CRPS – The Dutch Way: “Evidence-Based Guidelines CRPS type I” and possibly halting the early stages of CRPS in its tracks

The interesting part of living in a foreign country is seeing that there are different approaches to treating CRPS. Not that one country necessarily has the edge over another, simply that there are subtle differences in viewpoints that can bring forth an entirely different perspective. I am an Australian, living in the Netherlands, and have been here for years now. While some aspects of the Dutch medical system may seem somewhat lax at times and I've had many gripes with these sometimes infuriating differences; what I really found interesting was the research that they have done in the field of CRPS. Their approach differs somewhat to what I had been through, or found about about over the years. It has been getting great results in treatment of acute-stage CRPS, sometimes halting progression and even reversing the changes and the Pain!

Here in the Netherlands is the TREND (Trauma Related Neuronal Dysfunction) Consortium, which “is a collaboration of 5 University Hospitals, one Technical University and some industrial companies. Meanwhile there are also contacts with other institutes abroad.
From a multidisciplinary composition TREND aims to bring together forces and insights from different disciplines and expertise to an important contribution to research to the Complex Regional Pain Syndrome (CRPS-1)”(from their website)

A group of dutch medical practitioners, in association with the Netherlands Institute of Healthcare Improvement (CBO) and the patients association (Patiëntenvereniging CRPS) contributed to the drafting of the "Evidence Based Guidelines to Complex Regional Pain Syndrome type I" in 2006, which looked at the evidence of the effectiveness of different treatment options for CRPS.

Evidence Based Guidelines CRPS type I (patient pdf english version)

EvidenceBased Guidelines CRPS type I (practitioners pdf english version)

The second one is definitely more suited for doctors, GPs etc., as it's pretty long-winded (170pgs or so) and while thorough, it's probably way more that a patient would need. However, it still may be useful and goes into detail how effective each treatment is according to the research and evidence available.

The Guidelines are an interesting read if you have CRPS, or know someone who does. It may also be something to share with your GP. Their knowledge of this condition may be limited too, their medical training may not have adequately covered it. The vast majority of the doctors and specialists I have seen over the years have openly admitted that they don't really know a lot about CRPS; it is a fairly uncommon condition on the whole. While my GP has other chronic pain patients, I am his only CRPS patient. Any time I read an article or something useful from a reputable source (mostly academic or medical articles), I share it with him. Even if it doesn't help me, it may help the next person he encounters, or one of his other chronic pain patients.

GPs are the first-port-of-call medical professional we go to, and the one we also go to for ongoing management. They are expected to be experts on everything; whereas the reality is that they can only be “experts” on that which the majority of their patients are being treated. GPs work very long hours and are often paid much less than specialists for their services – how can we realistically expect them to know it all? They simply don't have the time to read every single journal for the latest research and most up-to-date treatment options for a disease they may only encounter once or twice in clinical practice. We, as patients, also have a responsibility to know as much as we can about our illness. Being well informed leads to greater understanding and control over the course of our treatments/medications and management. We may find out about something that our GPs don't hear about; by sharing it with them, they may be able to find further information to which we have no access. We are living in an age where a wider variety of information can be sourced; information that previously could only be obtained with great difficulty. It could lead to finding out about innovative options and treatments that potentially could change your life. It also gives us greater control over our own destiny, even if our condition remains.

Bear in mind that much of the research or compiling of information comes from the USA. However these websites tend to have a lot of great info and can be a good starting point, in a sea of murky wives-tales that litter the internet. It never hurts to know more about your condition anyway, and knowledge will help you feel more in control over your life even at times where it feels that the CRPS is calling the shots:


American RSDHope (by using AmazonSmile, donations to this organisation can be made each time you make a purchase on Amazon) This is perhaps one of the best websites. I often begin here when searching for information. 
RSD Hope (www.rsdhope.org)

Reflex Sympathetic Dystrophy Syndrome Association:
RSDSA (www.rsdsa.org)

Neurological Associates Pain Management Center, Vero Beach Florida
RSDrx (www.rsdrx.com)

What is of vital importance and is repeated throughout, is early intervention. That means recognising and treating in the first 3-6 months. It is possible for the symptoms to go into remission, or be stopped in its tracks. Many treatment options are only effective in the acute and early stages, such as sympathetic nerve blocks. Once it turns chronic, usually 6 months or so after initial injury, the chances of making a full recovery are a lot slimmer. Some people are fortunate enough to have it either go away on its own, or are able to halt its progression. But a significant number of people with CRPS are not so lucky, and they end up with the symptoms spreading further from the initial injury to other limbs, either spontaneously or from another injury/trauma that may have been minor to begin with.

