(Serbian Journal of Dermatology and Venereology) National Guidelines For The Treatment of Atopic Dermatitis

GUIDELINES Serbian Journal of Dermatology and Venereology 2016; 8 (3): 129-153
DOI: 10.1515/sjdv-2016-0012
National Guidelines for the Treatment of Atopic Dermatitis

Svetlana POPADI1, Mirjana GAJI-VELJI1, Sonja PRI2, eljko MIJUKOVI3,
Dragan JOVANOVI4, Lidija KANDOLF-SEKULOVI3, Milo NIKOLI1
1
Clinic of Dermatovenereology, Clinical Center of Serbia, Department of Dermatovenereology, School of Medicine,
University of Belgrade, Belgrade, Serbia
2
Institute for Child and Youth Health Care of Vojvodina, Faculty of Medicine, University of Novi Sad, Serbia
3
Clinic of Skin and Venereal Diseases, Military Medical Academy, Department of Dermatovenereology, School of Medicine,
University of Belgrade, Belgrade, Serbia
4
Department of Dermatovenereology, Clinic of Skin and Venereal Diseases, Clinical Center Ni, School of Medicine,
University of Ni, Ni, Serbia
*Correspondence: Svetlana Popadi, E-mail:spopadic@med.bg.ac.rs
OPEN
UDC 616.5-002-08(061.2)
Epidemiology of atopic dermatitis excoriated scaly papules, while typical skin thickening
Atopic dermatitis (AD) is a disease that usually with pronounced skin markings (lichenification) and
presents in the early childhood (1). AD is one pruritic papules are distinctive for the chronic course
of the most common skin diseases and it affects of the disease. In infants and young children, AD
approximately 20% of children and 1 - 3% of adults commonly starts as an acute or subacute condition,
(2). In 60% of patients the first manifestations appear whereas chronic forms are characteristic for older
within the first year of life, and in 90% of patients children and adults (5, 6, 7). These three distinct
before the age of five. In most patients manifestations phases are often observed in the same patient (6, 7).
of AD disappear before the adulthood, while in 25%
of patients AD persists throughout life (2). Rarely, Clinical presentations in children
the first AD manifestations appear in adulthood (2). During the first month of life, the first signs of
Approximately 25% of AD patients may develop atopic dermatitis may present as pronounced
some form of hand eczema during the life (3). yellowish scales on the scalp, commonly known
as cradle cap or infantile seborrheic dermatitis
Clinical presentations of AD (1). In infants, 3 - 6 months old, the predilection
The clinical presentations of AD vary depending sites for eczematous changes on the face are cheeks,
on the age and course of the disease; the major forehead and chin, whereas the central part of the
manifestations include erythema, edema, xerosis, face (nose, perioral region) and diaper area are often
erosions/excoriation, oozing and crusting, and spared. Skin changes are acute or subacute, with
lichenification (1, 4, 5, 6, 7). Intense itching is unclear margins, and present with erythema, edema,
common in AD resulting in excoriation, pruritic papulovesicles, excoriations, often associated with
papules, lichenification and eczematous skin lesions oozing and crusting, while chronic changes are rare
(2, 3, 4). The itch is particularly pronounced at night and manifest as erythematous papules and plaques
causing sleep impairment, thus having significant with desquamation. In infants 8 - 10 months old, AD
negative impact on the quality of life of both patients progresses to extensor surfaces of the extremities, and
and their families (2, 3, 5, 6). The disease may take after the first year it may affect the upper trunk, where
an acute, subacute or chronic course. Acute lesions the changes manifest as nummular dermatitis (1, 5, 6,
are characterized by intense pruritus, presence of 7). After the age of 2 years, the clinical presentations
papules and vesicles on erythematous skin, and change, that is, the disease takes a chronic course, or
are associated with excoriation, erosion and serous AD develops de novo. The symptoms include poorly
exudates. Subacute lesions manifest as erythematous, marginated lichenified plaques with excoriations
2016 The Serbian Association of Dermatovenereologists 129

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S. Popadi et al.
Serbian Journal of Dermatology and Venereology 2016; 8 (3): 129-153 National Guidelines for the Treatment of Atopic Dermatitis
localized to cubital and popliteal fossae, on the neck three main causes: reducedfilaggrin gene expression,
and in the region of wrist and ankle joints. Dry skin decreased level of ceramides in the skin, and increased
affects the entire body. Lichenification occurs as a activity of epidermal proteases. Almost 50% of patients
consequence of scraping and scratching due to intense with AD have a reduced expression for filaggrin gene
(predominantly nocturnal) itching. At intervals, acute synthesis, protein with a key role in maintaining the
eczematous eruptions, manifesting as papules and structural skin barrier function, while its absence,
papulovesicles, may develop on the lesions (1, 3, 4, 5). disturbing this structure, facilitates penetration of
Adolescents often present with persistent lichenified haptens and proteins (13, 14).
plaques in large joint flexures, associated with chronic Ceramides are natural lipids essential for
changes on the face (periorbital dermatitis), neck, theretention of water in the corneal layer of epidermis.
hands, feet and back (5, 7). Patients with AD exhibit a significant decrease of
ceramides, both in lesional and non-lesional skin.
Clinical presentations in adults The amount of ceramides in the skin is in a reverse
Adult patients with AD commonly present with relation with transepidermal water loss, which is a
lichenified plaques localized mainly in the flexural areas characteristic of AD skin. The fact that in children,
of the extremities and anogenital region. Facial edema decreased amount of ceramides is sometimes found
associated with lichenification on the neck and eyelids, only in lesional skin, is explained as a postinflammatory
as well as chronic eczema on the hands and/or feet is a reaction, not as a genetic factor (13, 14).
common finding. Pruritic type of AD is characterized In regard to immunological aspects, the
by excoriated pruritic nodules. The disease may have a etiopathogenesis of AD is very complex, since it
chronic recurrent course. Exacerbations often start with includes genes that encode factors of the adaptive
pronounced itching, without visible skin lesions, followed and innate immune system. Skin resident cells, as
by erythema, papules and infiltrations (1, 5, 6, 7). keratinocytes, dendritic cells, mastocytes, macrophages
Patients with AD have increased susceptibility to and innate lymphocytes, have a role in the inflammatory
skin infections, mostly those of bacterial etiology, but reaction in patients with AD. Besides, T-lymphocytes,
viral and fungalas well (5, 6, 7, 9). Bacterial infections plasmacytoid dendritic cells, monocytes and
are commonly associated with Staphylococcus aureus granulocytes from circulation also have a role in the
and somewhat more rarely with Streptococcus pyogenes etiology of eczematous reaction (13, 14).
(6, 7). Viral infections are more frequent in patients In the pathogenesis of AD, T helper (Th)
with AD, showing tendency of dissemination and lymphocytes have a central role. In AD patients,
spread of lesions (1, 8, 10). Depending on the causative activity of specific ThLy clones is unbalanced, with
viral agent, eczema herpeticum, eczema molluscatum, predominance of Th2 cell response to allergens, which
eczema coxsackium or eczema vaccinatum may differs in healthy individuals, where Th1 response is
develop (1, 9, 10, 11). Fungal infections associated dominant. Pathological activation of Th2 cells induces
with Malassezia sympodialis (Pityrosporum ovale) lead amplified production of IL4, IL5 and IL13, resulting
to head and neck dermatitis (12). in accumulation of other types of immune cells and
The extent and severity of AD are estimated by development of acute lesions in AD patients. Contrary
SCORingatopic dermatitis (SCORAD) (usually used to acute AD lesions, Th1 cell activity is dominant in
in Europe) and eczema area and severity index (EASI) chronic AD lesions (13, 14).
(usually used in USA) indices (8). Different incidence of AD in different geo-
graphical areas points to the significant role of
Etiopathogenesis of atopic dermatitis environmental factors in its etiopathogenesis, such as
The etiopathogenesis of AD is multifactorial, including climate factors, dietary factors, obesity, tobacco smoke
disturbances in skin barrier function, immune reaction exposure and microbiological exposure.
with key role of T-cells, dendritic cells, lymphocytes, Novel studies highlighted the role and effects of
mast cells, eosinophils, as well as environmental factors. skin microbiome both on its homeostasis as well as on
Skin barrier dysfunction in AD is a consequence to the onset of different pathological conditions, including
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AD. In episodes of AD exacerbation, increased Increases in Streptococcus, Propionibacterium

amount of S. aureus, but also S. epidermidis is evident. and Corynebacterium species on the skin are observed
Exacerbation of cutaneous inflammation is mediated following therapy, also with differences to the skin
by superantigens such as staphylococcus enterotoxins microbiota of healthy individuals (13). Differences
A and B, as well as toxic shock syndrome toxin 1 which of gut and intestinal microbiota between AD patients
result in T cells polyclonal activation (13, 14). and healthy individuals are also shown (13).
Table 1. Diagnostic criteria for atopic dermatitis by Hanifin and Rajka
Major (3 of 4) Minor (at least 3)
- Pruritus - Positive prick allergy tests

