Atopický ekzém / dermatitida

Synonyma

• Atopický ekzém
• Prurigo Besnier [6]
• Neurodermatitis atopica [6]
• AD

Historie

• „atopos“ = řecky podivný, nezvyklý
• 1982 Besnier
• Souvislost mezi AD, alergickou rinitidou a astmatem [6]
• Coca a Cooke
• Charakterizaci triády symptomů: ekzém, alergická rinitida a astma = atopie [6]
• 1930 Hill a Sulzberger
• Kritéria pro diagnózu AD
• Koncept této kožní choroby [6]

Epidemiologie

• Převážně kojeneckého a dětského věku
• Světová prevalence AD
• U dětí do 5 let 3 - 5 % [6]
• Vznik do 6. měsíce u 49 - 75 % dětí
• Vznik do 5. roku věku u 80-90 % [6]
• V dospělé populaci 2-10 % [6]
• Celková prevalence AD
• Ve střední Evropě cca 10 %
• Celosvětová 15-30 % [6]
• S mírnou převahou dívek [6]

Prevalence rapidně vzrůstá

• Chov domácích zvířat v bytě
• Dieta typu „fast food“
• Druhů koření, chemických aditiv, barviv [6]
• Pokud by nárůst atopie pokračoval stávajícím tempem, tak se předpokládá, že v roce 2015 bude každý druhý Evropan alergikem.
• současná data ?

ČR 2010

• AD 16 % dětí do 1 roku života
• AD 12 % dětí do 15 let věku
• AD 3 % nad 16 let

Symptomy

• Charakteristická triáda projevů:
• Dermatitida
• Xeróza
• Pruritus
• Klinický obraz
• Velmi variabilní
• Mění se v závislosti na věku pacienta
• 3 klinické formy choroby:
• Kojeneckou
• Dětskou
• Dospělou [6]

Kojenecká - Infants

• Typically erythematous papules and vesicles on the cheeks, forehead, or scalp
• Intensely pruritic
• Velmi plynule navazuje na seboroické dermatitidy
• Obličej s bilaterálním postižením tváří
• Silně svědivé papulky, občas i puchýřky
• Mokvání
• Povrch se pokrývá stroupky a šupinami
• Odsud se nález může šířit na celý obličej, trup a končetiny
• Na vlasaté části hlavy se často objevují mastné šupiny bílé barvy
• „crusta lactea“
• Bývá dáván do souvislosti s přechodem na mléčnou stravu [6]
• Kdy kojenec začíná lézt
• Ložiska ekzému na předloktích, kolenou a na bércích
• V místech stálého, mechanického dráždění [6]
• Často dochází k bakteriální superinfekci a impetiginizaci ložisek [6]
• Průběh onemocnění je nepředvídatelný co do rozsahu a dalšího vývoje
• Může během 2. roku života zcela zhojit
• Plynule přejít do další vývojové fáze

Dětská - 2 years - puberty [3] od 3 do 10 let [6]

• Méně mokvající charakter
• Sklon k lichenifikaci
• Nejčastěji ohybové partie končetin:
• Kubitální a popliteální jamky
• Krk
• Zápěstí
• Nárty
• často i prsty rukou a nohou
• I onychodystrofie [6]
• Kůže je zhrubělá, místy až lichenifikovaná
• S výraznými hlubokými kožními rýhami
• Asteatóza [6]
• Místy až jkao zvrásnělá, např. na očních víčkách
• V akutním stadiu
• červená
• S mnohočetnými exkoriacemi po škrábání [6]
• Kůže obličeje charakteristický vzhled
• Bývá bledá
• Tmavší a zhrubělou kůží očních víček
• Zdvojením záhybu pod očima (tzv. Dennieho-Morganiho infraorbitální řasa) [6]
• Less likely to have the exudative lesions
• More lichenified papules and plaques
• Hands, feet, wrists, ankles, and antecubital and popliteal regions

• Nejčastějšími provokačními faktory tohoto věku
• Vzdušné alergeny, např. prach, roztoči, peří, plísně, zvířecí anebo pylové alergeny
• Stres
• Se školou
• Změnou prostředí dítěte
• S těžkou formou AD, často i s potravinovou alergií
• V předškolním věku
• Ev. i astma či polinóza
• Charakteristický měnlivý průběh
• Exacerbace
• V jarních a podzimních měsících
• Zlepšování
• V létě
• S věkem dochází u většiny pacientů ke zlepšování
• Zvratovým momentem pro průběh AD
• Začátek školní docházky
• Start puberty
• Průběh se zmírňuje nebo nastává dlouhodobá až celoživotní remise až u 75 % případů

Dospělá - Adult

• Flexural folds, the face and neck, the upper arms and back, and the dorsa of the hands, feet, fingers, and toes
• Eruption is characterized by dry, scaling erythematous papules and plaques
• Formation of large lichenified plaques from lesional chronicity
• Obvykle předchází kojenecká a dětská forma choroby či astma
• Nejčastěji ve stejné lokalizaci jako u dětské formy nebo s predilekcí v:
• Obličeji
• Na šíji, horní části hrudníku
• Na ramenou
• Nad velkými klouby končetin
• Na hřbetech rukou
• I kštice
• Výrazným pruritem, šupením, vlasy jsou řídké a suché [6]
• Kůže je více lichenifikovaná a pruritus je intenzívnější
• Nejčastější provokační faktory v dospělém věku jsou:
• Hormonální změny (menses, gravidita) [6]
• Potravinové alergie [6]
• Psychické vlivy [6]

Dieferenciální diagnostika

• Other forms of eczema, especially in adulthood

Combination forms are prevalent with components of

• Atopic
• Contact
• Irritative eczema [4]

Atopic eczema of the hands and feet

• Must be differentiated from
• Psoriasis in the palms and soles
• Tinea [4]
• Scabies
• Must always be considered [4]

Acute Atopic Dermatitis

• Intense erythema of the skin
• Together with exudation or blistering [4]

Chronic lichenified forms of AD

Late-onset AD

• Vzniknout de novo v dospělosti
• Mezi těmito pacienty je část
• Bez prokázané senzibilizace zprostředkované IgE protilátkami
• Negativní rodinnou anamnézu
• žádné další známky atopie
• Průběh AD je mírnější [6]

Recalcitrant cases

• In children genodermatoses
• Netherton syndrome
• Recently described immune dysregulation
• Polyendocrinopathy
• Enteropathy X-linked syndrome [4]
• In both children and adults
• Vitamin deficiencies
• Malignancies
• Cutaneous T cell lymphoma/mycosis fungoides [4]

Larvované nebo frustní formy AD

• Kožní projevy ohraničené na jednu část těla
• Charakter je dosti odlišný od typických projevů AD
• „malé příznaky AD“ - „stigmata AD“

Pityriasis alba

• Neostře ohraničené
• Hypopigmentované skvrny
• S mírným olupováním
• Hlavně na obličeji a na končetinách

Xeróza kůže

• Abnormální suchost kůže
• U 80 až 98 % pacientů s AD

Keratosis pilaris

• Projevem folikulární hyperkeratózy na: [6]
• Zevních plochách paží
• Na hýždích
• Předních plochách stehen
• U dětí i na tvářích [6]
• Drobné papulky barvy kůže folikulárně vázané
• S mírným erytémem okolí
• Bez pruritu

Palmoplantární hyperlinearita

• Zmnoženou kresbu rýh na dlaních a na ploskách

Dennieho-Morganiho rýha

• Zvýrazněnou rýhou pod dolním víčkem
• Symetricky pod oběma očima
• Hlavně u kojenců a dětských pacientů
• Ev. i periorbitální edém, lichenifikace a tmavé kruhy pod očima [6]

Hertoghovo znamení

• Chyběním laterálního okraje obočí

Cheilitida

• Představuje suché, popraskané rty a nebo koutky
• častější u dětí než u dospělých pacientů

Dermatitida bradavek

Dermatitida bříšek prstů rukou (pulpitis sicca)

• Nohou a ušních boltců

Bílý dermografismus

• Paradoxní vazokonstrikční reakce na tlak

Oční komplikace

• Katarakta [6]
• Keratokonus [6]

Rizikové faktory

Hygienická teorie (David Štrachán, 1989)

• Infekce prodělaná v raném dětství by mohla zabránit rozvoji AD
• Další studie však tuto teorii neprokázaly
• Některé infekce (např. spalničky) riziko vzniku AD zvyšují [6]

OA a RA

• A personal or family history of eczema, allergies, hay fever or asthma [2]
• Having attention-deficit/hyperactivity disorder (ADHD) [2]
• Risk factor for persistent AD symptoms is the severity of disease in infancy [4]

Kojení

• Incidence of infantile AD is reduced by breast-feeding for a least 4 months
• Tends to disappear after 3 years of age [4]

Profese

• Health care worker
• Linked to hand dermatitis [2]

Životní prostředí

• Living in urban areas [2]
• Having parents with a high level of education [2]
• Attending child care [2]
• Tobacco smoke exposure in AD is inconclusive
• Exposure to aeroallergens (pets, mites, and pollen) has been clearly shown to increase the risk factors for AD and AD severity

Ftaláty

Ostatní

DnBP, BBzP and DEHP

• Significant associations between non-dietary exposures to DnBP, BBzP and DEHP in the indoor environment and allergic sensitization
• Mass fractions in dust or daily indoor intakes from dust ingestion, inhalation and dermal absorption [17]

