Tag Archives: cyclosporin

A primer on immunosuppressive medications for eczema from a parent’s point of view-cyclosporine, azathioprine and methotrexate

Posted on by

I am really sorry for not having written anything for a really long time now. I have been busy with my Functional Medicine Health Coaching Course (from the US based Functional Medicine Coaching Academy) and my Dietetics and Nutrition course. The Health Coaching course has been an immensely enjoyable and fulfilling experience and I become a Certified Health Coach next month! I will write more on that next time. This post is about something else.

I have written quite a while back on a comparison between 2 immunosuppressive medications that my daughter has been on earlier on. In this post, I want to write about one more immunosuppressive medication that my daughter has been on since the past couple of years and it is called methotrexate.

Before I go any further though, I would like to out some things in perspective. Since these medications are very powerful and potent drugs, these medications are the last line of treatment for Atopic Dermatitis. They do not “cure” eczema, they are given to manage severe eczema which are not being managed by other lines of treatment. These are usually given for many months or years depending upon the patient’s condition. These medications are not given to any patient, child or adult, unless all other forms of treatment (moisturisers, topical steroids, narrow band UVB, wet wrapping, oral steroids) have failed to reduce suffering due to severe eczema or even bring it under control.

Also, I would like to mention that while we certainly had no choice in giving our daughter these medications, initially I did not know that there was anything other way that we could bring her very severe eczema under control. However, I am really happy to say that this is no longer the case and if you have been following my blog posts you will know what I am talking about her Functional Medicine treatment. I would also like to mention here that my daughter’s condition is much better now. We have lowered her dosage and are looking at hopefully gradually continue to lower and finally discontinuing her medication in the near future. But I will cover that in my next post.

A few things which are common to all these types of medication are as given below-

  • they need to given and monitored regularly by health professionals to monitor for adverse side effects
  • dosages and frequency are different for each drug and must be followed meticulously
  • since these medications work by suppressing the immune system, precautions must be taken to limit exposure to infections
  • usually live vaccinations are not given to patients (children) who are on these medications

Cyclosporine and our experience

Cyclosporine was our first introduction to immunosuppressive medications in 2012. Aiyana was already on oral steroids at that time to manage her very severe eczema which had escalated beyond control and she initially needed an a fast acting intervention like oral steroids. The doctors prescribed cyclosporine as the systemic drug to help manage her severe eczema.

Cyclosporine works by blocking the body’s inflammatory process which can reduce itching and rashes. After about 6 months of being on this medication in 2012, we switched to azathioprine in 2013 as recommended by another dermatologist. However, we had to come back to this medication once again in mid 2013 since azathioprine had a disastrous effect on her health. She was on cyclosporine for another year till we switched over to the third immunosuppressive medication methotrexate in late 2104.

A word of caution

However like any other such drug, the side effects of cyclosporine are many and in particular it can affect the kidney and blood pressure adversely. Hence, regular blood tests need to be carried out to determine kidney function in particular and to monitor other health parameters.

Research

Cyclosporin in the treatment of severe atopic dermatitis: a retrospective study- https://www.ncbi.nlm.nih.gov/pubmed/15175770

Azathioprine and our experience

Azathioprine was the second medication that we used to manage our daughter’s eczema. She had already been on cyclosporine for a year and a half and the doctors wanted to get her off cyclosporine since it clearly had not been very effective in managing her eczema very well.

Azathioprine is another type of immunosuppressive medication which is used for many autoimmune conditions including atopic dermatitis. It was originally developed to prevent infections due to transplanted organs like the kidneys. It takes longer than cyclosporine to take effect and is not used for acute cases of eczema due to the time taken. Since one of the main side effects of azathioprine is bone marrow suppression, a blood test measuring an enzyme called TPMT (anthiopurine methyltransferase). Those with low levels of TPMT are unable to break down azathioprine in the normal way and are at high risk of dangerous bone marrow suppression. Hence, those with very low levels of TPMT are not given this medication.

A word of caution 

However, as we realised to our dismay, just getting the TPMT levels tested and taking a decision of giving azathioprine to someone may not work out as planned at all. And we also learned a HUGE lesson in terms of how things can go terribly wrong even when all known rules and protocol are followed. Our daughter was one of the outliers who suffered from the disastrous side effects of azathioprine inspite of having completely normal and within range TPMT levels. Infact, it was this experience that led me to search extensively another form of intervention for her. I have written about this in details in my earlier blog posts- https://eczema-anindianperspective.com/2013/10/27/the-tough-get-going-part-2/. 

Azathioprine can have a host of side effects apart from the bone marrow and can also affect the liver adversely.  Tests are done regularly to ensure liver, bone marrow and other organs are working properly.  Any symptoms like hair loss, flu like symptoms and any others should be looked into immediately.

Research-

A retrospective evaluation of azathioprine in severe childhood atopic eczema- https://www.ncbi.nlm.nih.gov/pubmed/12174104

Methotrexate and our experience

Methotrexate was the third immunosuppressive medication that our daughter was prescribed in 2014 and she is still on this medication as of now. This drug has worked for her pretty well and she is now on a reduced dosage. With a very good response to the Functional Medicine treatment which is now finally showing its impact after being on this treatment for almost 2 years.