- Increased total IgE concentration
- Typical morphology and distribution of skin - Early onset of disease
lesions: flexural dermatitis in children older than 2 - Dry skin
years and adults; facial dermatitis in infants - Facial pallor and/or redness
- Pityriasis alba
- Chronic or chronic relapsing course - Ichthyosis
- Orbital darkening
- Personal and/or family history of atopy - Dennie-Morgan infraorbital folds
- Palmar hyperlinearity
- Keratosis pilaris
- Cheilitis
- Hand and foot eczema
- Areolar eczema
- Pruritus upon sweating
- Wool intolerance
- White dermographism
- Perifollicular accentuation
- Anterior neck folds
- Subcapsular cataract and keratoconus
- Susceptibility to bacterial and viral infections
(S. aureus, HSV)
- Decreased cell-mediated immunity
- Worsening of skin condition under emotional,
environmental stressors and irritants
- Food intolerance, especially in children
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S. Popadi et al.
In regard to the climate factors, UV exposition skin and personal history of atopy (or family history
and worm climate show protective effects on the onset in children younger than 4 years) (17). These criteria
of eczema, contrary to decreased UV exposition and were validated in numerous studies, with specificity of
high humidity. 10 - 100% and sensitivity of 89 - 99%.
Acidic pH of the skin, which contributes to the Furthermore, the American Academy of
repair of the barrier function, has antibacterial effect Dermatology recommended criteria which were
and role in desquamation. In AD patients, pH of the divided into: essential, important, and associated
entire skin is increased, resulting in exacerbation of features, based on their frequency and importance
the disease. The most common factors that disturb the (18). Several other criteria were also recommended,
pH of the skin are detergents and soaps. They change but without wider acceptance in everyday clinical
the amount of the lipids on the skin surface, enhance practice (19, 20).
proteases and make the corneal layer thinner (13, 14). In recent analysis and systematic literature review
The interaction of above-mentioned genetic of all the studies that examined validity of different
factors, immune factors and environmental factors is diagnostic criteria, the authors concluded that
very complex in the etiopathogenesis of AD. With a methodology of validation should be more uniform in
great amount of new discoveries in this field, this is order to draw the final conclusion of their utility (16)
for sure a great challenge for further investigations in .
this area. Emollient therapy and skin care in AD
The management of AD requires efficient control of
Diagnostic criteria for atopic dermatitis flares by treatment of acute inflammatory symptoms,
The European Task Force on Atopic Dermatitis defined along with restoration of the skin barrier homeostasis,
atopy as a genetic susceptibility to Th2 immune and avoidance of trigger and exacerbating factors.
response to usual environmental allergens with clinical Certain moisturizers may improve the skin barrier
signs and symptoms of asthma, allergic and/or atopic function and reduce skin susceptibility to irritants
dermatitis. In the majority of patients, the diagnosis (21, 22).
of atopic dermatitis is based on personal history and
typical clinical manifestations. Various diagnostic Cleansing and bathing
criteria have been developed in recent decades, but In general, dryness is worse during cold months,
they are most important for epidemiological and when it is aggravated by heat in the house and low
clinical studies to define inclusion criteria (1, 15, 16). humidity. Daily baths are considered an excellent
Diagnostic criteria for atopic dermatitis include means of hydrating the skin. The skin must be
combinations of clinical signs and symptoms, allergy cleansed thoroughly, but gently and carefully. A daily
tests and laboratory test results that confirm the bath or shower removes scales, crusts, irritants, and
presence of atopy. The most popular diagnostic criteria allergens and provides an opportunity to moisturize
were developed by Hanifin and Rajka in 1980 (Table the skin. The water should be lukewarm, and 20 min
1) (15). According to these criteria, 3 major and 3 immersion is adequate. Short baths (only 5 minutes)
minor criteria are needed for the diagnosis of atopic and the use of bath oils (in the last 2 minutes of
dermatitis. These criteria were validated in 2 studies, bathing) are aimed at avoiding epidermal dehydration
showing a diagnostic sensitivity of 87.9% and 96% (8, 23). Soaps, shampoos, and shower gels and foams
and specificity of 77.6% and 93%, respectively (16). should be avoided; they can irritate and dry the skin.
The second, less frequently employed criteria are Prepubertal children produce little sebum and require
those of UK Working Partys Criteria. Based on these minimal shampoo. Bath oils may have a moisturizing
criteria, atopic dermatitis is diagnosed in persons with effect, but evidence for efficacy is limited. Neutral or
typical skin lesions in the last 12 months, and at least low pH non-soap cleansers that are hypoallergenic
3 of 4 following criteria: early onset under the age of and fragrance free are available, but any moisturizer
2 (not used in children under the age of 4), personal cream or lotion can be used as a soap substitute. It
history or current presence of flexural dermatitis, dry is easiest to apply the moisturizer before getting into

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the bath or shower, and then massage it into the skin (8). A regular use of emollient has a short and long
once in the water (19, 24). Topical emollients are term steroid sparing effect in mild to moderate AD.
preferentially applied immediately after taking a bath An induction of remission with topical corticosteroids
or a shower following gentle drying when the skin is is required first (short-term therapy). Maintenance of
still slightly humid. The key to maintaining hydration stable disease (long-term maintenance therapy) can be
after bathing in patients with atopic dermatitis is obtained with emollients used twice weekly or more
application of a thick emollient within 3 minutes after frequently in a subset of patients, after an induction
exiting the bath, before evaporative loss occurs (8, 22, of remission with topical corticosteroids. The 1-week
23). stand-alone application of an emollient, may offer
benets for the improvement of mild to moderately
Emollient therapy severe localized ares of AD (25).
Proper use of an emollient for hydration is a keystone An imbalance of skin microflora is suspected of
of AD treatment and emollients are the mainstay playing a key role in exacerbations of AD. A twice-
of maintenance therapy. Emollients are available in daily application of a new emollient balm, containing
various formulations. Lotions are thin with high water an extract of a non-pathogenic gram-negative bacteria,
content and are useful for hairy areas and weeping in children with mild AD, protects the skin from S.
eczema, but ineffective for severe xerosis. Gels are aureus proliferation and preserves biodiversity of the
similar to lotions, with high water content. Creams microflora (26, 27).
(emulsions of water and oil) are most popular: easily
rubbed in and do not leave a shine, but greasier than Topical anti-inflammatory therapy
lotions and gels. Some oils solidify in cold climates, but Effective topical therapy depends on three
soften at body temperature. Ointments are thick and fundamental principles: sufficient strength, sufficient
greasy and are suitable for very dry eczema. However, dosage and correct application. Topical treatment
they are less cosmetically acceptable, can cause heat should always be applied on hydrated skin, especially
trapping and folliculitis, and can stain clothing and when using ointments. Topical corticosteroids (TCS)
bedding. Additives can cause irritation or allergy, and and immunomodulators are first-line treatment of
added fragrance should be avoided (24). flares, whereas long-term management is based on the
Patients should be encouraged to try different use of emollients that aim to improve skin hydration,
emollients, as well as advised about the best type maintain the barrier integrity, relieve pruritus and
for their skin condition, climatic conditions, and prevent new flares (28).. Patients with acute, oozing
lifestyle. Hydration of the skin is usually maintained and erosive lesions, children in particular, sometimes
by application of moisturizers at least twice daily. do not tolerate standard topical application, and may
Patients might use a gel- or cream-based emollient first be treated with wet wraps until the oozing stops.
during the day and in hot weather, and an ointment They are highly effective in acute eczema and improve
at night and in cold weather. The amount needed is tolerance (29). Even without wet wraps, topical therapy
often underestimated. Approximately 600 g/week is is time consuming: patients should plan 30 min for
required for adults and 250 g/week for children with one session. One well-conducted treatment per day
generalized eczema. Emollients should be applied as is usually sufficient; oozing eczema may require a few
liberally and frequently as possible (up to 4 hourly), days with higher treatment frequency (8).
ideally when the skin is moist from a bath. They By tradition, anti-inflammatory topical therapy
should be used all over and not just to the affected has been administered to lesional skin only and has
skin and smoothed onto the skin in the direction of been stopped or tapered down once visible lesions
the hair follicles to avoid folliculitis (19, 24). were cleared. This traditional, reactive approach
The use of emollients is widely recommended has in the last years been challenged by a proactive
for the management ofAD, especially between flares. treatment concept, which is defined as a combination
The direct use of emollients on inflamed skin is poorly of predefined, long-term, low dose, anti-inflammatory
tolerated and it is better to treat the acute flare first treatment applied to previously affected areas of skin

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S. Popadi et al.
in combination with liberal use of emollients on the useful (31). The application amount of topical anti-
entire body and a predefined appointment schedule inflammatory therapy should follow the finger-tip
for clinical control examinations (30). The proactive, unit (FTU) rule. A FTU is the amount of ointment
usually twice a week treatment regimen is initiated expressed from a tube with a 5-mm diameter nozzle
after all lesions have successfully been treated by an and measured from the distal interphalangeal joint to
intensive, usually twice daily treatment approach in the tip of the index finger. One FTU is equivalent to
addition to ongoing emollient therapy for previously approximately 0.5 g and should cover an area equal to
unaffected skin (8). both palms (8, 24).
Topical corticosteroids Topical calcineurin inhibitors

Topical corticosteroids (TCS) are important anti- Topical calcineurin inhibitors (TCI) are immuno-
inflammatory drugs used in AD, especially in the suppressive agents which inhibit calcineurin in the skin,
acute phase. TCS are recommended for AD-affected blocking early T-cell activation, and cytokine release.
individuals who have failed to respond to good skin They are effective in reducing the skin inflammation
care and regular emollient use. Patient age, areas of the in AD patients. In the UK, tacrolimus 0.03%
body affected, degree of xerosis, patient preference, ointment and pimecrolimus 1% cream are approved
and costs of medicines should be considered. TCS for children aged 2 15 years; tacrolimus 0.1% can
are a first-line anti-inflammatory treatment, applied be used >16 years (28, 32). Both topical calcineurin
on inflamed skin as needed (pruritus, sleeplessness, inhibitors are approved in the EU in patients above 2
new flares) (8, 18, 22). Twice-daily application of years of age (8). In Serbia, pimecrolimus 1% cream is
TCS is recommended, although once daily may be approved for children older than 2 years.
sufficient (25). There is no evidence for higher efficacy TCI are recommended for short-term, long-
with application more than twice a day. Absorption term, and maintenance treatment of AD in adults and
is better with moisturized skin; after taking a bath children. TCI are preferable in situations that include
is ideal, 20 min before applying the emollient. Itch recalcitrance to steroids, sensitive areas, steroid-
is the key symptom for evaluation of response to induced atrophy, and long-term uninterrupted topical
treatment, and tapering should not be initiated steroid use. They are particularly useful for areas where
before the itch has disappeared. Dose tapering should the skin is already thin, such as the face and flexures.
be gradual to avoid withdrawal rebound; tapering TCI are recommended as steroid-sparing agents. For
strategies consist of using a less potent corticosteroid patients <2 years of age with mild-to-severe disease,
on a daily base, or keeping a more potent one while off-label use of TCI can be recommended. Proactive
reducing the frequency of application (intermittent intermittent use with TCI is recommended on areas
regimen) (8). Proactive, intermittent use of TCS that commonly flare (18, 22). Proactive tacrolimus
is recommended on areas that commonly flare (18, ointment therapy, used twice a week, has shown to
22). Potential side effects should be considered. be safe and effective for up to 1 year in reducing the
Monitoring for cutaneous side effects during long- number of flares and improving the quality of life in
term, potent TCS use is recommended. With mild adult patients and children (33).
activity, a small amount of topical corticosteroids Side effects, including skin burning and pruritus,
twice to three times a week (monthly amounts in should be considered and patients should be informed.
the mean range of 15 g in infants, 30 g in children, The most common side-effect is a transient feeling of
and up to 60 90 g in adolescents and adults), with warmth or burning at the application site during the
a liberal use of emollients, generally allows a good first days (34, 35). It starts about 5 min after each
maintenance keeping SCORAD values below 15 application and may last up to 1 h, but intensity and
20. Such monthly amounts of even potent topical duration typically decrease within 1 week to zero (36).
steroids usually do not have adverse systemic or local Clinicians should be aware of the black-box
effects (8). The combination of topical corticosteroids warning on the use of TCI (18, 22). Although effective
with topical calcineurin inhibitors does not seem to be sun protection is recommended in patients treated

