atopic dermatitis position paper - latin american society of allergy, asthma & immunology

ATOPIC DERMATITIS

Position Paper

• Revista Alergia México 2014; 61: 178-211

• Jorge Sánchez, Bruno Páez, A Macías, C Olmos, A de Falco

• http://www.revistasmedicasmexicanas.com.mx/nieto/Alergia/2014/jul-sep/pisition.paper_atopic.pdf

Atopic dermatitis (AD)• Atopic dermatitis affects a large part of the

population, particularly children under 5 years.• It usually precedes the development of other allergic

diseases such as: – Food allergy– Asthma,– Rhinitis and/or conjunctivitis

It is considered an important risk factor for these diseases.

Evaluation and management of AD

• Should be comprehensive and must include all participants in the process of health care– Patients– Families– Health care system

• The environmental characteristics of the tropics and subtropics make it necessary to create a guideline addressed to the particularities of atopic dermatitis in Latin America.

Methodology I

• The committee of atopic dermatitis of the Latin American Society of Allergy Asthma and Immunology (SLAAI) developed this guideline.

• The committee organized a table of contents that was divided into sections, reviewed by at least two committee members.

• The points regarding the diagnosis and management were defined by vote using the Delphi method.

• This guideline had a process of external validation to assess the clarity of the concepts and their applicability.

Methodology II

• Each management section concludes with a summary of the topic, which includes the strength of the recommendation and a statement of the group based on current evidence in Latin America.

• To facilitate understanding by health care staff and patients, recommendations on the diagnosis and treatment were divided into “strong”, “moderate” or “weak” according to the GRADE system (Grading of Recommendations Assessment, Development and Evaluation).

Strength of recommendation GRADE

Definitions I

• We use the nomenclature proposed by the World• Allergy Organization (WAO) in 2004.• According to the recommendation of the WAO, the

general term for a local inflammation of the skin should be “dermatitis”.

• While proposing the term “eczema” to replace the term previously used as “syndrome eczema/dermatitis”.

Johansson SG et al. J Allergy Clin. Immunol. 2004; 113:832-836

Definitions II

• They also recommend limiting the use of the term “atopic eczema” when a mediation IgE is demonstrated in the pathophysiology of the disease, and “nonatopic eczema” when it is discarded.

• While confirmatory immunological studies are done, they recommend only using the term eczema.

However, in many countries of Latin America the term “dermatitis” is used as equivalent to “eczema”, so in this guideline they are

used a common term

Epidemiology – AD• The most common skin allergic disease.• Affecting 1% to 20% of population.• It has an onset in 80% of cases in children under 2

years of age. • No significant differences between genders in the

first years of life. • It is most frequent in women (60%) than in men

(40%) after 6 years.

Atopic dermatitis

• Usually tends to remission symptoms before 5 years in 40% to 80% of patients, and in 60% to 90% at 15 years of age.

• This disease has been recognized as an important risk factor for the development of other allergic diseases such as food allergy, rhinitis and asthma.

Barnetson RS, Rogers M. BMJ 2002; 324:1376-1379

Atopic dermatitis

• Kemp et al observed that stress and psychiatric• problems in patients with moderate to severe• dermatitis were higher than those in patients with

diabetes mellitus.

Kemp AS Pharmacoeconomics 2003;21:105-113

Prevalence and incidence studies in Latin America (LA)

• The ISAAC study (International Study of Asthma and Allergies in Childhood) observed that among children aged 6-7 years, the presence of “actual eczema” varied from 0.9% in Jodhpur (India) to 22.5% in Quito (Ecuador).

• Among children between 13-14 years, the prevalence ranged from 0.2% in Tibet (China) to 24.6% in Barranquilla (Colombia).

Odhiambo JA et al J Allergy Clin Immunol 2009;124(6):1251-1258

Causes of increased prevalence of AD in LA

• Multiple causes…• Latin American factors as high exposure to mites, and

the high genetic heterogeneity.