Alergeny

• Sensitization to food allergens (cow's milk and hen's eggs) is associated with infantile AD and related to disease severity
• Predictive for persistence of symptoms throughout childhood
• Nejčastějším provokačním faktorem v kojeneckem věku potraviny
• bílkoviny kravského mléka [6]
• Vaječný bílek [6]
• Pšeničná mouka [6]
• Chlorovaná voda [6]
• Nebavlněné, neprodyšné oblečení [6]
• Virové anebo bakteriální infekce [6]

Asociovaná rizika

Allergic rhinitis

Allergic asthma

• AD during the first 2 years of life
• 50% will have asthma during subsequent years [4]
• Severity of AD [4]
• Early sensitization to food [4]
• Increases the risk of asthma and allergic rhinitis [4]
• In selected individuals sensitization to peanut allergen might occur through the skin [4]

Perzistence do dospělosti

• Severity of AD [4]
• Early sensitization to food [4]
• Complex interaction of genetics, environmental exposure, and sensitization [4]

Rasa

• Being African-American [2]

Genetika

• Parental atopy, in particular AD
• Significantly associated with the manifestation and severity of early AD in children [4]
• European study of about 200 families
• Region of highest linkage at human chromosome 3q21 [4]
• Study of 148 nuclear families
• Association with 5 regions, including 1q21, 17q25, 20p, 16q, and 5q31 [4]
• Swedish study of 197 affected sib pairs
• 4 phenotypes, as well as 11 locations, associated with all of the different phenotypes that ranged from severity of AD, specific IgE, and direct diagnosis of AD [4]
• Danish study
• Association with 3 locations within the genome [4]
• Candidate gene studies
• TLR2 Toll-like receptor 2
• IRF2 Interferon regulatory factor 2
• CSF2 Colony-stimulating factor 2
• 3606
• IL4
• IL13
• 111C/T
• IL5
• IL18
• CARD4 (12) Caspase recruitment domain-containing protein 4
• Monocyte differentiation antigen CD14
• IL12B Interleukin-12B
• SPINK5 Serine protease inhibitor
• FCER1B High-affinity IgE receptor, ß-chain
• GSTP1 Glutathione S-transferase
• PHF11 Plant homeodomain zink finger 11 protein
• CMA1 Mast cell chymase
• 1903
• IL4RA Interleukin 4 Receptor chain
• CARD15 Caspase recruitment domain - containing protein 15
• RANTES Regulated on activation
• EOTAXIN
• TGFß1 TGF-ß1
• SCCE Stratum corneum chymotryptic enzyme [4]

Filaggrin (FLG)

• Null mutations
• Associated with severe and early onset of atopic dermatitis [15]
• Increased the prevalence of foot dermatitis and persistent hand dermatitis only in participants with AD [15]
• 20–40% have an innate genetic filaggrin mutation
• Confer a risk for allergen sensitization through the skin
• Increased transepidermal water loss (TEWL)
• Increased surface pH
• Altered expression of antimicrobial peptides [16]

Příčiny

• Defekt kožní bariéry se považuje za primární. [6]
• Mutace genů pro
• Filagrin
• Ivolukrin
• Lorikrin [6]
• Mutace vedou k:
• Poruše maturace keratinocytů
• X integrity kožní bariéry
• Změněný profil spektra ceramidů
• Snížené funkci intercelulárních lipidů [6]
• Vysoká koncentrace kožních serinových proteáz
• Předčasné ztrátě soudržnosti keratinocytů a deskvamaci
• Zvýšená náchylnost ke kolonizaci kmeny Staphylococcus aureus [6]
• Kolonizace S. aureus
• Přispívá ke vzniku, intenzitě a udržování atopického zánětu
• K sensibilizaci [6]
• V nepostižené kůži atopiků
• Reziduální, minimální dermatitida vždy přítomna
• Opodstatňuje význam udržovací léčby [6]
• Porušená bariéra
• Vstupní branou pro vznik senzibilizace
• Vývoj atopického zánětu [6]
• Psychogenní složka
• Stresující životní události často předcházejí počátek exacerbace AD (Kodama et al., 1999, Pikardi et al., 2001) [6]
• Psychická zátěž ovlivňuje AD interakcí centrálního nervového systému a imunitního systému [6]
• Kolísání neurotransmiterů v neuroendokrinním a autonomním systému související se stresem
• Ke změně imunologické reaktivity a rozvoji alergického zánětu [6]
• Mohou ovlivňovat rovnováhu epidermální permeabilní bariéry, což následně vede k zánětu a svědění [6]
• Dospělí pacienti s AD jsou více úzkostní a depresivní ve srovnání s kontrolními skupinami (Ehlers et al., 1995, Hashiro a Okumura, 1997) [6]
• Přícina a následek ? Souvislost s metabolismem MK omega-3 ?

Dry, irritable skin

• Reduces the skin's ability to be an effective barrier

A gene variation

• Affects the skin's barrier function

Immune system dysfunction

Bacteria

• Such as Staphylococcus aureus, on the skin
• Creates a film that blocks sweat glands [2]

Environmental conditions

Histopathology

The skin

• Dry
• Greater irritant skin response
• Sparse perivascular T-cell infiltrate in unaffected AD skin [4]
• Not seen in normal healthy skin [4]

Atopické léze

• Marked infiltration of CD41 activated memory T cells in acute AD
• Antigen-presenting cells -APC (v menším rozsahu i v kůži bez lézí)
• Langerhans cells [LCs]
• Inflammatory dendritic epidermal cells [IDECs]
• Macrophages
• Bear IgE molecules [4]
• Mast cell degranulation can be observed [4]

Chronic AD skin lesions

• Tissue remodeling caused by chronic inflammation
• Thickened plaques with increased skin markings (lichenification)
• Increased collagen deposition in the dermis [4]
• Dry fibrotic papules
• Macrophages dominate the dermal mononuclear cell infiltrate
• Eosinophils also contribute to the inflammatory response
• T cells remain present [4]
• In smaller numbers than seen in acute AD [4]

Cytokines and chemokines

• Local tissue expression of proinflammatory cytokines and chemokines

TNF-alfa and IL-1 from resident cells

• From keratinocytes, mast cells, and DCs
• Binds to receptors on the vascular endothelium [4]
• Activating cellular signaling [4]
• Including the nuclear factor (NF) B pathway
• Inducing expression of vascular endothelial cell adhesion molecules
• Extravasation of inflammatory cells [4]
• Once the inflammatory cells have infiltrated into the tissue
• Respond to chemotactic gradients
• Play a central role in defining the nature of the inflammatory infiltrate [4]

The onset of acute AD

• Strongly associated with the production of TH2-produced cytokines [4]

IL-4 a IL-13

• Significantly higher in AD individuals compared with control subjects
• switching to IgE synthesis [4]
• Upregulating expression of adhesion molecules on endothelial cells [4]
• Implicated in the initial phase of tissue inflammation [4]

TH2 cytokine IL-5

• Involved in eosinophil development and survival
• Predominates in the chronic form [4]

GM-CSF

• Increased production is reported to inhibit apoptosis of monocytes
• Contributing to the chronicity - also:
• TH1-like cytokines
• IL-12
• IL-18 [4]
• Remodeling-associated cytokines (in chronic forms of the disease)
• IL-11
• TGF-beta 1 [4]

Increased expression of C-C chemokines

• monocyte chemoattractant protein 4
• eotaxin
• RANTES [4]

• Contributes to infiltration into acute and chronic AD skin lesions:
• Macrophages
• Eosinophils
• T cells [4]

Cutaneous T cell–attracting chemokine (CCL27)

• Highly upregulated in AD
• Preferentially attracts cutaneous lymphocyte antigen–positive T cells into the skin [4]

Selective recruitment of CCR4-expressing TH2 cells

• Mediated by macrophage-derived chemokine, thymus and activation-regulated cytokine
• Increased in patients with AD
• Severity of AD linked to magnitude of thymus and activation-regulated cytokine levels [4]

TH1 cell migration toward the epidermis

• Strongly upregulated in keratinocytes
• Fractalkine
• IFN-gamma–inducible protein 10

IgE and IgE receptors

• Cca 80% of adult patients with AD IgE levels >150 kU/L
• sensitization against aeroallergens and food allergens
• Concomitant allergic rhinitis and asthma
• 20% of adult patients with AD have normal serum IgE levels
• Often has a late onset (>20 years of life)
• Lack of IgE sensitization against inhalant or food allergens
• Might have IgE sensitization against microbial antigens
• Staphylococcus aureus enterotoxins
• Candida albicans
• Malassezia sympodialis - Pityrosporum ovale
• Some have positive reactions on the atopy patch test (APT)

Transient form of AD

• Low IgE serum levels in children
• Without any detectable sensitizations
• Develops into the extrinsic variant of AD with increasing IgE serum levels
• Developing sensitizations against aeroallergens and food allergens later in life [4]

Expression of IgE receptors

• high-affinity receptor for IgE [Fc RI]
• Can be found in the epidermal skin lesions
• Higher IgE-binding capacity of DCs in the skin and in the peripheral blood of patients with AD
• Fc RI is regulated distinctly on DCs of atopic and non-atopic subjects [4]