Methotrexate is actually a drug used mainly for treating psoriasis and rheumatoid arthritis. Methotrexate belongs to a class of drugs known as antimetabolites and also works by suppressing the immune system.

A word of warning

Methotrexate can also cause some serious side effects by affecting the bone marrow, liver or lungs and once again regular blood tests are a must to monitor the effects of this medication.

Research

http://www.mdedge.com/edermatologynews/article/100861/atopic-dermatitis/wcd-methotrexate-found-safer-less-effective

The other side of the story

While I have given above an account of our experiences with the various drugs, I would also like to point out the other side of the story- these drugs help save many lives. The primary objective of these medicines is to suppress the immune system. They improve the chances of a patient to successfully undergo an organ transplant by preventing the organ getting rejected by the immune system. These medications are also used in other conditions like severe eczema, rheumatoid arthritis and other conditions as well where the immune system is involved. No matter what the reason for taking these medications, these medications should be taken only if prescribed by a qualified medical professional and should be monitored regularly under his care.  

 

Just show up…

Show up

As someone once said, “sometimes the bravest and the most important thing you can do is just show up“. This is especially true when we really do not like the turn our life has taken. It is true when we want to find a better way of dealing with our problems but we do not have a choice right at that moment and so we go along with it. This is what it feels like for us when we give our daughter these medications. But I know that I am doing the right thing for her at this moment and at the same time I also know that I am doing whatever it takes to hopefully enable her to lead a healthy life without depending on any medications.

But whether I succeed in this or not, I will always know that I never shied away for showing up for whatever life has to offer us. This is what enables us to deal with eczema and its effect in our lives. This is also what makes life seem so enjoyable and memorable for all of us and is so much more than any difficult circumstances, illness and medication.

 

 

A summary of some of the regular reatments for eczema

Posted on by

Eczema - Printed Diagnosis on Blue Background and Medical Composition - Stethoscope, Pills and Syringe. Medical Concept. Blurred Image.

I have been writing about our experiences with eczema (or more specifically Atopic Dermatitis) for almost 2 years now. I have written about the various treatments we have tried in various posts but I realised that I have not really written in details and in a comprehensive manner about the first, second line and third line treatments that are usually used to treat eczema.

(Please note: I will refer to Atopic Dermatitis as eczema in my post from here on to simplify matters)

In this post I have written about the regular medical treatment that is used once the moisturisers alone are not able to control the inflammation. Moisturisers are an essential part of the treatment for eczema and works very well in mild forms but may not be sufficient to bring the eczema under control once the skin becomes red and inflamed in moderate to severe eczema. I have myself been confused at times with the myriad topical, steroidal and non steroidal creams that are prescribed by the doctors at various points in time. Then there are also the oral steroid medications and different immunosuppressants and phototherapy treatment that we have used to control flare ups. I believe it would help a lot of parents (and those adults suffering from eczema) if they had some idea about the basics of the different types of treatments and medications that they may be using on their child or even on themselves. It would definitely help in controlling and reducing the side effects that some of these strong medications can have on a person if not used properly.

Topical steroids

Steroid cream.

Topical corticosteroids are prescribed by the doctor/dermatologist when the skin becomes red and inflamed and the eczema does not clear up in spite of maintaining a healthy and regular bathing and moisturising routine. The topical corticosteroids range from very mild to very potent and you should be very careful in following the doctor’s instructions in using the same for your child both in terms of quantity and duration. This is especially true for young children and babies. In any case, the topical corticosteroids are prescribed only when the risks from eczema far outweigh the risks from the side effects of using these medicines. When a child suffering from eczema is unable to sleep at night due to incessant itching and thus starts affecting daily life at school and home, there is a risk of infection due to the cuts and inflamed skin, it is wise to use steroid creams/ointments as per the doctor’s advice till the time the rashes have gone.

Some important points to remember while using these medications-

  • One should start using the lowest potency steroid and only step up if required
  • Topical steroids are most effective if applied immediately after a bath but should only be applied on affected areas and not as a moisturiser
  • One should follow the doctor’s advice on the frequency of application (usually twice a day is more than enough on severely inflamed skin) and should start tapering off as instructed instead of stopping abruptly
  • Step up and the step down method (in terms of potency and frequency of steroid) needs to be maintained while using the topical steroids to keep the risks of side effects of these medications as low as possible
  • One should avoid using these medications on the face and other sensitive areas and this is all the more true for children who have very sensitive and delicate skin

Given below are the various common (but certainly not exhaustive) topical corticosteroid creams/ointments that are available in India (and ones I am most familiar with) and their potency

  • Low potency– Hydrocortisone creams (1%) are available as an OTC (over the counter) medicine in various forms like cream, ointment and lotions. This is the least potent amongst all the topical steroids but still should be used with caution especially for a child. This is especially true since this is easily available and one can unknowingly use this as a moisturiser without realising that it is still a steroid cream/ointment
  • Mild to mid potency– Steroidal creams/ointments like Desonide, Mometasone fuorate and Fluticasone propionate are available at the lower to mid end of the potency spectrum. These are brands like Desowen, Momate/Elocon and Flutivate brands in India for the respective steroidal creams/ointments respectively. The doctors will prescribe a particular steroidal cream based on the level of inflammation and rashes
  • Potent to highly potent– Steroidal creams like Betamethasone dipropionate and Halobetasol propionate are at the potent end of the corticosteroidal creams/ointment. In India we have brands like Fucibet (which also includes fucidic acid which is an antibacterial medication) and Halovate which include these steroids respectively.

