and its (Non-) Corticoid Therapy
MUDr. et MUDr.Pavel Konrád
Dermatologic clinic Cernosice
The name of the disease itself speaks volumes about its complexity. Several names are promiscuously used for this disease worldwide. Here, we call it atopic eczema or atopic dermatitis (AD). Since it is truly an inflammation of the skin, the proper medical term is dermatitis atopica. Neurodermitis is the term used in English and German speaking countries, which confirms the unclear aetiology of the disease and its multi-factorial pathogenesis
The disease was first named and clinically described in 1808 by English physician, Robert Willan (*1757, Sedbergh, Yorkshire, † 1812, Madeira) in his self-illustrated book, On Cutaneous Diseases (Fig.1). This famous physician is considered the founder of dermatology as an independent medical field as well as the founder of modern English dermatology (Fig. 2) (1)
The term eczema was derived from the Greek word, ekzeo, which means something that springs up on the surface, so on the surface of the skin (2). The problem may appear anywhere on the surface, usually as a reaction to irritation either from the external or internal environment.
Dr. Willan derived the term atopic from the Greek word, atopos, which means strange or unusual in Greek, which accurately describes the clinical picture of the disease. The disease has a different clinical picture, depending on the patient’s age, which is uncommon, to such an extent, in any other disease. The response to therapy cannot be predicted in advance with much certainty and the alternating remission and exacerbation is sometimes inexplicable. Given its clinical picture and course, the disease truly corresponds with its name – strange.
There are several different opinions on which group of diseases atopic eczema should be classified under. Many believe that it is a skin disease, others insist on it being a genetic abnormality and a third group thinks it is an immune disease.
The aetiology of AD is a summary of all three of these factors. Atopic eczema is a genetically determined disease that results in the body’s pathological immunity response that affects the skin (1).
It is a very common disease. Its prevalence in children is estimated at 10 to 20% and 1 -3% in adults. This number has tripled in industrial countries over the past thirty years (3). It is oftentimes also accompanied by other allergy-related diseases, like asthma bronchiale, hay fever, allergic conjunctivitis and hives, etc., which is referred to as atopic syndrome. It lasts a long time with repetitive exacerbations.
The occurrence and development of this disease is very individual. There are three causes of flare ups or worsening of the eczema.
The first cause is a defective composition of the skin’s outer layer, due to the atypical formation of skin lipids and the reduced number of urea in the skin. Urea is a natural hydration factor that osmotically binds water to itself, thus keeping it hydrated. Atopic skin only contains about 30% urea in comparison with healthy skin. Defective lipids mainly lack omega unsaturated fatty linoleic acid. This is the building block of bi-layer lipid layers in epidermis.
Excessive water is lost due to the reduced content of both substances. The skin is dry, thin and prone to damage, thus allowing the penetration of various allergens, including toxins. The skin’s barrier stops fulfilling its defensive physiological function, causing undesirable penetration of substances on both sides. Water leaves the body and allergens and toxic pathogens that multiply into eczema deposits (Diagram 1) penetrate the organism from the outer environment.
Pruritus occurs as a result of the dry skin, which maintains and deepens the pathological process in another serious way. This sometimes causes itchiness, erosion and ragads, which mean locusminorisrezistentiae. These areas are more prone to pathogens that multiply and produce toxins that penetrate through the defective outer layer of the skin. The most important pathogens in AD are Staphylococcus aureus, streptococci and yeast infections (Malasseziafurfur) on rare occasions. These toxins provoke an immune response (Diagram 2).
The second cause is a hyper pathological immune response to a specific allergen. Identifying this allergen is crucial to managing the course of this disease.
The third cause can be the mood of the nervous system. This causes increased itchiness, over-sensitivity and irritation of the skin, with regard to the individual’s mental health. Problems, stress and dissatisfaction lead to more deposits, frequent scratching and an overall worsening of the clinical picture. This is where the Anglo-Saxon term for the disease, neurodermitis, comes from.
One of the neglected but high risk factors for AD are foaming agents (known as sulphates) – sodium lauryl sulphate (SLE) and sodium laureth sulphate (SLES) in soaps and shampoos. Sulphates from common detergents destroy the already damaged skin barrier, not allowing the successful therapy. They are contained in almost all common hygiene agents. Therefore, sulphate-free antiseptic soaps (4) are recommended in the case of atopic eczema. It is generally recommended to avoid long baths in hot or cold water. Only lukewarm showers, not exceeding 5 minutes are recommended (5). Drying off should only be done by applying the towel to the skin, avoiding any friction, so as to prevent the formation of microscopic ragads.