Spreading of complex regional pain syndrome: not a random process 

(Journal of Neural Transmission, September 2011, 118/9, pp.1301-1309. Links to full article on PMC)

If nobody recognises the symptoms of CRPS, you may be sent for any number of scans or tests, or to any number of specialists. All these other investigations and consultations may end up taking you in the opposite direction than you should be; leading to unnecessary and most often, unsuccessful surgeries that only compound the problem and often making it worse! By opposite direction, I mean in having the expectation that by finding some damage/abnormality and fixing it, it will consequently improve the Pain; without realising that CRPS pain has its own separate cause and strange symptoms that require a completely different approach than a straightforward structural repair or reconstruction! I go into more detail below under “Scavengers”, but though CRPS may be caused by a trauma; it isn't maintained by it.

It can be as simple as having a GP /specialist who recognises the symptoms and begins treatment early while also looking at preventative measures. The CRPS can stop its progression, reverse or even goes away completely in some of these cases. Even in those who remain symptomatic, this can make a HUGE difference in quality-of-life and impairment outcomes. On the other side of the coin, it can lead to life-long and permanent impairment and Pain; spreading into other limbs; developing movement disorders, like tremors, contractures or dystonia; or circulation problems leading to infections and to the possible worse-case-scenario of amputation. It can mean a lifetime living in severe pain and with significant disability, often being unable to work for long periods of time. Mental health issues such as depression and anxiety stemming directly as a result of the chronic pain and chronic sleep-deprivation; all of these things impacting on their families and loved ones who live with this condition to much the same degree as the person with CRPS. These are only the things I can think of from the top of my head. These lists can be much longer, but you get my point. If you can raise your chances to win the lotto by buying more tickets – having knowledge and awareness is like buying a whole shop-fulls of tickets.

There are so many lives that end up affected by this, not for months or years – but for the rest of that person's life! I am relatively cheerful and upbeat; I'm mentally very strong (mainly because I keep a sense of humour about it all), as well as fiercely independent and stubborn. But this is not the life I wanted for myself and I certainly didn't want it for my family. For them to see me in so much unbearable pain, every single day; this kills me more than the actual pain. That they have to watch it, and not be able to do anything at all to fix it or somehow relieve it. I live with CRPS but my loved ones are the ones suffering with it!

It is not only my life that this disease is taking away, but also those family members who have to be my carers; whether it be physically, financially, emotionally or all three. Each one of them are affected by this. I say this not because I think of myself as a burden; neither do my family think of me as such. They do what they do for me out of love and respect. But what about those people who don't have that support network of trusty X-Men like I do? What happens to them? Or those who have families and loved ones who may not understand? I would never have foreseen any of this; that during my 20s to mid 30s I would end up unable to work and completely dependent upon my partner to not only be the sole breadwinner, but doing 100% of the grocery shopping and 90% of the housework AND being my carer. That when I return to Australia for a visit, I would be completely dependent upon my mother and brother. Who would want this sort of a life? No one does!

I should be working, I'm intelligent, educated and social; I should be raising a family by now. But instead I have been a prisoner of my own home in a form of solitary confinement for nearly 3 years. I will – unless by magic or miracle – continue to be disabled for the rest of my life! That could mean 60+ years of non-stop nerve pain; more than the pain than childbirth, or passing a kidney stone or cutting off a finger. That is the pain of CRPS; medication rarely even scratches the surface, merely stopping you from losing your mind. Suicide is a very real and widespread problem in CRPS patients. Do not underestimate the reality of this disease. Just because someone seems to be coping well with it, doesn't mean that they could be hiding the fact that they are living in hell.

This is a huge thing. If preventing this sort of outcome can be done in some, if not many, simply by these non-invasive treatments; the importance and significance of it, is something I cannot stress enough! They are even relatively safe compared with just about every other medication/treatment option available. However nothing in life is without risk, and these also have their own list of possible side-effects and risks of allergies or intolerance. Compared to the long-term risks of opioid/anti-inflammatory/anticonvulsant usage though, they are easy-peasey and generally well tolerated in most people - though not everyone.

Now, I don't really like these realities and don't focus on them. It's hard enough to live it! But I realise just how important it is to make my point crystal clear – if you can prevent any of this, you can live so much better. I make joke about my situation often, but that is my way of coping. The more I wrote about this, the stronger I felt about the subject. Early prevention/intervention is vital!