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with TCI, there is no significant systemic absorption Topical crisaborole 2% ointment, (formerly
and TCI have been used in children for more than 15 known as AN2728) is a benzoxaborole, nonsteroidal,
years with no evidence of increased malignancy (24). topical, anti-inflammatory phosphodiesterase 4 (PDE4)
inhibitor. By inhibiting PDE4 and thus increasing
Topical antipruritic therapy levels of cyclic adenosine monophosphate (cAMP),
There is little specific and effective antipruritic crisaborole controls inflammation. Once crisaborole
treatment for eczema itch (37). There is evidence that reaches systemic circulation after topical application,
TCS can be used in the initial phase of AD exacerbation it is metabolized to inactive metabolites. This limits
to control pruritus. Also, TCI significantly relieve systemic exposure to crisaborole and systemic PDE4
pruritus in AD. Itch is completely relieved after the inhibition. Crisaborole 2% ointment was generally
first days of treatment in adults and children. well tolerated and improved AD disease severity scores,
pruritus, and all other AD signs and symptoms. Two
Specific antipruritic therapies large, randomized, controlled, phase 3, clinical trials
Topical anesthetics (benzocaine, lidocaine, poli- assessing the efficacy and safety of topical crisaborole
docanol, mixture of prilocaine and lidocaine) 2% ointment, in children, adolescents, and adults
when used as short-term therapy may reduce with mild to moderate AD, were recently completed
itch in AD (8). Cannabinoid receptor agonists with positive results (44, 45, 46, 47).
(N-palmitoylethanolamine, applied twice a day) have Tofacitinib is a small-molecule Janus kinase
been described to exhibit antipruritic and analgesic (JAK) inhibitor that affects the interleukin (IL)4,
properties (38). Capsaicin is a naturally occurring IL-5, and IL-31 signaling pathways, interfering with
alkaloid which exerts its functions via binding to a the immune response that leads to inflammation.
capsaicin-specific receptor which is located on free nerve Tofacitinib 2% ointment, applied twice daily for 4
endings. There is preliminary evidence that capsaicin is weeks, showed significant efficacy and safety/local
useful in the treatment of AD itch (39). Topical doxepin tolerability with early onset of AD. JAK inhibition
(5% cream) exhibited antipruritic effects in controlled through topical delivery is potentially a promising
studies of AD (40). However, topical doxepin therapy therapeutic target for AD (48).
is not licensed or used in any European country due to
an increased risk of contact allergy. Topical mast cell Systemic treatment of AD
stabilizer sodium cromoglycate showed improvement The use of systemic corticosteroid therapy is not
in SCORAD (41). Other new topical agents include recommended in AD because of short-term, transient
thiol derivative N-acetylcysteine, but without positive, and potential side effects.
convincing evidence of its efficacy in AD (42). At the During flares, oral H1-antihistamines,
moment, there is not enough evidence by randomised cephalosporins and macrolides are indicated. In
controlled trials (RCT) to support the use of these severe, generalized and resistant forms of AD,
substances in the treatment of AD itch. However, none oral cyclosporine and methotrexate may be used.
of these substances is licensed for AD in Europe, and Methotrexate is not allowed before the age of two.
routine clinical use is not recommended as an adjuvant Antihistamines. Oral antihistamines (H1)
antipruritic therapy in AD (8). are safe for long-term treatment. Although there
are opinions that non-sedating antihistamines do
Other anti-inflammatory agents not relieve pruritus in AD patients as sedating
The development of a more specific anti-inflammatory antihistamines, modern treatment protocols and
treatment which is easy to use and targets pruritus our experience indicate that systemic therapy with
could provide clinically meaningful improvements for non-sedating antihistamines reduces pruritus, has
patients with AD. The majority of emerging therapies a positive impact on clinical presentations, and the
for AD are focused on inhibiting phosphodiesterase 4 quality of life in AD patients.
(PDE4), an enzyme which is increased in inflammatory H1 antihistamines act via H1 receptor by
disorders such as AD (43). inhibiting the response of mediators released by mast

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S. Popadi et al.
cells and basophils. Suppression of the inflammatory (52). Oral ketoconazole or itraconazole and topical
response is achieved by reducing chemotaxis and ciclopiroxilamine or imidazole (miconazole,
antigen presentation, reduced expression of cell clotrimazole), during 7 - 14 days, reduce inflammation
adhesion molecules and reducing the levels of pro- in patients with head and neck variant of the disease
inflammatory cytokines (49). Oral antihistamines (53). Another imidazole preparation, fluconazole is
alleviate pruritus in AD. Antihistamines are used also successfully used in this variant of AD.
once or several times a day, as recommended by the Viral infections, particularly Molluscum
manufacturer. contagiosum virus and herpes simplex, easily spread
Chloropyramine is an antihistamine that due disrupted skin barrier function in AD. Eczema
reduces pruritus and exhibits local anesthetic, local herpeticum occurs almost exclusively in AD patients
vasoconstrictor effect and central sedative effect. It and may be a life-threatening infection, particularly
is contraindicated during pregnancy and lactation, in pediatric patients. The treatment of choice for
in newborns and premature infants. In children, it is Molluscum contagiosum is liquid nitrogen and
recommended only in case of severe allergic reactions. curettage. Acyclovir is a drug of choice for eczema
We do not recommend it in the treatment of AD in herpeticum (10).
pediatric patients. In adult patients caution is advised Phototherapy. During summer and sunny
if there is an increased sensitivity to the sedative months, AD tends to improve in most patients.
effects of antihistamines and comorbidities such as Artificial, UVA and UVB phototherapy, have an
epilepsy, hyperthyroidism and others. It is used 1 - 3 important role in the treatment of AD in our country,
times during 24 hours by deep intramuscular or slow especially during the late fall and winter. It was found
intravenous injection. that UV rays have a beneficial effect on the sensory
The newer, oral non-sedating antihistamines innervations of the skin (54), induce apoptosis of
(loratadine, desloratadine, cetirizine, levocetirizine, inflammatory cells and reduce production of cytokines
etc.) are more comfortable and safe for long-term use. (55). UV radiation also recovers the skin/epidermal
According to the manufacturer, they are used in a single barrier function (56).
dose (1x1 tablet/day). However, in dermatology we use Currently, there are several available UV
it in up to four times higher doses. Desloratadine is an protocols:
oral solution that can be used from the sixth month Broadband UV (UVA + UVB = 290 - 400 nm)
of life, while levocetirizine is recommended after the Broadband Ultraviolet B (UVB-HB = 280 - 315 nm)
age of two. In addition to effects on H1 receptors, oral Narrow-band UVB (nbUVB = top: 311 - 313 nm)
antihistamines also have anti-inflammatory effects UVA1 (340 - 400 nm)
improving the signs and symptoms of AD. Phototherapy is good as a maintenance therapy
Antibiotics. Antibiotics (cephalosporins, and and as a support treatment. It is rarely used as a
macrolides) are crucial during flares. An impaired monotherapy in stages of disease exacerbation.
epidermal barrier function enhances the development PUVA therapy is not recommended in patients under
of infection. Furthermore, pruritus leads to scratching the age of 12. In general, depending on the physical
and dissemination of Staphylococcus aureus on inflamed characteristics of UV chamber and patients age, the
and non-inflamed skin areas. Superantigen stimulation initiation of UVB phototherapy in younger patients is
by S. aureus contributes to the development and individually estimated. Rarely the use of this type of
maintenance of inflammation in AD (50, 51). During therapy is possible before the age of five. During sunny
flares, cephalexin is considered to be the drug of months, controlled sun exposure is recommended.
choice, while azithromycin may be used in patients Cyclosporine. Cyclosporine inhibits production
allergic to penicillins and cephalosporins. of IL-2. The results of meta-analyses (57) confirm
Antifungals. Fungal infections can also be the efficacy of cyclosporine in the treatment of AD.
associated with the development and maintenance of Rapid recurrence is possible after discontinuation
inflammation in AD. Head and neck variant of AD is of cyclosporine treatment. Before cyclosporine is
often associated with increased Malassezia sympodialis initiated, control of blood pressure, serum creatinine,

Unangemeldet
and basic biochemical analysis of blood and urine used in the treatment of AD (59, 60). Larger studies
should be performed. The initial dose of cyclosporine and longer follow-up periods will point to efficacy and
is 2.5 - 5 mg/kg in two divided daily doses (every 12 safety of biologics in the treatment of AD.
h). At the beginning, lower doses of cyclosporine are
recommended. Later, if the renal function, the serum General measures in AD patients
concentration of cyclosporine and blood pressure are Hygiene
normal, the dose may be increased up to 5 mg/kg/day. The skin should be cleaned thoroughly, but gently and
Doses higher than 5 mg/kg/day may be associated carefully, in order to remove crusts in case of bacterial
with nephrotoxic effects. superinfection. Bathing should last approximately 5 -
Methotrexate. Methotrexate (MTX) is also 10 minutes, water temperature between 27 and 30C.
successfully used in the treatment of severe forms of AD. In order to avoid dehydration of the epidermis, patients
It is not recommended before the age of two. Before the are recommended to use a bath oil, during the final
introduction of MTX, complete blood count test (CBC), 2 minutes of bathing. Adding sodium hypochlorite
serum creatinine, AST, ALT as well as urine analysis, to the bath water may be useful, considering its
HBsAg and anti-HCV tests should be performed. The antibacterial effect (8). Taking a bath in salt water can
MTX test-dose is administered 5 - 7 days before the first be beneficial for patients with impetiginized lesions
therapeutic dose. In pediatric patients (under the age of or ichthyosis. It has been shown that water hardness
5) 1.25 mg (1/2 tablets) of MTX may be considered as a is linked with an increased AD prevalence, which
test dose, while in older and adult patients the test dose means that hard water can increase the risk of atopic
is 2.5 mg (1x1 tablet). After 5 - 7 days, CBC, hepatic dermatitis in children (61).
function and urine analysis should be performed and Emollients are primarily applied immediately
if they are within normal limits therapeutic doses of after a shower or bath, while the skin is still slightly
MTX may be introduced. The initial therapeutic dosage damp. Newer studies have suggested that by limiting
for pediatric patients is 0.2 - 0.4 mg/kg weekly and 0.2 the amount of products used to clean the skin and
mg/kg weekly in adult patients. MTX is administered by applying emollients at least once a day, the risk of
in a single dose orally or subcutaneously. Laboratory atopic dermatitis can be reduced (62).
tests (CBC, creatinine, hepatic function and urine) are
performed once a week during the first month, then Clothing
every two weeks in the second month, then monthly Wearing smooth, cotton clothes and avoiding irritating
during treatment. After withdrawal of skin lesions fabrics (primarily wool) is crucial for avoiding skin
or during remission we recommend slow tapering of irritation. In addition, overly occlusive clothing
MTX. In remission phase we recommend low doses of which increases the temperature of the skin should
MTX (5 - 10 mg) for several months. In adult patients, be avoided; in winter months, children should not be
contraception is necessary during the treatment and for dressed too warmly. Low humidity and indoor heating
six months after discontinuation of MTX. Folic acid, 5 make the skin drier, so the use of air humidifiers is
mg a week should be administered 48 hours after MTX. recommended. There is a consensus that patients with
Azathioprine. Azathioprine is used in the UK atopic dermatitis should avoid occupations which
and USA in the treatment of adult forms of AD. involve a risk of serious skin damage or contact with
Therapeutic dose is 2.5 mg/kg/day, in patients over irritating substances (8).
17 years of age (58). Before the introduction of
azathioprine and during the treatment, CBC, blood Lifestyle
and urine tests are recommended. Contraception is Numerous factors and substances in our surroundings
necessary during the treatment with azathioprine. can irritate the sensitive skin of patients with AD and
Biologics. Numerous biologics (ustekinumab, cause the development of eczema. The irritants may
fezakinumab, apremilast, dupilumab, OC000459) are be mechanical (for example, wool), chemical (acids,
used in the treatment of AD, with promising results. solvents, water) or biological (microorganisms).
However, so far, these preparations are not routinely Informing patients and their family members about