You should also know there is an overlap in these topical medications since they are usually available in both cream and ointment forms and the potency for the same dosage will differ based on the form. The cream form has roughly half water and half oil, they spread easily, are well absorbed and usually wash off with water. Ointments on the other had are about 80% oil and 20% water and are thus “occlusive” which means they trap moisture and help in better absorption of the main component. Being occlusive, an ointment will allow the medication to get absorbed much more completely than a cream and hence are more potent at the same dosage as a cream.  

https://www.psoriasis.org/sublearn03_mild_potency

Application and side effects

Topical corticosteroids should be used in a step up manner in terms of increasing potency starting from a low potency and only moving up if required. Usually the doctor will prescribe the milder ones like desonide cream (brand name- Desowen) and only graduate to a stronger medication like Fucibet if required later on. Similarly, once the rashes have been brought under control, one should use the step down method both in terms of potency as well as frequency as per the doctor’s instructions.

As mentioned earlier, these medications should only be applied on affected areas and not as a  moisturiser. However, sometimes the rashes may be quite widespread all over the body. In that case, the doctor may prescribe a 1:4 ratio of a mild potency steroid like desowen to an emollient like cetraban which is then mixed thoroughly and applied all over the affected areas.

Side effects from these steroidal creams are varied and depends on the age of the person, the frequency of application, the potency of the drug amongst other factors. The thinning of the skin or skin atrophy is one such side effect which can take place if potent to highly potent steroidal creams are applied too frequently or without any break. However, one can avoid this and other side effects by following the doctor’s instructions for using this treatment and thus using this treatment as and when required, in the required quantity and for an appropriate duration. The other thing to keep in mind that in case of excessive scratching due constant itchiness in case of under medication, the skin tends to become thick and discoloured. Thus the treatment needs to be carried out in a timely manner under the supervision of a doctor and the instructions should be properly followed to minimise the side effects.

(Further reading-http://www.eczema.org/corticosteroids)

Calcineurin inhibitors

Another type of topical treatment available for eczema is the group of medications known as Calcineurin inhibitors. These are non-steroidal immunomodulators and are of 2 types- pimecrolimus 1% (Pacroma and Elidel) and tacrolimus 0.3% (Protopic). These topical medications work by suppressing the immune system and are usually prescribed to children over 2 years of age and adults and are recommended for use as a second line treatment for eczema.pacroma-cream

As with steroidal medications, these type of immunomodulators should also be applied only when prescribed by the doctor and for the recommended duration of time. Even though it does not have the side effects like thinning of the skin which is associated with steroidal treatments, one still has to be cautious while using these medications since they are relatively new medications and not much is known about their long term usage. There is a possible risk of skin cancer only in the long run after prolonged usage but it is still advisable to apply these creams at night to avoid sunlight exposure. These medications are also prescribed for eczema on the face (unlike topical steroids) and are prescribed for moderate to severe eczema only when the combination of topical steroids and emollients have not been successful.

(Further reading- http://www.ncbi.nlm.nih.gov/books/NBK45568/

http://www.ncbi.nlm.nih.gov/pubmed/14693489)

Phototherapy or Narrow band UVB

Another treatment that is prescribed once the topical treatments have not really worked for a person in controlling the eczema is phototherapy. It is used as a safer alternative to avoid using  the third line treatments of  the powerful immunosuppressive medications like azathioprine, methotrexate and cyclosporine.

In this treatment light or a particular narrow band of Ultraviolet rays are used to treat the eczema which is beneficial for skin diseases. It can be used both for localised as well as general areas of the skin covering the entire body. This treatment works effectively for some people but not for everyone and usually takes about 1 to 2 months to show the desire results. If this treatment is effective then it can effectively put the eczema in remission for a while at least. It may also minimise the usage of topical steroids and there its side effects.

Phototherapy is carried out in a special booth filled with UV rays for general treatment of eczema all over the body and hand-held devices for treatment of specific areas like hands, ankles etc. Nowadays, a high intensity phototherapy treatment is available in the form of a laser called Excimer. It is much more powerful than the regular phototherapy and emits Ultraviolet rays of a particular frequency which is used to treat different skin conditions like eczema, psoriasis etc. It is given in the form of a hand-held gadget and takes much less time than a regular phototherapy due to the high intensity of the rays and is more useful for treatment for localised areas of the body. However, one needs to be careful in protecting the eyes when undergoing this treatment. The risks associated with prolonged treatment are skin burns, increased ageing and increased risk of skin cancer. Like any other such treatment this has to be carried out under the supervision of a medical professional and all the instructions need to be followed carefully. (I have written about our experience with phototherapy in my blog post https://eczema-anindianperspective.com/2013/10/17/when-the-going-gets-tough-part-1/).

