Rosacea – the NET Effect


Rosacea The NET Effect

Around 2001, I started noticing some issues on my nose, particularly around the creases, an issue I still experience today.  It normally starts with a stinging feeling, an indication I’m about to experience some sort of inflammation. What eventually happens is something which looks like a ‘whitehead’ which I now know to be a ‘pustule’.  Sometimes there are multiples and most are not normally bigger than 2mm, mostly smaller. These pustules nearly always disappear within a short period of time, normally after washing/showering but they tend to leave reddish marks which eventually fade.  Very infrequently, these pustules would appear on my chin.  After 18 years of the issue, my nose is slightly discoloured and more reddish than the rest of my face.

Shortly after I started experiencing this issue, a doctor diagnosed me with ‘mild rosacea‘. If this is a correct diagnosis, then I would appear to have Subtype 2 or papulopustular (acne) rosacea (see breakdown of types below).  I also have the minor irritation of a recurrent mild eczema inside my right outer ear which has run parallel to this issue (…. spookily).

For around two years, I was treated with a mixture of low dose oral antibiotics (tetracycline) and a skin medication known as metronidazole. This did clear up the issue but it always returned and I stopped the medication opting instead for a commercial product which I find works better.  It doesn’t clear it 100% but I’ve learned to live with it and it is a long-term chronic condition.  I looked at many Rosacea sites online and none of the pictures seemed to apply to me and I agree with my diagnosing doctor in terms of a ‘mild’ version.

I worked out early on that the triggers were stress, when ‘run down’, and too long in the sun. There were possibly others.  Stress was part and parcel of the work I was involved in and it was at a time when I left my life in the military after 29 years and started a second career in industry (often I think in hindsight, I may have been overly stressed at the life change without realising it).  Without any medical input, I decided to try to make sure I got sufficient vitamins and I now appear to get less coughs and colds then I used to.  I now try to stay out of the direct sun.  Other common triggers are listed on reputable sites andinclude alcohol, hot and cold weather, exercise, hot baths and spicy foods.

What is Rosacea

A common skin condition, usually occurring on the face, which predominantly affects fair-skinned but may affect all skin types in people aged 40 to 60 years old. It is more common in women but when affecting men, it may be more severe.  It is a chronic condition, and can persist for a long time and, in any individual, the severity tends to fluctuate. Rosacea tends to affect the cheeks, forehead, chin and nose, and is characterised by persistent redness caused by dilated blood vessels, small bumps and pus-filled spots similar to acne. There may also be uncomfortable inflammation of the surface of the eyes and eyelids.  I found this site to be a very useful Rosacea reference.

Rosacea is sometimes classified into 4 subtypes that may overlap:

  • Subtype one, known as erythematotelangiectatic rosacea (ETR), is associated with facial redness, flushing, and visible blood vessels.
  • Subtype two, papulopustular (or acne) rosacea, is associated with acne-like breakouts, and often affects middle-aged women.
  • Subtype three, known as rhinophyma, is a rare form associated with thickening of the skin on your nose. It usually affects men and is often accompanied by another subtype of rosacea.
  • Subtype four is known as ocular rosacea, and its symptoms are centred on the eye area.

What causes rosacea?  

The cause of rosacea is not fully understood. Your genetics, immune system factors, and environmental factors may all play a part. Factors that trigger rosacea cause the blood vessels in the skin of the face to enlarge (dilate). The theory that rosacea is due to bacteria on the skin or in the gut has not been proven. However, antibiotics have proven helpful to treat rosacea. This is because of their anti-inflammatory effect. Rosacea is not contagious.

Why is rosacea sometimes linked to NETs?

On certain sites and in certain texts about NETs, you will see mention of Rosacea, clearly as a misdiagnosis of someone who presents with flushing.  I started experiencing the sensation of NET related flushing in late 2009/early 2010 and I can honestly say this was a totally different experience to what I had with my mild rosacea. However, I don’t have the ‘blushing’ type of rosacea and I can see the presentational similarities.

Another issue commonly reported in both conditions is small visible blood vessels on the face, known formally as Telangiectasia or informally as ‘spider veins’ or ‘broken capillary veins’. This is quite common with erythematotelangiectatic rosacea (subtype 1).  I actually have at least two of these showing and this appears to be something I’ve only noticed since NET diagnosis and only in the last few years.  Interesting it says this is something normally caused by “chronic flushing” but I wouldn’t have labelled by flushing in that way. I have not felt any flushing since late 2010 after surgery and commencement of long acting somatostatin analogues.  Unless there has been something ‘sub-clinical’ going on, I’ve veered my minor issue towards long-term but mild rosacea as the cause rather than NETs.  Telangiectasia is mentioned in many NET texts including my own article “Neuroendocrine Cancer: A Witch’s Brew of Signs and Symptoms”

Histamine if often linked to both conditions.  Read about NET related histamine here and Rosacea histamine issues here.