Allergens are another risk factor, which has to be monitored, so that the patient can stay away from these agents. It’s important to eliminate these allergens from the patient’s living areas, where they are most often hidden in carpets, bedding and pets. Bed bugs, dist, pollen, bacteria and other aggressive agents pose the most risk. It is recommended to sleep under bed sheets made of special nano-fibre, which prevents bed bugs from seeping through. It is also recommended that patients with atopic eczema have air purifiers installed in their homes.
Various forms of food allergies are also known. Atopic eczema patients are usually advised to stay away from dairy products, eggs, fish, nuts, acidic, fermenting foods, soya, chocolate and irritating fruit and vegetables. However, this is only a recommendation because a food allergy is very specific and it is crucial to identify the allergen. A patient with AD should also make an appointment with an immunologist.
In general, it is recommended to wear cotton underwear, stay away from clothes made of wool and avoid sweating if it isn’t possible to take a shower after.
The flare ups are usually worse in the spring and fall due to a change in the weather conditions.
Since one’s genetic makeup has a lot to do with this disease, there is no truly effective prevention. If one parent has any type of allergic disease, there is a 20%-40% risk that the child will develop se atopic eczema. If the parents specifically have (or, as children had) atopic eczema, then the risk of developing atopic eczema throughout life ranges from 60% - 80% (6).
However, these problems may also develop in children, who have no history of the disease. The harmony of the internal and external environment and the intensity of the provocative factors also play an important role. If at least one of the parents suffers from atopic eczema, it is recommended to avoid eating food allergens when breast feeding. However, there was no proof that the duration of breastfeeding decreased AD flare ups. Then, the child should be fed hydrolyzed dairy products (hypo-allergenic milk, oatmeal) and sold foods should be added slowly, leaving enough time to observe any possible allergic reactions that make the eczema worse in children.
However, the most effective prevention for children with a history of atopic eczema in their family is using sulphate-free soaps and substitute emollients from birth (6).
The basic form of AD is a small, pinhead sized, pink to bright red papulo-vesicular rash. Once the blisters rupture, the wet maple-shapes quickly merge into diseased deposits.
AD usually affects the bends of extremities (the bend of the elbow, under the knees), neck, eyelids, face, wrists, the top of the hands and feet, but it can also spread all over the skin.
The clinical picture of AD differs significantly according to age. Therefore, AD is classified into 3 clinical forms:
1. Infant form of AD (children from 0 – 12 months) – Red, papulo-vesicular rash, scales or wetting on the face, chin, bodies, extremities or head (Fig. 3, 4) usually flares up at 3 months. The eczema is very itchy and unpleasant for children. Infants are restless and often wake up from their sleep.
2. Children’s form of AD (kindergarten and school-aged kids) – At this age, the eczema begins appearing in the preferred areas, so the bends of the elbow, under the knees, on the neck, hands and feet (Fig.5,6). The eczema manifests itself in several degrees. It can go from rough, dry skin to blisters to wet, map-like deposits, to painful ragad fissures very quickly. In 80% of the children, AD clinically goes away at about the age of seven. However, this does not mean that it is cured!
3. Adult form of AD – This type either continues on from childhood or it can flare up in adulthood. The affected areas are similar to those in the children’s form. However, it can also affect the face, lips and neck. In adults, we often see so-called facies atopica with orbiocular pigmentation. This is the result of recurring inflammation and typically the gives the impression of the patient’s very “sad” expression (Fig. 7).
AD is often accompanied by other disorders – the skin fades after pressure is applied to it by a dull object (so-called white dermographism), an inborn disorder of the top layer of the skin (ichthyosisvulgaris or ceratosispilaris) also affects up to 10% of the patients (Fig.8). Symptoms in the eyes may also appear (conjunctivitis, hordeolum, changes to the retina, cataracts)
Since there is no causal treatment for AD to date, the goal of therapy is to give the skin the substances it lacks and eliminate or at least reduce triggering factors in order to keep the eczema under control.
Patients or their parents are oftentimes trying to find a “miracle” cure or procedure that would put a definite stop to AD. Given today’s level of medicine, such therapy is unrealistic.