Skin barrier dysfunction

• dry skin
• Even involving nonlesional skin [4]
• Increased transepidermal water loss
• reduced content of ceramides in the cornified envelope of both lesional and nonlesional skin
• Major water-retaining molecules in the extracellular space of the cornified envelope [4]
• Matrix of structural proteins
• Bound to ceramides [4]
• Changes in stratum corneum pH levels
• Might impair lipid metabolism in the skin
• Overexpression of stratum corneum chymotryptic enzyme
• Likely to contribute to the breakdown of the AD epidermal barrier [4]
• Penetration of irritants and allergens
• Trigger an inflammatory response
• Contributing to the cutaneous hyperreactivity [4]

T cells

• Key role of immune effector
• Primary T-cell immunodeficiency disorders frequently have increased serum IgE levels and eczematous skin lesions
• Disappear after successful bone marrow transplantation [4]
• In animal models of AD, the eczematous rash does not occur in the absence of T cells
• treatment with topical calcineurin inhibitors (TCIs)
• Specifically target activated T cells
• Significantly reduces the clinical skin rash present in AD [4]

TH1 and TH2 play

• Transgenic mice with overexpress IL-4 in their skin
• Inflammatory pruritic skin lesions similar to those seen in patients with AD
• Local skin expression of TH2 cytokines may be a critical role in AD [4]
• Allergen-sensitized skin from IL-5–deficient mice
• No detectable eosinophils
• Decreased thickening [4]
• Skin from IL-4–deficient mice
• Normal thickening of the skin layers
• Reduction in eosinophil counts [4]
• Patients with AD
• activated T cells with skin-homing properties
• Express high levels of IFN-gama
• Predominantly undergo apoptosis in the circulation
• Skewing the immune response to surviving TH2 cells
• In the affected skin these T cells switch on effector cytokines
• Induce the activation and apoptosis of keratinocytes [4]
• T regulatory (TReg) cells
• Further subtype of T cells
• Immunosuppressive function
• Cytokine profiles distinct from those of either TH1 or TH2
• Able to inhibit the development of both TH1 and TH2 responses
• Mutations in a nuclear factor expressed in TReg cells, Foxp3
• Immune dysregulation polyendocrinopathy enteropathy X-linked syndrome
• Hyper-IgE
• Food allergy
• Eczema [4]
• staphylococcal superantigens
• Subvert TReg cell function
• Might thereby augment skin inflammation [4]

DCs

• Two types of Fc RI-bearing myeloid DCs
• Found in the lesional skin
• LCs and IDECs [4]

LCs

• Predominant role in the initiation of the allergic immune response
• Prime naive T cells into T cells of the TH2 type with high IL-4–producing capacity
• Predominate in the initial phase of AD
• Stimulation of Fc RI on the surface of LCs by allergens
• Induces the release of chemotactic signals
• Recruitment of precursor cells of IDECs and T cells in vitro [4]

IDECs

• Stimulation of Fc RI on IDECs leads to
• Release of high amounts of proinflammatory signals
• Contribute to the amplification of the allergic immune response [4]

Plasmacytoid DCs (pDCs)

• In contrast to other inflammatory skin diseases
• Allergic contact dermatitis
• Psoriasis vulgaris
• only very low numbers
• Major role in the defense against viral infections
• PDCs in the peripheral blood of patients with AD
• Bear the trimeric variant of Fc RI on their cell surface
• Occupied with IgE molecules
• Modified immune function of pDCs in patients with AD after Fc RI-mediated allergen stimulation might contribute to
• The deficiency of pDCs in patients with AD
• Produce type I IFNs
• High susceptibility of patients with AD toward viral skin infections
• Herpes simplex–induced eczema herpeticum [4]
• Undergoing apoptosis
• Spongioform morphology in the epidermis
• Hallmark of eczematous lesions
• Suppression of keratinocyte activation and apoptosis
• Potential target for the treatment of AD [4]

Eosinophils

• Major role in AD
• activated eosinophils in the peripheral blood and in the lesional skin
• Psychosocial stress
• Important trigger for the increase of eosinophil counts in the peripheral blood [4]
• Inhibition of eosinophil apoptosis in AD
• Autocrine release of IL-5 and GM-CSF
• Recruited to, and activated at, tissue sites by TH2 cytokines
• IL-5
• IL-13 [4]
• Chemokines (eotaxin and RANTES)
• Contribute to eosinophil chemotaxis and activation
• eosinophil extravasation and activation
• Eosinophil surface molecules
• Endothelial cells vascular cell adhesion molecule 1
• Intercellular adhesion molecule 1 [4]
• switching the TH1 response in AD
• Production of significant amounts of IL-12 on activation
• Activated
• Releasing an armory of potent cytotoxic granule proteins and chemical mediators
• Role in neuroimmunologic interactions

Pathophysiology of pruritus in AD

• Mediátory pruritu
• Zároveň mediátory zánětu i vazoaktivními látkami
• Působí na volná nervová zakončení
• Mohou vyvolávat až pocity bolesti [6]
• Reduced threshold for pruritus
• Cutaneous hyperreactivity
• Scratching after exposure to allergens, changes in humidity, excessive sweating, and low concentrations of irritants
• Usually worse at night
• Frequently disrupting the patient's sleep and overall quality of life
• Allergen-induced release of histamine from skin mast cells
• Not an exclusive cause of pruritus in AD
• Antihistamines are not effective in controlling the itch of AD unless there is associated urticaria
• TCIs and corticosteroids
• Effective at reducing pruritus
• Inflammatory cells play an important role in driving pruritus
• Cytokines
• Neuropeptides
• Proteases
• Eicosanoids
• Eosinophil-derived proteins

Dysbalance of skin microbiota

Resident flora

• Constantly present on body surfaces
• May prevent colonization by pathogens and possible disease
• Restoring the ecological skin niches [16]

Commensal microorganisms

• Mutualistic symbiosis
• Contribute to human health and welfare
• Production of defense molecules
• Natural antibiotics [16]

Transient skin flora

• Temporarily colonize the skin
• Unable to remain in the body for a long period of time
• Due to competition from resident microbes [16]

Meconium microbes

Presence of enterobacteria

• Associated with a history of atopic eczema in the mother [16]

Presence of lactobacilli

• Was associated with respiratory disorders in the baby [16]

Infant skin microbiome

• Different from that of an adult
• Differences in skin structure and function [16]
• Early colonization is dominated by Staphylococci
• Stratum corneum is better hydrated than that of an adult
• Site specific [16]
• Firmicutes
• Predominate on infant skin [16]
• Similar to an adult organism by the age of 12–18 months [16]

Kožní oblasti a různá mikroflora

• Density of sebaceous glands
• Dry, moist, or sebaceous

High density of sebaceous glands

• Face, chest, and back
• Encourage the growth of lipophilic microorganisms [16]
• Near the top of hair follicles - sebum
• Promotes the growth of facultative anaerobes
• Propionibacterium acnes
• Hydrolyzing the triglycerides present in sebum, releases free fatty acids
• Maintenance of the acidic epidermal pH
• Anoxic environment
• Hosts anaerobic microorganisms
• Cathelicidin LL37
• Defensin (HBD-2)

Eccrine sweat glands - main sweat glands

• water and NaCl
• Natural antibiotic, dermcidin [16]

Apocrine sweat glands

• Larger than eccrine sweat glands
• Underarms (axillae)
• Under the breasts
• Around the nipples
• In the groin and genital region [16]
• Secretions into the hair follicles
• Thick, milky fluid
• Can easily be turned into smelly body odour by germs
• Contains pheromones
• Respond to adrenaline
• Related to sexual attractiveness [16]

Komáři

• Individuals that are highly attractive to Anopheles gambiae s.s.
• Higher abundance, but lower diversity, of bacteria on their skin
• Volatile metabolites released by Staphylococcus spp. are attractive to A. gambiae females [16]

Antimicrobial peptides (AMPs)

Z kůže

• Cathelicidin LL37
• Beta-defensins [16]

AMPs from commensal microbes

-able to increase the production of AMPs by keratinocytes [16]

Staphylococcus epidermidis

• AMPs
• Phenol-soluble modulin (PSM)gamma
• Could be beneficial to the host
• Additional AMPs on normal skin surface [16]
• Exhibited bactericidal activity against skin pathogens
• Staphylococcus aureus
• Group A Streptococcus (GAS)
• Escherichia coli [16]
• Gram-positive bacterium
• More than 90% of the aerobic resident flora
• Mutualistic organism
• Many strains of S. epidermidis produce lantibiotics
• Lanthionine containing antibacterial peptides
• Bacteriocins
• Epidermin
• Epilancin K7
• Epilancin 15X
• Pep5
• Staphylococcin 1580 [16]
• Host-bacterium relationship one of mutualism
• Produce antibacterial peptides that amplify the keratinocyte response to pathogens via TLR2
• Influencing the innate immune response of keratinocytes through Toll-like receptors (TLRs) signaling
• Activation of TLR-2 by S. epidermidis
• Enhances the expression of tight junctions [16]
• Decreases the production of proinflammatory cytokines via TLR3 in the keratinocyte cultures [16]
• Keratinocytes are able to respond more effectively and efficiently to pathogenic insults [16]
• Colonization of body surfaces (especially in the nose) by S. epidermidis
• Impairs the establishment of S. aureus [16]
• Two different strains of S. epidermidis
• Strain JK16
• Inhibits biofilm formation by S. aureus
• Esp-secreting S. epidermidis
• Eliminates S. aureus nasal colonization [16]
• serine protease Esp inhibits biofilm formation and nasal colonization by S. aureus
• Correlates with the absence of S. aureus [16]
• Destroys preexisting S. aureus biofilms [16]
• Enhances the susceptibility of S. aureus in biofilms to immune system components through human beta-defensin-2 (hBD2) [16]
• Strain JK11
• Noninhibitory type