Pathophisiology I

• Complex and multifactorial disease.• It is currently known that not only Th2 and IgE-

mediated hypersensitivity are involved.• Also the Th1 and even an autoimmune response.• Multiple genes may be involved in its development,

conferring risk or protection between populations. Several genes from the immune system has been involved (STAT-6, RANTES, TGF-beta);20-22 Filaggrin gene is located in the locus 1q21.

Pathophisiology II

• Two main points are present in all phenotypes:1) An alteration of the integrity of the skin barrier2) An immune inflammatory process.

Alteration of the skin barrier I

• The skin is a physical barrier that prevents the entry of multiple agents as organic and inorganic contaminants.

• Alterations in proteins or cells involved in the barrier function carry the entry of microorganisms, irritants and allergens, leading to a neuroimmune-inflammatory response with the consequent development of symptoms such as ITCHING.

Alteration of the skin barrier II

• Dermatitis : Substance PNerve growth factor (NGF) Vasoactive intestinal polypeptid

(VIP) Exposure and stimulation of Malpighian receptors

Accelerated apoptosis of keratinocytes colonization of bacteria (S Aureus)

Immunological alterations in AD

• Langerhans cells

• Myeloid dendritic cells

• Inflammatory dendritic epidermal cells

• Favor an inflammatory response and present allergens to immature T lymphocytes (both CD4 + and CD8 +) which are activated and become mature T cells specific for the allergen that generated activation.

Risk factors according ISAAC in Europe

• Family history of atopy• Personal development of asthma• Urban environment• Early sensitization to food and aeroallergens• High socioeconomic strata• Few family members

Study FRAAT (Risk factors for asthma and atopy in the tropics)

• Birth cohort consists of 326 children from the lowest socioeconomic strata (lower income of $200 per month) of Cartagena (Colombia), and who have strong African ancestry.

• None of the children at age of three had developed atopic dermatitis

• Protective factors:– Genetic inheritance– Low sanitary conditions– Greater exposure to endotoxin

Acevedo N et al. BMC Pulm Med 2012; 12:13

ISAAC in Latin America

• The frequency of dermatitis in Barranquilla is one of the highest in Latin America.

• One possibility is that in some cities in Latin America, the onset of dermatitis is later (> 3 years) similar to that found in some European countries

Dei-Cas I et al. Clin Exp Dermatol 2009;34:299-303

The concept of “atopic march” and the “hygiene hypothesis” in Latin America

Favoring the development of allergic diseases:- Rapid urbanization in Latin American countries- Economic development- Improvement of water quality- Health coverage- Increasing adoption of Western lifestyle with

consequent changes in dietNumber of infections Th1 Th2

Helminthes infection in LA

• Appears to have an important role in sensitization and some respiratory allergies.

• Has been demonstrated in some cohorts in Brazil, Colombia and Ecuador.

Figueiredo CA et al J Allergy Clin Immunol 2013;131:1064-1068Figueiredo CA et al Clin Immunol 2011; 139:57-64

Diagnosis

• There is not a definitive diagnostic test.• Based on a set of clinical symptoms and signs:

- Pruritus- Eczematous lesions with periods of exacerbation and control. The distribution of eczema can change with time. In children under 2 years the involvement of the face and the extensor regions is usually more common that in the elderly, where the involvement of the folds becomes more relevant.

Williams criteria are based in original Hanifin and Rafka criteria

1) Pruritus2) Distribution and typical morphology (facial

involvement and extension areas in children, and in the areas of flexion in adults)

3) Chronic or recurrent symptoms and4) Personal or family history of asthma, rhinitis and/or

dermatitis• For diagnosis, it is essential the presence of pruritus

and at least two of the other criteria.

Diagnosis

Hanifin and Rafka proposed to support the diagnosis in the presence of at least three “minor criteria”:

• Xerosis• Pityriasis alba• Cheilitis• Follicular hyperkeratosis• White dermatographism• Ichthyosis• High total IgE

• Conjunctivitis• Tendency to skin infections• Facial erythema• Dennie Morgan bifold• Sensitization to food• Contact dermatitis • Seborrheic dermatitis

Severity

• Among the most frequently used are:– SCORAD (Severity Scoring of Atopic Dermatitis)– EASI (Eczema Area and Severity Index– POEM (Patient-Oriented Eczema Measure).

