Chronic urticaria (hives) is a disease that is extremely common in the society and often bothers patients and physicians alike. In order to treat the disease, it is necessary to find the absolute underlying cause and to highlight the treatments for the cause. Your immunology and allergist will assist you in the diagnosis and treatment of this disease. Despite all the researches of even we immunology and allergy specialists who are interested in the subject, it is sometimes not possible to find an underlying cause in some patients. We used to call these patients “chronic idiopathic urticaria” in the old medical language; we now call the disease “chronic spontaneous uricaria”. Although there are many methods applied for the treatment of this disease, it is usually very difficult to get definite and satisfactory results. For this reason, new treatments have emerged in a group of patients who do not respond to standard treatment methods and which we call resistant urticaria. Serious benefits can be obtained from these treatments aimed at correcting the immunological system (immune system) abnormalities. In the section you wrote below, I would like to talk about a few new treatment experiences that can be applied to patients with resistant urticaria.
There has been an increasing number of studies and observations on the subject recently. Based on the observations obtained from the benefits of chronic spontaneous urticaria disease from cortisone therapy, some of this disease is thought to be an auto-immune type of disease (i.e. an abnormal condition in which our cells in the immune system attack our own cells, tissues or structures). The treatment approach to be applied in auto-immune diseases can be achieved by suppressing the immune system of the person in a balanced way. However, a balanced immune system suppression is not always easy. There are some approaches that can be applied without damaging the general immune response of the patient, and these treatment models also provide benefits in patients with urticaria. These treatment experiences are listed below.
Plasmapheresis (Replacing the liquid part of the blood)
Plasmapheresis is based on taking the blood of the person through a special device and taking the liquid part of the blood (plasma) without touching the cells, giving this plasma back to the person by supplementing it in another way. It is a treatment method. In this method, the person’s own IgE type antibodies or auto-immune IgG type auto-antibodies developed against the receptors of these antibodies are cleared. There are literature data showing that good responses are obtained in plasmapheresis applications performed 2 consecutive months (1).
Cyclosporine
Another alternative treatment model for patients who use long-term cortisone and are in danger due to serious side effects is cyclosporine (2). This drug is a special immunosuppressant that is normally used in transplant patients to prevent the transplanted organ from being discarded (tolerant). The drug essentially suppresses T lymphocytes, which are the most basic elements of the body’s immune system. It does this by suppressing the production of certain messenger proteins in T lymphocytes. In addition, it prevents the explosion of allergic cells, which we call basophil and mast cells, which have serious roles in diseases such as hives, and the emergence of histamine and similar harmful, allergic substances from them. Despite all this, it would not be an exaggeration to say that cyclosporine is a drug that is not innocent at all. While using this drug, it is necessary to follow the patient very closely with routine urine tests as well as blood urea and creatinine tests in terms of a side effect of kidney failure, except for a side effect in the form of severe hypertension (3).
Hydroxychloroquine and Doxepin
Both drugs are used out of indications. Hydroxychloroquine is a drug mainly used for malaria, and is often used in modern medicine for the treatment of rheumatic diseases. This drug, which has very good results in rheumatological diseases with skin findings, is also combined with antihistamines in cases with chronic urticaria and some good results are obtained.
Doxepin is essentially a psychiatric drug. This drug, which normally has anti-depressant and stress-relieving effects, can yield good results when added to antihistamine and cortisone treatments in some chronic urticaria cases.
However, much larger series and experience are needed for both drugs.
Tacrolimus
Tacrolimus is also an immunosuppressive drug like cyclosporine and is used in some organ transplant cases. Good results have been obtained in some studies conducted in cases with chronic urticaria, which is thought to be auto-immune due to its immunosuppressive feature. However, this drug has been blacklisted by the FDA (American Food and Drug Administration) due to suspected cancer cases when using it in routine use areas.
IVIG (Intravenous Immunoglobulin = Intravenous use of antibodies)
IVIG is essentially a preparation used to replace antibodies in immunocompromised cases in the form of antibody deficiency. Apart from this, there are also some unusual uses. It works especially well in some auto-immune diseases because it blocks some auto-antibodies. Based on these experiences, it has been used in patients with chronic urticaria, which is thought to be of auto-immune origin. However, for this treatment, especially IVIG should be used in very high doses; this can cause serious problems in terms of cost (4,5).
Omalizumab (Xolair)
Omalizumab is a biologically produced recombinant humanized monoclonal antibody. In fact, since it binds antibodies of the IgE type, which plays a very important role in the mechanism of allergic diseases, it promises an approach that can be a radical solution in the treatment of all allergic diseases (6). However, in our country, only repayments are made in asthma cases that are difficult to treat. However, there are studies on the use of allergic diseases in very early stages in many countries of the world. Apart from this, it has also been used in resistant chronic urticaria cases and extremely satisfactory results have been obtained. When clinical studies were reviewed, very good results were obtained not only in severe asthma, but also in allergic rhinitis, chronic sinusitis, angioedema, bullous pemphigoid and Hyper-IgE (Job syndrome) cases, as well as chronic urticaria (7).
I used omalizumab in my 4 chronic spontaneous urticaria cases, which I could not control with standard treatments, except for difficult asthma cases, which I used in about 25 asthmatic patients and had very good results, when I took a look at my university and practice experiences. The results in these cases were also incredible. In order to apply this treatment in university hospitals, it is necessary to obtain an approval from the Ministry of Health for the use of off-label drugs. When such an approval is obtained, drugs can be obtained with a certain contribution margin; Although it varies from patient to patient, applications are made once every 15 days or once a month. It is a drug that has a special preparation method according to the drug recipe and must be carefully prepared and applied. Although no serious reaction has been reported about this drug so far, since it is a protein-based drug, some problems, including allergic reactions, may occur during and after the application. For this reason, the administration and follow-up of the drug should be done by an immunology and allergy specialist.
Sources:
1- Grattan CE, Francis DM, Slater NG, et al. Plasmapheresis for severe, unremitting, chronic urticaria. Lancet 1992;339:1078–1080.
2- DiGioacchino M, Stefano FD, Cavallucci E, et al. Treatment of chronic idiopathic urticaria and positive autologous serum skin test with cyclosporine: clinical and immunological evaluation. Allergy Asthma Proc 2003;24:285–290.
3- Fradin M, Ellis C, Goldfarb M, et al. Oral cyclosporine for severe chronic idiopathic urticaria and angioedema. J Am Acad Dermatol 1991;25:1065–1067.
4- Rutter A, Luger TA. High-dose intravenous immunoglobulins: an approach to treat severe immune-mediated and autoimmune diseases of the skin. J Am Acad Dermatol 2001;44:1010–1024.
5- O’Donnell B, Barr R, Black A, et al. Intravenous immunoglobulin in autoimmune chronic urticaria. Br J Dermatol 1998;138:101–106.
6- Mankad VS, Burks AW. Omalizumab: other indications and unanswered questions. Clin Rev. Allergy Immunol 2005;29:17–30.
7- Clinical trials.gov: a service of the US National Institutes of Health.Available at: www.clinicaltrials.gov.
Wishing you healthy days…
Prof. Dr. Cengiz KIRMAZ