In order for AD therapy to be effective, the treatment has to be complex and thorough. Once at the clinic, the patient has to have enough time to listen to the exact treatment procedure. In order for the result to be successful, the patient has to follow the therapeutic diagrams and their changes, which are caused by the progress of the treatment.
Local AD therapy is usually only divided according to the type of effective external corticoid treatment agents, calcineurin blockers and other non-corticoid substances used. However, reality is different and for everyday life, it is better to divide the therapy according to the stages of the disease combined with the patient’s age. The therapy is individual. What substance works on one patient may not be as effective on another patient. The physician’s experience plays a vital role in choosing the type of treatment and its modification after adjusting the clinical picture.
Local AD therapy is divided into acute and chronic, according to the stage of the disease.
The basic pillar for both acute and chronic stages of AD is a short, daily antiseptic bath / shower (5). We use so-called sulphate-free medicinal syndettes that contain an antiseptic (for example, Cutosan® gel) (5,7). Atopic eczema gets worse and feeds on pathogens, like Staphylococci, Streptococci and Malassezia, which spread all over the affected areas, produce toxins, so-called super-antigens and they maintain the circulus vitiosus. They are in large also responsible for the itch caused by atopic eczema. The goal of antiseptic hygiene is to reduce the colonies of atopic pathogens, thus to reduce the penetration of toxins into the patient’s organism. Antiseptics also reduce itching, which is mostly a subjective and annoying symptom of AD. This actively interrupts the above-mentioned circulus vitiosus!
Compared to other “dermatologically” advanced countries, the Czech Republic does not place enough emphasis on this pillar of the therapy. The result of the therapy cannot be compared to the other countries unless sulphur-free antiseptic syndettes are used.
The goal of the therapy in the acute stage of AD is to reduce the inflammation and prevent wetting. Physically drying the deposits off reduces the amount of pathogens on the affected areas. In the acute stage, it is ideal to use agents that galenically meet the dermatological treatment principle – wet on wet. In this stage, one has to choose galenic forms with a higher content of the hydro phase, like sprays, milks, creams and cream pastes. Ointments are completely unsuitable
In the acute stage of infant AD, we try applying non-corticoid therapy before using corticoids externally. Non-corticoid therapy tends to be highly effective, thus completely avoiding the use of corticoids. Prior to the corticoid era, AD was successfully treated by tar and ichtamol. Unfortunately, the EU banned the use of tar in 2002. Nevertheless, ichtamol is still available for treating the youngest patients. It is effective and has no side effects! (8).
The history of Ichtamol (fossil resin) is fascinating. The ancient Nabatean nation settled around the territory of the Dead Sea and ruled over the trade of resin in this region since ancient times. They pulled the resin out onto the shore, cut it and transported it to Egypt for medicinal purposes.
The pharaohs themselves used ichtamol in oils for various skin diseases. As a result, ichtamol was the most expensive substance during this time (Fig. 9). The Nabateans built one of the Seven Wonders of the World, the ancient city of Petra – from the money they made.
Over the centuries, ichtamol has been used to treat skin diseases and the Dead Sea still has one of the largest medically confirmed miraculous healing effects for diseases like eczema and psoriasis. Taking into account the most state of the art biological treatments, Dead Sea treatments (talaso-therapy) are still considered to be one of the most effective procedures for psoriasis and eczema!
First scientific research comparing the healing effects of ichtamol and coal and wood tar dates back to the 1980s. The author of this work was the famous German dermatologist, P. G. Unna, who applied ichtamol to a n number of other skin diseases, like frost bite and swelling. In some cases, he even recommended ichtamol be used internally.
In the most acute cases, wetting stages of eczema, we use a suitable galenic form for several days to dry the deposits. The galenic form contains water – spray (for example, Cutozic Ichtamo spray). This is applied twice a day to all wet areas (5,7). Once the wetting subsides (this usually takes about 3 – 5 days), we move to the galenic form of cream pastes (for example, Ichtyol cream paste) (5,7). This can be combined with “light” emollients. A cooling synderman is suitable this stage (for example, AD Calcis). This is always applied several times a day, approximately 5 minutes after applying ichtamol. We recommend up to six applications per day! The effectiveness of ichtamol should be evaluated no earlier than after 10 days. The onset of effects is slower than corticoids. If ichtamol is not effective enough, we use short-term corticoid therapy externally for about 4-7 days.