THE DUTCH WAY – how the Dutch treat CRPS in its acute stages:

I don't really know how well-known it is outside the country, but these are in the general practice of treatment here in the Netherlands. I don't remember ever coming across these early treatments detailed in the guidelines. I read a lot about medications and injections/blocks, physical therapy (gentle mobilisation, warm water), mirror box therapy, cognitive behavioural therapy and the importance of having goals; however this approach was something I had never seen before.

*** Before I go any further – make sure you talk to your treating doctor or GP about this, before taking anything that they have not prescribed you, even things you don't think are serious enough to mention. Do it just in case you have some weird oddities like I do, and some of these things you cannot tolerate (and you could have an allergic reaction, maybe even a life-threatening one, to anything – you have been warned!); or if you any other illness/condition affecting other areas of your body, or take ANY medications. Take special care if you have asthma, but that goes with all medical stuff. Do I need to go on? C'mon, let common sense rule – your health is the most important thing you own, so don't mess around with it! Everyone knows what happens to people who self-diagnose online, or take medical advice off people who have never studied medicine! Have a chat with your doc, take a printout of the Dutch guidelines or the journal articles if you want but remember that medical treatment ALWAYS should be a team effort! There's a very good reason that they went to medical school – it's to help you! ***

Number one – VITAMIN C:

If there's one thing to take from this, even if you don't read any more – if you have an accident, break a bone or whatever – take at least 500mg a day of Vitamin C for a few months. It's rather simple, won't hurt your body and can prevent CRPS developing in the first place, or spreading further. If you already have CRPS, it's not a bad idea to take it anyway in case you fall over or end up (god forbid) getting hurt again. If you're going into surgery or anything like that, definitely take it beforehand and afterwards for at least 50 days.

Now, this rather innocuous one is still one to take some care with and to mention to a doctor. I don't know your medical history – I'm a messenger – not a doctor! Though you will probably pee the excess out, and vitamin C is one of the vitamins that doesn't build up in the body (vitamin E, on the other hand – does – so even vitamins can be dangerous!). Even so, I wouldn't go dosing yourself with massive amounts or you could end up sick. But in general, vitamin C is fairly well tolerated, and anyway, we all really should be getting it from our diets!

Can vitamin C prevent complex regional pain syndrome in patients withwrist fractures? A randomized, controlled, multicenter dose response study

(Journal of Bone and Joint Surgery American, July 2007, 89/7 pp.1424-1431. Links to abstract on Pubmed)Efficacy and Safety of High-dose Vitamin C on Complex Regional Pain Syndrome in Extremity Trauma and Surgery

(Journal of Foot & Ankle Surgery, 2013, 52, pp.62-66. Links to full article on rsds.org)VitaminC is Effective in Preventing Complex Regional Pain Syndrome in Adults Following Trauma: An Evidence Based Review

(links to a powerpoint presentation on http://ptrehab.ucsf.edu/)

Number two – FREE RADICAL SCAVENGERS:

(Definitely don't do this without consulting your GP, for reasons following)

This approach was completely new to me. It is based on the assumption that CRPS is a response to an exaggerated inflammatory response to the initial injury, creating toxic oxygen radicals (free-radicals). The study was a randomized, double-dummy controlled, double-blind trial (pretty compelling, as far as studies go). It showed significant improvement in a large number of patients. There is an interesting division of CRPS patients in this approach: those of 'warm dystrophy' hot skin, “burning” etc., and tends to be the acute stage; as well as the 'cold dystrophy' types who had the cold skin etc. 'Cold dystrophy' tends to be in the chronic stages, but these divisions, like the older “stage” form of classification, aren't set in stone, merely generalities and observations.

From the Dutch guidelines linked above, pp14

Scavengers

Practitioners are advised to administer scavengers (substances that capture free radicals)

in the acute phase of CRPS-I as they appear to have a beneficial effect on CRPS-I

symptoms.

These scavengers are:

• 50% DMSO cream (dimethyl-sulphoxide) to be applied five times a day to the skin of the affected limb
• N-acetylcysteine effervescent tablets, 600 mg three times a day.

DMSO:

If you have had CRPS-I for less than a year, it is recommended that you apply 50% DMSO five times a day for three months.

If you have had CRPS-I for more than a year and have not used 50% DMSO five times a day before, a one-month course can be considered and continued for three months if it proves beneficial.

N-acetylcysteine:

600 mg three times a day for three months, is recommended if you have 'cold dystrophy' as it appears to be more effective than DMSO.