Unangemeldet
S. Popadi et al.
the importance of non-specific irritants and their There is sound evidence that probiotics are safe
role in the development of eczema is an extremely and efficient in the prevention of AD and that they
important precondition for successful treatment of decrease the risk by about 20% (67). However, it is
patients with AD. still unclear how probiotics should be taken (should
Many patients are aware of the fact that contact mothers take them during pregnancy, should they be
with animals can make their skin symptoms worse. given to children when they are born, or both) and
The exposure to cat fur in childhood can increase the which strain should be taken. In contrast to their
risk of AD, especially in children with a filaggrin gene positive effect with regard to prevention, the efficacy
mutations (8, 63). There is no evidence that contacts of probiotics in patients suffering from AD has not
with dogs increase the risk of AD (8). been established (68).
Cigarette smoking in facilities or rooms where
children with AD spend time should be avoided, Alternative treatments
since it can make the irritation and itching worse and There is insufficient evidence to determine whether
increase the tendency towards the development of phytotherapy, aromatherapy, acupuncture,
asthma later in life. homeopathy, traditional Chinese medicine, or
Many patients have problems with perspiration bioresonance therapy are effective forms of treatment
and sweat retention during the summer, which for AD (8).
can intensify the itching. However, children with
AD should be encouraged to actively play sports. Abbreviations
Swimming is an excellent activity for children with AD Atopic dermatitis
AD, if they can tolerate exposure to chlorinated water. EASI - Eczema area and severity index
Spending time in air-conditioned rooms during the FTU -finger-tip unit
summer months can significantly decrease the itching. JAK - Janus kinase
MTX- Methotrexate
Diet nbUVB - Narrow-band UVB
Among the food allergens, cows milk, eggs, wheat, PDE4 - phosphodiesterase 4
soy, walnuts, and peanuts are usually responsible for SCORAD - Scoring atopic dermatitis
the development or exacerbation of eczema in early Th - T helper
childhood. Double-blind, placebo-controlled food TCS - Topical corticosteroids
challenges are considered to be the gold standard for TCI - Topical calcineurin inhibitors
food allergy diagnosis (64). In a systematic review UVA - UltravioletA rays
of eight randomized, controlled trials (57) which UVB - UltravioletB rays
examined the effect of elimination diets in patients
with AD, no conclusive evidence has been found Disclosure
to support the claim that an elimination diet (for
This study was partially supported by the Fund of The
example, eggs and milk) is beneficial for AD patients.
Serbian Ministry of Education and Science (Grants
However, another study has shown that egg-free
No 175065, 175038, 41018 and 43012).
diet has led to the improvement of AD in patients
who have shown clinical symptoms since the last egg
consumption (65). References:
1. Wollenberg A, Oranje A, Deleuran M, Simon D, Szalai Z,
Restrictive diets are not recommended for
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Unangemeldet
Nacionalni vodi za terapiju atopijskog dermatitisa

Svetlana POPADI1, Mirjana GAJI VELJI1, Sonja PRI2, eljko MIJUKOVI4,
Dragan JOVANOVI3, Lidija KANDOLF SEKULOVI4, Milo NIKOLI1
1
Klinika za dermatovenerologiju Kliniki centar Srbije, Katedra za dermatovenerologiju, Medicinski fakultet Univerziteta u
Beogradu
2
Institut za zdravstvenu zatitu dece i omladine Vojvodine, Medicinski fakultet Univerziteta u Novom Sadu
3
Klinika za kone i polne bolesti Kliniki centar Ni, Katedra za dermatovenerologiju, Medicinski fakultet Univerziteta u
Niu
4
Klinika za kone i polne bolesti, Vojnomedicinska akademija, Medicinski fakultet, Vojnomedicinska akademija
Dopisni autor: Svetlana Popadi; e-pota: spopadic@med.bg.ac.rs
UDK 616.5-002-08(061.2)
Epidemioloke karakteristike atopijskog dermatitisa akutnog i subakutnog toka, dok kod starije dece i
Atopijski dermatitis (AD) je oboljenje koje obino odraslih poprima hronini oblik (57). Kod jednog
poinje u ranom detinjstvu (1). AD je jedno od pacijenta esto su prisutne sve tri faze promena (6, 7).
najeih oboljenja koe i javlja se kod priblino 20%
dece i 13% odraslih (2). Kod 60% pacijenata prve Klinika slika kod dece
manifestacije se javljaju u prvoj godini ivota, a kod U prvom mesecu ivota, ukaste, izraene skvame u
90% obolelih do navrene pete godine. Kod veine kapilicijumu, poznate kao temenjaa ili tzv. seboroini
pacijenata bolest se povlai do odraslog doba; kod dermatitis odojadi, mogu biti prvi znak atopijskog
25% perzistira tokom ivota, dok se kod manjeg broja dermatitisa (1). U uzrastu odojeta, od treeg do
obolelih prve manifestacije AD pojavljuju u adultnom estog meseca ivota, predilekciono mesto za nastanak
periodu (2). Priblino etvrtina obolelih od AD razvie ekcemskih promena je lice (obrazi, elo i brada), dok
i neku formu ekcema na akama tokom adultnog su centralni deo lica (nos, perioralna regija) i regija
perioda (3). koju pokriva pelena (tzv. pelenska regija) najee
poteeni. Promene na koi su akutnog i subakutnog
Klinika slika atopijskog dermatitisa toka, nejasno ograniene, u vidu eritema, edema,
Klinika slika se razlikuje u zavisnosti od ivotnog doba papulovezikula, ekskorijacija, esto sa vlaenjem i
i toka bolesti, a glavni znaci su eritem, edem, erozije i krustama, ree hronine u vidu eritematoznih papula
ekskorijacije, vlaenje, kruste, suva koa i lihenifikacija i plakova sa skvamom. Od osmog do desetog meseca
(1, 47). Intenzivan svrab je karakteristian za AD ivota, AD se iri na ekstenzorne strane ekstremiteta,
i dovodi do nastanka ekskorijacija, prurigo papula, a nakon prve godine ivota na gornji deo trupa, gde
lihenifikacije i ekcematoznih konih lezija (24). promene mogu imati numularan izgled (1, 57). Nakon
Posebno je izraen nou, to onemoguava spavanje i druge godine ivota, klinika slika se menja prelaskom
znaajno utie na kvalitet ivota i pacijenta i porodice prethodne forme u hronini oblik, ili AD moe nastati
(4, 5, 7, 8). Promene na koi mogu biti akutnog, de novo. Javljaju se nejasno ogranieni lihenifikovani
subakutnog i hroninog tipa. Za akutne lezije su plakovi sa ekskorijacijama, lokalizovani u kubitalnim i
karakteristini: intenzivan svrab, eritem, pojedinane i poplitealnim pregibima, na vratu i u okolini runih i
slivene papule (nekad i vezikule); prate ih ekskorijacije, skonih zglobova. Koa celog tela je suva. Lihenifikacija
erozije i serozni eksudat. Subakutne lezije se manifestuju je posledica eanja, zbog izraenog, preteno nonog,
kao eritematozne, ekskorisane papule sa skvamom, dok svraba. Povremeno se na ovim lezijama razvijaju akutni
su za hronini tip promena tipina zadebljanja koe s ekcemski naleti u vidu papula i papulovezikula (1,
naglaenim konim crteom (lihenifikacija) i prurigo 57). U adolescenciji perzistiraju lihenifikovani plakovi
papule. Kod odojadi i mlae dece, AD je preteno u pregibima velikih zglobova, uz nastajanje hroninih

Unangemeldet
S. Popadi et al.
promena na licu periorbitalni dermatitis, zatim na je koliina ceramida u epidermu u obrnutoj srazmeri
vratu, akama, stopalima i leima (5, 7). sa transepidermalnim gubitkom vode, bitnom
karakteristikom koe atopiara. Kod dece se meutim
Klinika slika kod odraslih smanjena koliina ceramida prema nekim autorima
Kod odraslih osoba, u klinikoj slici dominiraju nalazi samo u lezionoj, a ne i u neizmenjenoj koi,
lihenifikovani plakovi, koji se obino nalaze u pregibima to se objanjava postinflamatornom reakcijom, a
ekstremiteta i u anogenitalnoj regiji. esto je prisutan ne genetskom uslovljenou (13, 14). U odnosu na
edem lica sa lihenifikacijom na vratu i onim kapcima imunske aspekte, patogeneza AD je veoma sloena jer
i hronini ekcem aka i/ili stopala. Prurigo tip AD obuhvata sadejstvo uroenog i steenog imuniteta. elije
karakteriu ekskorisani pruriginozni vorovi. Bolest prisutne u koi, poput keratinocita, dendritinih elija,
ima hronino recidivirajui tok. Egzacerbacije bolesti mastocita, makrofaga i nezrelih limfocita, uestvuju u
esto poinju sa izraenim svrabom bez vidljivih lezija, a zapaljenskoj reakciji. Pored njih, u nastanku ekcemske
kasnije se pojavljuje eritem, papule i infiltracija (1, 57). reakcije takoe uestvuju T-limfociti, plazmocitoidne
Pacijenti sa AD pokazuju poveanu sklonost dendritine elije, monociti i granulociti iz cirkulacije
ka infekcijama koe, uglavnom bakterijskim ali i (13, 14). U patogenezi AD, T-helper (pomoniki)
virusnim i gljivinim (5, 6, 7, 9). Bakterijske infekcije limfociti imaju centralnu ulogu. Kod bolesnika sa AD
najee izaziva Staphylococcus aureus, ree Streptococcus postoji neuravnoteenost aktivnosti specifinih klonova
pyogenes (6, 7). Virusne infekcije su ee kod obolelih pomonikih T-elija, sa predominacijom TH2 tipa
od AD, sa sklonou ka diseminaciji i irenju promena elijskog odgovora na alergene, za razliku od normalnih
(1, 8, 10). U zavisnosti od virusa koji ih izaziva, moe osoba gde dominira TH1 tip. Patoloka aktivacija TH2
nastati eczema herpeticum, eczema molluscatum, eczema elija vodi pojaanoj produkciji IL-4, IL-5 i IL-13, to
coxsackium ili eczema vaccinatum (1, 911). Gljivina ima za posledicu nakupljanje drugih tipova imunskih
infekcija izazvana specijesom Malassezia sympodialis elija i razvoj akutnih lezija kod AD. Za razliku od
(Pityrosporum ovale) dovodi do nastanka takozvanog akutnih, u hroninim lezijama AD dominira TH1
head and neck dermatitisa (12). elijska aktivnost (13, 14).
Za procenu teine klinike slike AD kod dece i Razlika u incidenciji i prevalenciji AD u razliitim
odraslih koriste se indeksi SCORAD (vie u Evropi) i geografskim oblastima ukazuje i na znaajnu ulogu faktora
EASI (vie u Severnoj Americi) (8). sredine u etiopatogenezi, poput klimatskih faktora,
faktora ishrane, gojaznosti, izloenosti duvanskom dimu
Etiopatogeneza atopijskog dermatitisa i drugim zagaivaima okoline, kao i mikrobiolokoj
Etiopatogeneza AD je multifaktorska. Obuhvata defekt izloenosti. Novija istraivanja naglaavaju ulogu i uticaj
kone barijere, imunsku reakciju sa kljunom ulogom mikrobioma koe, kako na njenu homeostazu tako i na
T-elija, dendritinih elija, limfoidnih elija, mastocita pojavu razliitih patolokih stanja, ukljuujui i AD. U
i eozinofila, kao i faktora sredine. epizodama pogoranja klinike slike kod AD evidentno
Disfunkcija barijere koe kod AD posledica je je poveanje koliine S. aureus, ali i S. epidermidis.
tri bitna faktora: defekta ekspresije gena za filagrin, Egzacerbacija kutane inflamacije posredovana je
smanjene koliine ceramida u koi i poveane aktivacije superantigenima poput stafilokoknih enterotoksina A
epidermalnih proteaza. Skoro 50% pacijenata sa AD i B, kao i dejstvom toksinog ok-simptom toksina 1
ima defekt ekspresije gena za sintezu filagrina, proteina koji dovodi do poliklonske aktivacije T-elija (13, 14).
koji ima kljunu ulogu u odravanju strukturne Ustanovljeno je da poveana ekspozicija UV zracima i
barijere koe, dok njegov nedostatak remeenjem ove toploti deluju protektivno na pojavu ekcema, nasuprot
strukture olakava penetraciju haptena i proteina (13, smanjenoj ekspoziciji UV zracima i poveanoj vlanosti
14). Ceramid je lipid vaan za zadravanje vode u vazduha (13, 14). Kiseli pH koe doprinosi barijernoj
kornealnom sloju epiderma. funkciji, jer ima antibakterijsko dejstvo i ulogu u
Kod pacijenata sa AD, u odnosu na zdrave osobe, deskvamaciji. Pokazano je da je kod pacijenata sa AD
identifikovano je znaajno smanjenje koliine ceramida pH itave koe povean, to dovodi do egzacerbacije
u lezijama, ali i u neizmenjenoj koi. Dokazano je da bolesti, a najei faktori koji dovode do remeenja pH