SCORAD

• The scale goes from 0 to 104 points, and ranks as “mild”, “moderate”, and “severe”

• Scale: Mild < 15 puntos Moderate 16-40 Severe > 40

• Dermatitis classification divides patients in: Intrinsic Extrinsic

Normal IgE

Phenotypes

High levels of total IgE (generally accepted > 200 kU/L), or a demonstrated sensitization to aeroallergens or food allergens.

Population characteristics in Latin America

• A big part of the NON-ALLERGIC population in Latin American cities seem to have total IgE levels above 200 kU/L, so this cutoff would not serve as a criterion for classifying dermatitis as intrinsic or extrinsic.

• This higher concentration of total IgE in the tropical population seems to be due to the high frequency of helminthes infections.

Phenotypes according to immunological changes.

• Parallel to the better understanding of the pathophysiology of AD, a more accurate classification has been developed to allow, through the use of multiple biomarkers, a greater certainty in the prediction of the evolution of dermatitis, and also to define a more effective treatment for each patient.

Phenotype I

Th1 Response Expression of cytokines: IL-1IL-6TNF-betaDendritic cells with few exilon

receptors in the membranePredominates in patients classified with intrinsic dermatitis and in patients with extrinsic dermatitis during inter-critical periods

Phenotype II• Predominance of Th2 response• Airborne and food allergen sensitizationThis process: - associated with asthma - lower remission rate

- greater severity - associated with defects in filaggrin

geneMay be suspected: palmar hiperlineality

eczema herpeticum

Phenotype III

• Presence of an autoimmune response mediated by IgE.

• It is suggested that this may be due to the homology between human proteins and allergens from other species

• Represent the most serious phase in a patient with dermatitis as a result of the persistent exposure to intrinsic allergens

• These three processes represent different “endo-phenotypes” of the dermatitis

• Their identification would predict the likelihood of remission and the treatment required (whether or not avoidance of allergenic sources, treatment with topical or systemic immunomodulators, etc.).

These processes may occur separately,can also be different stages of a single process

Process 1 Th1 response

Process 2 Th2 response

Process 3 Sensitization to auto-allergens

Classification according to age of presentation

80% of the cases begin before age 2

• 43.2% had a complete remission between 2 and 7 years

• 18.7% persisted with symptoms• 38.3% had a intermittent pattern

Illi S et al, JACI,2004

Factors related to persistence early onset (before the 1er year of life) AD severity lower respiratory symptoms

Classification according to age of presentation

20% of the cases begin >14 years Only few studies about adult AD 45% of the adult AD begin before age

6

18% of the adult AD begin after 20 years

Higher sensitization and total IgE level

Higher persistence

Garmhausen et al. Allergy, 2013

Laboratory test

Total IgE

•Higher level in AD patients

•Biomarker associated with • Persistence (Kawamoto N et al; Lui FT et al)• Severity (Antunez C et al, Laske N et al)• Rate of sensitization (Laske N et al) • Topical and systemic treatment response

•It may persist elevated even with a AD improvement

•Other causes of elevated total IgE should be considered

Laboratory test

Total IgE

Indication:•Evaluation and monitoring of the patients with extrinsic and intrinsic AD

Committee recommendation:•Weak•May be used in children < 6 months with severe symptoms and children >5 years with persistent symptoms

Particular considerations in Latin America:•It is necessary to know normal total IgE in different regions of Latin America before performing this test routinely

Laboratory testAllergen sensitization

•AD patients are sensitized to a large number of sources than patients with asthma or rhinitis

(Johnke H, Pediatr Allergy Immunol 2006)•Sensitization to food occurs in the first years of life and then it is replaced by sensitization to aeroallergens (Acevedo N, BMC Pulm Med 2012)