The treatment of complex regional pain syndrome type I with free radical scavengers:a randomized controlled study

(Pain, 2003, 102 pp.297-307. Links to full article on rsds.org)

This is pretty good evidence, and it is used in a clinical setting quite often here in the Netherlands and I must admit, there doesn't seem to be as many people who have chronic-stage CRPS. At least not from what I've seen, nor judging by the different doctors and specialists I've been to. Naturally, this is just what I have observed (from my subjective view and not by objective findings!). Often the doctors/specialists I have seen are unfamiliar with my presentation of symptoms (chronic CRPS in multiple limbs and with movement disorder/dystonia) unless they were specific CRPS pain specialists. They may have known about it, but rarely seen it in their practice; even the pain rehabilitation doctors I've seen have had very few chronic CRPS patients. I've also known friends personally over here who had acute CRPS after a trauma, who have gone into full remission with their symptoms disappearing or decreasing after completing this treatment. I had never seen that before, only read about it happening. It gives me a lot of hope, as maybe there are people out there who would have ended up like me, had they not done this particular treatment. It's really wonderful to know that it doesn't have to be a downward slope; that some can actually recover, or at least have a much better outcome in the long term with regard to pain, symptoms and impairment.

*** A RATHER BIG WARNING THOUGH: Don't touch this stuff before speaking to your doctor, – even if you can get it without a prescription! Don't even look at it! Especially if you have asthma or any allergy whatsoever. I am speaking from personal experience here, I cannot put enough emphasis on this, so I'll repeat it – Don't try this without speaking to your doctor!! ***

I will counter with the fact that my experience is definitely a very rare side-effect here in the Netherlands, to the point that the doctors questioned if I was reacting to something else. This type of reaction was not seen in any of the 146 patients of the study, nor the thousands treated in the clinical setting by the specialist who prescribed this course of treatment. I am almost certain it had to be the N-acetylcysteine (or also known as NAC) that I was allergic to – or maybe the combination of the two made it worse – as there was nothing else new I was exposed to on the day. When I read up on NAC in the english patient info, I found that these rare serious side-effects are more likely to occur in asthma patients. It should be noted too that there also isn't as many people with asthma here in Europe, for whatever reason. So, err on the side of caution, even if you're not asthmatic. Chat to your doctor. But also don't discount what could be an effective option for you though. This is not a scare story; merely me sharing my personal experience, which really is the exception to this quite well-tolerated treatment in the vast majority of people. But don't mess around with your health – people can be allergic to the strangest things.

I have asthma, with a long history of drug allergies – There is a long list of drugs I cannot tolerate, (or which have given me strange reactions) such as asprin or NSAIDs. I'm allergic to a fairly common antibiotic, a couple of antidepressants... and now NAC and/or DMSO! I have rarely experienced any asthma symptoms since my late teens however when I have an allergic reaction, it can become serious.

I started this treatment a couple of months after the legs started going CRaPS-crazy. NAC + DMSO = a very serious anaphalactoid reaction in me, with swelling, itchy hives, dizziness, nausea and a very serious asthma attack; the first attack in 6 years after having no asthma symptoms. I was very lucky to have someone who came home and found me like that and was able to take me to hospital. Had I been alone.... well... as I said – very lucky!

So it took me back to another hospital that evening for a very unpleasant night of being a pincushion for injections of steroids and antihistamines which are usually given in different areas. It is never a good idea to get injected into CRPS-affected areas. Unfortunately that meant that I was unable to take any injections in my CRPS arm, nor my less-CRPS-affected good arm which is now my “crutch arm” and needed for walking; nor in my right bum cheek as it's where the CRPS is also... all of them had to be injected into my left buttock. It really was NOT my idea of a fun night out!! I had only one ventolin inhaler at home which was not effective, despite taking it in the crisis dose (i.e: very frequently). I was lucky to even have that, to be honest; as I hadn't needed it for years. The preventative inhaler (with a long-term bronchodialator and steroid) was well out of date, luckily the ventolin was just before expiry date. There are so many things that could have gone wrong that night. It was frightening both for myself, and for my partner who had never seen something like that before. It was lucky too that he had the frame of mind to get me to hospital so quickly, rather than panicking.

N-acetylcysteine, while being a free radical scavenger; it is also a mucolytic agent, which is used to clear the airways of mucus so it can be coughed up. My GP told me that he prescribes it in cases of flu, chest infection or the like. It is known as “Fluimicil” over here, and can be bought over the counter. Very rarely, it can induce the anaphalactoid reaction like I had; with the itching rash and breathing difficulties from bronchospasm; which is what can make it so problematic for asthmatics. It is also administered intravenously in hospitals for cases of paracetamol overdose, as it protects the liver and kidneys from damage from the high-dose paracetamol. Usually the rare side-effects like what I had, were only in cases of intravenous doses, but it seems I'm a freak of nature and got it from taking it orally and only one dose! That's why I would say NOT to try this on your own; make sure you do it ONLY with your doctor's advice and ONLY if you have never had asthma, drug sensitivities or allergies to ANYTHING.