Unangemeldet
koe su deterdenti i sapuni. Time se remeti sadraj lipida istraivanja koja bi ponudila nove i preciznije odgovore
na povrini koe, pojaava dejstvo proteaza i istanjuje na mnoga, jo uvek nedovoljno razjanjena pitanja.
kornealni sloj epiderma (13, 14). Veoma je sloena
interakcija ranije navedenih genetskih faktora, imunskih Dijagnostiki kriterijumi za atopijski dermatitis
faktora i faktora sredine u etiopatogenezi AD i, uz brojna Evropska radna grupa za atopijski dermatitis (engl.
aktuelna saznanja, predstavlja veliki izazov za budua Europan Task Force on Atopic Dermatitis) definisala
Tabela 1. Dijagnostiki kriterijumi za atopijski dermatitis (15)
Major (tri od etiri) Minor (najmanje tri)
- Pruritus - Pozitivni prik kutani testovi (I tip preosetljivosti)

- Poveana ukupna koncentracija IgE u serumu
- Dermatitis koji zahvata fleksorne povrine - Pojava bolesti u najranijem detinjstvu
kod dece starije od dve godine i odraslih ili lice (kod 90% pre pete godine)
u prvoj godini - Suvoa koe
- Bledilo i/ili eritem lica
- Pityriasis alba
- Hronini ili hronino-recidivirajui tok
- Ihtioza
bolesti
- Tamni podonjaci
- Deni-Morganovi (Dennie-Morgan)
- Lina i porodina anamneza o atopiji
infraorbitalni nabori
- Hiperlinearnost dlanova
- Keratosis pilaris
- Heilitis
- Ekcem aka i stopala
- Ekcem areola dojki
- Svrab prilikom znojenja
- Nepodnoenje vune
- Beli dermografizam
- Perifolikularna akcentuacija
- Nabori prednje strane vrata
- Supkapsularna katarakta i keratokonus
- Sklonost bakterijskim i virusnim infekcijama
koe (S. aureus, HSV)
- Smanjen elijski posredovan imunski odgovor
- Pogoranje promena na koi pod uticajem
emocionalnih faktora, faktora sredine i iritanasa
- Preosetljivost na hranu, naroito kod dece
mlae od dve godine

Unangemeldet
S. Popadi et al.
je atopiju kao porodinu sklonost ka razvoju Th2 Lokalna terapija i nega koe
imunskog odgovora na uobiajene antigene okoline sa Emolijentna terapija i nega koe
razvojem tipinih bolesti atopijskog dermatitisa, astme, Leenje AD zahteva efikasnu kontrolu akutnih
i/ili alergijskog rinitisa. Dijagnoza, atopijskog dermatitisa simptoma i znakova bolesti, obnavljanje funkcije
postavlja se pre svega na osnovu anamnestikih barijere koe i izbegavanje faktora sredine koji pokreu
podataka i karakteristine klinike slike, a proteklih i pogoravaju bolest. Pojedina sredstva za hidriranje
decenija razvijani su razliiti dijagnostiki kriterijumi koe poboljavaju barijernu funkciju koe i smanjuju
ija je pouzdanost razliita. Dijagnostiki kriterijumi osetljivost koe na iritanse (21, 22).
su neophodni, pre svega, u epidemiolokim i klinikim
studijama koje moraju imati precizno definisane Pranje i kupanje
kriterijume za ukljuenje pacijenata (1, 15, 16). Suvoa koe je vie izraena tokom hladnih meseci zbog
Dijagnostiki kriterijumi za atopijski dermatitis suvog toplog vazduha i niske vlanosti u stanovima.
veinom ukljuuju klinike znake i delom rezultate Kupanje svakog dana se smatra jednim od najboljih
alergolokih i laboratorijskih testiranja kojima se naina hidriranja koe. Koa se mora prati temeljno, ali
dokazuje atopija. Istorijski najpoznatiji i najvie neno i paljivo, kako bi se uklonili skvama i kruste sa
korieni u svakodnevnoj klinikoj praksi su povrine, iritansi i alregeni i obezbedila mogunost za
kriterijumi Hanifina i Rajke Tabela 1 (15). Prema hidriranje koe. Voda treba da bude topla, a optimalna
ovim kriterijumima, za dijagnozu je potrebno tri od duina boravka u vodi je do 20 minuta. Kratkotrajnim
etiri major kriterijuma i tri minor kriterijuma. Ovi kupanjem (samo 5 min), uz upotrebu uljane kupke
dijagnostiki kriterijumi validirani su u dve studije u (poslednja 2 minuta tuiranja), moe se izbei dehidracija
kojima je njihova dijagnostika senzitivnost bila 87,9% epiderma (8, 23). Sapuni, amponi i gelovi za tuiranje
i 96%, a specifinost 77,6% i 93% (16). koji stvaraju penu treba da se izbegavaju jer iritiraju i
Drugi, manje korieni kriterijumi su britanske isuuju kou. Kod dece u prepubertetskom sebumu se
radne grupe (engl. UK Working Party) kriterijumi koji ne produkuje, tako da je potrebna minimalna koliina
podrazumevaju da se atopijski dermatitis dijagnostikuje ampona. Uljane kupke mogu imati efekat hidriranja,
na osnovu prisustva promena na koi u poslednjih ali su dokazi o njihovoj efikasnosti nedovoljni. Na
12 meseci i jo najmanje 3 od sledeih kriterijuma: tritu su dostupna neutralna ili sredstva za pranje sa
pojava promena na koi pre druge godine ivota (ne fiziolokim pH koja su hipoalergogena i bez mirisa, ali
primenjuje se kod dece mlae od 4 godine), anamneza se kao zamena za sapun mogu primenjivati i kremovi i
o zahvatanju fleksornih povrina ili prisustvo ovakvih losioni koji hidriraju tako to e se naneti na kou pre
promena na pregledu, suvoa koe i lina anamneza o kupanja ili tuiranja i umasirati u kou tokom kupanja
drugim atopijskim bolestima (ili porodina anamneza (19, 24). Poeljno je nanoenje emolijenasa odmah
za decu mlau od 4 godine) (17). Ovi kriterijumi su nakon kupanja i brisanja koe, dok je koa jo uvek
validirani u najveem broju studija, a specifinost je vlana. Najbolji nain za odravanje vlanosti koe kod
varirala 10100%, a senzitivnost 8999%. pacijenata sa AD je nanoenje debljeg sloja emolijensa
Takoe, Amerika akademija za dermatologiju tokom prva 3 minuta posle kupanja, pre nego to doe
predloila je svoje kriterijume koji su podeljeni u do isuivanja koe (8, 22, 23).
obavezne, znaajne i udruene kriterijume u odnosu
na njihovu uestalost i dijagnostiku vanost (18). Emolijentna terapija
Nekoliko drugih dijagnostikih kriterijuma takoe Pravilna upotreba emolijenasa za hidriranje je kljuna
je objavljeno, ali nisu nali primenu u svakodnevnoj u leenju pacijenata sa AD. Emolijensi predstavljaju
praksi (19, 20). osnovu terapije odravanja. Dostupni su u razliitim
Nedavnom analizom i sistematskim pregledom oblicima. Losioni su retke konzistencije sa visokim
studija koje su validirale razliite dijagnostike kriterijume sadrajem vode, korisni su za regije obrasle dlakom i
utvreno je da je metodologija ovih validacija veoma za ekcem sa vlaenjem, ali su neefikasni kod izraene
razliita to onemoguava konane zakljuke (16). kseroze. Kremovi (emulzije vode i ulja) najee se