S. aureus

• Nonmotile
• Nonspore forming
• Catalase and coagulase positive
• Typical colonies
• Yellow to golden yellow
• Smooth, entire, slightly raised
• Hemolytic on 5% sheep blood agar [16]
• Extremely prevalent in people with atopic dermatitis.
• Predominantly localized in the anterior nares (vestibulum nasi)
• 20% of individuals are persistent S. aureus carriers
• 60% are intermittent carriers
• 20% are persistent noncarriers [16]
• Activates local inflammatory processes through the release of delta-toxin [16]
• There is a strong association between worsening disease severity and lower skin bacterial diversity [16]
• S. aureus is observed during disease flares [16]
• Increases in the proportion of Staphylococcus and reductions in microbial diversity precede the worsening of AD disease severity as observed in no-treatment flares [16]

Glucocorticoid receptor (GR) gene polymorphisms

• Associated also with variation in glucocorticoid sensitivity
• Changes in glucocorticoid sensitivity
• May predispose to or protect from microbial colonization or infection
• Novel environmental factor can influence
• The ability of S. aureus to bind to nasal mucosa
• Biocide triclosan
• Commonly found in the nasal secretions of healthy adults
• Presence of triclosan has a positive trend with nasal colonization by S. aureus [16]

Imunita kůže a Th2 reakce

• Microorganisms are recognized by innate immune receptors such as Toll-like receptors on the keratinocyte surface
• Keratinocytes produce antimicrobial molecules
• HBD-2, HBD-3, and NO
• IL-8 (neutrophil chemokine) is also produced
• Drive neutrophils from the bone marrow pool into inflamed skin [16]
• In a Th2 environment
• IL-4 and IL-13
• Induce the phosphorylation of STAT6
• Inhibits INF-gamma and TNF-alpha
• Inhibits the production of HBD-2 and HBD-3
• Reduction of IL-8
• Defective neutrophil accumulation in the skin
• Contribute to allowing microbes to grow in the Th2 environment of AD skin [16]

Allergic immune reactions

• Globally attenuated
• Differentially polarized in patients with AD
• Significant decreases in levels of TH1 products
• Some increases in levels of TH17 products
• Inconsistent upregulation in levels of TH2 products
• The overall hyporesponsiveness in skin from patients with background AD might be explained
• Baseline immune abnormalities
• Increased TH2, TH17
• Negative regulator levels

AD kontra psoriaza

• T-cell infiltration characterizes both diseases
• T-cell polarization differs
• Psoriasis
• IL-23/TH17 polarized
• AD
• Testing of targeted therapeutics against various immune axes
• TH2, TH22, and IL-23/TH17 [18]

Triggers of AD

Stress-induced immunomodulation - neuroimmunologic factors

• Epidermal nerve fibers in close association with epidermal LCs-
• neuropeptides
• Increased levels in the plasma:
• nerve growth factor
• substance P
• Correlate positively with the disease activity
• brain-derived growth factor
• Reduce eosinophil apoptosis
• Enhancing chemotaxis of eosinophils in vitro [4]

Allergens

Food allergens

• Can induce eczematoid skin rashes in a subset of infants and children with AD
• Positive immediate skin test responses
• Or serum IgE directed to various foods, particularly:
• Egg
• milk
• Wheat
• Soy
• Peanut [4]
• Food allergen– specific T cells
• Cloned from the skin lesions
• Direct evidence [4]
• Food can exacerbate AD
• Through allergic
• Nonallergic hypersensitivity reactions [4]
• Direct contact with the skin
• Preparation of meals or when feeding infants
• Might be an important factor for the aggravation of eczema [4]

Aeroallergens

• Pruritus and skin lesions after intranasal or bronchial inhalation
• Epicutaneous application of
• House dust mites, weeds, animal danders, and molds, Dermatophagoides pteronyssinus (Der p 1)
• Eczematoid reactions in a subset of patients
• Effective house dust mite reduction measures has been reported to improve AD [4]

Microorganisms

• Colonized with S. aureus
• Exacerbation of their skin disease after infection with this organism
• Antistaphylococcal antibiotics can result in reduction of skin disease
• Secreting toxins called superantigens
• Stimulate activation of T cells and macrophages [4]
• Most patients with AD make specific IgE antibodies directed against staphylococcal superantigens
• Correlate with skin disease severity [4]
• Superantigens
• Induce corticosteroid resistance [4]
• Deficient in antimicrobial peptides needed for host defense against bacteria, fungi, and viruses
• Underexpressed
• Because of the upregulation of TH2 cytokines [4]
• lower levels of proinflammatory cytokines, such as TNF-alfa and IFN-gamma
• Increased susceptibility to skin infections [4]
• Disseminated infections with herpes simplex or vaccinia virus
• Susceptibility to severe viral infections
• Smallpox vaccination is contraindicated in patients with AD unless there is imminent danger of exposure to smallpox [4]

Binding of S. aureus to skin

• Enhanced by AD skin inflammation
• Treatment with topical corticosteroids or tacrolimus reduces S. aureus counts in AD [4]

Yeasts

• Opportunistic yeast Malassezia species
• Contributing factor in AD
• Presence of specific serum IgE
• Positive skin prick test (SPT) response
• Positive APT response against Malassezia species in adults with AD [4]
• IgE sensitization to Malassezia species
• Specific for patients with AD [4]
• Not seen in patients with asthma or allergic rhinitis [4]

Autoantigens

• Autoreactivity of patients with AD to human proteins
• IgE against autoantigens could stimulate type 1 hypersensitivity reactions and DCs
• Induce the proliferation of autoreactive T cells
• IgE against manganese superoxide dismutase (MnSOD) from the skin-colonizing yeast M sympodialis cross-reacts with human MnSOD
• Patients reacting to human MnSOD were sensitized against the M sympodialis MnSOD
• Sensitization most likely occurs primarily by exposure to the environmental fungal MnSOD [4]

Irritant factors

• Rough or woolly clothing
• Mechanical irritation [4]
• Chemical irritants [4]

Zhoršující faktory atopické dermatitidy

Alergeny

Ve vzduchu

V jídle

• Eggs, milk, peanuts, soybeans, fish and wheat, in infants and children [2]

Dráždivé prostředí

• Mýdla
• Detergenty
• Rozpouštědla
• Wool in clothing, blankets and carpets
• Dust
• Pollen
• Tobacco smoke
• Air pollution
• Hot water temperature during showering or bathing [4]

Změny počasí

• Especially dry and cold

Psychika

• Stress

Stav kůže

Sucuhá kůže

• Long, hot baths or showers
• Detergenty

Infekce kůže

Škrábání se

• Further skin damage

Pocení se

• Stres
• Changes in heat and humidity

Terapie

• Základní a nepostradatelnou léčbou jsou:
• Emoliencia
• V akutních stadiích lokálně aplikované kortikosteroidy a topické imunomodulátory [6]

Pomoc dietou

• No universally recommended diet for patients with AD [4]
• Restrictions only in cases of an established diagnosis of food hypersensitivity [4]
• International guidelines for the diagnosis of food hypersensitivity have been published [4]
• Predictive value of a positive case history is lower than that for food-induced immediate reactions [4]

Snížení střevní propustnosti

Zlepšeno - vhodné

Zhoršeno - nevhodné

Potraviny s lepkem

Potraviny obsahující lektiny

• Rajče
• Tomatin
• Brambory
• Solanin
• Černý bez

Některé saponiny

Kontaminanty životního prostředí / potravin

Přídatné látky - E-čka v potravinách

Jiné látky v potravinách se schopností narušit střevní bariéru

• Rucolla ve vyšším množství

Probiotika

Inulin

Laktobacily

• 3x v kapslích [9]
• Bacterial products may induce an immune response of the Th 1 series instead of Th 2
• Therefore inhibit the development of allergic IgE antibody production [9]
• Limited benefit in preventive and therapeutic roles [9]
• Prenatal and postnatal administration of probiotics
• Reduced IgE levels in infants
• May protect against sensitization to hereditary allergies [9]
• But may not protect against asthma or wheezing [9]
• January 2015, the World Allergy Organization
• Recommend the use of probiotics by pregnant and lactating women and their breastfed infants to prevent the development of AD [9]
• Based on a meta-analysis of 29 studies [9]
• Probiotic use by pregnant women reduced the incidence of eczema by 9% during a 1- to 5-year follow-up [9]
• Use by lactating women was associated with a 16% reduction in eczema during a 6-month follow-up period [9]
• Probiotic consumption by breastfeeding infants was associated with a 5% reduction in eczema during the 6-month to 6-year follow-up period [9]
• Administration of heat-killed L-92
• Effective for AD symptoms in japanese adults
• May contribute to the suppression of Th2-dominant inflammation [14]

Protizánětlivě ev. "antimikrobně" působící potraviny

Kurkuma

Nibma

Vyšší poměr omega-3 MK

• Konopná semínka [9]
• Lněná semínka
• Fish oil [10]
• Evening primrose oil [10]
• Ryby high in EPA and DHA and lower in mercury
• Salmon
• Anchovies [11]
• Herring [11]
• Sardines [11]
• Pacific oysters [11]
• Trout [11]
• Atlantic mackerel [11]
• Pacific mackerel [11]