Nevertheless... I do believe there is a lot of promise in this approach and treatment – it is a really big shame that it wasn't possible for me to find out if it could work. I was disappointed in a huge way, as I was really hoping that it would be my saviour - that it could have given me my legs back and for it to be so simple - wow! For many others for whom may have ended up with progression into disability without it; it can potentially halt the progress of the disease! Wonderful news! It gives me a lot of hope. When I look at the new treatments that are available now, compared to the relative black-hole of knowledge and options that were available to me 13 years ago: times really have changed. However, one can look further back 20 or 30 years and see how far we have come in explaining some of the mechanisms contributing to, as well as the understanding of the condition itself. Back then, the "slice and dice" model was more common – sympathectomy (cutting nerves in the sympathetic nervous system) and amputations of painful limbs. None of these things really helped the pain itself in the long term, and many unsuccessful operations ended up causing undue suffering and even more Pain, or phantom pain in the amputated limbs that were removed. Nowadays, it really is the very last resort and only if it is medically indicated.

The specialists I saw even back in my very early days in 2001 were quite innovative in their approach, especially in their knowledge that operating often made these symptoms much much worse. I remember a few doctors almost literally jumping away once they had examined me and figured out what was wrong. They called it “reflex sympathetic dystrophy” in those days. Well, I'll certainly never forget the reflexes of that orthopedic surgeon literally jumping away from me, “I cannot advise any surgical procedures. We surgeons often somehow do more harm than good by interfering”!

He was the one who put me on gabapentin in the first place. This is one of the rare drugs that actually did anything for me before pregabalin was even on the market. It was not on PBS back then, so I had to pay full-price for it (back in 2001-2002 was $287 each prescription!). This huge expense really limited my ability to really use this drug in its therapeutic dose. That is an insight into the sometimes cruel world of pharma politics - if it's prescribed “off-label” and therefore is not subsidised; people who cannot work  cannot pay the full price and often miss out on the benefits of a medication that could actually enable them to return to work in the first place. Under Workers Comp., the insurer may have covered the costs, but I still needed to have the cash to pay for it to begin with, and to be able to do without that money for weeks before they actually got around to reimbursing it. Pregabalin came on the market later, in 2005 or so; and has since been listed under PBS, as is the generic gabapentin. Times change.

Effective treatment options are better now, but still mainly limited. Medications to control pain, intensive physical/occupational therapy, mirror box and graded motor imagery, and psychological CBT and rehabilitation programs. Progressing to the more invasive nerve blocks, ketamine infusions (which are uncommon) and spinal cord stimulators.

Spinal cord stimulators are something I will go into further in a future post. However, they have a strict selection criteria in order to qualify for a trial stimulator. Unless the Pain is reduced by more than 50%, the trial leads will be removed and they will not go ahead implanting the full device. It is very expensive; involves numerous hospital stays with normal risks associated with any surgical procedures as well as higher risks involved with CRPS. It is a bit of a 50/50 chance it is even effective, but if does work, it can significantly improve the quality of life for people whose CRPS hasn't responded to any other treatments. It's a personal choice, not everyone is comfortable with the idea of it and may not be appropriate for some people.

Treatment is certainly not the same for each CRPS patient, but each needs to have a multidisciplinary approach in order to have the best possible chance. The reality is that some people improve and go on to lead normal lives; while others do not and go on to experience significant Pain, disability and associated depression, as well as inability to work or function independently in society. The longer it lasts, the poorer the outcome and quality of life. The Dutch method, using the free-radical scavengers is certainly an innovative approach in the acute stages that may really revolutionise how it's treated in those crucial early stages. Maybe it can prevent the problems that crop up in later stages and vastly improve the outcomes. That lottery I mentioned – knowledge being multiple tickets; being able to prevent the progression could be like having the psychic ability to predict the first few numbers that will be drawn!

Perhaps one day soon, cases of full-blown chronic CRPS will become a thing of the past. Maybe there will also be a cure for, what depressingly was noted in a recent report: “chronic end-stage CRPS”. It really makes me hopeful and optimistic for a different future for people like me who live with CRPS and whose lives are so drastically altered by it.

Who knows, maybe I should keep my ice-skates and favourite high-heels around, just in case... Some day, I may be dancing again!