Unangemeldet
primenjuju jer se lako nanose, ne ostavljaju sjajan trag, Poremeaj ravnotee epidermalne mikroflore
ali su masniji od losiona. Pojedina ulja se zgunjavaju verovatno igra jednu od kljunih uloga u egzacerbaciji
u hladnijim klimatskim uslovima, ali postaju rea AD. Nanoenje novih tipova emolijenasa koji sadre
na temperaturi tela. Masti su guste, mogu se naneti ekstrakt nepatogenih gram-negativnih bakterija dva
u debelom sloju i pogodne su za veoma suv ekcem. puta dnevno titi kou od proliferacije patogenog
Meutim, manje su kozmetiki prihvatljive, mogu da stafilokoka i omoguava ouvanje raznolikosti
izazovu pretopljavanje i folikulitis i mogu da ostavljaju mikroflore (26, 27).
mrlje na odei i posteljini. Aditivi mogu da izazovu
iritaciju ili alergijske reakcije, a najbolje je da emolijensi Lokalna antiinflamatorna terapija
koji se koriste za atopiare budu bez parfema (24). Efikasna lokalna terapija se oslanja na tri osnovna
Pacijente treba podsticati da probaju razliite principa: dovoljna jaina, odgovarajue doziranje
emolijense, ali i preporuiti odgovarajue u zavisnosti i pravilna primena. Topikalnu terapiju uvek treba
od njihovog tipa koe, naina ivota i klimatskih aplikovati na hidriranu kou, posebno kada se
uslova u kojima ive. Hidriranje koe se obino postie primenjuju antiinflamatorni preparati u obliku masti.
nanoenjem preparata za hidriranje najmanje dva puta Topikalni kortikosteroidi (TKS) i imunomodulatori
dnevno. Pacijenti mogu primenjivati emolijense na bazi predstavljaju terapiju prvog reda za recidiv bolesti, dok
krema tokom dana i toplog vremena, a masti tokom se dugorona terapija bazira na primeni emolijenasa
noi i hladnog vremena. esto se ne upotrebljava koji poboljavaju vlanost koe, odravaju integritet
dovoljna i potrebna koliina emolijentnog preparata. epidermalne barijere, smanjuju intenzitet pruritusa
Kod odraslih pacijenata sa generalizovanim ekcemom i spreavaju novi recidiv (28). Pacijenti sa akutnim
potrebno je priblino 600 g emolijensa nedeljno, a kod ekcemom sa vlaenjem i erodovanim lezijama, posebno
dece 250 g nedeljno. U toku hladnijih meseci u godini, deca, ponekad ne toleriu standardnu lokalnu terapiju,
emolijense je potrebno primenjivati vie puta dnevno, tako da se mogu prvo tretirati vlanim oblogama (engl.
a najvanija je primena na vlanu kou, posle kupanja. wet wraps) dok se vlaenje ne zaustavi. Vlane obloge
Treba da se nanose na celu kou, ne samo na zahvaene su veoma efikasne kod akutnog ekcema i poboljavaju
zone, i da se utrljaju u kou u smeru rasta dlake kako bi toleranciju (29). I bez vlanih obloga, topikalna terapija
se izbegao nastanak folikulitisa (19, 24). zahteva dosta vremena: pacijenti treba da planiraju 30
Upotreba emolijenasa je iroko preporuena minuta za jednu aplikaciju lokalne terapije. Kako bi
za leenje AD, posebno izmeu recidiva. Potrebno je se postigao pozitivan efekat, jedan dobro sproveden
prvo primeniti diferentno terapijsko sredstvo na lezije, tretman dnevno je obino dovoljan, osim kod akutnog
a tek kasnije, na celu povrinu koe, emolijentni krem ekcema sa vlaenjem koji zahteva nekoliko dana sa
(8). Ako se emolijensi nanose posle primene lokalnih eim nanoenjem lokalne terapije (8).
kortikosteroida, savetuje se da proe 1520 minuta od Uobiajeno se antiinflamatorna lokalna terapija
aplikacije leka, a ukoliko se primenjuju posle topikalnih nanosi samo na kou sa promenama, a kada se vidljive
kalcineurinskih inhibitora, savetuje se da proe promene izgube, aplikovanje se postepeno proreuje.
30-ak minuta od primene leka. Redovna upotreba Ovaj tradicionalni, reaktivni pristup se poslednjih
emolijenasa ima kratkorone i dugorone steroid sparing godina zamenjuje proaktivnim konceptom leenja,
(uteda kortikosteroida) efekte kod pacijenata sa blagim koji se definie kao kombinacija unapred definisane,
do umereno tekim AD. Da bi se postigla remisija, dugotrajne antiinflamatorne terapije malim dozama na
prvo je potrebna primena lokalnih kortikosteroida prethodno zahvaenim podrujima koe u kombinaciji
(kratkotrajna terapija). Odravanje stabilne remisije sa slobodnom upotrebom emolijenasa na celo telo i
(dugorona terapija odravanja) moe se kod jednog unapred odreenim rasporedom kontrolnih klinikih
broja pacijenata postii primenom emolijenasa dva puta pregleda (30). Proaktivni postupak leenja, koji se
nedeljno ili ee, nakon postizanja remisije topikalnim sprovodi obino dva puta nedeljno, poinje nakon
kortikopreparatima. ak nanoenje emolijensa jedan uspenog tretiranja svih lezija intenzivnom terapijom,
put nedeljno moe biti korisno za poboljanje blagih do obino aplikovanom dva puta dnevno, pored redovne
umereno tekih lokalizovanih recidiva AD (25). emolijentne terapije prethodno neizmenjene koe (8).

Unangemeldet
S. Popadi et al.
Topikalni kortikosteroidi i trebalo bi da bude dovoljna za pokrivanje povrine

Topikalni kortikosteroidi (TKS) najvaniji su koja odgovara povrini oba dlana (8, 24).
antiinflamatorni lekovi koji se koriste u terapiji AD,
posebno u akutnoj fazi. Preporuuju se pacijentima Topikalni kalcineurinski inhibitori
sa AD kod kojih pravilna nega i upotreba emolijenasa Topikalni kalcineurinski infibitori (TKI) su
nije dovela do pozitivnog odgovora. Pri izboru imunosupresivni agensi koji inhibiraju kalcineurin
TKS preparata u obzir treba uzeti godine pacijenta, u koi, blokirajui ranu T-elijsku aktivaciju i
zahvaenu regiju, stepen kseroze koe, elje pacijenta i oslobaanje citokina. Oni su efikasni u redukovanju
cenu preparata. Topikalni kortikosteroidi predstavljaju inflamacije kod AD. U Velikoj Britaniji, takrolimus
terapiju prvog reda koja se primenjuje na inflamiranu 0,03% mast i pimekrolimus 1% krem su odobreni za
kou u zavisnosti od potrebe (pruritus, poremeaj sna, upotrebu kod dece od dve do 15 godina, a takrolimus
nove promene) (8, 18, 22). Preporuuje se aplikacija 0,1% mast kod dece starije od 16 godina (28, 32).
TKS dva puta dnevno, mada i jednodnevna primena U Evropskoj uniji oba TKI su odobrena od druge
moe biti dovoljna (25). Nije dokazana vea efikasnost godine ivota (8). U Srbiji, takrolimus 0,03% mast i
ukoliko se aplikuju ee od dva puta dnevno. pimekrolimus 1% krem su odobreni za decu stariju
Apsorpcija je bolja ukoliko je koa hidrirana. Najbolji od dve godine. TKI se preporuuju za kratkotrajnu,
trenutak aplikovanja TKS je posle kupanja, 1520 dugoronu i terapiju odravanja AD kod odraslih
minuta pre nanoenja emolijensa. i dece. Oni su poeljni u situacijama kada su
Svrab je glavni simptom koji slui za procenu kortikosteroidi kontraindikovani, na osetljivim
odgovora na terapiju. Sniavanje doziranja TKS ne bi regijama, zonama sa atrofijom usled primene
trebalo zapoeti pre nestanka pruritusa i treba da bude steroida i ukoliko bi bila potrebna dugotrajna
postepeno kako bi se izbegao rebound fenomen. Strategija kontinuirana upotreba TKS. Posebno su korisni za
sniavanja doze sastoji se od svakodnevne upotrebe regije gde je koa ve tanka kao to su lice i pregibi.
slabije potentnih kortikosteroida ili nastavka primene TKI se preporuuju kao steroid-sparing agensi. Kod
potentnijih TKS, uz smanjivanje uestalosti primene pacijenata mlaih od dve godine sa blagim do tekim
(intermitentni reim) (8). Proaktivna, intermitentna oblicima AD, moe se preporuiti tzv. off-label
upotreba TKS se preporuuje na podrujima gde su (zvanino neodobrena za ovaj uzrast) primena TKI.
recidivi esti (18, 22). Treba razmotriti mogunost Proaktivna, intermitentna upotreba TKI takoe se
razvoja neeljenih efekata. Potrebno je praenje u preporuuje na podrujima gde su recidivi najei
smislu nastanka neeljenih efekata tokom dugotrajne (18, 22). Proaktivna terapija pomou takrolimus
primene potentnih TKS. Kod pacijenata sa AD blage masti aplikovane dva puta nedeljno sigurna je i
aktivnosti, mala koliina TKS primenjena dva do tri efikasna do godinu dana trajanja, za redukciju
puta nedeljno (meseno 15 g kod beba, 30 g kod dece, broja relapsa i poboljanje kvaliteta ivota odraslih
6090 g kod adolescenata i odraslih), uz odgovarajuu pacijenata i dece sa AD (33).
primenu emolijenasa, obino omoguava dobro Potrebno je uzeti u obzir mogunost nastanka
odravanje remisije sa SCORAD indeksom ispod neeljenih efekata, ukljuujui oseaj peckanja i
1520. Ove mesene koliine, ak i potentnih TKS, svraba, i o njima informisati pacijenta. Najee uoen
obino nemaju negativne sistemske ili lokalne efekte sporedni efekat je prolazna toplotna senzacija na
(8). Kombinacija TKS istovremeno sa topikalnim mestu aplikacije tokom prvih dana primene (34, 35).
kalcineurinskim inhibitorima najverovatnije nema Poinje obino pet minuta nakon aplikacije, moe
koristan efekat u leenju AD (31). Koliina topikalnog trajati do jedan sat, ali se intenzitet i duina trajanja
antiinflamatornog preparata koja se nanosi treba obino smanjuju do potpunog nestanka tokom jedne
da bude odreena pravilom koje koristi vrh-prsta nedelje (36). Pacijentima koji primenjuju TKI se
jedinicu (engl. finger-tip unit, FTU). FTU je koliina preporuuje efikasna zatita od sunca. Nema znaajne
masti koja se istisne iz tube pomou mlaznice prenika sistemske apsorpcije TKI. TKI se primenjuju kod dece
5 mm i meri se od distalnog interfalangealnog zgloba due od 15 godina i nema dokaza o poveanom broju
do vrha kaiprsta. Jedna FTU odgovara priblino 0,5g maligniteta (24).

