching which is particularly annoying,  Chronic urticaria – in rarer cases, where the rash persists or comes and goes for more than six weeks, often over many years. After 8 months of putting up with this issue, this is what I’m now looking at. Neither is typically life-threatening, though any swelling in the throat or any other symptom that restricts breathing requires immediate emergency care. I have not experienced that but see below about my ankles.

None of my breakouts have gone beyond 3-4 days but recurrence is happening.  Using my regular NET diary, I have found linkages to various activities, events and other illnesses. I’ll cover that below. More chronic experiences may need closer attention and given the definitions above, my experience is becoming chronic.

My main locations appear to be legs, feet, arms (occasionally on the hands), buttocks, lower back.  I had a large one on my face which was quite disturbing. Thankfully that only happened once and it was some time ago.  A slightly more worrying symptom I noticed on a couple of occasions was ankle/feet angioedema, this is known to happen with hives (but also many other conditions). My diary indicates this was mainly on hot days.  When you look at the causes of angioedema, they are very similar to hives to the point that there is almost certainly a connection and overlap between the two – e.g. angioedema is probably a symptom of hives and vice versa. However, it appears there are different types of angioedema with different or overlapping causal sources.  These include allergic, idiopathic, drug-induced and hereditary.  I’m fairly certain it isn’t hereditary. The other 3 are possible given the diary entries listed so far and what I expanded in the common causes section below.

Edit March 2025. I spoke to my GP in March and I am on a trial of Fexofenadine.  Let’s see how that  goes

Histamine connections

Let’s talk about the elephant in the room …. Histamine.  Just because someone is allegedly ‘secreting’ histamine, does not mean they have NET; or that the cause of a symptom is a histamine secreting NET.  Millions and millions of people take anti-histamines but millions and millions of people don’t have a NET or a histamine secreting NET. In fact, when I read the most recent NET classification schemes, a “histamine secreting NET” is not even recognised. And some NET specialists in Europe state there isn’t enough science to formally link histamine to NETs. You can secrete histamine for several reasons but not necessarily from NETs. Yes, you can find many medical texts which link histamine to NET but as I said earlier, you can also find medical texts suggesting there is insufficient evidence to link histamine to NET.  Many texts will also say that histamine is predominately related to foregut NETs i.e. in the respiratory tract, thymus, stomach, duodenum, and pancreas.  For reference and completeness, midgut tumours develop in the small bowel, appendix, and ascending colon and hindgut tumours develop in the transverse colon, descending colon, and rectum.  The main reason why histamine is generally confined to foregut is because these group of tumours almost always have a low content of serotonin (5-HT), and often secrete the serotonin precursor 5-HTP rather than serotonin itself. To get around this mystery and scientific gap, sometimes foregut NETs are said to be potentially associated with an atypical carcinoid syndrome.  Both ends of the spectrum date from 1962 to 2023.  You will not find a single set of NET guidelines where histamine is tested as a marker. Go figure.

Of course histamine is involved in hives/urticaria but that is a totally different effect and pathophysiology than tumours releasing the hormone. 

I wrote an entire blog about Histamine, also included in ‘The NET Effect‘ series – you can read the Histamine post by clicking here.

Amine connections

Let’s talk about another elephant in the room …. Amines.  Just because someone is has an issue with amines, does not mean they have NET; or that the cause of a symptom is a amines.  Sure, they can make a particular side effect of a tumour or a NET syndrome worse, but I’m talking about ‘causal’ sources.  It is absolutely possible that individual, NET or not, can be affected by certain amines.  Vasoactive amines, also known as biogenic amines, are naturally occurring chemicals found in many common foods. These include:

I wrote an entire blog about Amines, you can read the Amines post by clicking here.

Causes of Hives and my own linkages from a diary

Instead of just making assumptions and spreading what might be misinformation to my doctors/nurses or in patient groups, I always like to research reputable sites.  What I found was that many things can cause hives (urticaria).  Let’s list them here.

1. 1. Exercise-induced urticaria is an allergic skin reaction brought on by exercise. It generally produces hives and other allergic symptoms. The hives, or welts, are large, raised bumps on the skin. They can occur on any part of the body. They often are redder around the edge than in the middle. Hives also can look like red spots, blotches, or blisters.  I have recorded breakouts shortly after long walks in hot conditions. So this overlaps with cause 2 below.
   2. Changes in temperature (up or down)
      
      • Cold urticaria is caused by exposure to low temperatures followed by re-warming.  I noticed this from my diary entries, particularly in the winter when wearing too many clothes.  Conversely, a higher body temperature.
      • Cholinergic urticaria is due to an increase in body temperature because of sweating, exercise, hot showers and/or anxiety. Cholinergic hives are often seen in people who are already diagnosed with asthma, allergies, eczema, and other types of hives. Some of these causal effects figures highly on my diary observations.
      • Solar Urticaria.  People with solar urticaria typically report itching and stinging sensations followed by an outbreak of hives after being exposed to sunlight or specific wavelengths of UV light. These hives are often mistaken for heat rash, although it is easy to detect the difference. Photo testing can help determine which wavelength of UV light your body is reacting to, and an allergist can prescribe oral antihistamines, lotions, and immunosuppressives to control these types of hives. I don’t believe this is connected to my own issues.
        