In tropical zones, mites sensitization could start early in life(before the first year)(Acevedo N, BMC Pulm Med 2012, López N, Eur resp J, 2002)

•Specific IgE (mites and cat dander) in Europa: has been related with AD severity

(Schöfer T, JACI 1999)

•High specific IgE in AD patients has been associated withan increased risk of food allergic reactions (Hill DJ, Pediatr Allergy Immunol 2008; Wahn U Pediatr Allergy Immunol 2008)

Laboratory test

Allergen sensitization

•Colombian study:Correlation between the pattern of sensitization to aeroallergens and the development of AD and asthma

•Other allergen sources must be consered in Latin America: corn,tomato and pork

A right interpretation of the test result is neccessary in order to increased the patient adherence to therapyand the quality of life

Sánchez J, Revista Alergia México 2012Sánchez J, Allergol Immunopathol 2013

Laboratory test


•Microbial proteins: 50-80% sensitization to the AD patients It has been correlated with the AD severety

•A greater sensitization to Malazzasia fufur has been observedin the AD patients; a clear correlation with severity is not demostrated

•Response against autoallergens (Hom s) appears to be specificof AD severe which could be important in predicting the prognosis

Laboratory test


Indication:•Diagnosis and monitoring of AD patients•Identification of environmental sources exacerbating symptoms

Committee recommendation:•Aeroallergens: strong. All patients with dermatitis•Food allergens: strong. Only when a clinical suspicion or AD severe or persistente.The test battery should be consistent with the geographical area

Particular considerations in Latin America:•There are many studies about aeroallergens but only a few about food allergens in specific regions

Laboratory test

Patch tests with food and/or aeroallergens

• Food• Tests have been carried out with milk, egg, soy, wheat…

•Drawback.• Wide range in predictive values and lack of standardization

•Adventages• Easy to perform• It can reduce the requeriment for provocation tests and avoid

unnecessary restriction diets

•Aeroallergens• The main experience with mites patch tests• Lack of standardizations so the routinely use is not recommended

•

(Isolauri E, JACI 1996; Niggemann B, Allergy 2000; Vanto T, Allergy 1999; Niggemann B, JACI 1999; Majamaa H, Allergy 1999; Darsow U, Allergy 2004

Laboratory test

Patch tests with food and/or aeroallergens

Indication:•Evaluation and monitoring of AD patients •When delayed reactions with food or aerollergens aresuspected

Committee recommendation :•Food: moderate. Useful in patients with negative IgE response or late-onset symptoms •Aeroallergens: weak. Few controled studies. Specific batteries of allergens should be used

Particular considerations in Latin America :Only a few studies but in favor of its useStandardization of the technique is necessary

Laboratory test

Patch with standard battery and other types of patch

15-30% of AD patients suffer from contact dermatitis

This test is very useful in patients with strong suspition of exacerbation by contac allergens or persistent symptoms without response to treatment

Considered a false positive result in AD

In some occasions a photo-pach test must be performed

It is important to know that if non standarizated contacts are used, pacth tests in 10 healthy controls must be performed

White JM, Clin Exp Allergy 2012; Spiewak R, Curr Opin Allergy Immunol 2012

Laboratory test

Patch with standard battery and other types of patch

Indication:•Patients with suspicion of AD•Patients with severe and persistent AD refractory to medical treatment

Committee recommendation :•Standard battery: strong•Other types of patch: moderate

Particular considerations in Latin America :Useful as diagnosis support in AD

Rodrigues DF, An Bras Dermatol 2012; Blancas-Espinosa R, Contact Dermatitis 2006; Rivas A, Revista Asociación Colombiana Dermatologia 2011)

Laboratory test

Provocation and food elimination diets

The provocation test with food is considered the gold standard for identifying if a suspected food is the cause of the patient´s symptoms

Due to the potential risk of this test, it is carried out when skin prick test and laboratory test cannot clarify the diagnosis

In many cases are carried out elimination diets for 4-6 weeks to assess the AD evolution; if doubt persists then a challenge test could be performed

