Simposio Internacional: Avances científicos en Dermatología
International Symposium: Lastest scientific advances in Dermatology
Madrid, 18 de enero de 2013Madrid, January 18, 2013
RESÚMENES/ABSTRACTS
v
1. What is new in contact dermatitis, Ann Goosens
2. What is new in psoriasis, Esteban Dauden
3. What is new in bullous disease, José Manuel Mascaró
4. What is new in Pediatric Dermatology, Antonio Torrelo
5. What is new in vascular malformation?, Alain Taieb
6. What is new in dermoscopy, Susana Puig
7. What is new in cutaneous lymphomas, Lorenzo Cerroni
8. What is new in dermatopathology, Luis Requena
What is new in contact dermatitis
Ann Goosens
Metals:
· Nickel still (illegally) found in jewelry, mobile phones, …
Palladium crossreacts with nickel and may cause granulomas. Disodiumpalladinate 2%pet. better screening agent than Palladiumchloride
· Spot test for cobalt based on disodium-1-nitroso-2-naphthol-3,6-disulfonate, able to identify cobalt at approximately 8 ppm
Occupational allergens
Resins:
· Epoxy: not only bisphenol-A (standard series) but also bisphenol-F-based (and other) resins
· Isocyanates: not only responsible for immediate-type reactions! Patch-test preparations not to be trusted! Keep refrigerated
· (Meth)acrylates: 2-HEMA, EGDMA (good screening agents*), Bis-GMA, 2-HPMA, … Volatile, to apply immediately before patch testing
Preservatives in water-based products:
· Isothiazolinones:
Methylchloro and methylisothiazolinone (MCI/MI)
Methylisothiazolinone (MI) to be tested separately in baseline series (min. 500 ppm)
Octylisothiazolinone (also in powderfree PVC gloves)
Benzisothiazolinone
· Formaldehyde (also in gloves!) and releasers: sensitization potential does not only depend from formaldehyde, but also from degradation products formed (e.g. in imidazolidinyl- and diazolidinyl urea)
Rubber derivatives:
· Carbamates and diphenylguanidine in synthetic rubber (so-called latex-free medical gloves are the actual allergens
Drugs
Systemic drugs administered to patients in health care personnel (nurses): tetrazepam and other benzodiazepines, ranitidine, … Hand and particularly airborne dermatitis from crushing tablets; budesonide-inhalations.
NSAID’s: ketoprofen
Photosensitivity (up to one year after use!).
Frequently associated positive tests: chemically but also non-chemically related materials.
Traces may reside in textiles, shoes …
Other pharmaceutical products
Recent allergens: calcipotriol, mupirocine, formaldehyde releasers in cortosteroid creams,
Pseudo?-pharmaceutical products and medical devices such as creams (methylisothiazolinone!), adhesive tapes, wound dressings, electrodes, TENS, …
Medical devices are not labelled while full labelling of cosmetics, pharmaceutical products, and of important allergens (fragrances, preservatives) in detergents.
Composition unknown, hence, many allergens unidentified!
Manufacturers do not often provide information nor send ingredients to test with!
Airborne dermatoses may occur on both exposed & non-exposed areas!
· E.g. resins, preservatives, e.g. methyl (chloro) isothiazolinone (methyl-dibromo glutaronitrile, not allowed in cosmetics since 2007).
· Inhalation producing “systemic” eruptions (e.g. mercury exanthema)
· Airborne + photosensitivity reactions may exceptionnaly be combined
Cosmetics
· “Natural” ingredients as allergens in cosmetics; cross-reactions with fragrances because of presence of common (oxidized) terpenes, particularly with Compositae (Asteraceae) plants ! Also in tea tree oil (antifungal!)
· Fragrances: To detect fragrance allergy: fragrance mix I and II in baseline series. Test also with own perfumes.