(This treatment is currently offered in the Comprehensive Skin Care Clinic run by senior pediatric dermatologist Dr Manish Shah in South Mumbai and the website is http://www.cscc.co.in/)

Oral Steroids

Steroids

The third line of treatment for eczema is the use of systemic medications like oral steroids. Prednisone is one of the most commonly used oral steroids given in cases of severe eczema where an immediate result is required and is given under strict supervision of the doctor. It is given as a daily dose starting with a high dosage and then is slowly tapered down once the eczema is under control. Oral steroids work by suppressing the immune system and helps in controlling the overactive immune system in the case of a person suffering from eczema. But this also makes it possible for the person to catch infections easily due to a weakened immune system and hence has to be monitored at all times. Also, in the case of a child, oral steroids may slow down growth and development and hence again one needs to be very careful.

There are other side effects as well which can be minimised by following instructions carefully and keeping a lookout for any symptoms which may arise on taking this medication. This is also done by carrying regular blood tests to determine adverse side effects if any. Due to the various side effects of this medication and its quick action, oral steroids are usually prescribed for short periods of time when results are needed fast. Bottomline, like any strong medications, one needs to take this under strict supervision and follow the doctor’s instructions about dosages  and how to start and stop taking this medication.

(Further reading: http://www.ncbi.nlm.nih.gov/books/NBK260241/)

Immunosuppressive medications

various tablets pills in bottle

The other third line of systemic treatments include the immunosuppressive medications like azathioprine, cyclosporine and methotrexate. These are all very powerful medications and are given only when all other options have failed to yield the desired results. All of these medications work by suppressing the immune system and hence bring the eczema under control. But once again, due to the various side effects these medications have to be given under strict supervision of the doctor prescribing this and by following all the instructions carefully. Since eczema is a chronic condition and these medications may be required to be given for long periods of time, regular testing is required to ensure that there are no side effects.

Azathioprine

Azathioprine works by tweaking the growth of certain white blood cells which contribute to the inflammation associated with eczema and thus suppresses the immune system. It takes a while longer to show results than cyclosporine and may not suitable for acute flare ups.The main side effect of azathioprine is bone marrow suppression and that is why a specific test is carried out before prescribing this medication which is called the TPMT enzyme test. This test determines the suitability of the person by determining the ease by which the person is able to break down azathioprine in the normal way. However regular testing would be required to keep a track of any adverse effect on the immune system. This medication is taken orally in the form of tablets and on a daily basis in the prescribed dosage.

We had a traumatic experience with this medication which was prescribed by a leading pediatric dermatologist in London for our then 7 year old daughter. In her case, even though she had a normal TPMT result, her body reacted disastrously to this medication and she suffered from bone marrow suppression and had to fight for her life. This was a one in a million kind of event and has never happened before to someone with normal TPMT levels. I have written about our experience in my post in 2013  and you can read about it at https://eczema-anindianperspective.com/2013/10/27/the-tough-get-going-part-2/.

Cyclosporine

Cyclosporine is another systemic immunosuppressant used to bring severe eczema under control and works by specifically blocking an important pathway in the immune system, and has different side effects than steroids. It is prescribed in low doses for eczema under strict supervision and once the eczema is under control, the medication is tapered off. One of the main risks associated with this medication is damage to the kidney especially with increased dosage and duration of medication and hence regular tests would be required to monitor the kidney activity. This medication has to be taken orally on a daily basis as per the prescribed dosage.

(I have written more about our experience of dealing with cyclosporine and azathioprine medications in my blog post where I have compared both at https://eczema-anindianperspective.com/2014/02/10/azathioprine-and-cyclopsorin-an-overview-of-two-immunosuppressive-medicines-used-to-control-my-daughters-eczema-from-a-parents-point-of-view/).

Methotrexate

Methotrexate is another systemic immunosuppressant which is used mainly in treatment for psoriasis and different types of arthritis. It is also given in low doses in cases of severe eczema and usually takes longer to work than cyclosporine. It has anti inflammatory properties and works by altering the body’s use of folic acid (a vitamin) which is needed for cell growth. Thus a folic acid supplement is a must on a daily basis for those taking this medication. This medication is taken once a week in the form of tablets. This dosage may also be split up into 2 doses taken within 24 hours to minimise any nausea that may occur. One of the main possible side effects of this medication is again adverse effects on the immune system especially on the white blood cells (which fight infection) and platelets (which help stop bleeding). Thus regular blood tests are required to keep a look out for any adverse side effects.

(Further reading- http://rheuminfo.com/medications/methotrexate/methotrexate-detailed-information)

Sometimes the hardest thing and the right thing are the same

Sometimes we don’t have a choice as far as giving strong medications to our child is concerned when the child is suffering from a severe chronic condition which adversely affects daily living. Of course we would prefer to find some alternative which is much safer and without any of the side effects that I have mentioned above. As of now we have not managed to bring our daughter’s eczema into remission and she needs constant medication in order to live a relatively normal life.

