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.
By 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®).
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”
Aiyana 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.
Hi, Thank you for sharing your story. My daughter is also on cyclosporine and i always live with a fear that this drug will increase her chance of getting skin cancer. It’s one of the rare side effect. I also always search for another alternative. If you ever find one, please post it up.
Thanks for writing in to me. How old is your daughter and how long has she been on cyclosporin? The side effects are always a huge matter of concern and reguar tests are the ony way right now to cope with this. We have already had a very traumatic experience with the side effects of azathioprine last year where our daughter battled a life threatening infection in the hospital for almost a month ( my post- “….the tough get going (Part 2)”. We know only too well what a medicine is capable of but right now we dont have any other choice. I am always searching for alternative but so far no luck..will keep sharing our experiences though.
Best wishes to your daughter and your family!
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