dermatitis atopi

ATOPIC DERMATITIS(ATOPIC ECZEMA)

Chapter 14

Donald Y. M. Leung, Lawrence F. Eichenfield, Mark BoguniewiczFitzpatrick’s Dermatology in General Medicine. 7th ed. New York: McGraw-Hill

Medical; 2008. P.146-58

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Atopic dermatitis (AD)

Chronically relapsing skin disease

Most commonly during early infancy and childhood

Frequently associated with abnonnalities in skin barrier function & allergen sensitization

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Epidemiology

AD major public health problem worldwide Prevalence in children of 10-20% Prevalence of AD in adults is approximately 1-3%The prevalence much lower in agricultural

countriesThere is also a female preponderance, with an

overall female/male ratio of 1.3:1.0

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Peningkatan penggunaan antibiotika

Faktor-faktor resiko

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Etiologi dan Patogenesis

Gangguan barier kulit

Gangguan sistem imun alamiah

Peningkatan respon

imunologik

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Penurunan regulasi gen yang berperan dlm kornifikasi/keratinisasi (filaggrin dan loricrin)

Penurunan fungsi barier kulit akibat:

Penurunan kadar ceramide

Peningkatan kadar enzim proteolitik endogen

Peningkatan penguapan kulit (trans-epidermal water loss)

Sabun dan detergen, meningkatkan aktifitas protease endogen, paparan thd protease eksogen dari debu tungau rumah dan Staph.aureus juga

merusak barier epidermis

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Immunopathology of Atopic Dermatitis

Unaffected skin:- mild epidermal hyperplasia- a sparse perivascular Tcell

infiltrate- surface IgE.

Acute eczematous lesions:- intercellular edema

(spongiosis) of epidermis,- dendritic APCs- influx of T cells- Eosinophils are rarely present

Chronic skin:- hyperplastic epidermis with elongation of the rete ridges- prominent hyperkeratosis- minimal spongiosis- surface IgE increased

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Cytokines and Chemokines

Orchestrated by the local expression of pro-inflammatory cytokines and chemokines.

Cytokines such as TNF-α & IL-1, bind to receptors onthe vascular endothelium, activating cellular signaling pathways extravasation of infIammatory cells.

Acute AD is associated with the production of Th-2 type cytokines, notably IL-4 and IL-13.

Chronic AD involved IL-5, IL-12, IL-13, IL-11 and TGF-β1.

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Genetics

Filaggrin gene is found on chromosome lq21Variants in the SPINK5 gene influence the balance

of protease versus protease inhibitor activityFunctional mutations in promoter region of the C-C

chemokines, RANTES and eotaxin.

Patogenesis

Disfungsi sawar kulit

Abnormalitas imunologik

Disregulasi apoptosis

Peran superantigen stafilokokus

Proksch dan Elias, 2001

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Clinical Findings

Typically begins during infancy. 50% by the first year of life and 30% between the ages of 1-5 years.

50 -80% of AD patients develop allergic rhinitis or asthmalater in chiJdhood.

Pruritus may be intermittent, but is usually worse in the early evening and night.

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Intensely pruritic, erythematous papules, excoriation, vesicles over erythematous skin, and serous exudate

Acute lesions

erythematous, excoriated and scaling papules.

Subacute lesions

thickened plaques of skin, accentuated skin markings (lichenification), and fibrotic papules (prurigo nodularis

Chronic lesions

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In chronic AD, all three stages of skin reactions frequently co-exist in the same individual.

During infancy, generally more acute and primarily involves the face, scalp, and the

extensor surfaces of the extremities.

In older children develops chronic lesions with lichenification and localization of the rash to the

flexural folds of the extremities

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Not needed in the routine evaluation.Serum IgE levels are elevated in approximately 70-80% patients

but 20-30% have normal result.Some of these patients may sensitive to microbial antigens, as

well some of these patients show positive reactions using the atopy patch test.

The majority of patients with AD also have peripheral blood eosinophilia and increased spontaneous histamine release from basophils.

Laboratory Tests

Diagnosis: based on clinical findings by Hanafin and Rajka

Diagnosis & Differential Diagnosis

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Lists of skin disorders that share symptoms and signs with AD.

Should be considered and ruled out before a diagnosis of AD is made.

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Complications

Ocular Problems

• visual impairment from corneal scarring, atopic keratoconjunctivitis, vernal conjunctivitis, keratoconus, cataract.

Infections

• recurrent viral skin infections, superficial fungal infections, Trichophyton rubrum infection, M.furfur infection.

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Hand Dermatitis

• irritant hand dermatitis repeated wetting/washing with harsh soaps, detergents and disinfectants

• intractable hand dermatitis in the occupational setting

Exfoliative Dermatitis

• associated with generalized redness, scaling, weeping, crusting, systemic toxicity, lymphadenopathy, and fever.

• usually due to superinfection

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Topical Therapy

CUTANEOUS HYDRATION

• Berendam atau kompres (wet dressing)• Emolien mengatasi kulit kering krn kekurangan ceramide dan steroid

sparing, serta utk terapi pemeliharaan.

TOPICAL GLUCOCORTICOID THERAPY Topical glucocorticoids are the cornerstone of treatment. The ultrahigh-potency glucocorticoids should be used only for very

short periods of time and in areas that are Iichenified but not on the face or intenriginous areas.

Mid potency glucocorticoids can be used for longer periods to treat chronic AD involving the trunk and extremities.