Things can also go horribly wrong like it did in our case in spite the very best of intentions. We have been very lucky and have learned to take this in our stride and be more vigilant in the future since our daughter still requires immunosuppressants to keep her severe eczema under control. This has not stopped us from looking for other options and neither should you. As one wise person had said, it does not matter how slowly you go as long as you do not stop.

Our tryst with Ayurveda and our first Eczema Support Group meeting in Mumbai

Posted on by

In my last couple of posts I had mentioned that I was trying out Ayurveda as an option of treatment for my daughter simultaneously with the immunosuppressive medication Cyclosporin that she is currently on. She was started on Ayurveda treatment in May and it carried on during her summer holidays till the end of June. She was given a mix of medicines  in the powder form ( made of natural ingredients) and others in the liquid form. In all there were quite a few medications before and after breakfast, evening snacks and dinner, and it is to my daughter’s credit that she took all the medicines without much fuss at regular intervals.

Dietary restrictions and Ayurveda

However, the more difficult part was to live with the many and varied dietary restrictions on a daily basis.  Foods which are restricted not only include food groups like fermented food products ( curd, yogurt, dosa, idli, cheese etc) ,cold foods like food straight from the refrigerator, ice creams, cold drinks or juices but also citrus foods like tomatoes, sweet lime, lemons; vegetables like potatoes, cauliflowers, leafy green vegetables like spinach; processed foods like cakes, pasta, noodles containing maida (refined wheat flour), fish and meat, cold cuts of meat, canned foods– the list was pretty comprehensive. Due to the fact that Aiyana was on vacation and at home, we did manage to follow almost all the restrictions but it was pretty tough for an 8 year old to remember and adhere to these restrictions on a daily basis. I guess given all that she has been through in the last couple of years she has matured beyond her age and understands what needs to be done even if she does not like it at all.

But inspite of following this treatment for almost 2 months, there was no marked improvement and infact her itching became progressively worse and she was unable to sleep throughout the night. It was once again a most difficult and stressful time for all of us and most of all for my daughter. As per our follow up which was scheduled in early July, I took her back to the institute and this time she was met by their skin specialist as well. Upon hearing that the medicines had made her very itchy, he changed most of her medicines and asked us to give it some more time.

Unfortunately, by that time Aiyana was extremely uncomfortable and I stopped all the ayurvedic medicines by second week of July. After showing her to her regular doctors (pediatrician and dermatologist), she was put on a low dose of oral steroids. Infact over the last couple of years we have noticed that whenever her skin has flared up or seems to be out of control even with her regular medication and routine, oral steroids is the only medication which brings it completely under control. Even cyclosporin has not had that effect on her in the past year that she has been on that medication. After consultation with her doctors, we were advised to increase and try a higher dose of cyclosporin (along with the oral steroids) for the next couple of months to see if that made her skin stable only after which it would be decided to change her medication.

The struggle is just a part of our story

Pinteresting with Koka Tawera Week 3

So this is where we are now, still looking for a stable alternative to her ongoing medication. We have our ups and downs and it has been a long journey for us since Aiyana was diagnosed with Atopic Dermatitis. But in the end, she is so much more than a child with eczema. Eczema and all the problems associated with it are just a part of our family’s walk through life.

There was always a risk trying out alternative medicine but I wanted to explore that option incase it proved to be a viable one for her and did not have the kind of risks associated with the side effects of the medication she is on currently. But the biggest risk in my opinion is that there is not much regulation with regards to the manufacturing of medicines. Unlike in mainstream medicines like steroids, immunosuppressive medication and other such medicines, ayurveda and other alternative medicines like homoeopathy are not that regulated. Thus I was not 100% sure about the purity of the medicine (especially since some of them were manufactured by little known Ayurvedic pharmaceutical companies in various parts of our country) and hence the efficacy and this always niggles at my mind.  I am not sure how this issue will be resolved in the near future and but this remains in my mind a stumbling block for ayurveda to become integrated with mainstream medicine. But there are ways to follow some of the simpler natural remedies prescribed in ayurveda by sourcing the natural ingredients and using them as home remedies as has been the case in many Indian families over the ages. In any case, this decision was taken out of our hands due to my daughter’s skin condition and I now look ahead in our family’s journey in dealing with eczema.

What kind of experience have you had in treating eczema with ayurveda (If any)? Please do let know your opinion on the same!

Eczema Support Group- our first meeting

I had mentioned that I was conducting the first Eczema Support Group meeting in Mumbai end of July. We finally had our first meeting early August and there were 4 of us, all mothers of children with severe eczema  residing in Mumbai who came together to share our experiences, stories, issues and most importantly our pain of watching our child suffer. Going ahead we will be sharing information and our own unique experiences in dealing with eczema, we will also have  experts talking to us on various topics associated with Atopic Dermatitis amongst other things. Incase you know someone residing in Mumbai who has a child suffering from moderate to severe eczema and wants to join our group, do ask them to get in touch with me at eczemaanindianperspective@gmail.com.