· Preservatives: contact allergy to the individual materials largely differs from one country to another. Methylisothiazolinone replaces the mixture MCI/MI but frequent cause of contact allergy (wipes!). Formaldehyde releasers also becoming more important allergens, since parabens being eliminated
· Sunscreens: octocrylene and benzophenone-3 (cross-reactions with ketoprofen!)
· Hairdyes (PPD and other hair dyes)
Immediate reactions (even rare anaphylactic reactions).
Temporary tattoos cause primary sensitization that may lead to very severe contact dermatitis to hair dyes afterwards.
· Unexpected allergens (also in cosmetic products “for sensitive skin”)
Hydrolysed proteins: may also cause immediate-type reactions
Emulsifiers, solvents, humectants, vehicle components, skin-conditioning agents:
potential (rare) allergens
- Ethylhexylglycerin
- Alkylglucosides (decyl glucoside in sunscreens, coco- and lauryl-glucosides,… also in wipes!)
- Butyleneglycol, pentylene and hexylene glycol
- Isononyl isononanoate, ascorbylpalmitate
- Tetrahydroxypropyl ethylenediamine (no cross-reaction with ethylenediamine)
- Copolymers: Methoxy-PEG -17/22 dodecyl glycol copolymer, PVP/hexadecene copolymer, phtalic anhydride/ trimellitic anhydride/glycols copolymer, VP/eicosene copolymer, C30–38 olefin/isopropyl maleate/MA copolymer, …
Textile dyes in clothing
More frequent than previously recognized (also in atopics!)
· True incidence unknown. Azo-dyes are the most frequent allergens! Need for Disperse mix in baseline series?
Diagnosis difficult because of clinical polymorphism:
- Unusual clinical patterns
- Unexpected locations
- Body areas with sweating and friction … eyelids and hands sometimes also involved!
What are the allergens? The dye itself (purity, identity, product intermediate? Metabolite in the skin?)
· Also non-disperse dyes responsible for textile dermatitis (in cotton, wool, silk, and/or polyamide,), particularly if badly coloured. Cases described mainly in an occupational context (also immediate-type reactions to reactive dyes).
Children
· Aluminium allergy, main source : vaccines or hyposensitisation therapy
· Shoe dermatitis with main frequent allergens
- Rubber derivatives (MBT’s, thiurams)
- Leather (dichromate)
- Glues (PTBP-resin)
- Dyes (PPD & derivatives), also in socks!
· Corticosteroids, also in atopic children
Not always “worsening” of eczema, no curing of the lesions
Patch tests may only become positive after 4 or 5 d or later …
Test: markers for corticosteroid allergy and own products used!
· Cosmetics: octocrylene in sunscreen products; wipes with fragrances and preservatives (isothiazolinones, formaldehyde releasers)!
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What is new in psoriasis
Esteban Dauden
The knowledge of psoriasis has expanded within the last few years. We will review some new data about this disease:
1) Genetics.
Driven by advances in molecular genetic technologies and statistical analysis methodologies, there have been huge strides taking in dissecting the complex genetic basis of psoriasis. Application of classical linkage analysis and genome-wide association studies (GWAS) has identified genetic loci of major and minor effect. Although most loci independently have modest genetic effects, they identify important biologic pathways potentially relevant to disease pathogenesis and therapeutic intervention. At least 9 GWAS have been carried out in the past few years. The analysis of 500,000 – 1,000,000 SNPs has allowed the identification of 22 novel psoriasis susceptibility regions. GMWAS has some limitations such as a lack of statistical power, underrepresentation of rare variants (SNPs ocurring at a frequency of < 5%) on genotyping chips, and a limited power for the detection of complex copy number variants
The advent of next-generation sequencing methods will permit a more detailed and complete map of psoriasis genetic architecture, a key step in developing personalized medicine strategies.
2) Psoriasis, A systemic disease?
Comorbidities are defined as the association of a given disease with one or more other diseases (usually multifactorial and often associated with underlying inflammation). About 73% of psoriatic patients have at least one comorbidity (HT, dyslipemia, diabetes,…). It is controversial whether they have common pathogenetic mechanisms. It is also controversial whether an early anti psoriatic systemic treatment may prevent cardiovascular disease.