Rutin

• Pohanka aj. mnohé rostliny, byliny a ovoce

Antihistaminová dieta

Eliminace alergenu

Assess for sensitization to a food

SPTs

Measurement of specific IgE

• Diagnostic sensitivity and specificity varies considerably
• Among different foods
• Reading systems
• Age groups
• Discriminating between clinical relevance of sensitization

Lymphocyte cytotoxicity tests

• Nepouziva se [4]

Basophil degranulation test

• Nepouziva se [4]

Measurement of serum IgG (or subclasses)

• Nepouziva se [4]

APT

• An elimination diet should not be recommended solely on the basis of a positive APT response to a food [4]

Physician-supervised food challenges

• Most accurate diagnostic tool
• Patients can present with reactions at least 24 hours after a food challenge
• In case of a negative challenge response
• The skin of the patient should be examined the following day [4]
• After a diagnosis has been established, a tailor-made education program for the patient should be initiated [4]

Mezi časté alergeny a dráždivé potraviny patří

• Vaječný bílek [6]
• Kravské mléko [6]
• lepek [6]
• Ořechy [6]
• Soja [6]
• Ryby [6]
• Sýry [6]
• Jahody [6]
• Mák [6]
• Citrusy [6]
• čokoláda [6]

Režimová opatření

Teplota

• Avoiding extreme temperatures [2]

Neškrabat se

• Cover the itchy area if you can't keep from scratching it [2]
• Trim nails and wear gloves at night [2]
• Apply cool, wet compresses, bandages and dressings
• Protect the skin and prevent scratching [2]

Warm bath

• With baking soda
• Uncooked oatmeal
• Colloidal oatmeal
• Ground oatmeal for the bathtub (Aveeno)
• 10 to 15 minutes
• Dry
• Medicated lotions, moisturizers

Behavioural therapy

• Can be helpful to develop strategies to reduce scratching [3]

Mýdla

• Mild soaps without dyes or perfumes
• Rinse the soap completely off your body
• Mild syndets with an adjusted pH value
• Acidified to pH 5.5–6.0 in order to protect the acid mantle of the skin [4]

Vlhkost vzduchu

• Use a humidifier
• Hot, dry indoor air can parch sensitive skin and worsen itching and flaking [2]
• Keep your humidifier clean
• Prevent the growth of bacteria and fungi [2]

Oblečení, povlečení

• Cool, smooth-textured cotton clothing [2]
• Avoiding clothing that's rough, tight, scratchy or made from wool [2]
• Prevent excessive sweating [2]

Treat stress and anxiety

• Emotional disorders can worsen atopic dermatitis [2]

Pracovní podmínky

• Používejte ochranné rukavice
• Zvenku gumové a zevnitř bavlněné
• Pracovní prostředí
• Bezprašné
• S minimem dráždivých látek
• Bez většího znečištění a nutnosti častého mytí
• Nevhodné např.
• Vaření
• Chov zvířat
• Práce na zahradě, atd.

Dovolená

• Vhodné jsou pobyty u moře
• Na horách ve vysokých nadmořských výškách

Praní prádla - vhodné při atopickém ekzému

• Půl hrnku sody do vodní lázně, ve které namáčíte pleny nebo utěrky [1]
• Lázeň ze sody a vody
• Silně znečištěné prádlo
• Mastné skvrny
• Skvrny od krve
• Nechejte prádlo namočené nejlépe přes noc a pak normálně vyperte [1]

Mýdlový sliz

Mýdlo na praní

• Jádrové mýdlo
• Marseilleské mýdlo se 72% olivového oleje aj.

Prášková prací soda (ne jedlá soda)

• Rozpouští tuk
• Změkčuje vodu
• Odstraňuje skvrny
• Desinfikuje

Recept 1

• Poměr mýdla a prací sody cca 1:1
• 250 g mýdla : 250 g sody : 5 l vařící vody, dolít na 10 l vody
• Celkem cca 10,5 litrů slizu do cca 12l nádoby

Recept 2

• Mýdlo 175 g : Soda 150 g : 1 l horké vody, dolít dalšími 9 l
• Celkem cca 10,3 l slizu

Recept 3

• 200 g mýdla : 100 g - 150 g prací sody : 5-10 l vody [8]

Postup

• Mýdlo nastrouháme na běžném struhadle
• Víc na jemno, tím lépe
• Do cca 1l horké vody
• Za stálého míchání necháme rozpustit
• Přidáme sodu, s mícháním necháme rozpustit
• Celý kyblík dolijeme další horkou vodou dle návodů
• Sliz vychladne - gelovou až pudinkovou konzistenci [3]

Použití

• Dávkujeme přímo do bubnu pračky
• Cca 250 ml na jedno praní
• Dávka závisí na koncentraci Vašeho slizu a také na stupni znečištění [3]

Rizika

Ucpání filtrů v pračce

• Příliš hustým slizem
• Málo vody
• Nedostatečně rozpuštěné mýdlo
• Málo změkčující sody
• Sraženiny
• Kombinace - soda s octem
• Prevence
• čas od času nechat pračku propláchnout na prázdno na 90 °C [5]
• Eroze gumových haidček pračky
• Použití příliš koncentrovaného octa

Zaprané prádlo

• Pobledlé barvy
• Pozor na překročení množství sody
• Mohlo by dojít k zašesnutí prádla

Skvrny na prádle

• žlučové mýdlo
• Sůl na skvrny - perkarbonát sodný
• Rozpadá na bělicí a desinfekční kyslík a sodu [3]
• Krásně vybělí například látkové pleny [3]

Aviváž

• žádnou
• Ekologické důvody
• Zdravotní důvody
• Na dětské prádlo je přímo nevhodná a na ostatní prádlo zbytečná [3]
• Prádlo vyprané v mýdlovém slizu je měkké a má jemnou mýdlovou vůni [3]

Náhrada

• Kápnout trošku 100% éterického oleje
• žádné olejové směsi
• Např. éterické oleje od firmy Eoné nebo Nobilis Tilia [6]
• Pro atopickou pokožku se doporučuje
• Levandule [6]
• Mandarinka (od 6-ti měs.) [6]
• Eukalypt polybractea [6]
• Lze přidat již do slizu [7]
• Do zásobníku na aviváž lze dát ocet smíchaný s vodou
• Prádlo změkčuje [7]

Ekologická bezpečnost pracích slizů

• Zasolení prostředí
• Na pražskou čistírnu odpadních vod by muselo denně přitéci 213 tun uhličitanu sodného denně, aby byl překročen limit
• V přepočtu by to bylo víc jak 21 milionů pracích dávek
• Opět zcela nereálná cifra... [5]
• Použití sody v čistících a pracích prostředcích v domácnostech nemá nepříznivý vliv na vodní ekosystémy [5]

Prací soda a ocet - ještě šetrnější praní při atopické ekzému

Praní

• Dlouhý cyklus 60°
• Cyklus „jemné prádlo" / hodinový cyklus – 40 - 60°
• 1 pytlíku jedlé sody + půl decilitru octa
• Funguje dobře i na fleky [6]
• Dobré reference stran snášenlivosti při akutní exacerbaci atopického ekzému [6]

Alternativa s kyselinou citronovou

• Místo octu lze použít i k. citronovou
• Obojí zároveň odvápňuje pračku [6]

Vysoká teplota vody a delší prací cyklus

• Dokážou běžně zašpiněné prádlo vyprat bez jakýchkoliv potřebných přísad [6]

Redukce roztočů v ložním prádle

Matrace

• Denně vysávejte vysavačem
• Odstranit odumřelé roztoče a prach

Chránič matrace a chránič polštáře

• Na polštář postačí každý den čistý ručník
• Zachytí veškerý pot a odpadávající kůži
• Chránič matrace
• Sníží množství živých roztočů během měsíce o více než 90%

Peřiny

• Ven pouze ve velkém mrazu
• Spolehlivě zabije roztoče
• Nejlépe přes noc, aby pořádně promrzly
• Pokud lze, ta vyprat

Větrání

• Před spaním a také ráno v pokoji pořádně vyvětrejte
• 5 - 10 minut otevřená okna
• Vlhkost v místnosti okolo 40%

Roztoči

Prachoví roztoči

• 0,250 - 0,3 mm
• Příbuzní pavouků
• 1694 holanďan Anton van Leeuwenhoek objevil pod mikroskopem
• Dermatophagoides farinae (americký)
• Dermatophagoides pteronyssinus (evropský)
• žijí 3 - 4 měsíce
• Samička zvýší populaci o 25 - 30 roztočích miminek týdně
• Alergii způsobuje
• protein v jejich trusu
• Rozpadlá, mrtvá těla

Literatura [prani pradla]:

[1] www.prozeny.cz/magazin/bydleni-a-zahrada/poradme-si/37388-tohle-vsechno-umi-jedla-soda-vypere-vycisti-mycku-a-odkyseli-telo
[2] www.nazeleno.cz/bydleni/domacnost/cisty-domov-bez-chemie-jak-vyuzit-jedlou-sodu-pri-uklidu.aspx
[3] www.ekozivot.cz/ekodomacnost/navod-na-vyrobu-mydloveho-slizu/
[4] www.rozpad.cz/forum/viewtopic.php?f=23&t=1506
[5] ekolist.cz/cz/zelena-domacnost/rady-a-navody/jeleni-sliz-praci-prostredek-z-mydla-a-sody-pro-opravdove-ekonadsence
[6] www.proalergiky.cz/magazin/uzivatelske-clanky/clanek/atopicky-ekzematik-v-cem-nejlepe-prat-ecover-ci-mydlove-orechy
[7] www.eshop.ekokoza.cz/Navod-na-vyrobu-domaciho-praciho-prasku/
[8] www.mydloteka.cz/mydloteka/eshop/2-1-mydla-na-prani/0/5/1670-Soda-na-prani-uhlicitan-sodny-1-kg