I had planned to write about some products that have been beneficial to my daughter and other children with eczema over the years but I realised that it is better if I write separately about that in my next post. Apart from natural supplements, moisturizer and creams, special therapeutic clothing (some formulated by other mothers whose children had severe eczema), there are some amazing books/CDs for children available  across the world which are immensely useful in dealing with eczema directly or indirectly by reducing the stress associated with this condition. These do much more than just provide information, they inspire and motivate children (and adults) in the face of eczema and other such difficulties. I will be putting up a post on this soon!

In the meantime, I leave you with a thought which is something that I try to live by and instill in my children-

“Happiness is not the absence of problems; it’s the ability to deal with them”– Steve Maraboli

Azathioprine and Cyclosporin ( an overview of two immunosuppressive medicines used to control my daughter’s eczema) from a parent’s point of view

Posted on by

I seem to be putting up a post quite infrequently off late but I hope to change that soon. In my defence I can only say that I have been enjoying myself too much and was quite tied up with my brother’s wedding late last month. It went off very smoothly and now the happy couple are spending quality time in Thailand.

Those of you who follow my blog and have read my earlier posts know what happened with my daughter due to the drug Azathioprine which was given to control her otherwise very severe eczema ( I have covered this in my post ….the tough get going Part II). I am pretty sure that other parents like me who have had to either put their child on this kind of immunosuppressive drug or have had to contemplate giving it go through the kind of jitters that I do from time to time.

I am very well aware about the reason and benefit of giving this medicine to my child without which leading a normal life for her would be almost impossible given the severity of her eczema at this point in time. But it does not stop me from thinking of all the possible side effects in the process of controlling her eczema especially given the life threatening consequences of giving her azathioprine last year. It is like having Hobson’s choice in this matter which means there is really no choice at all. I am sharing our experience with you in the hope that it may help you decide what is the best line of treatment for your child with the doctor’s support and bring a smile to your child’s face by making living with severe eczema bearable.

Hobson’s choice

IMG_1262By the time we gave Aiyana azathioprine last summer, we had exhausted all the other possibilities of various triggers like allergens, environmental causes like hot or cold temperatures, irritants like detergents amongst others. We also had an intensive moisturizing and bathing regimen to control her eczema but without much success. We had tried out all levels of topical cortisteroids and immunomdulators, wet wrapping therapies, phototherapy and oral steroids all of which are usually enough to manage mild-to-moderate atopic dermatitis. Although some mild cases of atopic dermatitis can be managed with emollients (creams, lotions and ointments) alone, there are some people who might require treatment with either topical corticosteroids or immunomodulators. When all these medicines and other measures to minimize environmental influences (elimination of allergens, dust mites, irritants like detergents and heat, perspiration and dry climates) fail, systemic options like oral steroids (prednisolone) and non-steroidal immunosuppressant agent such as azathioprine, methotrexate, ciclosporin or mycophenolate are often considered.

Azathioprine and cyclosporin- 2 different types of immunosppressant drugs

In Aiyana’s case azathioprine was prescribed by a leading pediatric dermatologist in London after doing a battery of tests including the enzyme test called TPMT (thiopurine methyltransferase). This enzyme plays a critical role in the chemical breakdown of azathioprine that is, in the way the body gets rid of this drug.  If a person is TPMT deficient, the effect of a particular dose of azathioprine will be exaggerated, and it could therefore become toxic to the bone marrow and hence the TPMT test is mandatory before giving this drug. Azathioprine has been in existence since the 1960s and was initially developed to prevent organ rejection and has been used for many years in the treatment of severe eczema. It is an immunosuppresant drug that is also known as antimetabolite. It hinders the growth of lymphocytes (a type of white blood cell) which are involved in inflammation associated with eczema. Azathioprine is given by mouth, usually once daily, and most often in the form of tablets of 25mg and 50mg.  It is also available in the liquid and allows more precise dosing for young children.

Cyclopsorin is another type of immunosuppressant drug which was also originally used to prevent organ rejection in transplant patients. It is in fact derived from a type of fungus. Even though the cause of Atopic dermatitis (eczema) is not completely understood and there is no cure as of now, what is known that immunological reactions occur in the skin of people with eczema and these are controlled by white blood cells (lymphocytes) that enter the skin from the blood. Cyclosporin decreases the production of chemical messengers which “switch on” these lymphocytes and thus dampen down strong allergic and immune reactions. It is available as capsules containing 10 mg, 25 mg, 50 mg and 100 mg of cyclosporin, however for children the liquid form is easier to give as a dose (one formulation is called Neoral®).

Side effects

Azathioprine has a very serious side effect and that is  ‘bone marrow suppression’, or ‘myelosuppression’.  The bone marrow is the site of production of the most important types of cell in the blood: the red cells (RBCs), the white cells (WBCs including neutrophils and lymphocytes) and platelets (important for blood clotting). White blood cells are critical in the body’s defence against infection, and if their numbers fall drastically (as did happen with my daughter),there will be a risk of potentially serious and even life threatening infection. Over the years it became clear that the patients who developed serious bone marrow suppression generally did so because they genetically inherited low TPMT activity. As mentioned earlier, this enzyme is essential in the chemical breakdown of azathioprine and thus has to be within a particular range for a person to be given this drug.