Summary

I’ll be honest with you, I’m actually not 100% convinced I have rosacea as it has similarities with many other skin conditions. In fact, skin issues are pretty common with NET patients, some are actually directly linked to NETs including Merkel Cell Carcinoma,  pellagra (linked to Carcinoid Syndrome) and Sweet’s syndrome (linked to Glucagonoma).  In addition, many people develop skin issues as a side effect of treatment.  Read more here.

Thanks for reading

Ronny

I’m also active on Facebook. Like my page for even more news. I’m also building up this site here: Ronny Allan

Disclaimer

My Diagnosis and Treatment History

Most Popular Posts

Sign up for my twitter newsletter

Read my Cure Magazine contributions

Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

Ronny Allan is an award winning patient leader and advocate for Neuroendocrine Cancer.

 

Please Share this post for Neuroendocrine Cancer awareness and to help another patient

Living with Neuroendocrine Cancer – the 7 Year Itch

7 year itch

I quite like the Facebook memory thing. This morning I got a reminder of a post I made from 7 years ago whilst I was in hospital recovering from my 9 Nov surgery.  It had taken 12 days for me to feel strong enough to venture onto social media with a simple message “I’m feeling perkier”.  For those not familiar with English localisms, it just means lively, spirited, bright, sunny, cheerful, animated, upbeat, buoyant, bubbly, cheery, bouncy, genial, jaunty, chirpy, sprightly, vivacious, in fine fettle, full of beans, bright-eyed and bushy-tailed.  I guess I met some of these descriptors most of the time! I had gotten through the worst and the light at the end of the tunnel was now a faint glimmer.

I’ve recently had a ton of ‘7 years ago cancerversaries’ and there’s still a few to go! I’m currently being reminded of an issue that started just after my initial treatment and by coincidence (perhaps?) the commencement of my Lanreotide (Somatuline Autogel).  Itching!  However, for me, it’s mainly the right leg below the knee (go figure!). Much less frequently on my arms and sides.  I know many people have the same issue but no-one ever seems to find out why – I guess it’s that Neuroendocrine jigsaw thing again?

Initially, I put the issue down to Lanreotide, as this is mentioned in the side effect list on the drug instructions.  The initial connection was made because it seemed to be happening immediately after my monthly ‘dart’.  A really annoying itch mostly around my ankles and which had to be scratched!  An application of a general emollient cream for a few days seemed to do the trick and after a week it was gone (until the next injection …..). However, after a few years, I sensed the issue was drifting away from the injection cycle and adopting a different and more random pattern.  I’m also suspicious of a nutritional connection and checking my article Nutrition for NETs -Vitamins and Mineral Challenges, I can see Vit B3 (Niacin) and Vit E are mentioned in regards skin issues.  I’d be confused if this was an issue today as I now take plenty supplements to offset GI malabsorption.  However, I probably wasn’t taking sufficient between surgery and 2013 as I lacked the knowledge to do so at the time.  So nutritional deficiency remains a possibility or at least an added complication.  The most recent outbreak has unusually gone on for the last 4 weeks.

I also seem to have had an eczema type issue in my right ear and mild rosacea for more than 7 years (pre diagnosis).  As you can imagine my ‘inner detective’ is working overtime!  One thing is clear – this itchy leg issue has plagued me for 7 years.

I know that many people have real issues with rashes and skin itching, I’ve seen this so many times with some people describing it as severe.  Clearly when this is the case, a doctor’s intervention is generally required.  I’ve seen the following connections to NETs and skin issues:

I bet my flush beats yours?

royal_flush_w
There are different types of flush!

Neuroendocrine Cancers can sometimes present with one or more vague symptoms which occasionally results in a lengthy diagnostic phase for some.  Sure, there can be issues with doctor experience and knowledge that can add to the problem. However, some people do present with multiple vague and confusing symptoms and some people have comorbidities which have similar symptoms.  Textbook diagnostics just don’t make sense, sometimes even when the doctor suspects Neuroendocrine Cancer i.e. classic symptoms of ‘something’ but with negative markers for NETs. Clearly those are extreme cases and just like other complex diseases, many diagnoses of Neuroendocrine Cancer can be extremely challenging.  Even for an experienced doctor, it can be a difficult jigsaw!

Most types of Neuroendocrine Cancer can be accompanied by a ‘syndrome’ i.e. the tumours are ‘functional’ and this is normally (but not always) associated with metastatic disease. At this point it’s also worthwhile saying that some Neuroendocrine Cancers can be ‘silent’ (non-functional) for years before any symptoms show and it’s normally only when they metastasize, that these clinical syndromes come to life. Ironically, the manifestation of the disease with a syndrome can occasionally turn out to be a life saver albeit the cancer is normally incurable at this stage – but still treatable.