Koupele a očista kůže

• Po koupeli se ručníkem jen „oplácat“ a ne stírat

Non-soap cleansers

Colloidal oatmeal

• Aveeno [1]

Desinfekční koupele - antiseptic solutions

Bleach baths

• Half a cup of household bleach (6% sodium hypochlorite solution) to a full bath and soak for 10 minutes [3]
• Decreases bacteria on the skin and related infections [2]
• May not be helpful for everyone who has atopic dermatitis [2]
• Too much bleach in the water can cause severe skin irritation [2]
• Even diluted bleach baths may cause dryness or skin irritation [2]
• Can be taken 2 or 3 times a week [2]
• Do not use bleach baths if you have an allergy to chlorine [2]

Lukewarm water [2]

Clorox liquid bleach [2]

Condy's crystals (potassium permanganate)

• In weak concentration - light rose pink colour

Cetrimide

Chlorhexidine

Chloroxylenol

Dibromopropamidine

Polynoxylin

Povidone iodine

Triclosan

Alterantivní koupele

Koupele se solí z Mrtvého moře - Osmóza

• Ponoříte lidské tělo (kožní buňky) do slané vody, začne vylučovat vodu
• S vodou ale odcházejí také iritanty aj. nečistoty z atopické pokožky
• V prvních dnech se ekzém může na pohled zhoršit a dokonce i objevit tam, kde dosud viditelný nebyl
• V dalších dnech se začne stav zlepšovat [9]
• Idealně soli s vysokým obsahem hořčíku [9]
• Vysušují

Šampóny

Exomega (a-derma)

• Dětský šampón v pumpičce

Měsíčkový šampón (weleda)

Podpora regenerace kůže a kožní bariery

• Ceramides, cholesterol and fatty acids
• Mimic the lipids naturally found in the horny layer of the skin [3]
• May reduce the need for anti-inflammatory medications [3]

Zvlhčování a promašťování kůže - emoliencia - Emollients

• Key feature of AD is severe dryness of the skin
• Increased transepidermal water loss
• Typically accompanied by intense pruritus and inflammation [4]
• Regular use of emollients together with skin hydration
• The mainstay of the general management of AD [4]
• Moisturize your skin at least twice a day
• Prevent further water loss
• Attempt to restore skin barrier function
• Clothing soaked in paraffin-based emollients becomes a fire hazard [3]
• Emollients should be applied continuously
• Even if no actual inflammatory skin lesions are obvious
• "Water-in-oil" or "oil-in-water" emulsions
• Ideálně do 3 minut po koupeli
• Největší schopnost pokožky absorbovat lipidy v krému

Test snášenlivosti

• Po 3 dny malé množství na malý okrsek kůže
• Před ucho nebo na zápěstí ap.
• Pokud se neobjeví svědění či pálení, začervenání, pupínky atp., pak teprve lze aplikovat na ostatní místa

Skupiny přípravků

Lotions

• Easy to apply but evaporate quickly and may not be oily enough [3]

Creams

• Oil in water emulsion (fatty cream)
• PHARMAC subsidises urea cream
• Very good for dryness but can sting active eczema [3]
• 3% wool fat with mineral oil lotion [3]
• Cetomacrogol
• Nonionic cream
• Cetomacrogol with 10% glycerol
• Aqueous cream and emulsifying ointment

Oleje k promazávání kůže

Oleje do koupele

• Léčebné koupelové oleje
• Navíc detergentní účinky - i mycí schopnosti
• Linola, Oilatum Balneum Hermal, Balmandol [5]
• U dospělých
• Vhodnější přímo nanést na kůži
• Nechat chvilku působit
• Pak lehce osprchovat [5]
• Léčebnou koupel max. 10 minut
• Jinak kůže nabobtnává a přesušuje se [5]

Masti

• More effective than creams in very dry skin [3]
• Hard to rub in and leave a greasy surface [3]
• Can also encourage folliculitis by blocking the hair follicles [3]

Protizánětlivé pasty

• Mohou i přesušovat [5]
• Jen na ekzémová ložiska a ne k běžnému promazávání
• Tak často během dne, jak je třeba
• žádná bezpečnostní omezení [5]
• Endiaron pasta
• Ichthyo Care
• Ictamo pasta
• Tanno-Hermal lotio [5]

Další blíže neurčené nálezy

• Lipikar (La Roche Posay)
• Dobra reference
• Multilind, Exomega, Atoderm
• Lipobase
• Dobrá reference
• Excipial
• Balneum, Linola, Oilatum, Physiogel, Trixera, Leciderm
• Konopné prostředky Cutis Help a Cannaderm [5]
• Linola

Aktivní substance

Ceramidy [1]

• Vhodne i u eczema, allergic contact dermatitis, and radiation dermatitis [1]
• CeraVe, TriCeram, Atopiclair, MimyX [1]

Polidocanol

• Effective in reducing pruritic symptoms [4]

Urea

• Intensive hydration of the skin [4]

Salicyl acid

• Can be added to an emollient for the treatment of chronic hyperkeratotic lesions [4]

Zinek

• Zinková pasta
• Zinková mast

Kamenouhelný dehet

Ichtamol

Tanin

St. John's wort

Vitamin B12

Nevhodná topika

• Parfémované

Heřmánek

• Vedou často k alergii
• ekzém kontaktní [7]

Propolis

• Vedou často k alergii
• ekzém kontaktní [7]

Topické kortikoidy - glucocorticosteroids

Vlastnosti

• Anti-inflammatory effect
• Reduction of skin colonization with S. aureus [4]
• Might affect a further trigger factor of AD [4]

Indikace

• Treatment of acute flare-ups AD

NÚ

Absorbce kůží a NÚ

• Max. v místech tenké kůže
• Eyelids
• Genitals
• Body folds
• Skin of infants

Systemic absorption and adrenal suppression

• Large amounts of potent topical steroids
• More than 100g/week over months [3]

Can further reduce the skin barrier function

• Best applied as intermittent courses
• Kůže zregeneruje
• Lowest strength and smallest quantity of topical steroid that is effective should be used
• To all areas affected
• No benefit from applying them more than once daily [3]

Oční víčka

• Topical corticosteroids for atopic dermatitis on the eyelids and periorbital region
• Is safe with the respect to induction of glaucoma or cataracts [9]

Redukce NÚ

• Risk of adverse effects can be reduced by
• Optimizing application protocols [4]
• Using new steroid preparations with lower atrophogenic potential [4]
• Prednicarbate
• Mometasone furoate
• Fluticasone
• Methylprednisolone aceponate

Zásady užívání

• Jen 1x denně
• Obvykle na noc
• Jako poslední prostředek
• Až po promazávání [7]
• Stav akutní
• Lze nárazově 2x denně
• Obvykle po 3 dny [7]
• Po zlepšení, obvykle do týdne
• Postupně snižujte
• Ob 1 den, ob 2 dny, ob 3 dny až do úplného vysazení
• Prevence relapsu
• Cílem je stabilizace stavu [7]
• Pokud se po počátečním zlepšení již ekzém dále neustupuje
• Zůstaňte na intervalu ob 3 dny
• Nebo individuálně i delší, který stačí udržet ekzém pod kontrolou
• Intervalová léčba [7]
• Používejte kortikoidy pouze bodově, na postižené partie [7]
• Jen nezbytně nutné množství léku
• Nemají účinky preventivní
• Nemohou zabránit opětovnému propuknutí ekzému [7]
• V akutní fázi na krátkou dobu silnější kortikoid
• Po zklidnění (cca do 3 - 5 dnů) se nahradí slabším [7]
• Intermittent use
• Might be as effective as an initial therapy with a high potent steroid
• Followed by a time-dependent dose reduction or change over to a lower potent preparation [4]
• Application of fluticasone on unaffected skin twice weekly [4]
• Prevents further flare-ups of AD [4]

• Topical steroid preparations should be applied no more than twice daily as short-term therapy for acute eczematous lesions
• Only mild to moderately potent preparations should be used on
• Genital
• Facial
• Intertriginous skin areas [4]
• In children only mild to moderately potent steroid preparations should be used [4]

Návod na e-medicine

• Initial therapy
• Hydrocortisone 1% powder in an ointment base
• 2 times daily
• To lesions on the face and in the folds [9]
• Midstrength steroid ointment: triamcinolone or betamethasone valerate
• 2 times daily
• To lesions on the trunk until the eczematous lesions clear [9]

Terapeutická odpověď

Mild eczema

• Respond to low potency topical steroids within a few days
• Complete clearance of eczema within one or two weeks
• Intermittent treatment works very well

Moderate eczema

• May require more potent topical steroids for at least two weeks before improving
• May require several weeks of treatment before clearing

Severe eczema

• May show only partial improvement with potent topical steroids alone even after several months of use
• Can often be maintained with emollients alone [3]
• Gradually reducing the number of days the stronger topical steroid is used
• F.e.: potent topical steroid at weekends and an emollient on weekdays
• The oral corticosteroids prednisone and prednisolone are often used in the short-term management
• Gain rapid control
• Cannot be continued for more than a few weeks without significant side effects [3]

