Atopic dermatitis (AD) is a common skin disease. In late August, Assist. Prof. Dr. Derrick Aw Wee Chen, MBBS, MMed, MRCP, FAMS; Dr. Unwati Sugiri, SpKK; and Prof. DR. Dr. Retno Widowati Soebaryo, Sp.KK (K) explained three presentations about atopic dermatitis (AD), it cause and severity factors, as well as updates therapy in PERDOSKI Conference National at Trans Hotel, Bandung.
Eczema Atopik and the Filaggrin Story
According to Prof. Derrick, AD is a complex skin disorder, which the progression is influenced by various genetic and environmental factors. In the recent study, it’s found the gene that encoded filaggrin (FLG) was strongly related with AD.
Filaggrin or filament-aggregating protein has important role for protecting the epidermis. FLG is in chromosome 1q21 which encode the differentiation of keratinocytes terminal. FLG serves to encode profilaggrin, which is one of the largest keratohialin granules content. In the keratin cell, filaggrin serves to combine keratin 1, keratin 10, and others intermediate filaments. This causes the keratin cells become increasingly flattened, the more to the top layers, thus they form a layer that resists water, microbes and allergens, as well as maintaining the integrity of the skin. After compressing the keratinocytes, the filaggrin protein is crushed into hygroscopic amino acids, which can protect the epidermis by retaining water and increasing the flexibility of the stratum corneum.
The Stratum Corneum Anatomy
The stratum corneum is the epidermis outermost layer and is responsible for function of the skin barrier. The structure of the stratum corneum is often referred to “brick and mortar” type structure. The bricks are the corneocytes and the mortar is the lipid lamellar bilayer. In addition, there are the Natural Moisturizing Factor (NMF), corneodesmosom, and cell envelope. NMF can be modified by the intake of external (topical application).
Natural Moisturizing Factor (NMF)
The NMF is a group of water-soluble elements which is 20-30% of the corneocytes content. The content of NMF can be seen in the table below. All of these elements are water-soluble humectant that maintains the skin’s moisture. The lipid layer that envelops corneocytes help keep NMF remains in the cell.
As previously explained, filaggrin plays an important role in keeping the skin integration. According to Prof. Derrick, 14-56% people with atopic eczema have more than one FLG gene mutations. For people with FLG mutations, the possibility of atopic eczema is 1.2 to 13 times greater than those who did not have mutations in these genes, which are R501X and 2282del4 mutase gene.
How can one know that he has the gene mutation? First, the person is suffering from eczema with rapid onset (age <2 years); persistent eczema until adulthood; ichthyosis vulgaris; hiperlinearis palmar; and keratosis piliaris. In addition, the possibility of recurrent skin infections (more than four times a year) that requires antibiotic is seven times greater than the ones do not have mutations in these genes, especially in mild or moderate.
NMF deficiency is influenced by two things, they are the decreasing of NMF production and the increasing of NMF disposal. How much the production of NMF is influenced by various things such as FLG mutation; certain skin conditions such as atopic eczema, psoriasis, ichthyosis vulgaris, and palmar xerosis; environmental conditions with low humidity and high UV radiation levels; as well as the natural aging process. In the other hand, the increasing of NMF disposal can be caused by the frequency of the patient to wash hands/feet with soap and high frequency of bathing.
If we get the well education about the things above, we can tell the patients how to cope with illness, what causes it, and can emphasize the importance of using a moisturizer to repair the epidermal barrier. In addition, we also can explain to the patient the reason for using a moisturizer regularly and how their protection layer is so damaged that can be easily irritated by the things that should not be irritating, such as his own sweat. Lastly, we can tell the patients that because her illness is severe enough, chances are you have FLG mutations, and using a moisturizer regularly becomes much more important.
Updated Therapies for Improving or Replacing the Damaged Epidermal Barrier
From Simpson, et al. research, it’s found that using a moisturizer containing ceramide precursors can improve the function of the skin. After using the moisturizer for four weeks, it clinically decreased the TEWL and skin dryness level, and it also increased the skin hydration in the skin that was given a moisturizer containing ceramide. The higher ceramide levels in moisturizers, the higher skin’s moisture levels. In a subsequent study, Simpson, et al., found that giving a moisturizer that contains a precursor of ceramides, PAI and ECC also gives better results than not giving any moisturizer at all.
Presentation of Assist. Prof. Dr. Derrick Aw Chen Wee, MBBS, MMed, MRCP, FAMS in the Morning Session 3 in Ballroom 3, Hotel Trans, Bandung at KONAS PERDOSKI, Thursday, August 28th 2014.
Overlooked Type of Dermatitis
Artefacta dermatitis (DA) is a condition in which the skin lesions suffered entirely caused by the patients themselves. It is usually a manifestation of a mental disorder or how the patient relieving stress level or looking for an attention. Its other name is factitial dermatitis.
DA is often happened to woman than man, adolescence or young adult. From the anamnesis, the patients had a history of mental illness or a history of occurrence of physical abuse/sexual abuse/trauma, previous treatment history, as well as the stressor factor.
The clinical description of artefacta dermatitis can be as lesions with irregular shapes in a linear or geometric pattern; the limit is clearer than the surrounding normal skin; the lesions display is vary depend on how the cut happened; could be mechanics, physics, or chemistry; there is no prodromal symptoms; lesions can be patches of redness, edema, blisters, flaking areas, crusting, cuts, burns, or scarring; lesions can appear suddenly; lesion found in areas that easily reached by hand or dental patients, such as face, hands, arms, legs, lips; patient can calmly smile like monalisa; and patient refuses to acknowledge that the cause of the lesion is themselves.
Because the cause is psychological factors, so besides the treatment from dermatologist, the treatment from psychiatrist and psychologist to address the mental health problems is also needed.