The most common type of Neuroendocrine Cancer can often present as a collection of symptoms known as Carcinoid Syndrome and the most common of these is flushing with approximately 84% frequency.  Others symptoms include (but are not limited to) diarrhoea, heart palpitations, stomach cramps and general abdominal pain/discomfort, shortness of breath, wheezing.  You can see the scope for confusion and misdiagnosis.  You may find my blog on the ‘5 E’s of Carcinoid Syndrome’ useful.

When you look at these general Carcinoid Syndrome symptoms, flushing seems to be the one that stands out as a ‘cardinal sign’ whereas many others are vague and easily confused with common/regular illnesses.  However, the flushing is reported to be different from most people’s perceptions of a ‘flush’.  The Carcinoid flush is almost always ‘dry’.  To quote my ‘amazing yellow book‘ (co-authored by Woltering, Vinik, O’Dorisio et al), “…. a good rule of thumb is if the flushing is wet (accompanied by sweating), it is due to a cause other than Carcinoid”.   Dr James Yao, another well known NETs guru also raises this distinction by stating…. “The facial flushing of carcinoid syndrome is usually a dry flushing, and not associated with sweating like other kinds of flushing. The flushing is often a symptom that others notice before patients do. They may not feel it themselves.”

Additionally, from the same source, there appears to be at least two varieties of flushing in Carcinoid Syndrome related to two different anatomical regions of the primary tumour (again a useful guide from my amazing yellow book):

What to Look For in Flushing – Distinguishing Signs and Symptoms

There are two varieties of flushing in carcinoid syndrome:
1. Midgut: The flush usually is faint pink to red in color and involves the face and upper trunk as far as the nipple line. The flush is initially provoked by alcohol and food containing tyramine (e.g., blue cheese, chocolate, aged or cured sausage, red wine). With time, the flush may occur spontaneously and without provocation. It usually lasts only a few minutes and may occur many times per day. It generally does not leave permanent discoloration.

2. Foregut tumors: The flush often is more intense, of longer duration, and purplish in hue. It is frequently followed by telangiectasia and involves not only the upper trunk but may also affect the limbs. The limbs may become acrocyanotic, and the appearance of the nose resembles that of rhinophyma. The skin of the face often thickens, and assumes leonine facies resembling that seen in leprosy and acromegaly.

Another source for flush descriptions comes from a paid article written by well known NET Endocrinologist – Kjell Öberg.

Four different types of flushing have been described in the literature.
Endocrinology: Adult and Pediatric – 7th Edition 2016.

The first type is the diffuse, erythematous flush, usually affecting the face, neck, and upper chest (i.e., normal flushing area). This flush is commonly of short duration, lasting from 1 to 5 minutes, and is related to early stages of malignant midgut NETs.

The second type is violaceous flush, which affects the same areas of the body and has roughly the same time course or sometimes lasts a little longer. These patients also may have facial telangiectasia. This flush is related to the later stages of malignant midgut NETs and is normally not felt by the patients because they have become accustomed to the flushing reaction.

The third type is prolonged flushing, lasting for hours up to several days. It sometimes involves the whole body and is associated with profuse lacrimation, swelling of the salivary glands, hypotension, and facial edema. These symptoms are usually associated with malignant bronchial carcinoids.

Finally, the fourth type of flushing reaction is bright red, patchy flushing, which is seen in patients with chronic atrophic gastritis and ECLomas (derived from enterochromaffin-like cells) of the gastric mucosa with evidence of increased histamine production.

Differential diagnoses for flushing?

The facial flushing associated with NETs should be distinguished from other causes of flushes. The carcinoid syndrome flush is provoked by spicy food, alcohol, and physical and psychological stress, and it is often worse in the morning. Patients with idiopathic flushes usually have a long history of flushing, starting rather early in life and sometimes with a family history without occurrence of a tumor. Menopausal flushes usually involve the whole body and might be related to release of calcitonin gene–related peptide (CGRP) with transient vasodilation, a so-called dry flush. Another type of menopausal symptom is the wet flush, which includes epinephrine-induced sweating. Proposed mediators of flushing in menopause are CGRP, histamine, prostaglandins, serotonin, lysyl-bradykinin, and substance P. Estrogen is known to have an impact on the production and release of different signaling substances such as noradrenaline and β-endorphin. Low estrogen levels cause lower β-endorphin activity, which in turn enhances the release of gonadotropin-releasing hormone (GnRH), which gives rise to high luteinizing hormone (LH)levels. Postmenopausal women in whom a true carcinoid syndrome is developing can tell the difference between the two types of flushes. Sometimes patients with medullary thyroid carcinoma have brief flushes provoked by alcohol. In patients with watery diarrhea, hypokalemia, achlorhydria syndrome (WDHA; vasoactive intestinal peptide [VIP]omas), a purple-red constant flushing of the whole body may develop. This flushing reaction is related to the vasodilator effects of VIP. Flushes seen in mastocytosis are related to release of histamine from mast cell granules. Mastocytosis is a rare disease of mast cell proliferation that occurs both cutaneously and systemically.