Unangemeldet
Topikalna antipruriginozna terapija antiinflamatorni inhibitor PDE4. Inhibicijom PDE4

Postoji mali broj specifinih i efikasnih anti- i poveanjem nivoa cAMP, krisaborol kontrolie
pruriginoznih sredstava za svrab kod ekcema (37). inflamaciju. Kada dospe u sistemsku cirkulaciju
TKS se zbog svog antipruriginoznog dejstva mogu posle topikalne aplikacije, metabolie se u inaktivne
primenjivati u inicijalnoj fazi egzacerbacije AD. metabolite. Ovo ograniava sistemsko prisustvo
Takoe, TKI znaajno smanjuju pruritus kod AD ve krisaborola i sistemsku PDE4 inhibiciju. Krisaborol
posle prvih nekoliko dana terapije i kod odraslih i kod 2% mast se uglavnom dobro tolerie i popravlja indeks
dece. teine AD, pruritus i sve druge znake i simptome AD.
Dve velike randomizirane kontrolisane klinike studije
Specifina topikalna antipruriginozna terapija (faza 3) koje su procenjivale efikasnost i bezbednost
Topikalni anestetici (benzokain, lidokain, polidokanol, krisaborol 2% masti kod dece, adolescenata i odraslih
kombinacija prilokaina i lidokaina) kratkotrajno sa blagim i umerenim AD su nedavno zavrene
mogu smanjiti oseaj pruritusa kod AD (8). Agonisti pozitivnim ishodom (4447).
kanabinoidnih receptora (N-palmitoiletanolamin, Tofacitinib je inhibitor malog molekula Janus
aplikovan dva puta dnevno) mogu uticati na kinaze (JAK) koji utie na interleukin (IL)-4, IL-5 i
smanjenje pruritusa i bola (38). Kapsaicin je prirodni IL-31 signalne puteve, menjajui imunski odgovor
alkaloid koji svoje funkcije ostvaruje preko kapsaicin- koji dovodi do inflamacije. Tofacitinib 2% mast,
specifinih receptora, lokalizovanih na slobodnim aplikovana dva puta dnevno tokom etiri nedelje,
nervnim zavrecima. Postoje preliminarni dokazi o pokazuje znaajnu efikasnost i bezbednost/lokalnu
pozitivnom uinku kapsaicina kod pruritusa kod podnoljivost u ranoj fazi AD. JAK inhibicija, ostvarena
AD (39). Topikalni doksepin (5% krem) ispoljava preko topikalnog dejstva, predstavlja potencijalno
korisne efekte u smanjenju pruritusa kod AD (40). obeavajui terapijski princip za AD (48).
Meutim, ovaj preparat nije registrovan i nije u
upotrebi u evropskim zemljama zbog poveanog rizika Opta terapija atopijskog dermatitisa
od kontaktne preosetljivosti. Topikalni stabilizator S obzirom da se radi o hroninom inflamatornom
mastocita natrijum-kromoglikat i inhibitori oboljenju, primena opte kortikosteroidne terapije
degranulacije mastocita smanjuju SCORAD indeks nije opravdana zbog kratkotrajnih i tranzijentnih
(41). Drugi novi lokalni preparati ukljuuju i tiolski pozitivnih efekata i potencijalnih neeljenih efekata.
derivat N-acetilcistein, ali do sada ne postoje ubedljivi U fazama pogoranja opravdana je upotreba
dokazi o efikasnosti kod AD (42). U sadanjem peroralnih H1 antihistaminika (zbog svraba), kao i
momentu nema dovoljno dokaza randomiziranih cefalosporina ili makrolida per os (u sluaju bakterijske
klinikih studija koji bi podrali upotrebu ovih infekcije). Kod tekih, generalizovanih i rezistentnih
preparata u terapiji pruritusa kod AD. Nijedan od ovih formi AD, savetuje se i terapija ciklosporinom per
preparata nije registrovan u Evropi i ne preporuuje os, a posle druge godine ivota u terapiju je mogue
se njihova rutinska klinika upotreba kao pomona uvesti i metotreksat.
antipruriginozna terapija kod AD (8). Antihistaminici. H-1 antihistaminici za
sistemsku primenu su bezbedni lekovi i tokom due
Drugi antiinflamatorni agensi primene. Iako postoje miljenja da nesedirajui
Razvoj specifine antiinflamatorne terapije koja je antihistaminici nemaju adekvatan uticaj na smanjenje
jednostavna za upotrebu i deluje na pruritus moe pruritusa kod obolelih od AD, savremeni terapijski
obezbediti kliniki znaajan napredak u leenju protokoli i naa iskustva ukazuju da sistemska terapija
pacijenata sa AD. Veina novih terapijskih preparata se antihistaminicima kod znatnog broja pacijenata
bazira na inhibiciji fosfodiesteraze 4 (PDE4), enzima umanjuje pruritus, poboljava lokalni status na koi i
iji je nivo povien kod inflamatornih poremeaja kao pozitivno utie na kvalitet ivota obolelih od AD.
to je AD (43). H1 antihistaminici, blokadom H1 receptora
Krisaborol 2% mast (ranije poznat kao dovode do blokade odgovora posredovanog
AN2728) je benzoksaborol, nesteroidni topikalni aktivacijom H1 receptora i na taj nain inhibiraju

Unangemeldet
S. Popadi et al.
oslobaanje medijatora iz mast-elija i bazofila. lekom izbora, dok azitromicin moe da se ordinira
Supresija inflamatornog odgovora postie se pacijentima preosetljivim na peniciline i cefalosporine.
smanjenjem prezentacije antigena i hemotakse, Antimikotici. Pored znaajne uloge bakterijskih
smanjenom ekspresijom elijskih adhezivnih molekula infekcija u pokretanju inflamatorne kaskade i pogor-
i smanjenjem nivoa proinflamatornih citokina (49). anja AD, gljivine infekcije takoe mogu da budu
Oralni antihistaminici ublaavaju pruritus u AD. udruene sa razvojem i odravanjem inflamacije kod
Sedativni antihistaminici pored navedenog olakavaju obolelih od AD. Antimikotici se savetuju kod tzv.
spavanje tokom noi koje je znaajno poremeeno head and neck varijante AD koja je esto udruena sa
zbog pruritusa (49). Antihistaminici se koriste jednom superinfekcijom gljivicom Malassezia sympodialis (52).
ili vie puta dnevno, prema preporuci proizvoaa. Opta terapija ketokonazolom ili itrakonazolom i
Hloropiramin, pored antipruriginoznog, ispoljava lokalna terapija ciklopiroksolaminom ili imidazolskim
i lokalno anestetiko i vazokonstriktorno dejstvo kao topikalnim antimikoticima (mikonazol, klotrimazol),
i centralno sedativno dejstvo. Kontraindikovana je tokom 714 dana, poboljava nalaz, odnosno
primena kod trudnica, novoroenadi i nedonoadi umanjuje inflamaciju kod pacijenata kod kojih su
kao i kod ena u periodu laktacije s obzirom da se preteno zahvaeni glava i vrat (53). Drugi sistemski
izluuje i putem mleka. Kod dece se primena ovog imidazolski preparati (flukonazol) takoe se sa
leka savetuje samo u sluaju tekih alergijskih reakcija. uspehom koriste kod ove varijante AD. Po supresiji
Ne savetujemo ga u terapiji AD u pedijatrijskom (super)infekcije gljivicama iz roda Malassezia,
uzrastu. Kod odraslih pacijenata treba biti posebno potrebno je nastaviti sa lokalnom (eventualno i
oprezan ukoliko postoji poveana osetljivost na sistemskom) antiinflamatornom terapijom, u skladu
sedativne efekte antihistaminika i komorbiditeti kako sa klinikim nalazom.
to su epilepsija, hipertiroidizam i dr. Primenjuju se Antivirusni lekovi. Virusne infekcije, pre svega
13 ampule tokom 24 h kao duboka intramuskularna molluscum contagiosum i infekcija Herpes simpex
ili spora intravenska injekcija. virusom lake se diseminuju kod obolelih od AD.
Noviji nesedativni antihistaminici (loratadin, Eczema herpeticum se praktino javlja samo kod
desloratadin, cetirizin, levocetirizin i dr.) nalaze se obolelih od AD i moe da bude ivotno ugroavajua
u formi tableta i oralnih rastvora, komforni su i infekcija, posebno kod pacijenata u pedijatrijskom
bezbedni za dugotrajnu primenu. Prema preporuci uzrastu. Terapija izbora kod molluscum contagioszum
proizvoaa, koriste se u jednoj dozi (1 x 1 tbl/dn), je primena tenog azota i kiretiranje promena, dok je
meutim, u dermatologiji su opravdane i primene sistemski dat aciklovir lek izbora za eczema herpeticum
do etiri puta vee doze. Desloratadin oralni rastvor (10).
moe da se primenjuje od estog meseca ivota Fototerapija. Tokom sunanih meseci, AD se
dok se upotreba levocetirizina savetuje od druge poboljava kod veine pacijenata. Arteficijalni UV
godine ivota. Pored dejstva na H1 receptore, oralni zraci (UVA i UVB fototerapija) imaju znaajnu ulogu
antihistaminici ispoljavaju i antiinflamatorna dejstava u leenju obolelih od AD, u naim krajevima posebno
tako da viestruko utiu na poboljanje znakova i tokom perioda kasne jeseni i zime. Ustanovljeno je da
simptoma AD. UV zraci povoljno utiu na senzornu inervaciju koe
Antibiotici. Antibiotici (cefalosporini i (54), indukuju apoptozu u elijama inflamatornog
makrolidi) imaju znaajno mesto u optoj terapiji infiltrata i smanjuju produkciju citokina koji
AD, u fazama pogoranja. Pored toga to naruena doprinose fazama pogoranja (55), poboljavaju
funkcija barijere epiderma kod pacijenata sa AD regeneriu barijernu funkciju koe (56) i drugo.
olakava nastanak i razvoj infekcije, pruritus i eanje Trenutno su dostupni sledei vidovi lampi:
doprinose diseminaciji bakterije Staphylococcus aureus Broadband UV (UVA + UVB = 290400 nm),
na inflamirane ali i na i neinflamirane delove koe. Sam Broadband ultraviolet B (BB-UVB = 280-315 nm),
S. aureus superantigenskom stimulacijom doprinosti Narrow-band UVB (nbUVB = peak: 311313 nm),
razvoju i odravanju inflamacije kod pacijenata sa AD UVA1 (340400 nm).
(50, 51). U fazama pogoranja, cefaleksin smatramo Fototerapija se najee uvodi ukoliko se ne

