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10 June 2015

WCD 2015 Vancouver - Paediatric dermatology and oncology

Intense! There has been a rapid succession of workshops and conferences in Vancouver's Convention Centre. Some of the braver delegates go for a jog in the nearby Stanley Park to let off steam and enjoy the sunshine. But you can count on our onsite dermatologist reporters to share their highlights with you every day. Wednesday was another resounding success with the ILDS vote on the venue of the next World Congress: we'll see you in Milan in 2019!

World congress of dermatology - Vancouver 2015


 

News on atopic dermatitis. R Fölster-Holst ( Germany) by Dr Florence Corgibet

A new strategy for managing atopic dermatitis (AD) is being implemented. Until recently, avoiding certain types of food was recommended as primary prevention, and restoring the skin barrier, notably via emollients, as secondary prevention. We now know that food contact with the digestive tract, on the contrary, stimulates tolerance. In addition, restoration of the skin barrier seems to contribute to AD prevention and is becoming a primary prevention element. (Ref.: Simpson et al. Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis prevention: J Allergy Clin Immunol 2014, 134: 818-23. Horimukai et al. Application of moisturizer to neonates prevents development of atopic dermatitis. J Allergy Clin Immunol 2014, 134: 824-30). Which children would this primary prevention target? A very good criterion in predicting skin barrier dysfunction is the measurement of transepidermal water loss. This non-invasive measurement, carried out at ages 2 days and 2 months (M Kelleyer et al. Skin barrier dysfunction measured by transepidermal water loss at 2 days and 2 months predates and predicts atopic dermatitis at 1 year. J Allergy Cli Immunol 2015, 135:930-5) precedes the clinical signs of AD. It can help target the children who have access to this primary prevention and specify the optimal timeframe. The speaker showed beautiful electron microscopy images (Lipbarvis° TEM, Lipid Barrier Visualization) to illustrate how emollients restore the organisation of the intercellular lipid lamellae, very disrupted in AD, from the 10th day of application (as with patients under local corticosteroid therapy or tacrolimus). 

Non-invasive techniques useful in paediatric dermatology. U Blume-Peytavi ( Germany) by Dr Florence Corgibet

This interesting presentation on the exploration of babies' skin notably outlines the measurement of transepidermal water loss (TEWL) demonstrating how the skin barrier works. The sensor is simply applied onto the baby's skin for 30 to 40 seconds. The results are affected by humidity and room temperature, the baby's cries and movements, if he/she has a fever. The speaker cited the TEWAMETER° TM 300 as an example, the world's most commonly used TEWL measurement instrument. 

New treatment possibilities. Kenji Kabashima ( Kyoto) by Dr Florence Corgibet

A promising treatment in atopic dermatitis: Dupilumab. This is a JAK-inhibitor monoclonal antibody targeting the alpha sub-unit of the interleukin-4 receptors, blocking both interleukin 4 and interleukin-13, which play a role in AD, as they are involved in the inflammatory response as well as the keratinocyte differentiation process and therefore in the skin barrier dysfunction (increased TEWL, reduced Natural Moisturising Factor - NMF). This is an effective treatment for allergic asthma and has just been tested in AD during a randomised, double-blind study versus placebo, as a monotherapy and in combination with local corticoids in adults suffering from moderate to severe AD. 85% of the patients from the dupilimab group improved their AD score by 50% compared with 35% in the placebo group, 100% in the dupilimab+ corticoids group compared with 50% in the Placebo + corticoids group, despite consumption being more than halved in the dupilimab group (Beck et al including T Bieber and Simpson. Dupilumab treatment in adults with moderate to severe atopic dermatitis. N Engl J Med 2014, 371:130-9). Skin infections are more severe in the placebo group; nasopharyngitis and headaches are the most frequent adverse effects. Dupilumab blocks the action of IL4 and 13 and enhances the keratinocyte differentiation process, increasing the NMF and restoring the skin barrier (reduced TEWL). 

Psoriasis in children: co-morbidities. K Cordoro (San Francisco) by Dr Florence Corgibet

All over the world, psoriasis in children and adults is associated, with obesity and the metabolic syndrome. Young patients and patients with a more severe disease are most at risk, probably because of persistent moderate systemic inflammation. Psoriasis is essentially associated with abdominal obesity. Weight loss reduces the modifiable cardiovascular risk factors (HTA, total cholesterol, blood glucose level, triglycerides and VLDL) but does not improve the endothelial microvascular function. Hence the relevance of prevention and acting at a very early stage with these children, to identify high-risk subjects and apply prevention or corrective measures (BMI evaluation and monitoring, healthier lifestyle, improved psychosocial approach, etc.) with a multidisciplinary treatment. 

Treatment and prognosis of guttate psoriasis (GP) in children. K Cordoro (San Francisco) by Dr Florence Corgibet

- There are clearly two distinct categories of GP in children.
-  Recent onset GP occurring in a context of a well identified streptococcus infection in a child with no family history of psoriasis: this form will probably disappear quickly with simple treatments and antibiotic therapy.
-  GP without streptococcus identification in a child with a family history of psoriasis: this form will require more significant treatments and this situation will more than likely evolve into severe psoriasis.
- The management of these forms of GP therefore depends on these prognosis factors and the 2nd category should involve a more systemic treatment, with the synergistic combination of UVB and retinoids ( 0.3 mg/kg/d) as first-line treatment. In practice, the systematic search for streptococcus in guttate psoriasis helps optimise the treatment while establishing a prognosis.