Laboratory test

Provocation and food elimination diets

Indication:When skin prick test and laboratory testcannot clarify the diagnosis

Committee recommendation :•Strong•After elimination diet, if doubt persists, a provocation must beperformed

Particular considerations in Latin America :•There are few studies about this subject. •It is necessary to establish protocols with native foods

Madrigal BI, Rev Aler Mex 1996)

Laboratory test

Complementary studies

-CSC, electrolytes determination, liver function or kidney function…. :

•They are not inicated as routined exams•They could be indicated as part of the follow up whenimmunosupressants or sistemic steroids are been administrated

-Skin biopsia: useful for differencial diagnosis

Active management

FIRST LINE MANAGEMENT

Skin care and hydratation

Dry skin is one of the main signs of AD due to

-filaggrin defects-lack of intercell lipids and other

stratum corneum alterations

In consequence, a lack of continuity of SKIN BARRIER occurs in AD

Briot A, J Exp Med 2009

Active managementFIRST LINE MANAGEMENT

Bathing:

• Removes debris of the skin that could stimulate the bacterial growth

• It is recommended very short bath (about 5 minutes) with slightly cold water to reduce xerosis and mechanical irritation

• Add sodium hypochlorite into bath water in patients with history of skin infection or risk of skin infection) aprox. 1 or 2 drops/liter of water prevent balterial growth

• Using bath salts or oils in final two minutes of the bath could improve skin hydratation and skin cleansing

• Avoid soaps and use neutral cleansing

Huang JT, Pediatrics 2009

Active management


• If a chielitis exits, moisturizing lipsticks are recommended• Keep nails short to prevent stcraching during sleep• Baggy clothing made of cotton is the best in order to avoid irritation and heat

There are a few controlled studies in relation to adjuvant treatment (moisturizing, general recommendatios, cleansing products …)

Méndez-Cabeza J. MEDIFAM 2003


Moisturizers appear to reduce

• Severity of AD exacerbations (Breternitz M, Skin Pharmacol Physiol 2008)• Bacterial infections (Verallo-Rovell VM, Dermatitis 2008)• Steroid requirement (Grimalt R, Dermatology 2007;

Szczepanowska J Pediatr Allergy Immunol 2008)

It is recommended to apply twice a day; one of them after bathing or shower(Chiang C, Pediatr Dermatol 2009)

Choosing the best depend on • AD extension• AD severity• patient´s tolerance

(Varothai S, Asian Pac j Allergy Immunol 2013

Active management


Moisturizers

• It’s considered a pillar in the treatment of AD• Another important factor in a good adherence is the cost of the product • Explain to the patient how to use moisturizers and apply the right amountRule of the fingers could be used: The amount of cream that covers a thumb must be cover the palm of hand),

Active management


Moisturizers • Vaseline is considered a AD moisturizers with a excellent cost/efficacy relation•Disadventages: it has an oily consistency and it produce a sense of heat and sweat retention

• Urea products impprove the skin renewal but tend to be lesstolerated than others, specially in areas with open lesions• Urea is recommended on skin with lichenification.

Some creams contain natural ingredients (nuts, oats…) with a small risk of sensitization

Lodén M, Acta Derm Venereol 2002Lack G, N Engl J Med 2003

Active management


Moisturizers Indication• In all AD patients• The frecuency and the amount depend on the severity

Committe recomendation • Strong• Choose the product that facilitate the better adherence

Particular considerations in Latin America :•At the moment, these products are not covered by the health systems in the most countries.•Factors such as cost/benefit must be considered to ensure a good adherence and a better response

"For anti-inflammatory treatment, topical steroids remain the cornerstone in the management of dermatitis"

Topical steroids

First line management

Topical steroids

• Reduce the risk of infection by S. aureus

• Lower frequency of systemic side effects

• Few controlled studies supporting their uses or how to use them

• Different schemes have been proposed in the use of steroids

Active management


• Schemes proposed in the use of steroids:

– Potency and regions

Active management


Topical steroids

•Schemes proposed in the use of steroids:

–Minimum possible time

–Switch to medium or low power steroids

according to the control of the patient.