But no tests are really 100% foolproof as we saw in my daughter’s case. In spite of her test results being absolutely bang in the middle of the normal range and thus determining her dosage, within 3 weeks of putting her on this drug, she was hospitalised in the ICU with a life threatening infection due to severe “neutropenia” or an abnormally low number of neutrophils as a result of azathioprine induced bone marrow suppression. Neutrophils usually make up 50-70% of circulating white blood cells and serve as the primary defense against infections by destroying bacteria in the blood.

Hence, as in my daughter’s case, she developed life threatening infection and it was only the prompt and quality of medical attention, broad-based and potent antibiotics and antifungal medicines that saved her life. The dermatologist who had prescribed this drug had never seen this reaction in the many years that he has been successfully prescribing this drug to other children with such severe eczema. It became clear from my daughter’s reaction that there are other genetic variants that can be missed that can also make occasional patients susceptible to such severe adverse effects even while having the desired TPMT levels and these have possibly not been studied or accounted for.

Cyclosporin on the other hand is a potent immunosuppressant and starts to work very quickly (within 1–2 weeks) and the side effects of cyclosporin are almost all ‘dose-related’. Hence the side effects depends almost entirely on the dosage a person is taking although some people are more susceptible to the side effects than others. It cannot be given for long since the longer this drug is taken the more severe the side effects become. The main side effects of cyclosporin are hypertension (high blood pressure) and reduced efficiency of the kidneys (renal toxicity).  Blood pressure and kidney function need to be checked before treatment and monitored closely throughout treatment.

Regular and strict monitoring 

As with any such potent drugs, one has to be extremely particular about monitoring the relevant organ functions throughout the course of treatment. In Aiyana’s case, blood tests are a regular feature and she has almost come to terms with it. Initially I used to take her to one of the premier hospitals in Mumbai but in the past few months a phlebotomist has been coming home to collect her blood sample. He was referred by Aiyana’s pediatrician and is very gentle with her and it has made a world of difference as far as her blood collection is concerned especially since she has to go through this on a very regular basis.

In the case of azathioprine, the blood count levels become extremely important to monitor on a regular basis to check for bone marrow suppression. The medical protocol followed worldwide in the case of azathioprine is to undertake a blood test 3 weeks after starting treatment, then 12 weeks after starting treatment, and thereafter every 3 months if all the results are normal. However, as a learning from our traumatic experience, I would urge you to be on the side of caution and undertake the blood tests for your child every week for the first one or two months and then gradually space it out as per your doctor’s advice if there is no abnormal result. Such regular blood tests are a painful thing especially for a child but it is a necessary evil and must be carried out. These tests normally comprise a full blood count (mainly to check that white blood cell numbers – particularly neutrophil numbers – are not falling below normal levels), and liver function tests to ensure that the liver is not stressed.

When cyclosporin is given as the immunosuppressant, since kidney is one of the main organs which is affected, kidney function will need to be monitored regularly particularly the serum creatinine levels since any condition that impairs the function of the kidneys is likely to raise the creatinine level in the blood. It is thus important to recognize whether the treatment is leading to kidney dysfunction or not. The other important level to be monitored are the cholesterol levels since the reduced efficiency of the kidneys can also adversely affect the cholesterol levels leading to increased risk of heart disease.

Medicine that heals is not always sweet and caring words are not always pleasant

The main reason I chose to write about these 2 powerful drugs is that while there is a lot of information available about these drugs today on the net, it is not always easy to get the most relevant facts. One can get lost in too much of information all of which might not be completely relevant to a parent but more to a medical professional. Information about the plethora of side effects and adverse reactions from these drugs is also enough to scare away any parent from giving these to their children. I have tried to compile all the relevant and important information a parent should know before giving this drug to their child and bring it in one place.

The plan of these kind of treatments to control very severe eczema is, first, to achieve major improvement in the severity of a child’s eczema and then if possible to see it clear completely, though to achieve this may take several months or even years. We have had no choice but to use this treatment on our 7-year-old daughter and I hope that our experience and learnings come of use to other children afflicted with this condition in a severe form which usually affects their lives on a daily basis.  Of course, it is not easy for a seven-year old to take this medicine twice a day and undergo repeated blood tests, but as her caregiver I do not give her any option not too simply because we do not have any. We will have to evaluate her medication in the next few months and then go ahead with the next course of treatment based on her doctors’ recommendations.

I also wanted to share our experience with azathioprine so that other parents can take an informed decision while giving this drug and not repeat our mistake. One can simply never be too cautious where one’s child is concerned.

“Being a mother is learning about strengths you didn’t know you had, and dealing with fears you didn’t know existed”

20131213_180745Aiyana now lives an almost completely normal life with minimal itching and with not much outward physical manifestations of this skin condition which has had an adverse bearing on her social life in the past. I know we are all doing the best we can with the best possible treatments available at this point in time though I am forever in search of other better options that might come our way in the future.