   3. Foods.  Some foods contain histamine including peanuts and other nuts, eggs, and shellfish.  I pretty much eat the same foodstuffs and there has been no major change of diet since I started seeing these issues.  I’m certain I can discount this one. However …. (there’s always one of these isn’t there?).
      
   4. Amines. I have to mention Amines.  I wrote a comprehensive article on this subject because there is an overlap with this and NET, particularly for hormonal syndromes where certain types of amines called vasoactive amines can exacerbate the effects of the syndromes.  I also include functioning Pheochromocytomas and Paragangliomas where there can be an effect from vasoactive amines. For reference you may also see vasoactive amines called ‘biogenic amines’. You may also come across the term ‘pressor amines’. Vasoactive refers to any substance that can alter the diameter of blood vessels, leading to either vasoconstriction (narrowing) or vasodilation (widening). Pressor amine is often used in the context of medication, describes a type of vasoactive agent that specifically raises blood pressure by causing vasoconstriction (or in some cases, increasing cardiac output)
      – Amines and Histamine?  So, note the last 5 letters of Histamine?  Yes, histamine is an amine. But histamine is also a neurotransmitter and it is produced by the body and consumed in foods. Many texts refer to histamine as a vasoactive amine, i.e. they can trigger hives by causing blood vessels to dilate and increase permeability, leading to fluid leakage and localised swelling and itching. This leads to an increase in blood flow to the area, causing the characteristic redness or pinkness of hives. As blood vessels become more permeable, fluid leaks from the blood vessels into the surrounding tissues. This fluid accumulation is what causes the swelling and raised appearance of hives.  But as I said above, histamine can be released from different cells e.g. activated mast cells release vasoactive amines like histamine and other mediators as an allergy reaction – this is not the same as releasing hormones from a tumour e.g. carcinoid syndrome.  See my histamine blog above.  I’m going to discount any relation to NET on this issue as I’m non-syndromic.  I think I can also discount it because the pathophysiology of hives (urticaria) indicates the causal source is not NET related.
      
   5. Stress.  Stress can lead to a rash or hives and worsen existing skin conditions.  I can definitely see this in my diary. Firstly, I’ve always tied in my mild rosacea to stress based on major life change when changing jobs.  Since I have been looking after a close blood relative since late 2023, I have been feeling the physical effects. When you’re all stressed out, your body releases hormones and other chemicals, including histamine, the powerful chemical that leads to allergy symptoms. While stress doesn’t actually cause allergies, it can make an allergic reaction worse by increasing the histamine in your bloodstream. This is definitely on my list of potential contributary factors.
   6. Pressure on your skin: Tight-fitting clothes, sitting, or straps etc, can apply enough pressure to cause hives. I have to add this one as a contributing factor given the main locations of my hives.  I also noticed issues in the area of my watch strap (silicone) so I intend to change it after noticing small red spots on my wrist. Latex in clothing may be a factor too. I’m trying to stick to loose clothing for the many walks and cycle rides and this is a potential overlap with 1 and 2 above.  Sometimes known as ‘pressure urticaria’.  There is almost certainly a connection here.
   7. Medications: Many medications, including antibiotics, aspirin, and ibuprofen, can be triggers. Always check the drug insert leaflets.  I tied in a new asthma med when the Hives started affecting me big time – but it’s still not easy because many other things happened at the same time including but not limited to; Covid Dec 2023 followed back-to-back with a regular chest infection (treated with antibiotics and steroids).  At the same time, number 5 was kicking in plus a sudden death in the family.  Following the covid and bacterial infections in Dec 2023/Jan 2024, my general practitioner changed my asthma meds to a single preventer/reliever inhaler.  As an experiment, he changed me to another drug in May 2024 and I have seen a reduction in hives outbreaks.  I will continue this new drug for the foreseeable future. As at 1st September, I am not seeing any major outbreaks (but see edit).  Still not excluded.
   8. Autoimmune Disease.  Research has found a strong association between certain autoimmune diseases and outbreaks of chronic hives. These types of hives are often seen in men and women already diagnosed with lupus, thyroid disease, rheumatoid arthritis, celiac disease, and Type 1 diabetes. Scientists are trying to determine if the autoimmune disease itself is the sole cause of the hives, or if the hives are associated with the immune system having a difficult time recognizing what is friend or foe. I have never been diagnosed with an autoimmune disease so I can probably discount this one.
   9. Viruses and infections. Aside from certain autoimmune diseases triggering a hive outbreak, a healthy person experiencing a virus or bacterial infection may also exhibit hives as the illness begins to clear from the body. Rhinitis, bronchitis, infectious mononucleosis, the common cold, and noroviruses (stomach flu) can trigger hives in both children and adults. In most cases, these types of hives clear up within a few hours to a week, and over-the-counter antihistamines can help with itching and burning sensations.  I can certainly tie in some hives outbreaks to my two Covid infections but I’m conscious of ‘correlation and causation’ assumptions.