3) Topical therapy
At present there are a huge number of topical agents in the pipeline. The last commercialized product is a gel combination of calcipotriol and betamethasone dipropionate. Different antibody formats, such as classic monovalent antibody fragments (Fab, scFv) or engineered variants (minibodies, diabodies, triabodies, tetrabodies, single-domain antobodies) are being investigated . The engineered antibody fragments retain the targeting specificity of whole mAbs, can be produced more economically, and possess other unique or superior properties (nonimmunogenic, superior biodistribution, and superior blood clearance). Also nanotechnology for topical delivery of drugs may be useful in a future. Nanosized carriers (50 – 500 nm) may be able to overcomethe skin carrier or target specific skin regions
4) Systemic drugs near future
Oral drugs that have shown efficacy and a safety profile include:
a. Tofacitinib. It is an inhibitor of the Janus kinase (JAK) family of kinases, with functional specificity for JAK1 and JAK1/3. The JAK family of kinases mediate proinflammatory cytokines (IL-2, -4, -7, -9, -15, -21) integral to lymphocyte activation, proliferation and function (tofacitinib à suppresses T-cell function)
b. Apremilast. It is a small molecule inhibitor of phosphodiesterase-4 (PDE4). PDE4 inhibition reduces the production of a network of proinflammatory mediatorssuch as tumor necrosis factor-α,IL-17, IL-22 and interferon-γ.In addition, it is believed that PDE4 interferes with the production of anti-inflammatory mediators such as IL-10.
Injectable drugs include those related to IL-17:
c. Anti IL-17:
i. Secukinumab (human IgG1k monoclonal antibody)
ii. Ixekizumab (humanized IgG4 anti IL-17A monoclonal antibody)
d. Anti IL-17 receptor:
i. Brodalumab (fully human IgG2 anti IL-17 receptor mAb that blocks signalling by IL-17A, IL-17F, IL-17A/F, and IL-17E (IL-25))
5) Biosimilars
Biosimilars are not likegeneric drugs. Key differences between original agent and the biosimilar are the following: a) original agent are manufactured in living systems (antibodies, recombinant proteins, and vaccines); b) the nature of the biologic drug is inexorably linked to its process of manufacture – the process used to manufacture a biologic agent determines the characteristics of the final product. The criteria for regulatory approval of biosimilars is likely to be an intensely debated topic over the next few years as government agencies strive to find an appropiate path forward. A substitution from innovator to biosimilar must be considered as a change in the clinical treatment of the patient. Patients should be monitored through time to generate a database that facilitates comparison of the biosimilar to the original drug (long-term pharmacovigilance, registries).
6) Pharmacogenetics
Systemic drugs used for the treatment of psoriasis show significant variability in efficacy and are associated with varying degrees of toxicity. Identification of pharmacogenetic markers of treatment response may be useful in predicting clinical response and would help in the development of individually tailored treatment. This would increase the cost effectiveness and reduce unnecessary exposure to treatment toxicity. In a future, personalized medicine will transform everyday clinical practice.
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What is new in bullous diseases
José Manuel Mascaró
Antimicrobial peptides and UV radiation
It has been recently demonstrated that UV radiation enhances the cutaneous expression of antimicrobial peptides (AMP) from keratinocytes and, presumably, vitamin D synthesis is involved in the pathogenesis of this overexpression. AMP are small peptides that guard the body-environment interface. They are constitutively expressed on the skin surface or rapidly inducible from keratinocytes and considered to be a major component of the innate immune system. In addition, AMP have a direct antimicrobial activity, but also a role in balancing cutaneous inflammatory response as well as a pivotal link between the innate and adaptive immune system. Importantly, overexpression of some AMP like psoriasin or RNAs-7 have been found in photoaggravated skin diseases like polymorphic light eruption and they are also deregulated in highly prevalent skin diseases like psoriasis, rosacea or atopic dermatitis. The relationship between UV radiation, AMP and clinical effects may be not so simple, as probably some of them may have pro-carcinogenic and some others tumor suppressor activities. However, the effect of RUV on AMP gives a wider and more comprehensive view about the immunologic action of UV radiation on the skin, that combines the effect of regulatory T cells - that of course may favor carcinogenesis but also prevents from autoimmunity- and could be compensated with the quick and direct effect of AMP against the risk of infection. This also means a new door to a better understanding how phototherapy works, as the effects over AMP should be also taken into account.