Even then there are some moments that I am plagued by some doubts as to whether we have done everything that we could have to prevent her eczema from being so severe or something else we have not tried so far. I am so grateful for being given a second chance with her and I am sure all those who know her and are greeted by her sunny smiles would agree with me when I say there must be something we are doing “right” after all.

When the going (eczema) gets tough…..(part 1)

Posted on by
IMG_0414

Aiyana and Shaunak in Goa

After Aiyana’s (and our) experience with Erythroderma in September 2012 we decided to take a much needed vacation. We ( Sudip and I, my mother and the kids) went for a one week holiday to Goa during the children’s Diwali break in November 2012. Goa is a small state in India on the Western coastline known as the Konkan region and is famed for its silvery beaches and is visited by tourists from all over the world. While we had a good time overall, her skin condition was just kept under control with oral steroids and immunosuppressants. Due to this reason, as a family we had decided to keep her away and stay away from the sea water and the swimming pool (the chlorine in the water tends to irritate sensitive skin).

Also, since Aiyana had been kept on a gluten free diet after her Ige ( blood allergy test) test had come positive to wheat allergen, it did pose some challenges as far as the food was concerned.  In order to manage her dietary restrictions, I had figured out the alternative food choices and some good gluten free products like Orgran and Bob’s Mill which are available in Mumbai (I wil be writing more on this in a separate post) . The hotel that we were staying in were also extremely helpful in catering to our special dietary needs and used to make us special gluten free parathas/rotis etc from the mix that I had taken with me. Overall I think we managed pretty well considering that in India dietary needs like gluten free/nut free/diabetic/allergy specific diets are not usually catered to in most places yet due to various reasons. As far as gluten allergy (foods containing gluten includes wheat or atta, maida, barley, malt, semolina or sooji) is concerned, it is quite uncommon in India and most people are not well versed with the specifics of this diet.

Under the influence of oral steroids (which we had started tapering) and after introducing an immunosuppressant (Cyclosporin)in September, her skin was much better overall. Itching however never completely went away.  The drug dosage was increased very slowly to the optimum level (depending on her weight) since the doctors did not want to take a chance with any adverse  reaction. With a powerful drug like Cyclosporin, it is imperative to monitor the effects ( increased blood pressure and reduced kidney function amongst others) of the drug on a regular basis. Hence, weekly blood tests were carried out initially after which it was carried out fortnightly and then monthly towards the end. I don’t know which was more traumatic for Aiyana, the skin condition or the blood tests.. This constant monitoring which is required made it difficult for Aiyana to go through with this treatment, but there was no option as such.

After consulting a Mumbai based senior pediatric dermatologist, we also started narrow band UV (ultra violet) treatment or phototherapy for her in November 2012. It is a type of treatment for adults and children with moderate to severe atopic dermatitis (also used for psoriasis) who have not responded well to other eczema treatments. Exposing the skin to UV light suppresses overactive skin immune system cells that cause inflammation and hence can control itching and rashes. The benefits of using phototherapy are that these therapies often work when other eczema treatments have not, and if done properly in a controlled environment and under supervision they can actually have fewer side effects than many of the prescription medicines used for eczema. In Aiyana’s case, her doctors wanted to eventually stop all oral medications and control her eczema with the help of narrow band UV therapy only.

Narrow band UV booth used for phototherapy

Narrow band UV booth used for phototherapy

So, while Phototherapy treatment continued, oral steroids was stopped completely in December 2012 and Cyclosporin (immunosuppressant) was stopped in February 2013. Her skin was overall in a good condition till the time that these medications were being given to her. Phototherapy treatment,  which had been started earlier was then continued as the solo treatment for her till April 2013. Phototherapy as a treatment did not prove to be very effective for Aiyana and her skin condition started relapsing  once again in April and within a few days became extremely dry, scaly and itchy. No amount of topical applications and moisturizers helped to control the same and Aiyana had to be once again put on oral steroids from mid April to stop it from deteriorating any further.

The good thing was that we had already planned for and arranged a trip end of April to meet a well known pediatric dermatologist in Great Ormond Street Hospital for Children and a pediatric allergy specialist in London. We came back to India and started her new medication at the end of May 2013 (I will write about our experience in Part 2 of  this post ; a lot happened after we came back and it might be an important lesson for parents using immunosuppressant for their child ) .While the results were not exactly what we had hoped for it did clear up some doubts as far as her allergies were concerned. The pediatric allergy specialist did a much more accurate (and painless) scratch test and patch test for her allergies and we were then able to include most of the foods back in her diet barring tree nuts (walnuts, hazelnut, peanut etc).

However, things were to become much worse for us before we got it back under control. There are so many things I wish I could have done differently for her if only I had known what was about to happen. But that is only wishful thinking on my part since it is only in hindsight that we have the perfect vision!

But what I do know is that we all do what we can for our children and that I will never give up finding the best possible treatments and course of action for my daughter. She is such a brave little girl who needs all my love, strength and support to see her through this difficult phase in life.