–Prolonged periods in wide body extensions

(even mild steroids) can have similar risk of

adverse effects than oral or intravenous

steroids.

–Intermittent treatment appears to reduce this

risk even with high potency steroids

Active management


Topical steroids


–High potency steroids:

• Should be used only in patients with

moderate to severe AD

• Should be avoided in the facial, folds

and perennial regions

• Should be used with caution in

children under two years

?


Active management

Topical steroids


–Steroid use with moisturizer seems to

improve the power of the steroid and

increase the time of its effect on the

skin

+

Topical steroids

Active management


•Recommendation of the Committee.

Strong.

•Particular considerations in Latin America.

–Latin America has a wide variety of

steroids

•It must be taken into account the

characteristics of the tropics and

subtropics regions when choosing the

consistency (cream, ointment, etc.) to

improve patient adherence.


Active management

Topical steroids

• In practice, they can be used for the same indications as a steroid of medium (tacrolimus 1%) or low power (tacrolimus 0.03%, pimecrolimus 1%)

• Advantages:

• Lower risk of adverse effects

• Not cause skin atrophy in continuous treatment

Calcineurin inhibtors


•Recommendation of the Committee. Strong

•Particular considerations in Latin America.

• Currently in most Latin American countries both tacrolimus and pimecrolimus are available.


Active management

Calcineurin inhibtors

“In the last two decades several controlled studies showing that a significant percentage of patients with atopic dermatitis can benefit from this therapy"


Allergen-specific immunotherapy

• ACTIONS

• Significant reduction in

symptoms compared to

placebo (by SCORAD)

• Significant increase in IgG4



• Indication. Patients with persistent moderate or severe atopic dermatitis who have a clear relationship of exacerbation with aeroallergens.

• Recommendation of the Committee. Moderate.

• Particular considerations in Latin America.

• Studies support the efficacy and safety of using the specific allergen immunotherapy with Dermatophagoides farinae and Dermatophagoides pteronyssinus

• Studies using other common allergen sources in the region, as Blomia tropicalis, Dermatophagoides siboney and some pollen grains are needed.


Active management


“Since the skin of patients with dermatitis is very sensitive, many agents can act as irritants increasing the inflammatory process and therefore should be avoided"


Enviromental and dietary control

Environmental control

• Irritants substances:

• Soap, detergent, some creams, polluted air

• Control the temperature and humidity is necessary

• Allergenic sources witch patients are sensitized must be avoided

• Prophylactic restrictions without clinical relevance are not recommended

• Removal of pets: unless there is clear clinical relationship and sensitization is demonstrated

Enviromental and dietary controlFIRST LINE MANAGEMENT

•Dietary control

• Top Ten allergenic foods

• Restricted diet should be very careful

• High prevalence of irrelevant

sensitizations

• Nutritional problems

Enviromental and dietary controlFIRST LINE MANAGEMENT


Enviromental and dietary control

“Have been used for many years…but controlled studies show minimal or no effect"

Second line management

Antihistamines

•NO EFFECT?

• Other mechanisms? IL-33?

• First-generation:

• Sedative effect

• Risk of side effects: drowsiness; low

concentration

• Second-generation:

• Loratadine, cetirizine, fexofenadine:

some impact on pruritus

Antihistamines

Active managementSECOND LINE MANAGEMENT

Active managementSECOND LINE MANAGEMENTAntihistamines

“Because the high risk of adverse effects (cataracts, osteoporosis, height), is notrecommended for prolonged use”


Systemic steroids

• High relapse rate after

suspension, compared with

other immunosuppressants,

like cyclosporine

• Adjust the dose according the

weight

• Reduce the dose as soon as

possible

• No standard way to do this

Systemic steroids



Systemic steroids

“Mild to moderate AD had a significantimprovement over the summer, with relapses in the other seasons”


