Акценти от 2-ри ден

General dermatology, Oncology/Dermatology, Atopic dermatitis, Sunscreens and the environment

Dr. Lise Boussemart

Dermatologist, Rennes, France

General dermatology

Dr. Ruth Ann Vleugels, Dermatologist, United States
Dr. David Eric Cohen, Dermatologist, United States
Dr. Edward W. Cowen, Dermatologist, United States
Dr. Jean L. Bolognia, Dermatologist, United States
Dr. Kenneth J. Tomecki, Dermatologist, United States

Dear all,

This morning, I signed up for the session on “general dermatology”. It was an update of knowledge in general dermatology and was very useful to me, as I have been specialising in oncodermatology for the past few years.

Dr Ruth Ann Vleugels described a relatively recent entity: dermatomyositis with circulating anti “MDA-5” antibodies.

This is a form of dermatomyositis that, as its name does not indicate, is amyopathic.

Most importantly, from a semiological standpoint, it is unique in that it induces painful ulcers on the dorsal surface of the fingers, where Gottron papules are generally located, as well as highly evocative and sensitive erythematous papulo-macules on the hands and feet.

In the presence of these clinical signs, it is necessary to consider dermatomyositis with anti MDA-5 antibodies and treat the rapidly progressing interstitial lung disease that often accompanies it.

Still regarding dermatomyositis, Dr Vleugels noted that only 10% of dermatomyositis cases with exclusive skin involvement improve with hydroxychloroquine on its own. She thus recommends:

• directly combining it with methotrexate, or
• IVIG 1g/kg/day (every four weeks at first, then gradually reduce the frequency over several years), or
• mycophenolate mofetil, which should be favoured if there is associated interstitial lung disease (positive anti-Jo1 or MDA-5 blood tests).

A JAK inhibitor, tofacitinib 10mgx2/day, also seems promising for the treatment of resistant dermatomyositis, due to interferon-mediated autoimmunity.

Regarding subacute cutaneous lupus erythematosus, a Swedish case-control study showed it was associated with the use of certain medications, in particular terbinafine (OR 52.9, 95% CI 6.6-∞), TNFα inhibitors (OR 8.0, 95% CI 1.6-37.2), antiepileptic drugs (OR 3.4, 95% CI 1.9-5.8) and proton pump inhibitors (OR 2.9, 95% CI 2.0-4.0) within six months before lupus diagnosis (Grönhagen et al., Br J Dermatol 2012).

A third of subacute cutaneous lupus erythematosus cases could be associated with exposure to one of these medications and could improve with discontinuation of use.

The following speaker, Dr David Cohen from New York University, reported cross-allergies between formaldehyde (contained in Brazilian straightening products) and aspartame which, as I did not know, is degraded after digestion into formaldehyde.

Dr Edward Cowen then delved into the topic of auto-inflammatory diseases, with overactivation of innate immunity, as opposed to auto-immune diseases, with overactivation of T cells or presence of circulating auto-antibodies.

He described the spectrum of CAPS syndromes (cryopyrin-associated periodic syndrome, whose forms include familial cold urticaria and Muckle-Wells syndrome) caused by “gain-of-function” mutations in the NLRP3 encoding gene for cryopyrin, which all respond to anakinra including Schnitzler's syndrome.

But most importantly, he spoke of two new auto-inflammatory syndromes, caused by mutations activating the NLRP1 gene: multiple self-healing palmoplantar carcinoma and familial keratosis lichenoides chronica (Zhong et al., Cell 2016).

Dr Jean Bolognia from Yale then described the cutaneous side effects of new treatments for metastatic melanoma.

These are particularly important to know since anti-PD-1 immunotherapy is now also commonly prescribed for lung and bladder cancer and Hodgkin's lymphoma. Lastly, PD-1 inhibitors have only recently been authorised as adjuvant therapy for stage III melanoma, and a study published on 25 February 2019 even proposed them for neoadjuvant therapy (Huang et al., Nature Medicine 2019).

Rashes occurring with anti-PD-1 therapy are usually lichenoid and eczematous; they are sometimes psoriasiform and very rarely bullous.

The therapeutic recommendations published in JCO in 2018 proposed topical corticosteroids +/- antihistamines for grades I-II, oral corticosteroids (1 to 2mg/kg/day) for grade III and intravenous corticosteroids for grade IV. Dr Bolognia criticised these recommendations and suggested adding, according to clinical practice, etretinate/acitretin, apremilast or methotrexate by analogy to standard psoriasis treatments. In my experience, acitretin has been very effective against anti-PD-1-induced psoriasis. Moreover, the cutaneous side effects of targeted therapies have been minimal since BRAF inhibitors have been systematically combined with an MEK inhibitor. The main thing to keep in mind is the risk of secondary tumours, erythema nodosum and drug-induced maculopapular rash.