Dermatitis Autoimmune Progesterone and Estrogen
The Autoimmune progesterone dermatitis (DP) and dermatitis Estrogen (DE) are a rare skin condition that occurs in women in a certain cycle, following the menstrual cycle. Skin lesions occur when hormone levels increase in the time before menstruation. When the hormone levels decrease, the lesions will heal itself. It also occurs to patients who use hormonal contraception. This disease etiology is type III hypersensitivity reaction.
From the patients anamnesis, it is found that lesions occur every month, irregular/regular menstrual cycle, happen 3-10 days before the menstruation begins, and heals within 1-3 days after a completed menstrual cycle. The possibility is that patients take oral contraceptives or in therapy for infertility. In addition, patient doesn’t complain any symptom during the pregnancy.
The DP & ED treatments are depending on their rank. In the mild case, it can be treated by giving topical corticosteroids and oral antihistamines. In the severe case, it can also be treated by giving oral corticosteroids. Furthermore, the production of progesterone can also be suppressed with hormonal therapy. In addition, women with this disease should avoid taking drugs that contain progesterone. In the refractory case, it can also be done by doing oophorectomy.
Presentation of Dr. Unwati Sugiri, SpKK(K) in Morning Session 3 in Ballroom 3, Hotel Trans, Bandung at KONAS PERDOSKI, Thursday, August 28th 2014.
Looking Ahead: How is the Comprehensive Management of Dermatitis?
In this seminar, Prof. Retno had the opportunity to give a presentation about contact and atopic dermatitis, and the best way to handle it.
According to Prof. Retno, in general, rash or skin lesions, which are reddish and causing itch, are called dermatitis. The common dermatitis is DK and AD. There are many factors that affect these skin diseases, one of them is skin layer or skin barrier. The first skin that protects the body from the outside world is the epidermis stratum corneum. The layer consists of multiple layers of corneocytes cells with empty core, which is surrounded by multiple planar lamellar sheets which are rich in ceramides, cholesterol, and FFA.
The damaged skin barrier is characterized by dry skin condition. Subjective symptoms are experienced by the patient such as pruritus, pain, pin and needles, rough and gritty skin. The visible objective symptoms are redness, dull skin, dryness, white patch, cracked skin (fissures), or flaky skin.
To overcome it, the most important is to fix the damaged skin barrier. The skin barrier can be repaired when TEWL increased by 1%. Meanwhile, the time required for full restoration depends on the degree of damage that occurred, the patient’s age, and the patient general condition.
Contact Dermatitis (CD)
CD is a complex disease, in which the skin inflammatory reaction occurs in direct exposure to toxic materials in the neighborhood. The affecting factors are genes, environmental factors, as well as the patient’s own internal milieu.
There are two types of CD, which are irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD). The CD regimen can be done by avoiding allergen or irritants, the inflammation reduction drugs (corticosteroids, calcineurin inhibitors, cyclosporine, azathioprine, etc.), UV light therapy, using retinoid (alitrenoin), and also using emollients to improve the skin barrier. To determine the causative agent, it can be done by patch testing for 4 days.
AD is a chronic, relapsing inflammatory skin disease that commonly occurs in infants or children. AD can develop into atopic syndrome, where eczema will develop into allergic rhinitis and asthma. According to Dahl, et al., and Chan, et al., the AD prevalence happened at 13-14 years old was 1.1% in Indonesia; 5.3% in the Philippines; 6.3 to 9.5% in Malaysia; 6,8- 9,5% in Thailand; and 17.9% in Singapore. Based on consensus guidelines for AD treatment in the Asia-Pacific region, there are five pillars for AD management which are (1) the patients/caretaker education and empowerment; (2) avoid exposure and trigger factors modification; (3) the optimal barrier function improvement and maintenance; (4) remove/cure the inflammatory skin disorders; and (5) control and eliminate the itch-scratch cycle.
Patients and their families must be explained about pathogenesis and AD treatment, long-term and short-term treatment targets, patient and family education program (written and verbal). Furthermore, it should also be explained about predisposing factor, precipitation factors, and slow-healing factors.
The therapy was given of three components, which are Cleanse, Moisturize, and Medicate. The beginning of emollient therapy is 2-3 times a day or when the dry skin depends on the climate and room humidity. In the first until second week, the patient is given emollients and topical corticosteroids (TCS) twice daily. The selection types of topical corticosteroid depend on the severity degree of disease and patient’s age. In the third and fourth week, there will be improvement consolidation. In addition to emollients, the patient will be given TCS in the morning and topical calcineurin inhibitors (TCI) in the afternoon. For the next four weeks, the new skin barrier will be developed. Patient will be given TCI twice a day and emollients. After that, the further therapy is only emollient.
A good moisturizer contains humectant, ceramide, and emollients. Up until now, there are 4 generations of moisturizer. The last generation is Dermal Membrane Structure (DMS), the alkaline cream that is physically and chemically similar to normal skin barrier membrane structure. This form is free from emulsifiers. Multi-Lamellar Emulsion (MLE), an oil in water emulsion which follows the stratum corneum lamellar structure and lipid bilayer. MLE contains pseudoceramide (like Restoraderm®) and has a long lasting moisturizing effect.
Thus, the dermatitis treatment, both atopic and contact, in addition to finding the trigger & causative factors, should be accompanied with a material that can repair the damaged skin barrier by using emollients/moisturizers and topical medications (TCS / TCI).
Presentation of Prof. DR. Dr. Retno Widowati Soebaryo, SpKK(K) in the Morning Session 3 in Ballroom 3, Hotel Trans, Bandung at KONAS PERDOSKI, Thursday, August 28th 2014.