Tachyphylaxis

• If used continuously topical steroids may lose their effectiveness after a few weeks [3]
• Can be avoided by reducing the strength and frequency of the topical steroid as the eczema comes under control [3]
• Changing to a different topical steroid of the same strength can be helpful [3]
• Treatment of infection, if present, may again make the topical steroid effective [3]
• A stronger topical steroid or an additional treatment such as phototherapy may be required [3]

Druhy kortikoidů

Prednison

Hydrocortizon

• At least 1 % hydrocortisone [2]
• Can temporarily relieve the itch [2]
• To the affected area before you moisturize [2]

Prednicarbate

Mometasone furoate

Fluticasone

Methylprednisolone aceponate

Topical immunomodulators - TCIs

• Steroid-free
• Anti-inflammatory
• Immunomodulatory activity

NÚ

• Observed side effect
• Transient burning sensation of the skin [4]
• Pimecrolimus achieved better local tolerability than tacrolimus in children [4]
• Not associated with a risk of skin atrophy
• Useful alternative for the treatment of sensitive skin areas
• Face [4]
• Intertriginous regions [4]
• Generalized viral infections observed during TCI treatment
• Eczema herpeticum [4]
• Eczema molluscatum [4]
• No evidence of a causal link of cancer and the use of TCIs, but black-box warning for
• Pimecrolimus (Elidel; Novartis, Basel, Switzerland)
• Tacrolimus (Protopic; Astellas, Deerfield, Ill)
• Lack of long-term safety data
• Recommended as second-line treatments
• Use in children younger than 2 years of age is currently not recommended

Užívání

• V akutní fázi mohou imunomodulátory dráždit
• Při výrazném zhoršení ekzému 1 - 3 dny kortikoidy
• Pak přejít na imunomodulátory
• První měsíc se aplikují 2x denně
• Pak 1x denně
• S přechodem na intervalovou léčbu 2 - 3x týdně
• Hodinu před a po aplikaci imunomodulátorů se nesmí aplikovat jiný krém či mast [7]

KI

• Virová či bakteriální infekce (opar, impetigo atp.)

Calcineurin inhibitors affect your immune system

• Used only when other treatments have failed or if someone can't tolerate other treatments [2]
• Approved for children older than 2 and for adults [2]
• Useful for mild to moderate atopic dermatitis
• Antiinflammatory but do not thin the skin or affect its barrier function
• Main side effect is initial burning, feeling of warmth or itching [3]
• Useful for eczema in thin-skinned areas (face, genitals and body folds) [3]

Tacrolimus (Protopic) v masti

• More potent and may have greater immunosuppressive activity
• Tacrolimus ointment (0.03%)
• Approved for the treatment of children aged 2 years and older [4]
• Tacrolimus ointment (0.1%)
• Only approved for use in adults
• Anti-inflammatory potency of ointment is similar to a corticosteroid with moderate potency
• Good safety profile for a treatment period of up to 4 years with tacrolimus

Pimecrolimus (Elidel) v krému

• Most effective when used at the earliest sign of eczema (such as redness or itching) to prevent flares
• Pimecrolimus cream (1%)
• Approved for the treatment of children aged 2 years and older [4]
• Pimecrolimus cream is less antiinflammatory active than moderate corticoids
• Good safety profile for a treatment period of up to 2 years with pimecrolimus

Tar preparations

• Creams, bandages and bath additives
• Reducing itch and inflammation
• Smelly and messy
• Do not appear as effective as topical steroids

Coal tar

Pine tar

Ichthammol preparations

Topical antimicrobial therapy

• Toxins secreted by the majority of S. aureus on the skin behave as superantigens
• Can directly influence the disease activity
• Clinical signs of bacterial superinfection might be absent
• Can be used in emollients
• Part of an additional wet-wrap dressing therapy
• AD seems not to be associated with a higher risk of sensitization against topical antimicrobials [4]

Triclosan (2,4,4’-trichloro-2’-hydroxydiphenyl ether)

• Low sensitizing potential [4]
• Low resistance rate [4]
• Effective in significantly reducing skin colonization with S. aureus and skin symptoms [4]
• Irritative, photoallergenic, phototoxic, mutagenic, or carcinogenic potential of triclosan has not been observed [4]

Chlorhexidine

• Low sensitizing potential [4]
• Low resistance rate [4]

Silvercoated textiles

• Can reduce S. aureus colonization and eczema severity [4]

Silk fabric with a durable antimicrobial finish

• Can reduce S. aureus colonization and eczema severity [4]

Erythromycin

Fusidic acid

• High resistance rates of S. aureus to erythromycin have resulted in a preferential use of fusidic acid
• Proved to be very effective against S. aureus [4]
• Low minimal inhibitory concentration [4]
• Good tissue penetration
• Long-term therapy with fusidic acid is suspected to be responsible for increasing resistance [4]
• Restricted topical application for only 2 weeks is advisable [4]

Mupirocin topical

• Intranasal eradication of methicillin-resistant S. aureus - shown to be effective [4]:

Terapie mokvavých ložisek

Wet dressings / wraps - Wet-wrap therapy

• Bandages applied over emollients +/- topical steroids [3]
• In acute red, hot, weeping eczema and usually require admission to hospital [3]
• Wrapping the affected area with topical corticosteroids and wet bandages [2]
• Effective, intensive treatment for severe atopic dermatitis [2]
• Control signs and symptoms within hours to days [2]
• They can be repeated for several days or longer, reapplied as they dry out. [3]
• Wet layer of cotton dressing
• Then covered with tubular bandages
• Applied over emollients
• In combination with antiseptics or topical steroids [4]
• Beneficial in cases of exacerbated AD skin lesions
• More practical alternative approach using clothing rather than bandages [4]

Odpařující obklady

• S borovou vodou
• S Jarischovým roztokem
• Studený obklad jen na několik minut
• Pak tekutinu s povrchu kůže odpařit
• Několikrát opakovat

Spray

• Aplikace termální léčebné vody
• La Roche Possay, Avéne [5]
• Kůže se ochlazuje, zmírňuje se zánět i mokvání [5]

Phototherapy

• If the eczema has failed to respond to topical treatments or is too severe for topical treatment alone [3]
• Phototherapy may aggravate dryness [3]
• KI: transport problems, very fair skin or a history of photosensitivivity [3]

• Standard second-line treatment for adults [4]
• In phases of acute flares, a combination with corticosteroids is often practiced [4]

-UV therapy should be restricted to adolescents older than 12 years [4]

Broad-band UVB (280–320 nm) [4]

Narrow-band UVB (311–313 nm) [4]

UVA (320–400 nm) [4]

UVA1 (340–400 nm) [4]

PUVA [4]

Balneo-PUVA [4]

UVB and topical glucocorticosteroids [4]

UVB with UVA [4]

UVA1 medium- and high-dose therapy [4]

Natural sunlight

• Controlled amounts [2]

Artificial ultraviolet A (UVA) and narrow band UVB

• Controlled exposure to UV-B and/or UV-A for a few minutes two to three times each week
• Treatment course may continue for several months
• Alone or with medications
• Reserved for severe eczema
• Expensive [3]
• Time-consuming
• Potential side effects [3]

Photochemotherapy

Psoralen plus ultraviolet light therapy (PUVA)

• Long-term light therapy has harmful effects, including premature skin aging and an increased risk of skin cancer [2]
• Not used for infants and young children [2]

Celková terapie

Antihistamines

• Sedative properties
• Short-term adjuvant to topical treatment during relapses associated with severe pruritus
• Nonsedating antihistamines
• Only very modest value in atopic eczema [4]
• There are no large controlled studies to date [4]

Cetirizine

• Zyrtec
• Several months theraphy may be helpful
• May have disease-modifying effects in adults and children [3]

Fexofenadine

• Allegra

Diphenhydramine

• Benadryl etc.
• Ospalost [2]

Další protisvědivé medikamenty

Hydroxyzine

• Certain degree of relief from itching [9]
• Not effective without other treatments [9]

Diphenhydramine hydrochloride

• Certain degree of relief from itching [9]
• Not effective without other treatments [9]

Ketotifen

• calcium channel blocker
• May be effective [9]

Oil of evening primrose

• Was believed to be effective
• In a randomized controlled study
• No benefit in children [9]
• Little improvement in adults [9]

Neúspěšná terapeutické pokusy

• Everolimus [9]
• Rapamycin-derived macrolide [9]
• Combination therapy with either prednisone or cyclosporine A was not effective [9]
• Thymopentin [9]
• Gamma interferon [9]
• Chinese herbs [9]

Kortikoidy

Interferon

• Sometimes used in adults if other treatment doesn't work [1]

Cyclosporin A - (CyA)

• Inhibits calcineurin-dependent pathways
• Reduced levels of proinflammatory cytokines
• IL-2
• IFN-gamma [4]
• Effective treatment for adult and childhood AD
• Relapse after discontinuation of therapy is often observed [4]
• Posttreatment disease severity often does not return to baseline levels [4]
• Renal toxicity
• Limited to patients with severe refractory disease
• Blood pressure and laboratory parameters must be monitored closely
• Short- or long-term therapy
• High-dose (3–5 mg/kg/d)
• Low-dose (2.5 mg/kg/d)
• Aim for the lowest effective dose
• Shortest treatment period
• Vaccinations might not be effective during immunosuppression