To close the morning session, Dr Kenneth Tomecki from Cleveland presented a review of HIV, regretting that only half of the 33 million HIV-positive people around the world are currently receiving a specific treatment. There are now more than 30 different antiretroviral drugs, and patients should take at least three at the same time as soon as their HIV-positive status is known, before their CD4 count starts to decline. He also mentioned a new recombinant shingles vaccine, Shingrix*, which will probably overshadow its competitor Zostavax* (live attenuated vaccine), considering its high level of efficacy (90% of shingles cases prevented in the three to five years following its administration compared to a placebo) and its probable safety for immunocompromised subjects (Lal et al., NEJM 2015).

Oncology/Dermatology

Dr Abigail Baird Waldman, Dermatologue, États-Unis
Dr Matthew D. Belcher, Dermatologue, États-Unis
Dr Murad Alam, Dermatologue, États-Unis
Dr Ashley Decker, Dermatologue, États-Unis
Dr Evan A. Rieder, Dermatologue, États -Unis
Dr Jason Riis, Psychologue, États-Unis

In the afternoon, I attended a more “cancer”-oriented session. Dr Abigail Waldman started the session by discussing the various classifications for cutaneous squamous-cell carcinomas (AJCC8, BWH, etc.). According to the American National Comprehensive Cancer Network (NCCN), a >2cm (vs <2cm) diameter and a poorly differentiated nature multiply the risk of recurrence by two to three, whereas a >6mm thickness or hypodermal involvement multiplies this risk by 10 to 11. The most worrisome histological marker in primary tumours is perineural or vascular invasion (x23 risk of local recurrence, x12 for distant recurrence), which means priority should be given to a complete circumferential histological analysis of the peripheral and deep margins, and adjuvant radiotherapy should be discussed. In the event of lymph node metastasis, nodal dissection is indicated, with 30 sessions of 60 Gy adjuvant radiotherapy over a six-week period.

Cemiplimab or Libtayo* (PD-1 inhibitor) has been approved by the US FDA as the first therapy for metastatic cutaneous squamous-cell carcinoma.

The following presentation, by Dr Matthew Belcher, dealt with the 8th edition of the AJCC melanoma staging system. For information, this latest edition lowered the melanoma severity threshold to 0.8mm in Breslow depth (vs 1mm previously). The sentinel lymph node technique should now be discussed for melanoma from the T1b stage, i.e. from 0.8mm in Breslow depth or regardless of Breslow depth when there is ulceration. Since Breslow depth is now to be expressed with only one number after the period, a melanoma with Breslow depth of 0.75mm should be considered a 0.8mm and thus stage T1b melanoma. A positive sentinel lymph node (with metastasis > 1mm) enables adjuvant treatment to be proposed based on pembrolizumab or dabrafenib+trametinib for one year. Operated stages IIIb, IIIc and IV can also be treated with nivolumab as adjuvant therapy. We are thus witnessing a complete change of habits in the therapeutic care of melanomas, with the sentinel lymph node technique moving from “optional” to “decisive” – until stage II adjuvant trials have been undertaken.

Dr Murad Alam then spoke of the relevance of publishing official expert recommendations, as part of an inter-speciality collaboration if possible, for both common and rare cancers, to guarantee at least some homogeneity and safety in practices. In the United States, there are “NCCN” and “AAD” recommendations for the main forms of skin cancer, and there are equivalent guidelines in Europe.

The next speaker, Dr Ashley Decker, spoke of the advantages of using multimedia content such as explanatory videos to improve the “patient experience”. Of course, videos cannot replace patient dialogue, but a well-designed video can, without taking up more of the doctor’s time, enhance the patient's level of understanding and education and thus improve the treatment experience (randomised clinical trial by Love et al., JAAD 2016).

In aesthetic dermatology, Dr Evan Rieder then warned about dysmorphophobic patients, who are almost always dissatisfied, with an unknown risk of suicide, and whose truly “enlightened” consent is questionable. Little research has been conducted into dysmorphophobia, described in relatively few publications, contrasting with the danger these patients impose on their own bodies and on their doctors (laws uits, physical and verbal violence, etc.). Some short questionnaires can help screen for dysmorphophobia, such as the BDD Q questionnaire: Body Dysmorphic Disorder Questionnaire (BDDQ)

Among doctors specialising in aesthetic procedures, the reported proportion of dysm orphophobic patients ranges from one speciality to the next (15% for dermatologists, 5% for general practitioners). This variation gives rise to concerns about a lack of “identification”. Dr Rieder recommends refusing to perform aesthetic procedures for this “fragile” population, saying: “I wonder if you might have dysmorphophobia. I sense that you feel frustration going beyond your external appearance. Would you agree to first work on this dislike instead of undergoing multiple aesthetic procedures?” Of course, a good psychiatrist colleague or a psychodermatology specialist will be invaluable if exploring the why and how of things is not our strong point.

To conclude, Dr Jason Reis, a psychologist, sought to show us how dermatology can benefit from knowledge of behavioural sciences. Behavioural sciences are based on the observation that human beings constantly make judgement/decision errors, through automatic thoughts and emotions, which can be improved with intention and technique. This requires motivation, living in the present moment (“here and now”), facilitation (people are lazy by nature) and intentional positive feedback. I insist on the word “intentional” since studies have shown that we always think we have given more positive feedback than what has actually been perceived.