In acute stages of the children’s form of AD, local corticoids are the most effective part of treatment because they have very strong anti-inflammatory effects. Unfortunately, there are some side effects. Improper dose of corticoids may lead to skin atrophy with vasodilation or excessive hair growth. This can be prevented by following certain principles. We recommend using corticoids for only the necessary period of time, usually 3 – 4 days. As many people believe, corticoids do not have preventive effects. Then, we choose hydrophilic galenic forms, like solutions, milks, skin emulsions or creams. For example, methylprednisolon is available in all these ideal galenic forms. Galenic ointments are not suitable in the acute stage! External corticoids must be moisturized with suitable emollients. We again choose hydrophilic galenic forms (for example, AD Calcis) in the acute and sub-acute stages
After improving the clinical picture, we try moving on to the non-corticoid therapy as quickly as possible by using ichtamol to maintain the anti-inflammatory effects without any side effects.
Local corticoids are the therapy of choice in treating acute stages of AD in adults.
In adult patients with severe stages of AD, we often choose general therapy with cyclosporine, methotrexate or the most modern biological therapy. This therapy is available at specialized worksites
In chronic stages of AD, emollients and sulphate-free hygiene is mainly used in the therapy of all three types. The basis of treatment is thorough and regular moisturizing using so-called substitute emollients. Urea is one of the natural hydrating factors, which prevents excessive water loss. Linoleic, an omega unsaturated fatty acid that co-forms bi-layer lipids, is another substance that is missing in AD. These act like “lids” in the skin, also preventing excess water loss.
The basic principle in the chronic stage of AD therapy is to regularly supplement the above-mentioned missing substances into the skin.
The galenic form of milk with urea is most suitable for widespread use. The most suitable concentration of urea in emollients intended for AD is 3-5% (for example, AD lotio Chronic) (6). This concentration provides ideal replenishment of the hydration factor, yet there is no subjective burning feeling, which occurs at higher concentrations.
Almond oil, coconut oil, shea and Babassu oil are most suitable for supplementing linoleic acid. The oils are either directly applied onto the skin or added to the bath. Since an AD patient should prefer taking a shower over taking a bath, we recommend applying the oils directly onto the skin right after taking a shower. Some oils contain emulsifiers and cannot be applied onto the skin without rinsing! Therefore, emulsifier-free oils have to be chosen (for example, Balmandol, Cutoil®) (6). In cases of extreme dryness, we choose so-called vitamin ointments (for example, Tocozulen® ointment). These may also be used on the lips.
The general therapy for AD is antihistamines, which partially prevent itching. Fenistil drops are given to infants and Ketof syrup is given to children from 6 months because it is more effective in preventing the itching. There is a whole line of antihistamines on the market for adults with comparative effects.
Recent studies have confirmed the positive effects of lactobacillus on eczema. We recommend drops and lactobacillus (for example, Biopron, Biogaia) at night for the youngest children
Local imunomodulation in the form of creams and pastes are an alternative to corticoids when treating atopic eczema. They are used when conventional treatments fail. The advantage of this pharmaceutical is that it doesn’t have an atrophicating effect. It is recommended for long-term use and they can prevent new deposits of eczema. However, there is an age limit for using these pharmaceuticals in children.
The principles of successful treatment include regimen measures, which primarily mean trying to eliminate known allergens and creating a hypo-allergenic environment.
Places, where people live should be vacuumed often. Carpets, duvet covers, pillows and other dust collectors should be removed. This also includes pets that have fur and feathers. Cats and rodents are among the most aggressive allergens.
Furthermore, smoking should be prohibited in areas, where patients suffering from eczema live. This includes smoke from stoves. Fumes from paint may also cause irritation. Therefore, it is important to open the windows to let sufficient fresh air in regularly.
It is advisable to wear cotton clothes because it lets air circulate and prevents the patient from sweating. Cold compresses or cold creams may also help reduce the persistent itching. It is also advisable to wear cotton gloves at night.
In addition to the daily treatment described above, spa treatments and staying seaside are also beneficial treatment options. Phototherapy could also be part of the treatment. Phototherapy involves deliberately exposing the skin to UV rays from artificial sources. This takes place at specialized worksite under professional supervision.
Atopic eczema is a common disease that not only significantly limits the life of the patient but the life of the patient’s family. Since there is no causal therapy, our aim is to maintain the atopic skin in such a condition to make the disease as less problematic for the patient as possible.
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