Summary. With sometimes such as Hives (urticaria), sometimes the cause is unknown but with careful diary keeping, you can narrow it down to a shortlist of possibilities.  I guess this is like a perfect storm when lots of conditions are involved and you’re sat in the middle trying to deconflict.  Many sites say that the causes of Hives are never known (oner site suggested up to 80% of cases, the cause is never known).  But you still need to treat it.

Edit August 2025.  After a few months of relief once my prescription antihistamines started to work, I had a recurrence which lasted for one month and is just clearing up – I can definately relate that to a period of stress.

Stress and Hives

Cortisol hives, also known as stress-induced urticaria, are a type of rash that can appear when the body releases cortisol in response to stress. The elevated cortisol levels can trigger the release of histamine, a chemical that causes inflammation and the characteristic itchy, raised welts of hives. What does that mean?  Here’s a more detailed explanation:
1. Stress and Cortisol: When a person experiences stress, the body releases cortisol, a hormone that plays a key role in the body’s stress response.
2. Cortisol and Histamine: Increased cortisol can lead to the release of histamine, a chemical that causes inflammation and the appearance of hives.
3. Other Stress-Related Skin Issues: Stress can also exacerbate other skin conditions like eczema and psoriasis, and it can also lead to acne breakouts.

So, that is a totally different scenario to hives being caused by Histamine release from NETs and the more likely cause of hives in any cancer patient.  The most common cause of hives is an allergic reaction but hives can also can be caused by a reaction to stress. Treatment is the same as other hive types (mainly antihistamines) but where there is swelling or difficulty breathing, it’s important to seek medical advice.

Hives vs Rash

Very difficult sometimes but read this nicely structured summary

Hives vs. rash: How to tell the difference

The Laundry Connection

I’ve been to see my GP about some of these issues – itching in general.  The first question I was asked “have you recently changed your washing detergent”.  I dismissed that angle straight way but I can see why hives and issues with laundry detergent may crossover!   So here is some science on that for your information.

Laundry Detergent Allergy: Causes, Symptoms, and Prevention

Resources used:

1. Foods high in Histamine

2. Angioedema | NHS inform

3. Cholinergic Urticaria: What It Is, Causes, Symptoms & Treatment (clevelandclinic.org)

4. 10 ways to get relief from chronic hives (aad.org)

5. Hives: FAQs (aad.org)

6. 5 Common Triggers of Sudden-Onset Hives – AIR Care (aircaremd.com)

7. Hives on face: Treatments, symptoms, causes, and outlook (medicalnewstoday.com)

8. Stress rash: Effects, treatment, and alternative causes (medicalnewstoday.com)

9. Exercise-induced Urticaria: Prevention, Causes and Treatment (familydoctor.org)

10. Uncommon causes of hives

11.  Hives vs. rash: How to tell the difference

12. Laundry Detergent Allergy: Causes, Symptoms, and Prevention

13. Amines and Hives

14. Plain English guide to Sensitivity to histamines and other vasoactive amines

15. What to Know About Autoimmune Hives or Rash

The NET Effect Series

Disclaimer

I am not a doctor or any form of medical professional, practitioner or counsellor. None of the information on my website, or linked to my website(s), or conveyed by me on any social media or presentation, should be interpreted as medical advice given or advised by me.

Neither should any post or comment made by a follower or member of my private group be assumed to be medical advice, even if that person is a healthcare professional.

Please also note that mention of a clinical service, trial/study or therapy does not constitute an endorsement of that service, trial/study or therapy by Ronny Allan, the information is provided for education and awareness purposes and/or related to Ronny Allan’s own patient experience. This element of the disclaimer includes any complementary medicine, non-prescription over the counter drugs and supplements such as vitamins and minerals.

Thanks for reading.

Ronny

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