Sun exposure and phototherapy

Sun exposure: • 15 a 20 minutes (7:00-8:00 am; 3:00 -

4:00 pm) – beneficial effect• High temperature and humidity in tropics

can exacerbate pruritus

Sun exposure and phototherapySECOND LINE MANAGEMENT

Phototherapy: • Controlled environments - 40 to 50% of

substancial improvements• Mechanisms (not clear):

• Antimicrobial effect• Inhibiting the Langehans cells activity• Production of Vitamin D

• Wavelengths types:• UVA1, UVB, UVB broadband• UVB can use in children

• Side effects:• Burns, hyper pigmentation, fatigue, nausea,

headache


“This therapy is clinically effective,but with high relapse rate”


Cyclosporine A

Cyclosporine A:• Mechanisms:

• Potent inhibitors of T lymphocytes immune

responses• Clinical response is observed after 2 weeks,

reaching great effect at 2 to 3 months• Risks:

• Nephrotoxicity and hypertension• Side effects:

• Nausea, paresthesias, abdominal pain


SECOND LINE MANAGEMENTActive management

Cyclosporine A

“Although there are numerous reportshowing its positive effect in patients with AD, there are few controlled studies”

Third line management

Mycophenolate mofetil

Mycophenolate mofetil:• Mechanisms:

• Inhibitors of purine synthesis; • Stop the division of diverse cell lines,

including lymphocytes• Side effects:

• Nausea, vomiting, herpes and retinitis

Active managementTHIRD LINE MANAGEMENT


Mycophenolate mofetil:

“Several controlled studies supported it, use especially in severe cases in population over 6 years of age”


Azathioprine

Azathioprine: • Mechanisms:

• Not know• High incidence of adverse effects

• Nausea, vomiting and abdominal pain• Clinical response: 4 to 8 weeks



Azathioprine:

“There are few controlled studiesfor AD treatment. Therefore the appropriate dose and frequencyof adverses effects is limited”


Methrotrexate

Methrotrexate:• Mechanisms:

• Inhibitor of dihydrofolatereductase, it

prevents the activity of thymidilate

synthetase necessary for the

incorporation of nucleotide dTMP into

DNA• Efficacy similar to Azathioprine

• 10 to 25 mg/week



Methrotrexate:

Probiotics and prebiotics

Pro Contra• Kalliomäki et al: Lactobacillus

rhamnosus• Dotterud et al: Lactobacillus sp• Osborn, Cochrane Review 2007:

reduction in eczema, but not enough to recommend

• Williams et al• Bath-Hextal, Cochrane Review 2012

• Osborn, Cochrane Review 2013: more studies are needed

Kalliomäki, Lancet 2003. Osborn, Cochrane Database Syst Rev. 2007Dotterud, Br J Dermatol 2010. Williams, Clin Exp Dermatol 2010

Bath-Hextal, Cochrane Database Syst Rev 2012, Osborn, Cochrane Database Syst Rev. 2013

Active managementFOURTH LINE MANAGEMENT

Omalizumab

• Conflicting evidence: studies with promising results and some

without clinical effect.

• Some reports suggest good results even with high levels of IgE

Caruso, Allergy 2010. Park, Ann Dermatol 2010. Lane, J Am Acad Dermatol 2006.Belloni, JACI 2007. Sheinkopf, Allergy Asthma Proc 2008.

Heil, J Dtsch Dermatol Ges 2010. Iyengar, Int Arch Allergy Immunol 2013


Interferon gamma

• One study compared high dose, low dose and placebo, with good

results in the 2 groups treated with interferon gamma.

• Adverse effects: transient fever, myalgias, respiratory distress, elevated

transaminases and lipid profile.

Jang, J Am Acad Dermatol 2004.


Others therapies:

• Contradictory results: rituximab, efalizumab, aterizumab, alafacept,

mepolizumb and etanercept; can not be recommended to all

patients.

• Satisfactory results but not standardized: intravenous

immunoglobulin, autologous serum, some herbal products; can not

be recommend.