Azathioprine

• Affecting purine nucleotide synthesis and metabolism
• Efficient for many dermatologic conditions [4]
• As monotherapy in nonlicensed indications, including AD [4]
• Accumulating evidence for its efficacy in severe recalcitrant AD [4]
• Number of side effects
• Myelosuppression
• Hepatotoxicity
• Gastrointestinal disturbances
• Increased susceptibility for infections
• Possible development of skin cancer [4]
• Metabolized by the thiopurine methyltransferase
• Deficiency of this enzyme should be excluded before starting oral immunosuppression with azathioprine [4]
• Recommended dosage of azathioprine for dermatologic indications
• 1 to 3 mg/kg daily
• Determined based on thiopurine methyltransferase levels
• Regular blood tests must be performed [4]
• Onset of action is usually slow
• Benefit might not be apparent until 2 to 3 months after starting treatment [4]

Methotrexate - MTX

Mycophenolate mofetil

Immunotherapy

• Hyposensitization is not an established instrument for the treatment of AD [4]
• Case reports suggest clinical benefit from allergen-specific desensitization in AD [4]
• Double-blinded controlled trials have failed to show consistent efficacy [4]
• Allergen-specific immunotherapy of house dust mite preparations in patients with AD sensitized to house dustmite allergens for 1 year [4]
• Dose-dependent effect on disease symptoms [4]

Zkoumané možnosti terapie AD

Rituximab

• B-cell antibody, shows promise [3]
• Has severe side effects [3]
• Not effective in every case [3]

Omalizumab

• Monoclonal antibody that blocks IgE function
• Case reports suggest that it may be an effective
• got the indication in Europe for the treatment of chronic spontaneous urticaria after escapement to antihistamines [12]
• Randomized, placebo-controlled trial did not demonstrate improvement in the clinical course [9]

Dupilumab

• Monoclonal antibody that blocks the IL-4 receptor
• Randomized, double-blind, placebo-controlled trials have demonstrated marked and rapid improvement in AD disease activity
• Drug remains to be FDA-approved for AD [9]

Corynebacterium bovis

• Induced robust T helper 2 cell responses in mice skin
• Langerhans cells were required for eliciting immune responses against S. aureus inoculation [13]
• Possible target for future therapeutics in eczematous dermatitis [13]

Oficiální prohlášení

• Insufficient evidence exists to recommend:
• Probiotics
• Leukotriene inhibitors
• Essential fatty acids
• Traditional Chinese medicines
• Allergen immunotherapy
• May be useful in a small number of individuals with proven sensitisation to inhalant allergens [3]

Komplikace

Asthma and hayfever

Neurodermatitis - lichen simplex chronicus

• Starts with a patch of itchy skin
• Scratch the area, which makes it even itchier
• Affected skin become discolored, thick and leathery

Skin infections

• Penicillin derivatives flucloxacillin or dicloxacillin [3]
• Usually prescribed
• Erythromycin
• In those allergic to penicillin
• Another drug active against staphylococcus and streptococcus may be preferred
• On discontinuing the oral antibiotic, the patient may suffer another flare
• Occurs repeatedly
• Antibiotics may be prescribed for several weeks or months
• Low risk of side effects from such treatment
• Main concern is the development of MRSA [3]
• Antibiotic creams and ointments are not recommended for use in extenisve atopic dermatitis
• Not as effective as oral antibiotics
• May also cause contact allergic dermatitis [3]
• May promote the development of bacterial resistance [3]
• Intranasal mupirocin ointment and diluted bleach (sodium hypochlorite) baths
• Improved atopic dermatitis symptoms in patients with clinical signs of secondary bacterial infection [9]

Celková ATB terapie - Systemic antibiotic treatment

• Widespread bacterial secondary infection (primarily S. aureus)
• First- or second-generation cephalosporins
• 7 to 10 days are usually effective [4]
• Semisynthetic penicillins
• 7 to 10 days are usually effective [4]
• Erythromycin-resistant organisms
• Fairly common [4]
• Macrolides less useful alternatives [4]
• Penicillin or cephalosporin allergy
• Clindamycin
• Oral fusidic acid [4]
• Recolonization after a course of antistaphylococcal therapy occurs rapidly
• Maintenance antibiotic therapy
• Should be avoided [4]
• Might result in colonization by methicillin-resistant organisms [4]

Eczema herpeticum - Kaposi's varicelliform eruption

• Severe and possibly life-threatening complication
• Systemic antiviral treatment
• Acyclovir [4] [9]
• Valacyclovir [4]

Eye problems

• Severe itching around the eyelids, eye watering
• Inflammation of the eyelid - blepharitis and conjunctivitis

Irritant hand dermatiti

• Exposed to harsh soaps, detergents and disinfectants

Allergic contact dermatitis

• Common in patients with atopic dermatitis
• Including corticosteroids
• To topical medications frequently occurs, especially in adults [4]
• Cases of worsening eczema despite treatment
• Needs to be ruled out by means of patch testing [4]

Sleep problems

• Itch-scratch cycle

Behavioral problems

• Link between atopic dermatitis and attention-deficit/hyperactivity disorder
• Especially if a child is also losing sleep [2]
• Omezení pracovní činnosti
• Psychosociální problémy

Časté exacerbace či kontinuální průběh bez remisí

Nedostatečná odpověď na léčbu

Přechod do dospělosti

• Silná dědičná zátěž [5]
• Přítomnost alergie na mnohé látky (tzv. polyvalentní alergie) [5]
• Nedostatečně zvládání zánětu/ekzému v dětském věku [5]
• „early onset AD“
• Přetrvává do dospělosti až u 30 % případů [6]

Prognosticky špatné ukazatele

• Pozitivní rodinná anamnéza
• Těžší průběh AD v dětství
• Přítomnost respirační atopie
• Vysoké hodnoty IgE v pupečníkové krvi
• Nulová alela genu pro filagrin

Literatura:

[1] Atopic Dermatitis (Eczema) - Treatment Overview, Last Updated: March 12, 2014 www.webmd.com/skin-problems-and-treatments/eczema/tc/atopic-dermatitis-treatment-overview
[2] www.webmd.com/skin-problems-and-treatments/bleach-baths-for-atopic-dermatitis
[3] Treatment of atopic dermatitis. Is there a cure for atopic dermatitis? DermNet NZ www.dermnetnz.org/dermatitis/treatment.html
[4] Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report, C. A. Akdis1, M. Akdis1, T. Bieber2, C. Bindslev-Jensen3, M. Boguniewicz4,5, P. Eigenmann6, Q. Hamid7, A. Kapp8, D. Y. M. Leung4, J. Lipozencic9, T. A. Luger10, A. Muraro11, N. Novak2, T. A. E. Platts-Mills12, L. Rosenwasser4, A. Scheynius13, F. E. R. Simons14, J. Spergel15, K. Turjanmaa16, U. Wahn17, S. Weidinger18, T. Werfel19, T. Zuberbier17 andthe European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Group†, Article first published online: 28 JUN 2006, DOI: 10.1111/j.1398-9995.2006.01153.x onlinelibrary.wiley.com/doi/10.1111/j.1398-9995.2006.01153.x/full
[5] www.ordinace.cz/clanek/atopicky-ekzem-atopicka-dermatitida/?chapter=1
[6] Jiráková, A., Slavíková, Š., Vojáčková, N., Hercogová, J. Atopic dermatitis, Atopická dermatitida; 7.4.2010 zdravi.e15.cz/clanek/postgradualni-medicina/atopicka-dermatitida-450827
[7] www.ordinace.cz/clanek/atopicky-ekzem-atopicka-dermatitida/?chapter=4
[8] Atopický ekzém (atopická dermatitida) a jeho léčba? Jak léčit atopický ekzém? 15. 08. 2014 www.solnajeskyneletnany.cz/novinky/atopicka-dermatitida-atopicky-ekzem-jak-lecit-a-vylecit-atopicky-ekzem/
[9] Atopic Dermatitis Treatment & Management; Brian S Kim, MD; Chief Editor: William D James emedicine.medscape.com/article/1049085-treatment
[10] Atopic Dermatitis (Eczema) - Other Treatment www.webmd.com/skin-problems-and-treatments/eczema/tc/atopic-dermatitis-other-treatment
[11] Essential Fatty Acids (Omega-3 and Omega-6 Fatty Acids) www.webmd.com/hw-popup/essential-fatty-acids
[12] www.ncbi.nlm.nih.gov/pubmed/26021140
[13] Immunity. 2015 Apr 21;42(4):756-66. doi: 10.1016/j.immuni.2015.03.014. Dysbiosis and Staphylococcus aureus Colonization Drives Inflammation in Atopic Dermatitis. Kobayashi T1, Glatz M2, Horiuchi K3, Kawasaki H4, Akiyama H5, Kaplan DH6, Kong HH2, Amagai M4, Nagao K7. www.ncbi.nlm.nih.gov/pubmed/25902485
[14] www.ncbi.nlm.nih.gov/pubmed/25660281
[15] www.ncbi.nlm.nih.gov/pubmed/25659224
[16] Microbiota in Healthy Skin and in Atopic Eczema; Giuseppe Baviera, 1 , 2 ,* Maria Chiara Leoni, 2 , 3 Lucetta Capra, 2 , 4 Francesca Cipriani, 2 , 5 Giorgio Longo, 2 , 6 Nunzia Maiello, 2 , 7 Giampaolo Ricci, 2 , 5 and Elena Galli www.ncbi.nlm.nih.gov/pmc/articles/PMC4122000/
[17] www.ncbi.nlm.nih.gov/pubmed/25625823
[18] www.ncbi.nlm.nih.gov/pubmed/25541257
[11]
[11]
[11]
[11]
[11]
[11]
[11]