Mucosal damage in children. D Marcoux (Montreal) by Dr Florence Corgibet

- Citing the clinical case of a young girl, the author pointed out that orofacial granulomatosis in children is often the initial manifestation of CD. At age 2, the child suffered from constipation and encopresis. At age 5, swelling and erythema appeared on the lips, gums and labia majora as well as anal fissures. At age 6, radiological and endoscopic colonic examinations were normal. At age 7, lip and labia majora biopsies revealed an epithelioid and giant-cell granulomatous infiltrate. The digestive re-examinations were positive. The oral manifestations of CD are very frequent in children (more than 40% of the subjects affected), appear at a very young age, often years before the digestive signs and are more common in boys. Anal fissures can be painless and must be looked for. 
- Anal damage is common in lichen sclerosus (LS) in young girls but rarer in boys. Between the ages of 9 and 11, LS is responsible for 40% of phimosis cases.
- Gingival hypertrophy, when combined with traditional medicinal product causes (anticonvulsants, calcium channel blockers and ciclosporin) and granulomatous causes (Crohn's disease, sarcoidosis), can be a sign of hemopathy: leukaemia, Langerhans cell histiocytosis.

Surgical treatment of lentigo melanoma - D. Zloty (Vancouver) by Dr Jean-François Sei

The surgical treatment of in situ lentigo melanoma raises the issue of size and resection margins. Recommendations in France since 2005 have been of 10 mm (instead of the 5 mm previously recommended, that remain acceptable for other types of in situ melanomas). This high margin requires fairly large resections, for lesions that are often facial, and could in fact be considered too large. However this is not the case: the communication issued by David Zloty, a dermatologist in Vancouver (University of British Colombia) confirms that an average of 7.1 mm (between 4 and 19 mm) of lateral margin is required for full resection: our standard margin of 10 mm is therefore insufficient at times. Micrographic surgery is used to adapt the margin according to the extent of the treated tumour, so full resection can be accomplished. With this technique, the relapse rate after 5 years is only 4.3%.
Radiotherapy - only seldom used in France - is an option, whereas the use of imiquimod has not yet been sufficiently assessed in such cases. 

Mohs surgery revision - Vanessa Palmer (London) by Dr Jean-François Sei

Following the resection of a basal cell carcinoma, anatomopathological responses sometimes indicate that the resection was incomplete. Immediate recommended revision surgery is once again analysed, and the response is more often than not "changes in fibro-scarring structure with no residual tumour proliferation found". Revision surgery could thus be deemed useless: Vanessa Palmer, from St John's Institute of Dermatology in London, recounts her experience in the revision of 100 Mohs surgeries for basal cell carcinomas in which resection was incomplete: 12% of these patients had a clinically visible residual tumour, which was found in 69% of all cases. The recommendation for immediate revision surgery is confirmed, as opposed to a "wait and see" strategy: relapse is in fact common in the event of incomplete resection, and treating a relapse tumour is always more difficult, in addition to there being a higher risk of relapse than with primary tumours - including with Mohs surgery.  

Incidence and characteristics of squamous cell carcinoma - Chrysalyne Schmults (USA) by Dr Jean-François Sei

According to Chrysalyne Schmults - an American Mohs surgeon - squamous cell carcinoma is becoming a more and more common tumour in the USA, reaching the incidence of basal cell carcinomas. Its gravity is greatly underestimated: it is responsible for more deaths than melanoma in the central and southern American states, i.e. close to 9,000 deaths per year. It is therefore essential to identify high-risk squamous cell carcinoma characteristics, and a clinical tumour classification is provided - if more than 1,393 patients are treated - by the Brigham and Women’s Hospital (BWH) (Jambusaria and Schmults: JAMA April 2013; Karia, Schmults et al: J Clinical Oncology December 2013) based on the acronym 3D/PNI, i.e. 4 criteria: Clinical diameter >2 cm, Depth in sub-cutaneous fatty tissue, Low differentiation and Perineural invasion
T1: no criteria, T2a: 1 criterion, T2b: 2 or 3 criteria, T3: 4 criteria or bone invasion
The T1 stage shows a good prognosis with 0.6% of relapsing and 0.1% of nodal metastasis: in these cases and in the event of full resection, the patient is considered cured.
Stage T2a shows an intermediary prognosis: the risk is low, but this group still presents a 17% chance of death by squamous cell carcinoma - the importance here resides in finding additional bad prognosis elements, such as a diameter smaller than but close to 2 cm, and immunosuppression for instance.
The T2b stage (and rare T3 cases) only represents 6% of the BWH group, but also 76% of nodal metastasises and 83% of deaths by squamous cell carcinoma. The first goal is therefore to fully resect the tumour and carefully assess the area's nodal extent - first using radiology and/or an ultrasound; if these tests are negative, a sentinel lymph node test is conducted. Chrysalyne Schmults greatly insisted on how important the early detection of node involvement is: 7% of all T2a and 29% of T2b patients show a positive sentinel lymph node (Schmidt JAMA dermatol January 2014). Yet the death rate for squamous cell carcinoma is linked - in 85% of all cases - to loco-regional involvement (which makes the search for sentinel nodes quite different to melanoma, where metastasises can exist remotely at the time the sentinel node is searched for): in the event of a positive sentinel node, a lymph node dissection could thus improve overall survival in high-risk squamous cell carcinoma patients. Furthermore, additional radiotherapy is recommended in T3 and certain T2a stages.
We could in the end be surprised to notice the absence of certain clinical criteria from this classification (relapse tumours, location in the body's extremities), as well as certain histological criteria (tumour thickness and desmoplasia), but the focus should be set on searching for the sentinel node in high-risk squamous cell carcinomas.