Simon, JACI 2008. Sedivá, JACI 2008. Ponte, J Am Acad Dermatol 2010.Ibler, J Eur Acad Dermatol Venereol 2010. Bremmer, J Am Acad Dermatol 2009.

Jee, Allergy Asthma Immunol Res 2011. Pittler, Br J Dermatol 2003. DiNicola, Clin Rev Allergy Immunol 2013. Zhang, Cochrane Database Syst Rev 2005.


Hospital management

• Should be avoided because high risk of complications.

• Should be consider when:

– Involvement >50% of skin surface with moist lesions or erythrodermia

– Sepsis or severe cutaneus infection, disseminated or extensive

– Involvement of other systems: renal, respiratory, etc.

– Limitation to perform daily activities

– Failure to follow established treatment

– Rapid deterioration

Buhles, J Dtsch Dermatol Ges 2011. Holling, J Eval Clin Pract 2010

Active management

Primary prevention:

• Vitamin D supplementation during pregnancy has contradictory results

• Some foods (fruits, vegetables, unsaturated fatty acids) may have a

preventive effect

• Polyunsaturated fatty acid supplementation during pregnancy appears to

reduce the risk, but further studies are needed

• In a meta-analysis, the presence of dogs in the house reduced the risk by

25%

Reinholz, clin Exp Allergy 2012. Bäck, Acta Derm Venereol 2009Hyppönen, Ann N Y Acad Sci 2004. Nwaru, Pediatr Allergy Immunol 2010

Foolad, JAMA Dermatol 2013. Palmer, BMJ 2012. Pelucchi, JACI 2013

Secondary prevention

• The goal is to prevent common complications such as exacerbations and

bacterial superinfection.

• Topical antibiotics one week per month, although they appear to prevent

infection, no statistically significant changes and exists the risk of antimicrobial

resistance.

Boguniewicz, JACI 2010. Bath-Hextall, Br J Dermatol 2010

Pregnancy:

• During second half of pregnancy, 66% of patients present exacerbation

• Treatment is almost like non-pregnancy, but try to use small doses of topical

steroids (Category C)

• Only in extreme cases: calcineurin inhibitors, oral steroids, azathioprine and

cyclosporine

• Avoid: methotrexate, mycophenolate mofetil, psolarens and PUVA therapy

• First-generation antihistamines (Category B): chlorpheniramine, cyproheptadine

and diphenhydramine

• Second-generation antihistamines: loratadine seems to be a safe option, there few

studies

Babalola, Dermatol Ther 2013. Cho, Ann Dermatol 2010Koutroulis, Obstet Gynecol Surv 2011. Kar, J Pharmacol Pharmacother 2012

Special situations

Breastfeeding:

• Elimination diet in the mother for food to which the child is allergic

• Breastfeeding seems to have a beneficial effect

• If the mother takes immunosuppressive drugs for dermatitis:

– Steroids can pass into breast milk

– Ideally cyclosporine should be discontinued

– Second-generation antihistamines approved after the sixth month of life

Orru, Int J Immunopathol Pharmacol 2013. Paveglio, Clin Exp Allergy 2012. Verhasselt, Nat Med 2008

Special situations

Adult dermatitis:

• Onset after 14 years: 5-15%

• Tendency to have more non-allergic comorbidities

• It may be necessary skin biopsy and / or patch tests

Garmhausen, Allergy 2013. De Bruin Weller, Clin Exp Allergy 2013

Special situations

Interdisciplinary managementAllergist

Dermatologist

Ophtalmologist

Pulmonologist

Pediatrician

Dentistry

Psychiatrist /

Psychologist

Otolaryngologist

Silverberg, Pediatr Allergy Immunol 2013. Yaghmaie, JACI 2013. Kemp, Pharmacoeconomics 2003

Table 2. Immunosuppressive drugs

Committee of Atopic DermatitisDra. Ana María Agar, Chile

Dra. Milagros Lázaro, EspañaDr. Bruno Paes Barreto, Brasil

Dra. Alejandra Macías Weinmann, México

atopic dermatitis position paper - latin american society of allergy, asthma & immunology

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