So it’s clear from our experts that the flushing symptom has many potential triggers and can be attributed to the secretion of excess hormones associated with Neuroendocrine Tumours. It’s also clear that the symptom is not just associated with carcinoid syndrome. Although many people focus on serotonin as the main culprit, there appears to be significant evidence to suggest that other hormones may be playing a bigger part with this symptom, e.g. histamine (particularly foregut), tachykinins (Substance P), bradykinins, and prostaglandins.

If you study the online forums, there are frequent questions about flushing, particularly from those looking for a diagnosis and are suspecting Carcinoid Syndrome due to a flushing symptom. However…… even flushing cannot always be attributed to a NET, particularly if it’s the only symptom being presented.

Flushing tests

This is a very useful table taken from my amazing yellow book which gives the tests required to determine the potential source of a flushing (differential diagnosis).  I strongly suspect this is not an exact science (…..is anything in medicine?) but it’s extremely useful.  Personally I would have included Rosacea :-).  The referenced article “>Endocrinology: Adult and Pediatric – 7th Edition 2016 by Öberg, Grosssman et al, generally agrees with this list but adds WHDA Syndrome (a pNET called VIPoma), food, drugs, ethanol and idiopathic. It also generalises Neurologic disorders (see more below).

Öberg, Grosssman, et al list the following drugs that can cause flushes:

  • Bromocriptine
  • Tamoxifen
  • Nicotinic Acid
  • Opiates
  • Calcium channel blockers
  • Ketoconazole
  • Chlorpromazine
  • Cephalosporin

Öberg, Grosssman, et al list the following foods that can cause flushes:

  • Spicy food
  • Glutamate
  • Sodium nitrate
  • Sulfites
  • Hot beverages

Öberg, Grosssman, et al also list the following neurologic disorders that can cause flushes:

  • Anxiety
  • Migraine
  • Parkinson’s disease
  • Spinal cord lesions
  • Brain tumors

Clearly these lists are those that can cause a flush but not everyone will experience this.  For example, when I was syndromic with flushing, I never had any issues with hot beverages.

My own experience with flushing brings back some memories and it emphasises something I say a lot – the patient has a big part to play in their own diagnosis.  Please check out this 90 second video about how I did not play my part!  I was experiencing a mild and innocuous flushing sensation for some months before I was diagnosed with metastatic Neuroendocrine Cancer.  Even though I knew it was weird and something I hadn’t experienced before, I totally ignored it.  I failed to mention it at any of my routine GP appointments or my annual asthma clinic.  I failed to mention it to my specialist who was investigating a GP/PCP diagnosis of Iron Deficiency Anemia/weight loss.  After a CT scan, the specialist appeared to be scratching his head …..  at that point he knew I had cancer but he also knew it was unusual.  I suddenly mentioned the flushing and ‘bingo’.  It was the face of a man who had just found a missing piece of a jigsaw and he correctly predicted the output from my subsequent liver biopsy.

For the next few months, I was keeping my condition private at work but it was sometimes difficult to disguise the flushing. At least  one person thought my blood pressure was going up! Fortunately, my flushing disappeared after treatment.

I’ll complete this post with an interesting summary from an online forum post in which I was participating. There was a general discussion about the severity of ‘syndrome symptoms’ including triggers and I was staggered to read that people were experiencing flushing whilst carrying out routine day-to-day tasks. I’m so happy I don’t flush when I eat one square of chocolate (that would be a complete disaster!).  The one which caught my attention was the simple act of washing hair. Whilst I initially raised my eyebrows and laughed, it did make me think back to the last flush I experienced (and touch wood it was the last …..).  Following my diagnosis, I commenced daily injections of Octreotide. These injections reduced the flushing but it didn’t eliminate it. However, after my ‘debulking’ surgery in Nov 2010, my flushing disappeared.  However, I do remember this small flush coming out of nowhere whilst I was recovering in hospital after that surgery. I was cleaning my teeth and I do vividly remember this minor task taking some effort!

I haven’t had a flush since and if this symptom comes back, I’ll know I have a new problem to contend with.

Thanks for reading

Ronny

I’m also active on Facebook.  Like my page for even more news.  I’m also building up this site here: Ronny Allan

Disclaimer

My Diagnosis and Treatment History

Most Popular Posts

Sign up for my twitter newsletter

Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

patients included

wego blog 2018 winner