Limits of topical photoprotection
Nowadays, topical photoprotection has spread towards cosmeceuticals as sunscreens are usually included in several moisturizers. However, the effects of sunlight may vary from different countries and seasons. Even in a sunny country from Southern Europe like Spain, the risk of having erythema secondarily to sunlight is presumably very limited even after long expositions during winter months. In addition, the application of sunscreen as recommended by the institutional guidelines (2ng/cm2) may in fact inhibit vitamin D synthesis, which may be particularly true during winter months. Furthermore, the – uncommon- risk of photoallergic reactions from sunscreen should be taken into account after the indiscriminate use of these molecules. So that, photoprotection strategies and guidelines should still be optimize and adapted to the erythematic irradiance.
Phototherapy of psoriasis in the biologic era
Phototherapy of psoriasis ( NBUVB and PUVA therapy ) still remains to be a good option in the management of moderate to severe patients despite the incoming of biologic therapy. PUVA therapy was found to be the second best option after infliximab in a series of 173, with more than 85% achieving PASI 75 score after the induction therapy.
Regarding photodynamic therapy, the biggest advance during past months has been the introduction of daylight- mediated PDT. In three clinical trials performed in Northern Europe daylight-mediated PDT has been demonstrated to be a simpler, effective and more tolerable for thin actinic keratosis compared to standard PDT. However, a wider evaluation in different countries –including Southern Europe- is needed. Furthermore, we need to know the effect of daylight mediated PDT in the treatment of basal cell carcinoma and bowen disease.
References
- Ibbotson SH, Valentine R, Hearn R. Is the pain of topical photodynamic therapy
with methyl aminolevulinate any different from that with 5-aminolaevulinic acid?
Photodermatol Photoimmunol Photomed. 2012 Oct;28(5):272-3
- Felton S, Navid F, Schwarz A, Schwarz T, Gläser R, Rhodes LE. Ultraviolet
radiation-induced upregulation of antimicrobial proteins in health and disease.
Photochem Photobiol Sci. 2012 Dec 13;12(1):29-36
- Sola Y, Lorente J, Ossó A. Analyzing UV-B narrowband solar irradiance:
Comparison with erythemal and vitamin D production irradiances. J Photochem
Photobiol B. 2012 Dec 5;117:90-6.
- Gelfand JM, Wan J, Callis Duffin K, Krueger GG, Kalb RE, Weisman JD et al. Comparative effectiveness of commonly used systemic treatments or phototherapy for moderate to severe plaque psoriasis in the clinical practice setting. Arch Dermatol. 2012
Apr;148(4):487-94.
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What is new in Pediatric Dermatology
Antonio Torrelo
Pediatric Dermatology is a young specialty experiencing continuous and rapid advances. Genetics is the most exciting area of advance in Pediatric Dermatology; not only advances in Genetics have permitted disclosing the pathophysiology of many skin diseases in children, but in the near future, it is foreseeable that the next generation sequencing techniques will change our ways to practice Dermatology in children. Genetic diagnosis will become cheap and virtually every genetic disease will be easily diagnosed. The next generation sequencing techniques are permitting the genetic characterization of common diseases, such as atopic dermatitis, through the analysis of the so-called copy number variations. Exome sequencing or whole genome sequencing have permitted to find genes for formerly enigmatic diseases, and even mosaic disorders are no longer a genetic mistery.