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TOPICAL CALCINEURIN INHIBITORS

Tacrolimus ointment 0.03% has been approved for intermittent treatment of moderate to severe AD in children aged 2 years and older, with tacrolimus ointment 0.1 percent approved for use in adults.

Pimecrolimus cream I percent is approved for treatment of patients aged 2 years and older with mild-moderate AD.

Both drugs have proven to be effective with a good safety profile for treaonent up to 4 years with tacrolimus ointmencSl and up to 2 years with pimecrolimus cream

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Identification and elimination of triggering factors

Important to identify and eliminate aggravating factors that trigger the itch scratch cycle.

These include soaps or detergents, contact with chemicals, smoke, abrasive dothing, exposure to extremes of temperature and humidity, alcohol, astringents, formaldehyde and other added chemicals in new clothing.

Living conditions (temperature and humidity) control to avoid problems related to heat, humidity and perspiration.

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Potential allergens can be identified by taking a careful history and carrying out selective skin prick tests or specific serum IgE levels.

Positive skin or in vitro tests should be confirmed with controlled food challenges and elimination diets

lnfants and young children are more likely to have food allergies, whereas older children and adults are more likely to be sensitive to aeroallergens.

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Emotional stress does not cause AD, it often exacerbates the illness.

Infectious treatment such as anti-staphylococcal antibiotics (cephalosporins, dicloxacillin, oxacillin or cloxacillin) or antiviral treatment for cutaneous herpes simplex infections.

Treatment of pruritus (systemic antihistamines or doxepin hydrochloride)

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Preparat Tar

Memiliki efek anti-pruritus dan anti-inflamasi

Berguna utk menurunkan potensi glukokortikoid topikal, ttp tdk boleh digunakan utk kulit yg

inflamasi. skin

Sampo Tar dapat berguna utk dermatitis skalp

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Fototerapi

Broadband UVB, broadband UVA, narrowband UVB (311 nm), UVA-I (340 to 400 nm), and kombinasi UVA-B dpt berguna utk tambahan terapi DA.

Fotokemoterapi dgn psoralen dan sinar UVA diindikasikan utk pasien-pasien DA dgn lesi luas atau berat.

Hospitalisasi

Pasien-pasien DA yg mjd eritroderma atau DA berat dan resisten thd terapi rawat jalan hrs dihospitalisasi sebelum mempertimbangkan

terapi-terapi sistemik alternatif.

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Terapi Sistemik

GLUKOKORTIKOID SISTEMIK

Jarang diindikasikan untuk pengobatan DA kronik.Glukokortikoid oral jangka pendek dpt berguna utk

eksaserbasi akut DA sementara modalitas terapi lainnya diberikan.

Penting utk menurunkan dosis dan memulai perawatan kulit secara intensif.

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SIKLOSFORIN

• Bekerja terutama pd sel-sel T dgn menekan transkripsi sitokin.• Pengobatan siklosporin jangka pendek bermanfaat utk

anak-anak dan dewasa dgn DA berat atau refrakter thd terapi konvensional.• Umumnya digunakan dosis 5 mg/kg BB efektif utk

pengobatan jangka pendek atau jangka panjang (1 thn), beberapa penulis menggunakan dosis 150 mg (dosis rendah) atau 300 mg (dosis tinggi) per hari siklosporin mikroemulsi.

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ANTIMETABOLIT

Open-label studies melaporkan mikrofenolat mofetil jangka pendek, 2 g per hari, sebagai monoterapi memberikan remisi lesi-lesi kulit pd dewasa dgn DA resisten thd pengobatan lain. Tetapi, hrs dihentikan jika pasien tdk berespon dalam 4-8 minggu.

Metotreksat telah digunakan untuk pasien-pasien DA dengan penyakit yg rekalsitran, meskipun studi-studi terkontrol msh kurang.

Azatioprin telah digunakan utk DA berat, meskipun belum ada percobaan-percobaan terkontrol yg pernah melaporkan hal ini.

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Terapi-terapi yg belum terbukti

Menekan respon IgE dan penurunan regulasi proliferasi dan fungsi sel Th2.Penurunan derajat beratnya klinis DA berkaitan dgn penurunan jumlah eosinofil dalam sirkulasi.

INTERFERON-

Anti-lgE monoklonal kurang efektif untuk pasien DA dewasa, tetapi memberikan perbaikan yg signifikan pada pasien-pasien DA remaja.

OMALIZUMAB

a

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Studi-studi terkontrol msh diperlukan utk menentukan peran imunoterapi thd penyakit ini.

IMUNOTERAPI ALERGEN

Penyaluran psoralen-treated leukocytes melalui sistem sinar UVA ekstrakorporeal.

FOTOFERESIS EKSTRAKORPOREAL

Pemberian probiotik perinatal berupa strain GG Lactobacillus rhamnosus menunjukkan penurunan insiden DA pd anak yg beresiko tinggi selama 2 tahun pertama kehidupan.

PROBIOTIK

Respon biasanya bersifat temporer, dan efektifitasnya bisa hilang meskipun terapi dilanjutkan.

CHINESE HERBAL

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Periode remisi lebih sering terjadi dengan pertambahan usia pasien.

Resolusi spontan DA telah dilaporkan tjd setelah usia 5 thn (40%-60%) selama masa bayi, terutama jika penyakitnya ringan.

Prognosis dan perjalanan penyakit

TERIMA KASIH