Unangemeldet
postiu zadovoljavajui efekti primenom optimalne kod odraslih pacijenata iznosi 0,2 mg/kg telesne mase/
lokalne terapije i odlina je kao terapija odravanja. jedanput nedeljno. MTX se ordinira u jednoj dozi,
Retko se koristi kao monoterapija u fazama pogoranja. per os ili supkutano. Laboratorijske analize (KKS,
PUVA terapija se ne savetuje kod pacijenata mlaih kreatinin, hepatogram, pregled urina) rade se jednom
od 12 godina. Generalno, zavisno od izgleda kabine u nedeljno tokom prvog meseca, zatim na svake dve
kojoj se nalaze UV lampe i saradnje samog pacijenta, nedelje u drugom mesecu, a kasnije jednom meseno
individualno se procenjuje mogunost zapoinjanja ili na dva meseca. Savetuje se postupno sniavanje
UVB fototerapije kod mlaih pacijenata. Retko je doze MTX po postizanju stabilnog znaajnog
primena ovog vida terapije, uz asistenciju medicinskih poboljanja klinike slike ili remisije. Po postizanju
radnika ili roditelja (ukoliko u kabini za UVB remisije, savetuje se primena niih doza MTX (510
fototerapiju ima prostora za dete i odraslu osobu), mg) tokom nekoliko meseci. Kod odraslih pacijenata,
mogua pre pete-este godine ivota. Tokom sunanih neophodna je kontracepcija pre zapoinjanja terapije,
meseci, savetuje se kontrolisana fotoekspozicija. tokom terapije i est meseci po obustavljanju terapije.
Ciklosporin. Ciklosporin ostvaruje dejstvo Folna kiselina, 5 mg, primenjuje u jednoj dozi, 48 h
spreavanjem produkcije IL-2. Rezultati metaanalize nakon ordiniranog MTX.
(57) potvrdili su efikasnost ciklosporina u terapiji Azatioprin. Azatioprin se koristi u Velikoj
AD. Ciklosporin dovodi do klinikog poboljanja, Britaniji i SAD u leenju adultnih formi AD.
poboljanja sna i umanjuje potrebu za lokalnom Savetuje se doza od 2,5 mg/kg telesne mase/dnevno,
kortikosteroidnom terapijom. Po iskljuivanju posle sedamnaeste godine ivota (58). Rutinski se pre
ciklosporina mogui su brzi recidivi. Pre uvoenja uvoenja azatioprina kontroliu KKS, biohemijski
ciklosporina u terapiju neophodna je kontrola parametri krvi i pregled urina. Kontrola ovih
arterijske tenzije, nivoa kreatinina u serumu parametara neophodna je i tokom terapije. Neophodna
kao i osnovne biohemijske analize krvi i urina. je kontracepcija tokom terapije azatioprinom.
Ciklosporin se primenjuje 2,55 mg/kg telesne mase Bioloki lekovi. Vei broj biolokih lekova
dnevno, podeljeno u dve doze (na 12 h). Savetuje (ustekinumab, fezakinumab, apremilast, dupilumab,
se zapoinjanje terapije niim dozama ciklosporina, OC000459) primenjivan je u leenju AD, sa
a zatim, uz kontrolu bubrene funkcije, nivoa rezultatima koji obeavaju, meutim, za sada se nigde
ciklosporina u serumu i kontrolu arterijske tenzije, u svetu ovi preparati jo uvek ne koriste u rutinskoj
podizanje doze do 5 mg/kg. Nije opravdano ordinirati terapiji AD (59, 60). Potreban je vei broj studija i
vie od 5 mg/kg zbog povienog rizika od razvoja due praenje pacijenata da bi se pouzdano procenili
nefrotoksinih efekata. efikasnost i bezbednost primene ovih preparata u
Metotreksat. Metotreksat (MTX) takoe se sa leenju AD.
uspehom koristi u leenju teih formi AD. Primena
metotreksata se ne preporuuje pre druge godine Opte mere
ivota. Pre uvoenja MTX u terapiju kontrolie se Odravanje higijene
KKS, kreatinin, AST, ALT, kao i nalaz urina. Inicijalno Kou treba temeljno oistiti, ali neno i paljivo,
je znaajno uraditi virusoloke analize (HBsAg i anti- kako bi se uklonile kruste u sluaju bakterijske
HCV ukupni). Probna doza MTX ordinira se 57 dana superinfekcije. Kupanje treba da traje oko 510
pre ordiniranja prve, pune terapijske doze leka. Kod minuta, pri temperaturi vode od 27 do 30 C.
pedijatrijskih pacijenata, do 4-5. godine ivota probna Savetuje se nanoenje uljanih kupki poslednja 2
doza moe da iznosi 1,25 mg (1/2 tbl) dok kod starijih minuta kupanja, kako bi se izbegla dehidracija
i odraslih pacijenata probna doza iznosi 2,5 mg (1 x epiderma. Dodavanje natrijum-hipohlorita u kadu
1 tbl). Posle 57 dana kontroliu se KKS, hepatogram s vodom moe biti koristno, s obzirom na njegovo
i sediment urina i, ukoliko su nalazi uredni, smatra antibakterijsko dejstvo (8).
se da se moe zapoeti sa terapijskim dozama MTX. Kupanje u slanoj vodi moe pogodovati pa-
Inicijalna doza kod pedijatrijskih pacijenata iznosi cijentima sa impetiginizovanim lezijama ili prisutnom
0,20,4 mg/kg telesne mase jedanput nedeljno, dok ihtiozom. Pokazano je da je tvrdoca vode u vezi

Unangemeldet
S. Popadi et al.
s povecanom prevalencijom AD, tj. da tvrda voda Mnogi pacijenti imaju problem s luenjem i
povecava rizik za razvoj atopijskog dermatitisa kod dece retencijom znoja tokom letnjih meseci, to dovodi
(61). do povecanja svraba. Ipak, decu s atopijskim
Emolijensi se prvenstveno nanose odmah posle dermatitisom treba ohrabriti da se aktivno bave
kupanja ili tuiranja, dok je koa jo uvek vlana. sportom. Plivanje moe biti odlian sport za decu sa
Noviji radovi ukazuju da ograniavanje koricenja atopijskim dermatitisom, ukoliko se dobro tolerie
sapuna i primena emolijenata najmanje jednom izlaganje hlorisanoj vodi. Pre plivanja se savetuje
dnevno moe smanjiti rizik od nastanka atopijskog aplikacija emolijenata na celu povrinu koe i odmah
dermatitisa (62). posle plivanja kupanje uljanom kupkom uz dodatnu
aplikaciju emolijenata. Boravak u klimatizovanim
Odevanje prostorijama tokom letnjih meseci znaajno moe
Noenje mekane pamune odece i izbegavanje smanjiti oseaj svraba.
iritirajuih tkanina u kontaktu s koom (pre svega
vune, ali i svile) od sutinskog je znaaja za izbegavanje Ishrana
iritacije koe. Takoe, treba izbegavati okluzivnu odecu Meu alergenima hrane, kravlje mleko, jaja, penica,
koja poveava toplotu koe, a tokom zimskih meseci soja, orasi i kikiriki su najece odgovorni za nastanak
treba izbegavati pretopljavanje dece. Niska vlanost ili pogoranje ekcema u ranom detinjstvu. Dvostruko
tokom zime i grejanje u stanovima povecava suvou slepo, placebo-kontrolisano izlaganje hrani smatra se
koe, tako da se moe savetovati upotreba ovlaivaa zlatnim standardom za dijagnozu alergije na hranu
vazduha. Postoji konsenzus da osobe sa atopijskim (64). U sistematskom pregledu osam randomizovanih,
dermatitisom treba da izbegavaju zanimanja kod kojih kontrolisanih studija (57) koje su prouavale efekat
postoji mogunost oteenja koe ili postoji kontakt s eliminacione dijete kod pacijenata sa atopijskim
iritantnim supstancijama (8). dermatitisom pokazano je da ne postoje ubedljivi dokazi
da je eliminaciona dijeta (npr. jaja i mleko) korisno
Uslovi ivljenja za pacijente sa atopijskim dermatitisom. Meutim,
Brojni faktori i supstancije iz okoline mogu da iritiraju u drugoj studiji pokazano je da je izostavljanje jaja u
osetljivu kou pacijenata sa atopijskim dermatitisom ishrani dovelo do poboljanja atopijskog dermatitisa
i mogu da dovedu do nastanka ili pogoranja kod pacijenata koji su imali klinike simptome posle
ekcema. Oni mogu biti fiziki, kao to su mehaniki prethodnog konzumiranja jaja (65).
iritansi (npr. vuna), hemijski (kiseline, rastvarai, Ne savetuje se da pacijenti sa atopijskim
voda) ili bioloki (mikroorganizmi). Informisanje dermatitisom, kod kojih nije dokazana alergija na
pacijenata i lanova njihovih porodica o znaaju i hranu, sprovode restrikcione dijete (66). Pacijenti
ulozi nespecifinih iritanasa za nastanak ekcema je s umerenim i tekim atopijskim dermatitisom treba
veoma vaan preduslov za uspeno leenje pacijenata s da se pridravaju eliminacione dijete one vrste hrane
atopijskim dermatitisom. koja provocira ranu ili kasnu reakciju na koi koja je
Mnogi pacijenti su vec svesni injenice da pokazana posle sprovedenog kontrolisanog oralnog
kontakt sa ivotinjama moe da dovede do pogoranja provokacionog testa (8).
simptoma na koi. Izloenost majoj dlaci tokom Postoje odreeni podaci da probiotici mogu
detinstva moe poveati rizik od nastanka atopijskog biti korisni i bezbedni u prevenciji atopijskog
dermatitisa, naroito kod dece koja imaju mutaciju dermatitisa, sa smanjenjem rizika za oko 20% (67).
gena za filagrin (8, 63). Nema dokaza da kontakt Meutim, i dalje postoji nejasnoa kada i kome treba
sa psima poveava rizik za nastanak atopijskog dati probiotike (majkama pre roenja deteta pod
dermatitisa (8). rizikom za razvoj AD, deci posle roenja, ili oboje)
Puenje cigareta treba izbegavati u prostorijama i koji specijes i soj bakterija treba dati. Za razliku
gde borave deca s atopijskim dermatitisom, jer to od verovatno pozitivnog preventivnog dejstva, nije
moe dovesti do povecanja iritacije i svraba i moe da pokazana efikasnost probiotika kod pacijenata s ve
poveca sklonost ka kasnijem razvoju astme. razvijenim atopijskim dermatitisom (68).

Unangemeldet
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GUIDELINES Serbian Journal of Dermatology and Venereology 2016; 8 (3): 129-153

National Guidelines for the Treatment of Atopic Dermatitis

2016 The Serbian Association of Dermatovenereologists 129

130 2016 The Serbian Association of Dermatovenereologists

AD. In episodes of AD exacerbation, increased Increases in Streptococcus, Propionibacterium

Major (3 of 4) Minor (at least 3)

- Pruritus - Positive prick allergy tests

2016 The Serbian Association of Dermatovenereologists 131

132 2016 The Serbian Association of Dermatovenereologists

2016 The Serbian Association of Dermatovenereologists 133

Topical corticosteroids Topical calcineurin inhibitors

134 2016 The Serbian Association of Dermatovenereologists

2016 The Serbian Association of Dermatovenereologists 135

136 2016 The Serbian Association of Dermatovenereologists

2016 The Serbian Association of Dermatovenereologists 137

138 2016 The Serbian Association of Dermatovenereologists

2016 The Serbian Association of Dermatovenereologists 139

140 2016 The Serbian Association of Dermatovenereologists

Nacionalni vodi za terapiju atopijskog dermatitisa

2016 The Serbian Association of Dermatovenereologists 141

142 2016 The Serbian Association of Dermatovenereologists

Major (tri od etiri) Minor (najmanje tri)

- Pruritus - Pozitivni prik kutani testovi (I tip preosetljivosti)

2016 The Serbian Association of Dermatovenereologists 143

144 2016 The Serbian Association of Dermatovenereologists

2016 The Serbian Association of Dermatovenereologists 145

Topikalni kortikosteroidi i trebalo bi da bude dovoljna za pokrivanje povrine

146 2016 The Serbian Association of Dermatovenereologists

Topikalna antipruriginozna terapija antiinflamatorni inhibitor PDE4. Inhibicijom PDE4

2016 The Serbian Association of Dermatovenereologists 147

148 2016 The Serbian Association of Dermatovenereologists

2016 The Serbian Association of Dermatovenereologists 149

150 2016 The Serbian Association of Dermatovenereologists

2016 The Serbian Association of Dermatovenereologists 151

152 2016 The Serbian Association of Dermatovenereologists

2016 The Serbian Association of Dermatovenereologists 153

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